NeuroTOC

- Biorxiv

• Astrocytic GABA transport contributes to abnormal inhibition in Fragile X Syndrome
  Authors: Wagner, V.; Thapa, R.; Kulinich, A. O.; Varallo, A.; Wimberly, J.; Rais, M.; Gerasymchuk, D.; Piepponen, T. P.; Razak, K.; Castren, M. L.; Ethell, I.
  Published: 2025-08-12 (new results)
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  Fragile X syndrome (FXS) is a leading genetic cause of autism-like symptoms associated with sensory hypersensitivity and circuit hyperexcitability. Recent observations in humans and Fmr1 knockout (KO) models of FXS suggest abnormal GABAergic signaling may underlie pathophysiology of FXS. However, the role of astrocytes in mediating defective inhibition in FXS is unknown. Here we show that human FXS astrocytes derived from patient-specific induced pluripotent stem cells (iPSCs) and mouse Fmr1 KO astrocytes show a significant increase in levels of GABA and GABA-synthesizing enzyme GAD65/67. Our study implicates reverse GABA transport in astrocytes in suppressing PV expression and increasing cortical cell activity in astrocyte-specific Fmr1 KO mice, which also show reduced inhibitory connectivity and impaired cortical sound-evoked gamma synchronization, as well as increased locomotor activity and altered social behaviors. Our findings suggest astrocytes play a key role in the development and function of inhibitory circuits, and contribute to FXS-associated phenotypes. Highlights[vrecto] FXS astrocytes show elevated levels of GABA and its synthesizing enzyme GAD65/67 [vrecto]Fmr1 KO cortical astrocytes suppress PV expression leading to enhanced overall cell activity through reverse GABA transport [vrecto]Astrocyte-specific postnatal deletion of Fmr1 results in reduced inhibitory cortical connectivity, impaired cortical responses to stimuli and behavioral hyperactivity [vrecto]Acute blockade of astrocytic GABA transport was sufficient to restore EEG responses and correct hyperactive mouse behaviors

• Neurovascular Coupling in the Basolateral Amygdala Modulates Negative Emotions
  Authors: Ruan, J.; Quan, X.; Zhang, Y.; Xie, H.; Zhang, D.; Wang, W.; Zhao, B.; Lu, D.; Jia, J.-M.
  Published: 2025-08-14 (new results)
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  Emotion induces changes in regional cerebral blood flow (rCBF), a manifestation of neurovascular coupling (NVC), yet whether NVC might feedback to modulate emotion actively remains unexplored. Here, we demonstrated that NVC actively modulates stress-induced negative emotions. We established bidirectional manipulations of NVC in freely moving mice by employing integrated pharmacological, genetic, and arteriolar optogenetic approaches. Our results showed that both systemic and basolateral amygdala (BLA) regional specific NVC deficiencies heightened emotional responses when mice transitioned from a home cage to anxiogenic environments, and local restoration of NVC in the BLA normalized these responses. Furthermore, by combining BLA neuronal activity mapping with behavioral measures of responses to various stressors, we revealed that the spatial patterns of BLA neuronal activation predicted emotional response magnitudes, with hyper- and hypoactive BLA predicting heightened and blunted behavioral responses, respectively, in the NVC-deficient mice. Finally, enhancing NVC, achieved through either pharmacological or genetic manipulations, promoted resilience to chronic-stress-induced NVC impairments and alleviated emotional distress. These findings established NVC as an allostatic program for fine-tuning emotional responses, with implications for understanding and treating emotional disorders.

• SKOOTS: Skeleton oriented object segmentation for mitochondria
  Authors: Buswinka, C. J.; Osgood, R. T.; Nitta, H.; Indzhykulian, A. A.
  Published: 2025-08-13 (new results)
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  Segmenting individual instances of mitochondria from imaging datasets can provide rich quantitative information, but is prohibitively time-consuming when done manually, prompting interest in the development of automated algorithms using deep neural networks. Existing solutions for various segmentation tasks are optimized for either: high-resolution three-dimensional imaging, relying on well-defined object boundaries (e.g., whole neuron segmentation in volumetric electron microscopy datasets); or low-resolution two-dimensional imaging, boundary-invariant but poorly suited to large 3D objects (e.g., whole-cell segmentation of light microscopy images). Mitochondria in whole-cell 3D electron microscopy datasets often lie in the middle ground--large, yet with ambiguous borders, challenging current segmentation tools. To address this, we developed skeleton-oriented object segmentation (SKOOTS)--a novel approach that efficiently segments large, densely packed mitochondria. SKOOTS accurately and efficiently segments mitochondria in previously difficult contexts and can also be applied to segment other objects in 3D light microscopy datasets. This approach bridges a critical gap between existing segmentation approaches, improving the utility of automated analysis of three-dimensional biomedical imaging data. We demonstrate the utility of SKOOTS by applying it to segment over 15,000 cochlear hair cell mitochondria across experimental conditions in under 2 hours on a consumer-grade PC, enabling downstream morphological analysis that revealed subtle structural changes following aminoglycoside exposure--differences not detectable using analysis approaches currently used in the field.

• Mechanistic explanation of neuroplasticity using equivalent circuits
  Authors: Nilsson, M. N. P.
  Published: 2025-08-12 (new results)
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  This paper presents a comprehensive mechanistic model of a neuron with plasticity that explains how information input as time-varying signals is processed and stored. Additionally, the model addresses two long-standing, specific biological challenges: Integrating Hebbian and homeostatic plasticity, and identifying a concise synaptic learning rule. A biologically accurate electric-circuit equivalent is derived through a one-to-one mapping from the known properties of ion channels. The often-overlooked dynamics of the synaptic cleft is essential in this process. Analysis of the model reveals a simple and succinct learning rule, indicating that the neuron functions as an internal-feedback adaptive filter, a common concept in signal processing. Simulations confirm the models functionality, stability, and convergence, demonstrating that even a single neuron without external feedback can act as a potent signal processor. The model replicates several key characteristics typical of biological neurons, which are seldom captured in other neuron models. It can encode time-varying functions, learn without risking instability, and bootstrap from a state where all synaptic weights are zero. This paper explores the function of neurons with a focus on biological accuracy, not computational efficiency. Unlike neuromorphic models, it does not aim to design devices. The electronic circuit analogy aids understanding by leveraging decades of electronics expertise but is not intended for physical implementation. This interdisciplinary work spans a broad range of subjects within the realm of neurobiophysics, including neurobiology, electronics, and signal processing. Significance statementMechanistic neuron models with plasticity are crucial for understanding the complexities of the brain and the processes behind learning and memory. These models provide a way to study how individual neurons and synapses in the brain change over time in response to stimuli, allowing for a more nuanced understanding of neuronal circuits and assemblies. Plasticity is a key aspect of these models, as it represents the ability of the brain to modify its connections and functions in response to experiences. By incorporating plasticity into these models, researchers can explore how changes at the synaptic level contribute to higher-level changes in behavior and cognition. Thus, these models are essential for advancing our understanding of the brain and its functions. PhySH termsNeuroplasticity, Neural basis of learning and memory, Synapses. MeSH 2023 termsNeuronal Plasticity [G11.561.638], Association learning [F02.463.425.069.296], Memory [F02.463.425.540], Synaptic transmission [G02.111.820.850]

• Pupil size predicts the onset of exploration and changes in prefrontal dynamics
  Authors: Shourkeshti, A.; Abbaszadeh, M.; Marrocco, G.; Jurewicz, K.; Moore, T.; Ebitz, R. B.
  Published: 2025-08-12 (new results)
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  In uncertain environments, intelligent decision-makers exploit actions that have been rewarding in the past, but also explore actions that could be even better. Several neuromodulatory systems are implicated in exploration, based, in part, on work linking exploration to pupil size-a peripheral correlate of neuromodulatory tone and index of arousal. However, pupil size could instead track variables that make exploration more likely, like volatility or reward, without directly predicting either exploration or its neural bases. Here, we simultaneously measured pupil size, exploration, and neural population activity in the prefrontal cortex while two rhesus macaques explored and exploited in a dynamic environment. We found that pupil size under constant luminance specifically predicted the onset of exploration, the first exploratory trial in a sequence, beyond what could be explained by reward history. Pupil size also predicted disorganized patterns of prefrontal neural activity at both the single neuron and population levels, even within periods of exploitation. Ultimately, our results support a model in which pupil-linked mechanisms promote the onset of exploration via driving the prefrontal cortex through a critical tipping point where prefrontal control dynamics become disorganized and exploratory decisions are possible. Significance StatementHumans and other animals learn about the world through exploration: through making decisions that offer the opportunity to learn and discover, even when these decisions are not the best option in the moment. Neuroscience research has historically focused on understanding good choices, delivering many key insights into the neural mechanisms involved in these calculations. However, much less is known about how the brain generates exploratory decisions. This study identifies certain "early warning signs" of exploratory decisions in the brain and body, including certain signals in size of the pupil and the speed of neural activity in the prefrontal cortex. These early warning signs suggest that exploration may be the result of a critical tipping point in prefrontal brain states.

• Modulation of Karyopherin Levels Attenuates Mutant Ataxin-1-Induced Neurodegeneration
  Authors: Ruff, E. K.; Timperman, D. L.; Amador, A. A.; Aguirre-Lamus, I.; Salim, k.; de Haro, M.; Al-Ramahi, I.
  Published: 2025-08-15 (new results)
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  Neurodegenerative diseases are characterized by the abnormal accumulation of disease-driving proteins. Emerging evidence suggests that nucleocytoplasmic transport (NCT) components play a critical role in neurodegeneration. This study investigates the effects of modulating the levels of different karyopherins on mutant Ataxin-1 (mATXN1)-induced neurodegeneration in Spinocerebellar Ataxia Type 1 (SCA1) Drosophila and cell models. Our findings reveal that ATXN1 [82Q] interacts with KPNAs in the nucleus and cytoplasm of neurons. Increasing KPNA levels ameliorates ATXN1 [82Q]-induced neurodegeneration and progressive neuronal dysfunction. Surprisingly, elevated KPNA levels did not increase nuclear mATXN1, instead, mechanistic analyses demonstrate that KPNA retains mATXN1 in the cytoplasm, reducing its nuclear accumulation. Moreover, higher KPNA leads to a decrease in soluble oligomeric mATXN1. Interestingly, inhibition of a different karyopherin, KPNB1, elevated KPNA levels and reduced nuclear mATXN1 in human neuronal precursor cells. Consistently, knockdown of KPNB1 attenuates ATXN1 [82Q]-induced neurodegeneration and reduces its nuclear aggregation in Drosophila. These results indicate that KPNAs may act as chaperones for mATXN1, preventing its nuclear translocation and reducing its pathological effects. Importantly, they also constitute a proof of principle that retaining mATXN1 in the cytoplasm represents an attractive and viable therapeutic option. Given the dysregulation of karyopherins in many neurodegenerative diseases and their emerging role as chaperones, the results presented here may extend beyond SCA1 into other disorders like Alzheimer's or Parkinson's disease.

• Emergent Neuronal Mechanisms Mediating Covert Attention in Convolutional Neural Networks
  Authors: Srivastava, S.; Wang, W. Y.; Eckstein, M. P.
  Published: 2025-08-15 (new results)
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  Covert visual attention allows the brain to select different regions of the visual world without eye movements. Predictive cues of a target location orient covert attention and improve perceptual performance. In most computational models, researchers explicitly incorporate an attentional mechanism that alters processing at the attended location (gain, noise reduction, divisive normalization, biased competition, Bayesian priors). Here, we assess the emergent neuronal mechanisms of Convolutional Neural Networks (CNNs) that exhibit behavioral signatures of covert attention, despite lacking a built-in attention mechanism. We use neuroscience-inspired approaches to analyze 1.8M units of CNNs trained on the cueing paradigm. Consistent with neurophysiology, we show early layers with retinotopic neurons separately tuned to the target or cue, and later layers with neurons with joint tuning and increased cue influence on target responses. CNN computational stages mirror a Bayesian ideal observer (BIO), but with more gradual transitions. The cue influences the target sensitivity through four mechanisms. A BIO-like cue-weighted location summation, and three mechanisms absent in the BIO: an opponency across locations, a summation/opponency location combination, and interaction with the thresholding Rectified Linear Unit (ReLU). Re-analyses of mice's superior colliculus neuronal activity during a cueing task show CNN-predicted but previously unreported cue-inhibitory, location-summation, and location-opponent cells in addition to the commonly reported cue (attention) excitatory cells. The novel single-unit CNN analysis approach establishes a likely system-wide characterization mediating covert attention and a framework to identify new neuron types and emergent computational mechanisms contributing to perceptual behavior.

• MALDI-IM-MS Imaging of Brain Sterols and Lipids in a Mouse Model of Smith-Lemli-Opitz Syndrome
  Authors: Li, A.; Xu, L.
  Published: 2025-08-12 (new results)
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  Smith-Lemli-Opitz syndrome (SLOS) is a neurodevelopmental disorder caused by genetic mutations in the DHCR7 gene, which encodes the enzyme 3{beta}-hydroxysterol-{Delta}7-reductase (DHCR7) that catalyzes the last step of cholesterol synthesis, resulting in deficiency in cholesterol and accumulation of its precursor, 7-dehydrocholesterol (7-DHC). To understand how the brain regions are differentially affected by the defective Dhcr7, we aim to map the regional distribution of sterols and other lipids in neonatal brains from a Dhcr7-KO mouse model of SLOS, using mass spectrometry imaging (MSI). MSI enables spatial localization of biomolecules in situ on the surface of a tissue section, which is particularly useful for mapping the changes that occur within a metabolic disorder such as SLOS, and in an anatomically complex organ such as the brain. In this work, using MALDI-ion mobility (IM)-MSI, we successfully determined the regional distribution of features that correspond to cholesterol, 7-DHC/desmosterol, and the precursor of desmosterol, 7-dehydrodesmosterol, in WT and Dhcr7-KO mice. Interestingly, we also observed m/z values that match the major oxysterol metabolites of 7-DHC (DHCEO and hydroxy-7-DHC), which displayed similar patterns to 7-DHC. We then identified brain lipids using m/z and CCS at the Lipid Species-level and curated a collection of MALDI-IM-MS-derived lipid CCS values. Subsequent statistical analysis of regions-of-interest allowed us to identify differentially expressed lipids between Dhcr7- KO and WT brains, which could contribute to defects in myelination, neurogenesis, neuroinflammation, and learning and memory in SLOS.

• A human-specific microRNA controls the timing of excitatory synaptogenesis
  Authors: Soutschek, M.; LoBianco, A.; Galkin, S.; Wuest, T.; Wentinck, K.; Colameo, D.; Germade, T.; Gross, F.; von Ziegler, L.; Bohacek, J.; Elfving, B.; Germain, P.-L.; Winterer, J.; Kleele, T.; Schratt, G.
  Published: 2025-08-13 (new results)
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  Neural circuit development in the human cortex is considerably prolonged in comparison to non-human primates, a trait that contributes to the remarkable cognitive capacity of modern humans. Here, we explore the regulatory role of non-coding RNAs, which dramatically expanded during brain evolution, in synapse development of human-induced pluripotent stem-cell derived neurons. We found that inhibition of a human-specific microRNA, miR-1229-3p, alters the trajectory of human neuronal maturation and enhances excitatory synaptic transmission. Transcriptome analysis following miR-1229 knockdown revealed a downregulation of mitochondrial DNA (mtDNA) encoded genes. We further show that miR-1229 regulates mitochondrial morphology, mtDNA abundance and matrix calcium concentration, and that stimulation of mitochondrial metabolism rescues decreased calcium buffering in miR-1229-3p depleted neurons. Accordingly, miR-1229 directly targets an entire network of genes involved in mitochondrial function and ER-associated protein homeostasis. Our findings reveal an important function of human-specific miR-1229-3p in developmental timing of human synaptogenesis and generally implicate non-coding RNAs in the control of human connectivity and cognition. One-Sentence SummaryA human-specific microRNA slows down the formation and maturation of neuronal synapses by reducing mitochondrial metabolism.

• Temporal transcriptomic changes during neurodevelopment in a mouse model of Smith-Lemli-Opitz syndrome
  Authors: Li, A.; Tomita, H.; Xu, L.
  Published: 2025-08-12 (new results)
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  Smith-Lemli-Opitz syndrome (SLOS) is a cholesterol biosynthesis disorder that arises from mutations in the gene DHCR7, leading to decreased production of cholesterol and accumulation of its precursor, 7-dehydrocholesterol. SLOS displays a wide range of neurodevelopmental defects, intellectual disability, and behavioral problems. However, an in-depth study on the temporal changes of gene expression in the developing brains has not been done before. In this work, we carried out the transcriptomic analysis of whole brains from WT and Dhcr7-KO mice at embryonic day 12.5 (E12.5), E14.5, E16.5, and postnatal day 0 (PND0). First, we observed the expected downregulation of the Dhcr7 gene in the Dhcr7-KO brains, as well as changes of other genes involved in cholesterol biosynthesis at all time points. Pathway and GO term enrichment analyses revealed affected signaling pathways and biological processes that were shared amongst time points and unique to individual time points. Specifically, the pathways important for embryonic and neural development, including Hippo, Wnt, and TGF-{beta} signaling pathways, are the most significantly affected at the earliest time point, E12.5. Additionally, neurogenesis-related GO terms were enriched in earlier time points, consistent with the timing of development. Conversely, pathways related to synaptogenesis, which occurs later in development compared to neurogenesis, are significantly affected at the later time points, E16.5 and PND0, including the cholinergic, glutamatergic, and GABAergic synapses. In vitro neurogenesis experiments using GABAergic neuronal precursors isolated from embryonic mouse brain confirmed that loss of Dhcr7 led to decreased proliferation and premature neurogenesis, consistent with the transcriptomic changes.

• Desynchronized Somas and Terminals in a Morning Clock Neuron: Presynaptic Ca2+ Spiking and Native Neuropeptide Release Peak As Somatic Ca2+ Declines
  Authors: Klose, M. K.; Kim, J.; Gregg, S. N.; Schmidt, B. F.; Xia, X.; Li, Y.; Levitan, E.
  Published: 2025-08-12 (new results)
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  Drosophila sLNv clock neurons release the co-packaged neuropeptides PDF and sNPF to regulate circadian behaviors (e.g., morning anticipation) and nighttime sleep1-3. Previous studies of membrane potential and cytoplasmic Ca2+ at the soma suggested that sLNv neuron activity peaks at night4,5, but exocytosis of neuropeptide-containing dense-core vesicles (DCVs) at their terminals peaks hours later at midmorning6. To resolve the basis of the timing mismatch between somatic physiology and terminal exocytosis, recently developed probes were used to measure daily rhythms in sLNv neuron synaptic Ca2+ and sNPF release. Remarkably, at midmorning after soma Ca2+ has dropped, both Ca2+ spiking and clock-dependent native neuropeptide release peak in the distal terminals of the protocerebrum. Furthermore, Ca2+ in the soma and terminals differ in dependence on Ca2+ influx. Finally, synaptic DCV exocytosis requires Ca2+ spike activity at terminals that is not evident at the soma. These results lead to two striking conclusions. First, soma Ca2+ recording, which is the focus of many circuit studies, is not indicative of presynaptic Ca2+ and neuropeptide release in distal sLNv terminals. Second, daily clock- and activity-dependent sLNv terminal neuropeptide release occurs [~]9-18 hours in advance of known sLNv neuropeptide effects on nighttime sleep and morning behavior.

• Supramodal and modality-specific neural information supports multi-feature prediction errors across cortical levels
  Authors: Niedernhuber, M.; Fardo, F.; Allen, M.; Bekinschtein, T.
  Published: 2025-08-16 (new results)
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  Predictive coding posits that the brain actively anticipates inputs from different senses, generating prediction errors when incoming information deviates from internal expectations. While much research has focused on prediction errors elicited by violations of single sensory features, natural environments frequently present more complex events deviating across multiple stimulus dimensions and sensory modalities. In this study, we employed a hierarchical oddball paradigm (n=30) manipulating auditory and somatosensory stimuli to violate one or two sensory features while high-density EEG was recorded. Temporal decoding revealed that while both single- and double-deviants evoked sustained supramodal activation patterns, double-deviants uniquely elicited a supramodal response starting at 100 ms after the oddball. Effective connectivity analyses identified shared interhemispheric interactions between inferior frontal gyri across modalities, as well as distinct modality-specific connectivity within early and associative sensory cortices. Our findings demonstrate that multi-feature prediction errors recruit both rapid supramodal integration mechanisms and hierarchically organized modality-specific pathways. These results advance our understanding of how the brain flexibly integrates multiple sensory expectation violations across different levels of cortical processing, providing new insights into the neural architecture supporting predictive perception.

• Dissociable memory modulation mechanisms facilitate fear amnesia at different timescales
  Authors: Ni, Y.; Wang, Y.; Zhu, Z.; Hu, J.; Schiller, D.; Li, J.
  Published: 2025-08-14 (new results)
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  Memory reactivation renders consolidated memory fragile and thereby opens the window for memory updates, such as memory reconsolidation. However, whether memory retrieval facilitates update mechanisms other than memory reconsolidation remains unclear. We tested this hypothesis in three experiments with healthy human participants. First, we demonstrate that memory retrieval-extinction protocol prevents the return of fear expression shortly after extinction training and this short-term effect is memory reactivation dependent (Study 1, N = 57 adults). Furthermore, across different timescales, the memory retrieval-extinction paradigm triggers distinct types of fear amnesia in terms of cue-specificity and cognitive control dependence, suggesting that the short-term fear amnesia might be caused by different mechanisms from the cue-specific amnesia at a longer and separable timescale (Study 2, N = 79 adults). Finally, using continuous theta-burst stimulation (Study 3, N = 75 adults), we directly manipulated brain activity in the dorsolateral prefrontal cortex, and found that both memory reactivation and intact prefrontal cortex function were necessary for the short-term fear amnesia after the retrieval-extinction protocol. The differences in temporal scale, cue-specificity, and cognitive control ability dependence between the short- and long-term amnesia suggest that memory retrieval and extinction training trigger distinct underlying memory update mechanisms. These findings suggest the potential involvement of coordinated memory modulation processes upon memory retrieval and may inform clinical approaches for addressing persistent maladaptive memories.

• Dependence of Contextual Modulation in Macaque V1 on Interlaminar Signal Flow
  Authors: Zhu, S.; Oh, Y. J.; Trepka, E. B.; Chen, X.; Moore, T.
  Published: 2025-08-14 (new results)
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  In visual cortex, neural correlates of subjective perception can be generated by modulation of activity from beyond the classical receptive field (CRF). In macaque V1, activity generated by nonclassical receptive field (nCRF) stimulation involves different intracortical circuitry than activity generated by CRF stimulation, suggesting that interactions between neurons across V1 layers differ under CRF and nCRF stimulus conditions. Using Neuropixels probes, we measured border ownership modulation within large, local populations of V1 neurons. We found that neurons in single columns preferred the same side of objects located outside of the CRF. In addition, we found that cross-correlations between pairs of neurons situated across feedback/horizontal and input layers differed between CRF and nCRF stimulation. Furthermore, independent of the comparison with CRF stimulation, we observed that the magnitude of border ownership modulation increased with the proportion of information flow from feedback/horizontal layers to input layers. These results demonstrate that the flow of signals between layers covaries with the degree to which neurons integrate information from beyond the CRF.

• Acetylcholine demixes heterogeneous dopamine signals for learning and moving
  Authors: Jang, H. J.; McMahon Ward, R.; Golden, C. E. M.; Constantinople, C. M.
  Published: 2025-08-15 (new results)
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  Midbrain dopamine neurons promote both reinforcement learning and movement vigour. A major outstanding question is how dopamine-recipient neurons in the striatum parse these heterogeneous signals. Previous work suggests that cholinergic striatal interneurons may play a role, perhaps by gating dopamine-dependent plasticity, but this has not been tested in behaving animals. Here we studied rats performing a decision-making task with reward- and movement-related events at distinct time points. Optical measurement of dopamine and acetylcholine release in the dorsomedial striatum (DMS) revealed distinct dynamics at task events. Reward cues evoked cholinergic pauses with different phase relationships relative to dopamine. When dopamine slightly lagged cholinergic dips, dopamine predicted future behaviour, and DMS firing rates on subsequent trials. In contrast, when dopamine slightly preceded cholinergic dips, there was no observable relationship between dopamine and learning. Finally, when dopamine was coincident with cholinergic bursts, it preceded and predicted the vigour of upcoming contralateral orienting movements. Our findings suggest that the precise phase relationship between dopamine and acetylcholine allows dopamine to be used for either movement or learning depending on instantaneous behavioural context.

• Syncing Minds for Learning: Student-Teacher Inter-brain Coupling Forecast Cross-semester Academic Fluctuation in Real-World Classrooms
  Authors: Xu, X.; Zhang, D.; Zhang, Y.
  Published: 2025-08-12 (new results)
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  Student performance exhibits dynamic fluctuates throughout the learning process, which reflects deeper educational myths and impacts educational quality and equity. Although teachers are believed to play a pivotal role in shaping these changes, the mechanisms through which student-teacher interactions drive performance variations across individual students remain unclear. The present study investigates student-teacher inter-brain coupling in authentic classroom environments through longitudinal neurophysiological recordings spanning three academic semesters. Using wearable hyperscanning technology, a total of 4,175 longitudinal EEG recordings were collected from 107 junior and senior students across 393 regular Chinese and math classes. While static models revealed a negative association between student-teacher inter-brain coupling and math performance--likely reflecting teacher selection effects--dynamic analyses showed that increased coupling, particularly in the high-beta frequency band, causally predicted academic improvement in both subjects. These findings highlight the functional significance of inter-brain coupling in real-world classroom learning, providing robust ecological validity and supporting its potential as a measurable marker of effective pedagogy. Significance StatementThis study is the first to provide causal evidence, based on real-world classroom data, that enhanced student-teacher inter-brain coupling improved academic performance. Leveraging 4,175 longitudinal EEG recordings from 107 students across three semesters, we show that higher coupling levels predict better learning outcomes over time. Capturing neural dynamics in authentic classrooms, this research offers high ecological validity and strong potential for practical application and large-scale educational implementation.

• Aberrant Molecular Myelin Architecture in Charcot-Marie-Tooth Disease Type 1A and Hereditary Neuropathy with Liability to Pressure Palsies
  Authors: Moss, K. R.; Arowolo, M. A.; Gutierrez, D. R.; Hoke, A.
  Published: 2025-08-15 (new results)
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  Charcot-Marie-Tooth Disease Type 1A (CMT1A) and Hereditary Neuropathy with Liability to Pressure Palsies (HNPP) are the most common inherited peripheral neuropathies and arise from copy number variation of the Peripheral Myelin Protein 22 gene (PMP22). While secondary axon degeneration has been proposed as a primary driver of pathogenesis, our prior work demonstrated neuromuscular deficits in CMT1A mice in the absence of overt axonal loss, prompting investigation into primary myelin dysfunction. Here, we reveal that altered PMP22 dosage profoundly disrupts molecular architecture at critical myelin subdomains, Schmidt-Lanterman incisures (SLIs) and Nodes of Ranvier. Using high-resolution confocal imaging of teased peripheral nerve fibers from CMT1A and HNPP model mice, we identified disorganization of adherens junctions, mislocalization of Connexin29, and altered distribution of nodal ion channels in CMT1A and HNPP, with several defects more pronounced in CMT1A, aligning with clinical severity. Notably, Kv1.2 and Caspr mislocalization along the internode and Nav nodal widening suggest disruption of axoglial domains essential for saltatory conduction. Together, these phenotypes support a model in which PMP22 governs myelin architecture, likely through adherens junction regulation, with its dysregulation predicted to impair metabolic support and axonal ion homeostasis, thereby compromising the structural and functional integrity of myelin and contributing directly to disease pathogenesis. These findings shift the pathogenic paradigm for CMT1A and HNPP from axonal degeneration to primary myelin failure and highlight actionable molecular targets for therapeutic intervention. This study offers mechanistic insight into CMT1A and HNPP and provides a conceptual framework with broad relevance to other dysmyelinating disorders.

• Antibiotic-induced changes to the gut microbiome attenuate neuroinflammation in a mouse model of TBI
  Authors: Flinn, H.; Marshall, A.; Holcomb, M.; Cruz-Pineda, L.; Soriano, S.; Treangen, T.; Villapol, S.
  Published: 2025-08-15 (new results)
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  Traumatic brain injury (TBI) induces both neuroinflammation and gut microbiome dysbiosis, yet the influence of antibiotics (ABX) on TBI-related neuropathology remains unclear. We administered a broad-spectrum oral ABX regimen to deplete the gut microbiome in single and repeated TBI mouse models. In male mice, ABX treatment significantly reduced neuroinflammation and neurodegeneration post-TBI, with no effects observed in uninjured controls. ABX also altered microbiome composition and decreased serum and fecal short-chain fatty acid levels, while intestinal damage and dysbiosis were further exacerbated by TBI severity. Notably, germ-free male mice exhibited heightened neuroinflammation and larger lesion volumes following TBI, underscoring the essential role of the microbiome in recovery. Metagenomic analyses revealed Parasutterella excrementihominis and Lactobacillus johnsonii as potential ABX-resistant taxa post-injury. These findings suggest that short-term ABX treatment may attenuate TBI-induced neuroinflammation by reshaping the gut microbiome, offering directions for microbiome-targeted therapies in TBI.

• Adult-neurogenesis allows for representational stability and flexibility in early olfactory system
  Authors: Chen, Z.; Padmanabhan, K.
  Published: 2025-08-14 (new results)
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  In the early olfactory system, adult-neurogenesis, a process of neuronal replacement results in the continuous reorganization of synaptic connections and network architecture throughout the animal s life. This poses a critical challenge: How does the olfactory system maintain stable representations of odors and therefore allow for stable sensory perceptions amidst this ongoing circuit instability? Utilizing a detailed spiking network model of early olfactory circuits, we uncovered dual roles for adult-neurogenesis: one that both supports representational stability to faithfully encode odor information and also one that facilitates plasticity to allow for learning and adaptation. In the main olfactory bulb, adult-neurogenesis affects neural codes in individual mitral and tufted cells but preserves odor representations at the neuronal population level. By contrast, in the olfactory piriform cortex, both individual cell responses and overall population dynamics undergo progressive changes due to adult-neurogenesis. This leads to representational drift, a gradual alteration in sensory perception. Both processes are dynamic and depend on experience such that repeated exposure to specific odors reduces the drift due to adult-neurogenesis; thus, when the odor environment is stable over the course of adult-neurogenesis, it is neurogenesis that actually allows the representations to remain stable in piriform cortex; when those olfactory environments change, adult-neurogenesis allows the cortical representations to track environmental change. Whereas perceptual stability and plasticity due to learning are often thought of as two distinct, often contradictory processing in neuronal coding, we find that adult-neurogenesis serves as a shared mechanism for both. In this regard, adult-neurogenesis in the mammalian olfactory bulb that has been the focus of considerable study in chemosensory neuroscience may be the mechanistic underpinning behind an array of complex computations.

• Social Decision Preferences for Close Others are Embedded in Neural and Linguistic Representations
  Authors: Guassi Moreira, J. F.; Esparza, L. C.; Silvers, J. A.; Parkinson, C.
  Published: 2025-08-16 (new results)
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  Humans frequently make decisions that impact close others. Prior research has shown that people have stable preferences regarding such decisions and maintain rich, nuanced mental representations of their close social partners. Yet, if and how such mental representations shape social decisions preferences remains to be seen. Using a combination of functional magnetic resonance imaging (fMRI) and natural language processing (NLP), this study investigated how neural and linguistic representations of close others relate to social decision-making. After nominating a parent and friend, male and female participants (N = 63) rated their characteristics and made hypothetical social decisions while undergoing fMRI. Neural representations of parents and friends, relative to the self, were linked to social decision preferences. Specifically, greater neural similarity between self and parent in the temporoparietal junction (TPJ) and nucleus accumbens (NAcc) was associated with a preference for parents, while greater self-friend similarity in the medial prefrontal cortex (mPFC) was associated with friend-preference. Additionally, linguistic analysis of written descriptions of close others from a separate sample of males and females (N = 1,641) revealed that social decision preferences could be reliably predicted from semantic features of the text. High correspondence between neural and linguistic data in the imaging sample further strengthened the association with social decision preferences. These findings help elucidate the neural and linguistic underpinnings of social decision-making, emphasizing the critical role of mental representations in guiding choices involving familiar others.

• FORCE trained spiking networks do not benefit from faster learning while parameter matched rate networks do
  Authors: Newton, T. R.; Nicola, W.
  Published: 2025-08-13 (new results)
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  Training spiking recurrent neural networks (SRNNs) presents significant challenges compared to standard recurrent neural networks (RNNs) that model neural firing rates more directly. Here, we investigate the origins of these difficulties by training networks of spiking neurons and their parameter-matched instantaneous rate-based RNNs on supervised learning tasks. We applied FORCE training to leaky integrate-and-fire spiking networks and their matched rate-based counterparts across various dynamical tasks, keeping the FORCE hyperparameters identical. We found that at slow learning rates, spiking and rate networks behaved similarly: FORCE training identified highly correlated weight matrix solutions, and both network types exhibited overlapping hyperparameter regions for successful convergence. Remarkably, these weight solutions were largely interchangeable--weights trained in the spiking network could be transferred to the rate network and vice versa while preserving correct dynamical decoding. However, at fast learning rates, the correlation between learned solutions dropped sharply, and the solutions were no longer fully interchangeable. Despite this, rate networks still functioned well when their weight matrices were replaced with those learned from spiking networks. Additionally, the two network types exhibited distinct behaviours across different sizes: faster learning improved performance in rate networks but had little effect in spiking networks, aside from increasing instability. Through analytic derivation, we further show that slower learning rates in FORCE effectively act as a low-pass filter on the principal components of the neural bases, selectively stabilizing the dominant correlated components across spiking and rate networks. Our results indicate that some of the difficulties in training spiking networks stem from the inherent spike-time variability in spiking systems--variability that is not present in rate networks. These challenges can be mitigated in FORCE training by selecting appropriately slow learning rates. Moreover, our findings suggest that the decoding solutions learned by FORCE for spiking networks approximate a cross-trial firing rate-based decoding. Author summaryTraining spiking neural networks is much harder compared to training standard recurrent neural networks that are more closely tied to neural firing rates. To understand why, we trained parameter matched spiking and rate-based networks on the same supervised learning tasks with the FORCE technique. We found that the learned spike weights were highly correlated and interchangeable across spiking and firing rate networks for slow learning rates. However, when both networks learn fast, the spiking networks show no tangible improvements in their performance in comparison to the rate networks, with instabilities caused by faster learning in the spiking network. These networks also discover uncorrelated solutions to their weights when the learning is fast, that are only interchangeable in one direction, from spike to rate. This suggests that the decoding solutions learned by FORCE for spiking networks approximate a cross-trial firing rate-based decoding. We then analytically determine that, with slower learning rates, FORCE acts as a low-pass filter on the principal components of the neural bases, where the leading components are highly correlated across spiking and rate networks.

• Ultra-low-field brain MRI morphometry: test-retest reliability and correspondence to high-field MRI
  Authors: Vasa, F.; Bennallick, C.; Bourke, N. J.; Padormo, F.; Baljer, L.; Briski, U.; Cawley, P.; Arichi, T.; Wood, T. C.; Lythgoe, D. J.; Dell'Acqua, F.; Booth, T. C.; Venkataraman, A. V.; Ljungberg, E.; Deoni, S. C. L.; Moran, R. J.; Leech, R.; Williams, S. C. R.
  Published: 2025-08-13 (new results)
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  Magnetic resonance imaging (MRI) enables non-invasive monitoring of healthy brain development and disease. Widely used higher field (>1.5 T) MRI systems are associated with high energy and infrastructure requirements, and high costs. Recent ultra-low-field (<0.1T) systems provide a more accessible and cost-effective alternative. However, it remains uncertain whether anatomical ultra-low-field neuroimaging can be used to reliably extract quantitative measures of brain morphometry, and to what extent such measures correspond to high-field MRI. Here we scanned 23 healthy adults aged 20-69 years on two identical 64 mT systems and a 3 T system, using T1w and T2w scans across a range of (64 mT) resolutions. We segmented brain images into 4 global tissue types and 98 local structures, and systematically evaluated between-scanner reliability of 64 mT morphometry and correspondence to 3 T measurements, using correlations of tissue volume and Dice spatial overlap of segmentations. We report high 64 mT reliability and correspondence to 3 T across 64 mT scan contrasts and resolutions, with highest performance shown by combining three T2w scans with low through-plane resolution into a single higher-resolution scan using multi-resolution registration. Larger structures show higher 64 mT reliability and correspondence to 3 T. Finally, we showcase the potential of ultra-low-field MRI for mapping neuroanatomical changes across the lifespan, and monitoring brain structures relevant to neurological disorders. Raw images are publicly available, enabling systematic validation of pre-processing and analysis approaches for ultra-low-field neuroimaging.

• A flexible high-precision photoacoustic retinal prosthesis
  Authors: Leong, A.; Li, Y.; Ruikes, T. R.; Voillot, J.; Yuan, Y.; Chen, G.; Bradic, C.; Facon, A.; Chhuon, C.-A.; Joffrois, C.; Tessier, G.; Cornebois, M.; Degardin, J.; Louise, J.-D.; Cheng, J.-X.; Yang, C.; Moulet, H.; Picaud, S.
  Published: 2025-08-14 (new results)
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  Retinal degenerative diseases of photoreceptors are a leading cause of blindness with no effective treatment. Retinal prostheses aim to restore sight by stimulating residual retinal cells. Here, we present a photoacoustic retinal stimulation technology. We designed a polydimethylsiloxane and carbon-based flexible film that converts near-infrared laser pulses into a localized acoustic field with 56-m lateral resolution, allowing precise stimulation of mechanosensitive retinal cells. This photoacoustic stimulation robustly and locally modulated retinal ganglion cell activity in both wild-type and degenerated ex vivo rat retinae. In animals subretinally implanted with a millimeter-sized photoacoustic film, pulsed laser stimulation generated neural modulation along the visual pathway to the superior colliculus, as measured by functional ultrasound imaging. The biosafety of the film was confirmed by the absence of short-term adverse effects, while local thermal increases were measured below 1 {degrees}C. These findings demonstrate the potential of photoacoustic stimulation for high-acuity visual restoration in blind patients.

• Developmental Potassium Channel Maturation Enables Robust and Flexible Learning
  Authors: Watanabe, H.
  Published: 2025-08-14 (new results)
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  Modern AI has flourished without molecular detail. Here I examine neural maturation in computational and molecular-physiological contexts. Immature transmission supports learning but collapses beyond task/load thresholds. A developmental screen identified KCNH7, upregulated in mouse cortex, incorporating its channel kinetics elevated spike threshold and stabilized recall, linking maturation to robustness without mechanistic elaboration. In unsupervised Restricted Boltzmann Machines, greater dynamical instability improved performance on complex tasks, highlighting a complementary regime. Developmentally plausible changes in KCNH7 conductance re-tuned reservoir dynamics and chaos, with appropriate levels improving memory and generalization, whereas excessive conductance degraded stability. Brief GPCR-like K modulation balanced responsiveness and accuracy, suggesting neuromodulatory K control as a lever for high-dimensional learning.

• The orbitofrontal cortex updates beliefs for state inference
  Authors: Schiereck, S. S.; Perez-Rivera, D. T.; Mah, A.; DeMaegd, M. L.; Hocker, D.; McMahon Ward, R.; Savin, C.; Constantinople, C. M.
  Published: 2025-08-13 (new results)
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  While the orbitofrontal cortex (OFC) is implicated in learning and inferring latent states, the precise computation performed by OFC for state inference is unclear. Here we show that rat OFC updates beliefs about states, and this process is decipherable from OFC dynamics in rats performing state inference, but not alternative strategies. We trained rats to perform a temporal wagering task with hidden reward states. Well-trained rats used state inference when deciding how long to wait for rewards, and OFC inactivations impaired belief updating about states. Electrophysiology and novel population analysis methods identified latent neural factors reflecting inferred states in rats performing inference, but not other strategies. Neural firing rates and latent population factors showed abrupt changes following trials that were informative of state transitions. These results identify a precise computation performed by OFC, and reveal neural signatures of inference.

• view larger version (49k): org.highwire.dtl.dtlvardef@169ea8org.highwire.dtl.dtlvardef@10a673dorg.highwire.dtl.dtlvardef@1ffeef2org.highwire.dtl.dtlvardef@1a0634e_hps_format_figexp m_fig spatially separated pheromone detection drives adaptive navigation in c. elegans males. the upper panel illustrates how c. elegans males utilize spatially separated pairs of sensory neurons, awa (head) and phd (tail), that detect the same volatile sex pheromone molecule via the receptor srd-1. despite sharing this receptor, head neurons detect gradient changes and activate when concentration increases, suppressing turning, and promoting forward movement and acceleration. in contrast, tail neurons detect absolute concentration and activate at preferred moderate concentrations, inducing reversals and deceleration. the bottom panel shows that upon initial pheromone introduction, simultaneous activation of head and tail neurons cancels each other out, causing males to transition from random walking to a stationary anchoring state, preventing them from chasing the concentration wave initially. as pheromone concentration increases, head neurons dominate, driving forward locomotion and acceleration. at the highest concentrations, tail neurons become less active while head neurons are highly activated, leading to rapid, goal-directed movement (sprinting). incorrect directional choices result in awa deactivation and persistent phd activity, inducing pausing and local exploration. repeated unsuccessful attempts trigger area-restricted searching. c_fig" data-authors="wan, x.; zhou, t.; susoy, v.; park, c. f.; groaz, a.; brady, j. f.; samuel, a. d. t.; sternberg, p. w."> Efficient pheromone navigation via antagonistic detectors
  Authors: Wan, X.; Zhou, T.; Susoy, V.; Park, C. F.; Groaz, A.; Brady, J. F.; Samuel, A. D. T.; Sternberg, P. W.
  Published: 2025-08-12 (confirmatory results)
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  Chemotaxis to a moving potential mate emitting a volatile sex pheromone poses a navigation challenge that requires rapid, precise responses to maximize reproductive success. Volatile chemicals form gradients that differ from soluble compounds, potentially making navigation based on comparisons between spatially separated sensors unreliable for small-bodied animals. Contrary to this model of simple spatial comparison, C. elegans employs an antagonistic strategy, comparing inputs from head (AWA) and tail (PHD) sensory neurons with distinct response properties. Despite sharing a receptor, SRD-1, these detectors play different roles: AWA head neurons promote forward movement and acceleration, while tail PHD neurons induce reversals and deceleration. In increasing pheromone gradients AWA dominates; whereas decreasing gradients inactivate AWAs, allowing PHDs to fine-tune the response and correct the trajectory. Head AWAs are essential for mate-searching, while tail PHDs are crucial for complex tasks. Using a minimal-parameter computational model that recapitulates key findings, we infer the interplay between head and tail signals in adaptive navigation. This study reveals a sexually dimorphic dual-detector system that integrates antagonistic sensory inputs from head and tail neurons to enable adaptive navigation strategies essential for efficient free-moving target location in dynamic environments. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/624901v2_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@169ea8org.highwire.dtl.DTLVardef@10a673dorg.highwire.dtl.DTLVardef@1ffeef2org.highwire.dtl.DTLVardef@1a0634e_HPS_FORMAT_FIGEXP M_FIG Spatially separated pheromone detection drives adaptive navigation in C. elegans males. The upper panel illustrates how C. elegans males utilize spatially separated pairs of sensory neurons, AWA (head) and PHD (tail), that detect the same volatile sex pheromone molecule via the receptor SRD-1. Despite sharing this receptor, head neurons detect gradient changes and activate when concentration increases, suppressing turning, and promoting forward movement and acceleration. In contrast, tail neurons detect absolute concentration and activate at preferred moderate concentrations, inducing reversals and deceleration. The bottom panel shows that upon initial pheromone introduction, simultaneous activation of head and tail neurons cancels each other out, causing males to transition from random walking to a stationary anchoring state, preventing them from chasing the concentration wave initially. As pheromone concentration increases, head neurons dominate, driving forward locomotion and acceleration. At the highest concentrations, tail neurons become less active while head neurons are highly activated, leading to rapid, goal-directed movement (sprinting). Incorrect directional choices result in AWA deactivation and persistent PHD activity, inducing pausing and local exploration. Repeated unsuccessful attempts trigger area-restricted searching. C_FIG

• Phase-specific premotor inhibition modulates leech rhythmic motor output
  Authors: Radice, M.; Sanchez Merlinsky, A.; Yulita, F.; Szczupak, L.
  Published: 2025-08-12 (new results)
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  Understanding how motoneuron activity is finely tuned remains an open question. Leeches are a highly suitable organism for studying motor control due to their well-characterized behaviors and relatively simple nervous system. On solid surfaces leeches display crawling, a rhythmic motor pattern that can be elicited in the isolated nerve cord or even in single ganglia isolated from it. This study aimed to learn how this motor output is shaped by concurrent premotor signals. Specifically, we analyzed how electrophysiological manipulation of a premotor nonspiking (NS) neuron, that forms a recurrent inhibitory circuit (analogous to that formed by vertebrate Renshaw cells), shapes the leech crawling motor pattern. The study included a quantitative analysis of putative motor units active throughout the fictive crawling cycle that shows that the rhythmic motor output in isolated ganglia mirrors the phase relationships observed in vivo. Taken together, the study reveals that the premotor NS neurons, under the control of the segmental pattern generator, modulated the degree of excitation of motoneurons during crawling in a phase-specific manner.

• Complex opioid driven modulation of glutamatergic and cholinergic neurotransmission in a GABAergic brain nucleus associated with emotion, reward and addiction.
  Authors: Chittajallu, R.; Vlachos, A.; Caccavano, A. P.; Yuan, X.; Hunt, S.; Abebe, D.; London, E.; Pelkey, K. A.; McBain, C. J.
  Published: 2025-08-15 (new results)
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  The medial habenula (mHb)/interpeduncular nucleus (IPN) circuitry is resident to divergent molecular, neurochemical and cellular components which, in concert, perform computations to drive emotion, reward and addiction behaviors. Although housing one of the most prominent mu opioid receptor (mOR) expression levels in the brain, remarkably little is known as to how they impact mHb/IPN circuit function at the granular level. In this study, our systematic functional and pharmacogenetic analyses demonstrate that mOR activation attenuates glutamatergic signaling whilst producing an opposing potentiation of glutamatergic/cholinergic co-transmission mediated by mHb substance P and cholinergic neurons, respectively. Intriguingly, this latter non-canonical augmentation is developmentally regulated only emerging during later postnatal stages. In addition, we reveal that specific potassium channels act as a molecular brake on nicotinic receptor signaling in the IPN with the opioid mediated potentiation of this arm of neurotransmission being operational only following attenuation of Kv1 function. Thus, mORs play a complex role in shaping the salience of distinct afferent inputs and transmitter modalities that ultimately influences synaptic recruitment of downstream GABAergic IPN neurons. Together, these observations provide a framework for future investigations aimed at identifying the neural underpinnings of maladaptive behaviors that can emerge when opioids, including potent synthetic analogs such as fentanyl, modulate or hijack this circuitry during the vulnerable stages of adolescence and in adulthood.

• Delayed, Reduced and Redundant: Information Processing of Prediction Errors during Sleep
  Authors: Blume, C.; Dauphin, M.; Niedernhuber, M.; Spitschan, M.; Meyer, M. P.; Cajochen, C.; Bekinschtein, T.; Canales-Johnson, A.
  Published: 2025-08-12 (new results)
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  During sleep, the human brain transitions to a sentinel processing mode, enabling the continued processing of environmental stimuli despite the absence of consciousness. Here, we employed advanced information-theoretic analyses, including mutual information (MI) and co-information (co-I), alongside event-related potential (ERP) and temporal generalization analyses (TGA), to characterize auditory prediction error processing across wakefulness and sleep. We hypothesized that a shared neural code would be present across sleep stages, with deeper sleep being associated with reduced information content and increased information redundancy. To investigate this, twenty-nine young healthy participants were exposed to an auditory local-global oddball paradigm during wakefulness and during an 8-hour sleep opportunity monitored via polysomnography in a cross-sectional study. We focused on local mismatch responses to a deviating fifth tone following four standard tones. ERP analyses showed that prediction error processing continued throughout all sleep stages (N1-N3, REM). Mutual information analyses revealed a substantial reduction in the amount of encoded prediction error information particularly during N3 and REM, although ERP amplitudes increased with deeper NREM sleep. In addition, we observed delayed information encoding during sleep and co-information analyses showed that neural dynamics became increasingly redundant with increasing sleep depth. Temporal generalisation analyses revealed a largely shared neural code between N2 and N3 sleep, although it differed between wakefulness and sleep. Here, we showed how the neural code of the sentinel processing mode changes from wake to light to deep sleep and REM, characterised by delayed processing, more redundant and less rich neural information in the human cortex as consciousness wanes. This altered stimulus processing reveals how neural information changes with the changes of consciousness states as we traverse the night.

• 85.4% of cases when considering time windows beyond one minute for detection. to detect non-wear intervals based on black bag use and lack of motion, we employed an algorithm detecting clusters of low illuminance and clusters of low activity. performance was higher for illuminance (f1=0.78) than activity (f1=0.52). light exposure metrics derived from the full dataset, a dataset filtered for non-wear based on self-reports, and a dataset filtered for non-wear using the low illuminance clusters detection algorithm showed minimal differences. our results highlight that while non-wear detection may be less critical in high-compliance cohorts, systematically collecting and detecting non-wear intervals is feasible and important for ensuring robust data pre-processing." data-authors="guidolin, c.; zauner, j.; hartmeyer, s. l.; spitschan, m."> Collecting, detecting and handling non-wear intervals in longitudinal light exposure data
  Authors: Guidolin, C.; Zauner, J.; Hartmeyer, S. L.; Spitschan, M.
  Published: 2025-08-16 (new results)
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  In field studies using wearable light loggers, participants often need to remove the devices, resulting in non-wear intervals of varying and unknown duration. Accurate detection of these intervals is an essential step during data pre-processing. Here, we deployed a multi-modal approach to collect non-wear time during a longitudinal light exposure collection campaign and systematically compare non-wear detection strategies. Healthy participants (n=26; mean age 28{+/-}5 years, 14F) wore a near-corneal plane light logger for one week and reported non-wear events in three ways: pressing an "event marker" button on the light logger, placing it in a black bag, and using an app-based Wear log. Wear log entries, checked twice daily, served as ground truth for non-wear detection, showing that non-wear time constituted 5.4{+/-}3.8% (mean{+/-}SD) of total participation time. Button presses at the start and end of non-wear intervals were identified in >85.4% of cases when considering time windows beyond one minute for detection. To detect non-wear intervals based on black bag use and lack of motion, we employed an algorithm detecting clusters of low illuminance and clusters of low activity. Performance was higher for illuminance (F1=0.78) than activity (F1=0.52). Light exposure metrics derived from the full dataset, a dataset filtered for non-wear based on self-reports, and a dataset filtered for non-wear using the low illuminance clusters detection algorithm showed minimal differences. Our results highlight that while non-wear detection may be less critical in high-compliance cohorts, systematically collecting and detecting non-wear intervals is feasible and important for ensuring robust data pre-processing.

• Scaling Up Social Behavior Studies: Real-Time, Large-Scale and Prolonged Social Behavior Analysis with PrecisionTrack
  Authors: Coulombe, V.; Monfared, M. S.; Leboulleux, Q.; Peralta, M. R.; Aghel, K.; Gosselin, B.; Labonte, B.
  Published: 2025-08-13 (new results)
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  Large-scale ethological behavioral studies can provide novel insights into the neuronal processes underlying complex and social behaviors, potentially opening new mental health research avenues. However, conducting such studies remains a tedious and time- consuming process, often requiring manual annotation of predefined ethological features. Although researchers are aware that current protocols constrain the potential scope of their experiments, they have limited alternatives. Despite recent advancements, automatically monitoring complex behaviors in socially interacting animals remains difficult. Even gold- standard tools struggle to reliably track more than a few interacting animals, forcing researchers to conduct short, small-scale social experiments in confined environments. Here, we present PrecisionTrack, designed to remain accurate and reliable, even when tracking large groups of interacting animals over prolonged periods. PrecisionTrack outperforms both DeepLabCut and SLEAP in crowded social settings, maintains its tracking performance over time, and supports real-time, online responsiveness. Researchers can therefore use it to gather ethological data on the fly during ongoing experiments. We also introduce the Multi-animal Action Recognition Transformer (MART), which can be seamlessly integrated with PrecisionTrack to extract behavioral insights beyond spatiotemporal localization, including individual actions and social interactions. The entire system is open source and accessible through high-level APIs. Users can follow step-by-step guides to configure, train, test, and deploy their own social behavior monitoring systems.

• Differentiating BOLD and non-BOLD signals in fMRI time series using cross-cortical depth delay patterns
  Authors: Chen, J. E.; Blazejewska, A. I.; Fan, J.; Fultz, N. E.; Rosen, B. R.; Lewis, L. D.; Polimeni, J. R.
  Published: 2025-08-12 (new results)
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  Over the past two decades, rapid advancements in magnetic resonance technology have significantly enhanced the imaging resolution of functional Magnetic Resonance Imaging (fMRI), far surpassing its initial capabilities. Beyond mapping brain functional architecture at unprecedented scales, high-spatial-resolution acquisitions have also inspired and enabled several novel analytical strategies that can potentially improve the sensitivity and neuronal specificity of fMRI. With small voxels, one can sample from different levels of the vascular hierarchy within the cerebral cortex and resolve the temporal progression of hemodynamic changes from parenchymal to pial vessels. We propose that this characteristic pattern of temporal progression across cortical depths can aid in distinguishing neurogenic blood-oxygenation-level-dependent (BOLD) signals from typical nuisance factors arising from non-BOLD origins, such as head motion and pulsatility. In this study, we examine the feasibility of applying cross-cortical depth temporal lag (CortiLag) patterns to automatically categorize BOLD and non-BOLD signal components in modern-resolution BOLD-fMRI data. We construct an independent component analysis (ICA)-based framework for fMRI de-noising, analogous to previously proposed multi-echo (ME) ICA, except that here we explore the across-depth instead of across-echo dependence to distinguish BOLD and non-BOLD components. The efficacy of this framework is demonstrated using visual task data at three graded spatiotemporal resolutions (voxel sizes = 1.1, 1.5, and 2.0 mm isotropic at temporal intervals = 1700, 1120, and 928 ms). The proposed CortiLag-ICA framework leverages prior knowledge of the spatiotemporal properties of BOLD-fMRI and serves as an alternative to ME-ICA for cleaning moderate- and high-spatial-resolution fMRI data when multi-echo acquisitions are not available.

• dlmoR: An open-source R package for the dim-light melatonin onset (DLMO) hockey-stick method
  Authors: Thalji, S. M.; Spitschan, M.
  Published: 2025-08-14 (new results)
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  The dim-light melatonin onset (DLMO) is a commonly used circadian phase marker indicating the start time of evening melatonin synthesis in humans. Several quantitative techniques have been developed to determine DLMO from melatonin time-series, including fixed- or variable-threshold techniques and the hockey-stick method developed by Danilenko and colleagues (2014). Here, we introduce dlmoR, an open-source implementation of the hockey-stick method implemented in the R programming language and licensed under the permissive MIT License. Our clean-room implementation followed the algorithm description from the original article, supported by iterative validation against the existing binary executable software. We benchmark our implementation using a total of 112 melatonin time-series data sets from two different studies (Blume et al, 2024; Heinrichs and Spitschan, 2024), and find high agreement between our implementation and the reference implementation. The mean DLMO point discrepancy between implementations was -2.1 {+/-} 11.1 minutes for the Blume et al. (2024) dataset and -1.482 {+/-} 21.7 for the Heinrichs and Spitschan (2024) dataset. Circular correlation coefficients were 0.986 and 0.964, respectively, and paired t-tests (p > 0.05) were not significant, suggesting no systematic difference or bias between the methods. dlmoR allows for the programmatic and batchable analysis of evening melatonin concentration data, enabling transparency and reproducibility of analytic techniques.

• Thalamic involvement defines distinct slow-wave subtypes in NREM sleep
  Authors: Bergamo, D.; Handjaras, G.; Picchioni, D.; Ricciardi, E.; Legendre, G. Y. T.; Ozbay, P. S.; de Zwart, J.; Duyn, J. H.; Bernardi, G.; Betta, M.
  Published: 2025-08-12 (new results)
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  Slow waves (0.5-4 Hz) are a key feature of non-rapid-eye-movement (NREM) sleep, traditionally believed to arise from neocortical circuits. However, growing evidence suggests that subcortical structures, particularly the thalamus, may play a crucial role in initiating and synchronizing slow waves. We tested the hypothesis that single slow waves may arise from distinct cortico-cortical and thalamo-cortical mechanisms using simultaneous EEG-fMRI in healthy adults. Spatial mapping based on thalamic fMRI responses revealed two types of slow waves. The first type (C1) characterized by an early thalamic fMRI-signal increase, corresponded to large, efficiently synchronized waves associated with sleep spindles and with markers of higher arousal and autonomic activation. The second type (C2) is marked by an initial negative fMRI response and corresponds to smaller slow waves potentially resulting from cortico-cortical synchronization. These waves occur more often during phases of stable NREM sleep. These findings highlight distinct slow-wave subtypes with different thalamic involvement and, potentially, synchronization mechanisms.

• Thalamic involvement defines distinct slow-wave subtypes in NREM sleep
  Authors: Bergamo, D.; Handjaras, G.; Picchioni, D.; Ricciardi, E.; Legendre, G. Y. T.; Ozbay, P. S.; de Zwart, J.; Duyn, J. H.; Bernardi, G.; Betta, M.
  Published: 2025-08-12 (new results)
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  Slow waves (0.5-4 Hz) are a key feature of non-rapid-eye-movement (NREM) sleep, traditionally believed to arise from neocortical circuits. However, growing evidence suggests that subcortical structures, particularly the thalamus, may play a crucial role in initiating and synchronizing slow waves. We tested the hypothesis that single slow waves may arise from distinct cortico-cortical and thalamo-cortical mechanisms using simultaneous EEG-fMRI in healthy adults. Spatial mapping based on thalamic fMRI responses revealed two types of slow waves. The first type (C1) characterized by an early thalamic fMRI-signal increase, corresponded to large, efficiently synchronized waves associated with sleep spindles and with markers of higher arousal and autonomic activation. The second type (C2) is marked by an initial negative fMRI response and corresponds to smaller slow waves potentially resulting from cortico-cortical synchronization. These waves occur more often during phases of stable NREM sleep. These findings highlight distinct slow-wave subtypes with different thalamic involvement and, potentially, synchronization mechanisms.

• Standardised TruAI automated quantification of intracellular neuromelanin granules in human brain tissue sections
  Authors: Filimontseva, A.; Cuadros, T.; Chatterton, Z.; Burke, A.; Ansari Mahabadian, A.; Compte, J.; Fu, Y.; Vila, M.; Halliday, G.
  Published: 2025-08-14 (new results)
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  Aims: To standardise and automate the quantitation of human-unique neuromelanin granules in catecholamine neurons in post-mortem tissue sections from healthy individuals at different ages to understand any changes in these granules with age. Methods: 5-6m thick fixed and paraffin-embedded transverse midbrain tissue sections were supplied from 47 cases from three brain banks following ethics approvals. Sections were prepared and automated digital images acquired. Standardisation and automation of the quantification of neuromelanin granules was performed using the TruAI feature of the Olympus VS200 desktop platform. Comparisons between stained and unstained sections as well as correlations with age were performed. Results: The automated platform reliably identified both stained and unstained intracellular and extracellular neuromelanin granules, showing high reproducibility in measurements across laboratories using different tissue processing methods. Extracellular neuromelanin granules were significantly smaller than intracellular neuromelanin granules. Sections processed for hematoxylin and eosin staining impacted on size and colour of both neuromelanin and the neurons containing neuromelanin. Hematoxylin made neuromelanin bluer and the increased tissue processing made the intracellular area occupied by neuromelanin smaller in younger people. There was an increase in neuromelanin optical density and colour change (more brown) with age. Conclusions: The TruAI automated platform reliably quantifies individual neuromelanin granules in catecholamine neurons. Extracellular neuromelanin is considerably smaller in size than intracellular neuromelanin, and intracellular neuromelanin changes its properties with age. The darkening and colour change of intracellular neuromelanin suggests an increase in eumelanin over time in healthy individuals. These changes can be reliably identified using the automated platform.

• Readiness potential in human functional magnetic resonance imaging motor task data
  Authors: Strindberg, M.; Tian, Y.; Fransson, P.
  Published: 2025-08-14 (new results)
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  The readiness potential (RP), also known as the Bereichtschaftspotential, is commonly observed in EEG recordings as a slow build-up of negative electrical potential prior to self-directed motor movements (Kornhuber et al. 1965). In this study, we analyzed motor task-based functional magnetic resonance (fMRI) data acquired from 262 human participants, focusing on the degree of signal phase synchronization across different frequency spans and brain regions. A new method that clusters brain regions based on instantaneous phase allowed for time resolved estimation of cross-subject phase synchronization. We show that during rest periods that precede movement, an fMRI equivalent of the RP is gradually established in a network that encompasses the bilateral supplementary motor area and parts of the cingulo-opercular network, recently described as the brain's Action Mode network (Dosenbach et al. 2025). Importantly, an anticipatory negative shift in the fMRI signal was observed in both single subjects and single epochs. Tongue movement elicited strong synchronization between the orbitofrontal, ventromedial, and temporal pole cortices. Our findings suggest a link between fMRI and electrophysiological recordings of anticipatory motor events in the brain. The method presented here grades brain synchronization along an in-phase and anti-phase continuum and has applications in clinical settings, as well as for cognitive brain mapping that goes beyond anticipation.

• Age and Learning Shapes Sound Representations in Auditory Cortex During Adolescence
  Authors: Praegel, B.; Chen, F.; Dym, A.; Lavi-Rudel, A.; Druckmann, S.; MIZRAHI, A.
  Published: 2025-08-11 (new results)
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  Adolescence is a developmental period characterized by heightened plasticity. Yet, how ongoing development affects sensory processing and cognitive function is unclear. We investigated how adolescent (postnatal day 20-42) and adult (postnatal day 60-82) mice differ in performance on a pure tone Go/No-Go auditory discrimination task of varying difficulty. Using dense electrophysiological recordings, we measured spiking activity at single neuron resolution in the auditory cortex while mice were engaged in the task. As compared to adults, adolescent mice showed lower auditory discrimination performance in a difficult task. This difference in performance was due to higher response variability and weaker cognitive control expressed as higher lick bias. Adolescent and adult neuronal responses differed only slightly in representations of pure tones when measured outside the context of learning and the task. However, cortical representations after learning within the context of the task were markedly different. We found differences in stimulus- and choice-related activity at the single neuron level representations, as well as lower population-level decoding of the difficult task in adolescents. Overall, cortical decoding in adolescents was lower and slower, especially for difficult sound discrimination, reflecting immature cortical representations of sounds and choices. Notably, we found age-related differences, which were more pronounced after learning, reflecting the combined impact of age and learning. Our findings highlight distinct neurophysiological and behavioral profiles in adolescence, underscoring the ongoing development of cognitive control mechanisms and cortical plasticity during this sensitive developmental period.

• Effective connectivity between the medial temporal lobes and early visual cortex modulated by unrestricted viewing predicts memory retrieval and gaze reinstatement
  Authors: Ladyka-Wojcik, N.; Liu, Z.-X.; Ryan, J. D.
  Published: 2025-08-12 (new results)
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  Memory and gaze behavior are intricately linked, guiding one another to extract information and create mental representations of our environment for subsequent retrieval. Recent findings from functional neuroimaging and computational modeling suggest that reciprocal interactions between the extended hippocampal system and visuo-oculomotor regions are functionally relevant for building these mental representations during visual exploration. Yet, evidence for the directionality of information flow during encoding within this reciprocal architecture in humans is limited. In the current study, we used dynamic causal modeling (DCM) to give a non-invasive account for the directional influences between these systems when new memories are created. Here, we provide novel evidence demonstrating how unrestricted, naturalistic visual exploration induces changes in this connectivity. Subsequent memory retrieval performance was also predicted by the pattern of connectivity modulated by unrestricted visual exploration, identifying the mechanism underlying a rich history of previous work linking increased gaze behavior during encoding to later memory. Together, these findings suggest that gaze behavior shapes the ways in which brain dynamics within and between the hippocampal system and early visual cortex unfold during encoding in humans. Importantly, these directional interactions support the building of coherent, lasting mental representations.

• Sleep Resolves Competition Between Explicit and Implicit Memory Systems
  Authors: Kleespies, K.; Paulus, P. C.; Zhu, H.; Pargent, F.; Jakob, M.; Werle, J.; Czisch, M.; Boedecker, J.; Gais, S.; Schonauer, M.
  Published: 2025-08-12 (new results)
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  Sleep supports stabilization of explicit, declarative memory and benefits implicit, procedural memory. In addition, sleep may change the quality of memory representations. Explicit and implicit learning systems, usually linked to the hippocampus and striatum, can compete during learning, but whether they continue to interact during offline periods remains unclear. Here, we investigate for feedback-driven classification learning, whether sleep integrates explicit and implicit aspects of memory. The negative relationship between implicit and explicit memory components was resolved over sleep, but not wakefulness. Additionally, sleep benefitted performance on a task that allows the cooperative use of explicit and implicit memory, and participants who slept showed superior performance in generalizing their knowledge to unseen exemplars. A reinforcement learning model relates this to better transfer of the learned exemplar value representation after sleep. Together, this suggests that sleep integrates information learned by different routes and helps us respond optimally to everyday life contingencies.

• Patchy Striatonigral Neurons Modulate Locomotor Vigor in Response to Environmental Valence
  Authors: Hawes, S.; Liang, B.; Oldham, B.; Sullivan, B. T.; Song, B.; Chang, L.; Wang, L.; Lin, D.-T.; Cai, H.
  Published: 2025-08-13 (new results)
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  Spiny projection neurons (SPNs) in the dorsal striatum play crucial roles in locomotion control and value-based decision-making. SPNs, which include both direct-pathway striatonigral and indirect-pathway striatopallidal neurons, can be further classified into subtypes based on distinct transcriptomic profiles and cell body distribution patterns. However, how these SPN subtypes regulate spontaneous locomotion in the context of environmental valence remains unclear. Using Sepw1-Cre transgenic mice, which label a specific SPN subtype characterized by a patchy distribution of cell bodies in the dorsal striatum, we found that these patchy striatonigral neurons constrain motor vigor in response to valence differentials. In a modified light/dark box test, mice exhibited differential walking speeds between the light and dark zones. Genetic ablation of these patchy SPNs disrupted restful slowing in the dark zone and increased zone discrimination by speed. In vivo recordings linked the activity of these neurons to zone occupancy, speed, and deceleration, with a specific role in mediating deceleration. Furthermore, chemogenetic activation of patchy SPNs--and optical activation of striatonigral neurons in particular--reduced locomotion and attenuated speed-based zone discrimination. These findings reveal that a subtype of patchy striatonigral neurons regulates implicit walking speed selection based on innate valence differentials.

• Alpha modulation of spiking activity across multiple brain regions in mice performing a tactile selective detection task
  Authors: Kelley, C.; Slater, C.; Sorrentino, M.; Noone, D.; Hung, J.; Sajda, P.; Wang, Q.
  Published: 2025-08-12 (new results)
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  Many cognitive and sensory processes are characterized by strong relationships between the timing of neuronal spiking and the phase of ongoing local field potential oscillations. The coupling of neuronal spiking in neocortex to the phase of alpha oscillations (8-12 Hz) has been well studied in nonhuman primates but remains largely unexplored in other mammals. How this alpha modulation of spiking differs between brain areas and cell types, as well as its role in sensory processing and decision making, are not well understood. We used Neuropixels 1.0 probes to chronically record neural activity from somatosensory cortex, prefrontal cortex, striatum, and amygdala in mice performing a whisker-based selective detection task. We observed strong spontaneous alpha modulation of single-neuron spiking activity during inter-trial intervals while mice performed the task. The prevalence and strength of alpha phase modulation differed significantly across regions and between cell types. Phase modulated neurons exhibited stronger responses to both go and no-go stimuli, as well as stronger motor- and reward-related changes in firing rate, than their unmodulated counterparts. The increased responsiveness of phase modulated neurons suggests they are innervated by more diverse populations. Alpha modulation of neuronal spiking during baseline activity also correlated with task performance. In particular, many neurons exhibited strong alpha modulation before correct trials, but not before incorrect trials. These data suggest that dysregulation of spiking activity with respect to alpha oscillations may characterize lapses in attention.

• The encoding of interoceptive-based predictions by the paraventricular nucleus of the thalamus D2R+ neurons
  Authors: Machen, B.; Miller, S.; Xin, A.; Lampert, C.; Assaf, L.; Tucker, J.; Herrell, S.; Pereira, F.; Loewinger, G.; Beas, S.
  Published: 2025-08-15 (new results)
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  Understanding how the brain integrates internal physiological states with external sensory cues to guide behavior is a fundamental question in neuroscience. This process relies on interoceptive predictions, which are internal models that anticipate changes in the physiological state of the organism, based on sensory inputs and prior experiences. Despite recent advances in identifying the neural substrates of interoceptive predictions, the precise neuronal circuits involved remain elusive. In our study, we demonstrate that Dopamine 2 Receptor (D2R+) expressing neurons in the paraventricular nucleus of the thalamus (PVT) play key roles in interoception and interoceptive predictions. Specifically, these neurons are engaged in behaviors leading to physiologically relevant outcomes, with their activity highly dependent on the interoceptive state of the mice and the expected outcome. Furthermore, we show that chronic inhibition of PVTD2R+ neurons impairs the long-term performance of interoceptive-guided motivated behavior. Collectively, our findings provide insights into the role of PVTD2R+ neurons in learning and updating state-dependent predictions by integrating past experiences with current physiological conditions to optimize goal-directed behavior.

• Three types of remapping with linear decoders: a population-geometric perspective
  Authors: Martin-Sanchez, G.; Machens, C. K.; Podlaski, W. F.
  Published: 2025-08-11 (new results)
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  Hippocampal remapping, in which place cells form distinct activity maps across different environments, is a well-established phenomenon with a range of theoretical interpretations. Some theories propose that remapping helps to minimize interference between competing spatial memories, whereas others link it to shifts in an underlying latent state representation. However, how these interpretations of remapping relate to one another, and what types of activity changes they are compatible with, remains unclear. To unify and elucidate the mechanisms behind remapping, we here adopt a neural coding and population geometry perspective. Assuming that hippocampal population activity can be understood through a linearly-decodable latent space, we show that there are three possible mechanisms to induce remapping: (i) a true change in the mapping between neural and latent space, (ii) modulation of activity due to non-spatial mixed selectivity of place cells, or (iii) neural variability in the null space of the latent space that reflects a redundant code. We simulate and visualize examples of these remapping types in a network model, and relate the resultant remapping behavior to various models and experimental findings in the literature. Overall, our work serves as a unifying framework with which to visualize, understand, and compare the wide array of theories and experimental observations about remapping, and may serve as a testbed for understanding neural response variability under various experimental conditions.

• Comparing a computational model of visual problem solving with human vision on a difficult vision task.
  Authors: Khajuria, T.; Tulver, K.; Aru, J.
  Published: 2025-08-12 (new results)
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  Human vision is not merely a passive process of interpreting sensory input but can also function as a problem-solving process incorporating generative mechanisms to interpret ambiguous or noisy data. This synergy between the generative and discriminative components, often described as analysis-by-synthesis, enables robust perception and rapid adaptation to out-of-distribution inputs. In this work, we investigate a computational implementation of the analysis-by-synthesis paradigm using genetic search in a generative model, applied to a visual problem-solving task inspired by star constellations. The search is guided by low-level cues based on the structural fitness of candidate solutions compared to the test images. This dataset serves as a testbed for exploring how inferred signals can guide the synthesis of suitable solutions in ambiguous conditions, framing visual inference as an instance of complex problem solving. Drawing on insights from human experiments, we develop a generative search algorithm and compare its performance to humans, examining factors such as accuracy, reaction time, and overlap in drawings. Our results shed light on possible mechanisms of human visual problem solving and highlight the potential of generative search models to emulate aspects of this process. Author summaryHuman vision is not just about passively receiving information from the environment. Rather, it also involves actively making sense of what we see. When faced with unclear or incomplete visual input, our brains use prior knowledge to fill in gaps and create the most likely interpretation. This ability helps us recognize objects and patterns even in difficult conditions. In this study, we explore how this process can be replicated using computer models. Specifically, we test a method that generates possible interpretations of ambiguous visual data, inspired by the way people recognize star constellations. By comparing the models performance with human participants, we examine how well it mirrors human perception. We analyze factors such as accuracy, response time, and similarities in the interpretations produced. Our findings offer insights into how people make sense of uncertain visual information and suggest ways in which computer models can be designed to mimic this ability. These results can contribute to our understanding of human perception as well as help advance artificial vision systems beyond simple pattern recognition.

• Serotonin selectively modulates visual responses of object motion detectors in Drosophila
  Authors: Bertsch, D. J.; Palacios Castillo, L. M.; Frye, M. A.
  Published: 2025-08-13 (new results)
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  Serotonin (5-HT) is a hormonal messenger that confers state-level changes upon the nervous system in both humans and flies. In Drosophila, lobula columnar (LC) cells are feature-detecting neurons that project from the optic lobe to the central brain, where each population forms an anatomically-distinct glomerulus with heterogeneous synaptic partners. Here, we investigated serotonins effect on two LC populations with different 5-HT receptor expression profiles. Receptor expression does not predict neuromodulatory effects: LC15 expresses inhibitory 5-HT1A and 5-HT1B receptors, yet serotonin increases the amplitude of calcium responses to visual stimuli. LC12 expresses inhibitory 5-HT1A and excitatory 5-HT2A receptors, yet serotonin application does not influence visual responses. Serotonin targets select visual response properties, potentiating LC15 responses to a motion-defined bar and tuning the gain of responses to varying object velocity but has no influence on contrast sensitivity. Serotonin does not significantly facilitate LC15 responses in postsynaptic dendrites, only in the presynaptic terminals of the glomerulus, which suggests that the neuromodulatory effects are strongest in the central brain. Connectomics confirms that LC12 and LC15 share neither presynaptic inputs nor postsynaptic outputs in the central brain. The wiring diagram shows no synaptic interactions between the LC15 circuit and major serotonergic 5-HTPLP neurons, nor to other serotonergic neurons of the central brain, suggesting that endogenous 5-HT acts via paracrine transmission on non-serotonergic pathways. Lobula- and glomerulus-specific GABAergic and glutamatergic inhibitory partners, positioned to filter visual stimuli, are putative 5-HT targets. These results provide a comparative framework for the neuromodulatory mechanisms involved in visual processing. New & NoteworthyHow does neuromodulatory state affect visual feature detection? In this work, we demonstrate highly specific facilitated visual responses of object-detecting neurons after serotonin bath application in Drosophila. Serotonin potentiates motion-defined bar responses in object-detecting LC15 neurons and tunes response gain to translating bars of mid-range velocities in presynaptic axon terminals. Our calcium imaging extends what is known about extra-synaptic neuromodulation in the visual system and shows that serotonin heightens visual processes that inform object-specific behavior.

• Unraveling the mesoscale resting-state functional connectivity of ocular dominance columns in humans using high-resolution functional MRI.
  Authors: Schmidt, M. E.; Aganj, I.; Stockmann, J.; Bilgic, B.; Chang, Y.; Hoge, W. S.; Kirilina, E.; Weiskopf, N.; Nasr, S.
  Published: 2025-08-14 (confirmatory results)
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  Despite their importance in shaping visual perception, functional connectivity between ocular dominance columns (ODCs), the building blocks of neuronal processing within the human primary visual cortex (V1), remains largely unknown. Using high-resolution functional MRI (fMRI), we localized ODCs and assessed their resting-state functional connectivity (rs-FC) in 12 human adults (4 females). Consistent with anatomical studies in animals, we found stronger rs-FC in the middle compared to deep and superficial cortical depths and selectively stronger rs-FC between ODCs with alike compared to unalike ocular polarity. Beyond what was known from animal models, and consistent with human perceptual biases, we found stronger intra- and interhemispheric rs-FC in peripheral (compared to central) and in dorsal (compared to ventral) V1 subregions. Lastly, we found a significant correlation between rs-FC patterns and ODC maps, supporting the hypothesis that ODC maps can be predicted from rs-FC patterns within V1. These results highlight the heterogeneity in functional connectivity between ODCs across cortical depths and V1 subfields, underscoring their likely association with human perceptual biases.

• Autism-associated Scn2a haploinsufficiency disrupts in vivo dendritic signaling and impairs flexible decision-making
  Authors: Wu, H.; Shen, L.; Indajang, J.; Savalia, N. K.; Johnson, T. G.; Qu, J.; Bender, K. J.; Kwan, A. C.
  Published: 2025-08-14 (new results)
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  SCN2A is a high-confidence risk gene for autism spectrum disorder. Loss-of-function mutations in Scn2a reduce dendritic excitability in neocortical pyramidal cells. However, the impact of Scn2a haploinsufficiency on dendritic signaling in vivo, particularly during behavior, is unknown. In this study, we used two-photon microscopy to image dendritic calcium transients in deep layer pyramidal cells in the mouse medial frontal cortex. Scn2a+/- mice had diminished coupling between apical and proximal dendritic compartments. Pyramidal tract neurons had abnormal event rates, while intratelencephalic neurons had compartment-specific alterations indicative of diminished dendritic integration. In a matching pennies task, Scn2a+/- mice were inflexible in the face of changing competitive pressure. Apical dendritic tuft in IT neurons typically encoded reward and strategy, but these task-specific representations were altered in Scn2a+/- mice. Collectively, the findings demonstrate that Scn2a haploinsufficiency weakens dendritic integration in vivo and disrupts the dendritic encoding of decision variables, potentially contributing to the cognitive rigidity in autism spectrum disorder.

• Vascular endothelial-specific loss of TGF-beta signaling as a model for choroidal neovascularization and central nervous system vascular inflammation
  Authors: Wang, Y.; Rattner, A.; Li, Z.; Smallwood, P. M.; Nathans, J.
  Published: 2025-08-12 (new results)
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  In mice, postnatal endothelial cell (EC)-specific knockout of the genes coding for Transforming Growth Factor-Beta Receptor (TGFBR)1 and/or TGFBR2 eliminates TGF-beta signaling in vascular ECs and leads to distinctive central nervous system (CNS) vascular phenotypes. Knockout mice exhibit (1) reduced intra-retinal vascularization, (2) choroidal neovascularization with occasional anastomoses connecting choroidal and intraretinal vasculatures, (3) infiltration of diverse immune cells into the retina, including macrophages, T-cells, B-cells, NK cells, and dendritic cells, (4) a close physical association between immune cells and retinal vasculature, (5) a pro-inflammatory transcriptional state in CNS ECs, with increased ICAM1 immunoreactivity, and (6) increased Smooth Muscle Actin immunostaining in CNS pericytes. Comparisons of the retinal phenotype with two other genetic models of retinal hypovascularization - loss of Norrin/Fzd4 signaling and loss of VEGF signaling - shows that the immune cell infiltrate is greatest with loss of TGF-beta signaling, more modest with loss of Norrin/Fzd4 signaling, and undetectable with loss of VEGF signaling. The phenotypes caused by loss of TGF-beta signaling in ECs recapitulate some of the cardinal features of retinal and neurologic diseases associated with vascular inflammation. These observations suggest that therapies that promote TGF-beta-dependent anti-inflammatory responses in ECs could represent a promising strategy for disease modulation.

• Experience reorganizes content-specific memory traces in macaques
  Authors: Abbaspoor, S.; Aljishi, A.; Hoffman, K. L.
  Published: 2025-08-12 (new results)
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  Memory formation relies on the reorganization of neural activity patterns during experience that persist in subsequent sleep. How these processes promote learning while preserving established memories remains unclear. We recorded neural ensemble activity from hippocampal and associated regions in freely moving macaques as they recalled item sequences presented that day ("new"), one day prior ("recent"), or over two weeks prior ("old"). Cell assemblies biased for old sequences showed less drift, greater network connectivity, and stronger sleep reactivation than new-biased assemblies. Pairs of old and recent assemblies formed persistent task-to-sleep coupling ("metassemblies"), unlike new assembly pairs. In the hippocampus, the propensity for superficial and deep CA1 pyramidal cells to form integrated assemblies increased with memory age. These findings reveal rapid organization and stabilization of neural activity in the primate brain, suggesting potential mechanisms for balancing learning with memory linking and durability.

• Newly trained navigation and verbal memory skills elicit changes in task-related networks but not brain structure
  Authors: Zheng, L.; Boogaart, Z.; McAvan, A.; Garren, J.; Doner, S.; Wilkes, B. J.; Groves, W.; Yuksel, E.; Cherep, L.; Ekstrom, A.; Weisberg, S. M.
  Published: 2025-08-14 (new results)
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  Training cognitive skills, such as remembering a list of words or navigating a new city, has important implications for both health and disease. Yet, understanding what brain changes underlie the acquisition of complex cognitive skills remains unresolved. Here, we developed and validated intensive multiweek interventions in which participants were randomly assigned training in either navigation or verbal memory. Healthy young participants (N=75) underwent structural and functional imaging prior to and following the training. Based on pre-registered and exploratory analyses, we did not find any evidence for changes to hippocampal volume, hippocampal subfields, cortical brain volume, or white matter connectivity due to the training. In contrast, network-based analyses suggested changes in task-related informational connectivity, which occurred primarily between cortical areas and mostly involved putative cognitive control networks. These results suggest that cognitive interventions target more transient configurations in network connectivity rather than more durable structural changes.

• view larger version (35k): org.highwire.dtl.dtlvardef@9f69b8org.highwire.dtl.dtlvardef@1d5c2d7org.highwire.dtl.dtlvardef@eac7bcorg.highwire.dtl.dtlvardef@1df3853_hps_format_figexp m_fig c_fig" data-authors="willis, j. a.; wright, c. e.; zhu, r.; ruan, y.; stallings, j.; abrego, a. m.; medani, t.; moitra, p.; mosher, j. c.; ramakrishnan, a.; joshi, a. a.; leahy, r. m.; tandon, n.; seymour, j. p."> Optimizing electrode placement and information capacity for local field potentials in cortex
  Authors: Willis, J. A.; Wright, C. E.; Zhu, R.; Ruan, Y.; Stallings, J.; Abrego, A. M.; Medani, T.; Moitra, P.; Mosher, J. C.; Ramakrishnan, A.; Joshi, A. A.; Leahy, R. M.; Tandon, N.; Seymour, J. P.
  Published: 2025-08-12 (new results)
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  Recent neurosurgery advancements include improved stereotactic targeting and increased electrode contacts. This study introduces a subject-specific, in silico modeling tool for optimizing electrode placement and maximizing coverage with a variety of devices. The basis for optimization is the Shannon-Hartley information capacity of field potentials derived from dipolar sources. The approach integrates subject-specific MRI data with finite element modeling (FEM) used to simulate the sensitivity of subdural and intracortical devices. Sensitivity maps, or lead fields, from these models enable the comparison of different electrode placements, contact sizes, contact configurations, and substrate properties, which are often overlooked factors. One tool is a genetic algorithm that optimizes electrode placement by maximizing information capacity. Another is a sparse sensor method, Sparse Electrode Placement for Input Optimization (SEPIO), that selects the best sensor subsets for accurate source classification. We demonstrate several use cases for clinicians, engineers, and researchers. Overall, these open-source tools offer a quantitative framework to juxtapose devices in ones neurosurgical armament or optimize device and contact placement. It may help users refine electrode coverage with low channel count devices and minimize invasive surgery burden. The study demonstrates that optimized electrode placement significantly improves the information capacity and signal quality of local field potential (LFP) recordings. The tools developed offer a valuable approach for refining neurosurgical techniques and enhancing the design of neural implants. HighlightsO_LItool for simulating subject-specific local field potentials and electrode sensitivity. C_LIO_LIptimized electrode placement enhances ROI source coverage, and signal quality. C_LIO_LIsensor-based classification boosts data quality without extra electrode cost. C_LIO_LIcomparisons of devices and contact arrangements. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=78 SRC="FIGDIR/small/650658v2_ufig1.gif" ALT="Figure 1000"> View larger version (35K): org.highwire.dtl.DTLVardef@9f69b8org.highwire.dtl.DTLVardef@1d5c2d7org.highwire.dtl.DTLVardef@eac7bcorg.highwire.dtl.DTLVardef@1df3853_HPS_FORMAT_FIGEXP M_FIG C_FIG

• Parallax error in the head-direction system indicates simple cue-anchoring mechanism
  Authors: Krausse, S.; Duszkiewicz, A. J.; Neftci, E.; Sommer, F. T.; Renner, A.
  Published: 2025-08-11 (new results)
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  Spatial navigation relies on the head-direction (HD) system, which integrates angular head velocity (AHV) to track orientation. Since integration accumulates drift over time, visual landmarks provide corrective cues. However, such sensory cues are perceived egocentrically and must therefore be transformed into allocentric coordinates. The parallax effect, where nearby objects appear to shift more than distant ones during movement, should lead to a systematic position-dependent HD error unless there is a correction mechanism. How the HD system solves this problem remained an open question. Here, we analyzed postsubicular HD cell activity in mice navigating in a restricted environment with a single visual cue. We discovered a systematic parallax bias in the decoded HD, indicating that the HD system misinterprets the cues position depending on the viewing angle. The observed error was smaller than predicted by a pure vision model, which can be explained by the combination of AHV integration with simple visual anchoring. In less restricted experimental settings with multiple cues available, the parallax effect is drastically decreased. These experimental findings indicate that the HD system does not actively correct for parallax in a position-dependent manner, but instead relies on a simple cue anchoring mechanism for the transformation of the egocentrically observed cues into an allocentric reference frame. The use of AHV integration and multiple cues is sufficient to account for parallax and produce a stable HD signal for spatial navigation. This sheds light on the mechanisms of ego-to-allocentric transformation in neural systems, which is crucial for the formation of the cognitive map. Furthermore, it highlights a fundamental trade-off in neural coding between computational efficiency and positional accuracy, with implications for biological and artificial navigation systems.

• Distinguishing Lifelong Individual Differences from Divergent Aging Trajectories of Adult Brain Volumes
  Authors: Grodem, E. O. S.; Vidal-Pineiro, D.; Sorensen, O.; Bartres-Faz, D.; Brandmaier, A. M.; Cattaneo, G.; Garrido, P. F.; Henson, R. N.; Kühn, S.; Lindenberger, U.; MacIntosh, B. J.; Nyberg, L.; Pascual-Leone, A.; Smith, S. M.; Sole-Padulles, C.; Solana-Sanchez, J.; Watne, L. O.; Walhovd, K. B.; Bjornerud, A.; Fjell, A. M.
  Published: 2025-08-13 (new results)
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  Differences in the volumes of brain structures between individuals are often linked to various conditions, including Alzheimers disease, schizophrenia, and overall brain health. However, it remains unclear to what extent these differences reflect individual levels present at young adulthood or diverging aging trajectories at later ages. In this study, we analyze the aging dynamics of the volume of six brain structures based on MRI scans from a large cross-cohort longitudinal sample of cognitively healthy adults (n = 8,311 with 18,520 MRIs, ages from 18 to 97 years). From general assumptions about structural brain dynamics and measurement noise, a stochastic dynamical model was fit to the data to estimate both the variability and persistence of structural changes across adulthood. Using this model, we calculated how much of the variance in individual volumetric differences can be attributed to stable levels from young adulthood versus systematic changes at older ages, as well as the theoretical sensitivity of longitudinal studies to detect individual differences in changes. The findings were as follows: 1) Before age 60 years, inter-individual differences in neuroanatomical volumes almost exclusively reflect stable differences between individuals, while the influence from systematic differences in rate-of-change increases thereafter; up to 40 % of the variation being due to differences in change at 80 years. In contrast, ventricular volume reflects differences in change from early adulthood. 2) Current brain-age models are unlikely to be sensitive to detect differences in aging trajectories. 3) Imaging studies have a low reliability to detect inter-individual brain change before age 60. After 60 years, the study reliability increases sharply with longer intervals between scans and more modestly with additional intermediate observations. In conclusion, it is critical to distinguish between stable levels from early adulthood and systematic differences in change when studying adult brain aging.

• Interpersonal alignment in infra-slow EEG rhythms and bodily signals anticipates mutual recognition
  Authors: Gravel, N. G.; Formento, N.; Froese, T.
  Published: 2025-08-16 (new results)
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  Across multiple timescales, neural rhythms play a crucial role in coordinating cognitive and physiological processes, with slower frequencies potentially relevant during social interaction. While electroencephalography (EEG) has been widely used to study such processes, examining these slower aspects during social interaction presents unique methodological challenges. Here we address this issue by investigating infra-slow EEG, respiratory, and electrodermal signals recorded simultaneously during a perceptual crossing experiment (PCE)-a recently established paradigm in social cognition and EEG hyperscanning. Through innovative spectral characterization methods and a novel dyadic regression approach, we establish a methodological framework for examining infra-slow dynamics that coordinate brain and body during social interaction. Our analysis revealed that, when time-locked to task responses, the spectral power of infra-slow oscillations (ISOs) at 0.05 Hz and 0.1 Hz showed enhanced inter-participant similarity in dyads achieving mutual recognition relative to those that did not. Although not strictly simultaneous, this inter-personal alignment in the spectral power of ISOs was accompanied by concurrent dynamics both in respiratory pressure and electrodermal activity, suggesting that ISOs reflect the integration of autonomic, cognitive, and social processes, with their alignment facilitating shared understanding and joint action. Crucially, we find that task-responses in participants who successfully engaged in the PCE task were coupled to the phase of the 0.1 Hz rhythm. Additionally, we show that ISOs and aperiodic activity tracked behaviorally relevant transitions, notably prior to and during the perceptual crossing task. Taken together, our findings highlight an important role for ISOs in mediating the temporal dynamics of social cognition and show that inter-participant alignment in ISOs and physiological signals can serve as a proxy for the complex interplay between body physiology, cognition, and social behavior.

• Multivariate pattern analysis reveals resting-state EEG biomarkers in fibromyalgia
  Authors: Soldic, D.; Martin-Buro, M. C.; Lopez-Garcia, D.; del Pino, A. B.; Fernandes-Magalhaes, R.; Ferrera, D.; Pelaez, I.; Carretie, L.; Mercado Romero, F.
  Published: 2025-08-12 (new results)
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  Fibromyalgia (FM) involves widespread musculoskeletal pain and hypersensitivity, often accompanied by neurological, cognitive, and affective disturbances. Resting-state (RS) electroencephalography (EEG) studies have revealed abnormal brain activity in chronic pain conditions, with anxiety and symptom duration potentially exacerbating these alterations. This study applied multivariate pattern analysis to differentiate RS-EEG signals between FM patients and healthy controls across frequency bands associated with pain processing, incorporating state and trait anxiety scores. It also examined differences between patients with short and long duration symptoms and identified the most relevant scalp regions contributing to the models. Fifty-one female participants (25 FM patients, 26 controls; aged 35-65) were included. Patients were classified into short-term (12) and long-term (13) groups. Normalized power spectral density values were extracted from EEG data and used to train machine learning classifiers, with Haufe-transformed weights computed to determine key scalp contributions. The models distinguished patients from controls with accuracies exceeding 0.70 across all frequency bands, reaching 0.99 in beta and gamma bands when anxiety was included. Symptom duration was also a relevant factor, as the model differentiated short-from long-term FM patients with accuracies up to 0.96 in beta and gamma bands. Alterations in theta power within frontal and parietal regions, along with frequency-specific contributions, highlight disrupted pain processing in FM and suggest cumulative effects of prolonged symptom duration. RS-EEG combined with multivariate pattern analysis may support the development of biomarkers to improve diagnosis and guide treatment strategies in clinical settings.

• Deciphering the combinatorial expression pattern and genetic regulatory mechanisms of Beats and Sides in the olfactory circuits of Drosophila
  Authors: Duan, Q.; Okuwa, S.; Estrella, R.; Yeung, C.; Chen, Y.-C. D.; Rio, L. Q.; Vien, K. M.; Volkan, P. C.
  Published: 2025-08-14 (new results)
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  Over the past decades, many critical molecular players have been uncovered to control distinct steps in olfactory circuit assembly in Drosophila. Among these, multi-member gene families of cell surface proteins are of interest because they can act as neuron-specific identification/recognition tags in combinations and contribute to circuit assembly in complex brains through their heterophilic or homophilic interactions. Recently, a multi-protein interactome has been described between the Beat and Side families of IgSF proteins. Here, we use the publicly available single-cell RNA-seq datasets and newly generated gene trap transgenic driver lines to probe the in vivo spatial expression pattern of the beat/side gene families in odorant receptor neurons (ORNs) and their synaptic target projection neurons (PNs). Our results revealed that each ORN and its synaptic target PN class expresses a class-specific combination of beat/side genes, hierarchically regulated by lineage-specific genetic programs. Though ORNs or PNs from closer lineages tend to possess more similar beat/side profiles, we also found many examples of divergence from this pattern among closely related ORNs and closely related PNs. To explore whether the class-specific combination of beats/sides defines ORN-PN matching specificity, we perturbed presynaptic beat-IIa and postsynaptic side-IV in two ORN-PN partners. However, disruption of Beat-IIa-Side-IV interaction did not produce any significant mistargeting in these two examined glomeruli. Though without affecting general glomerular targeting, knockdown of side in ORNs leads to the reduction of synaptic development. Interestingly, we found conserved expression patterns of beat/side orthologs across ORNs in ants and mosquitoes, indicating the shared regulatory strategies specifying the expression of these duplicated paralogs in insect evolution. Overall, this comprehensive analysis of expression patterns lays a foundation for in-depth functional investigations into how Beat/Side combinatorial expression contributes to the olfactory circuit assembly.

• Neuronal avalanches as a predictive biomarker of BCI performance- towards a tool to guide tailored training
  Authors: Mannino, C.; Sorrentino, P.; Chavez, M.; Corsi, M.-C.
  Published: 2025-08-12 (new results)
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  Motor imagery-based Brain-Computer Interfaces (BCIs) restore control in persons with motor impairments, but up to 30% of users struggle--a phenomenon known as "BCI inefficiency". This study tackles a key limitation of current protocol: the use of fixed-length sessions training paradigms that ignore individual learning variability. We propose a novel approach based on neuronal avalanches-- spatiotemporal cascades of brain activities--as biomarkers to characterize and predict user-specific learning. From electroencephalography data across four sessions in 20 subjects, we characterized avalanches by their length and their spatiotemporal size. These features showed significant training and task effects and were found to correlate to BCI performance across sessions. We further assessed their ability to predict BCI success through longitudinal models, achieving up to 91% accuracy, improved by spatial filtering on selected brain regions. These findings demonstrate the utility of neuronal avalanche dynamics as robust biomarkers for BCI training, supporting the development of personalized protocols aimed at mitigating BCI illiteracy.

• Projection-Specific Intersectional Optogenetics for Precise Excitation and Inhibition in the Marmoset Brain
  Authors: Shaw, L. H.; Padmanabhan, K.; Bucklaew, A.; Mitchell, J. F.; Wang, K. H.
  Published: 2025-08-15 (new results)
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  The primate cerebral cortex relies on long-range connections to integrate information across spatially distributed and functionally specialized areas, yet tools for selectively modulating these pathways remain limited. Here, we present an optimized intersectional viral and optogenetic strategy for precisely exciting and inhibiting projection-specific neurons in the common marmoset. Building on a mouse-to-marmoset pipeline, we first validated that optogenetic activation of inhibitory neurons (via AAV9-Dlx-ChR2) enables robust local cortical inhibition. We then combined retrograde delivery of Cre-recombinase (AAVretro-Cre) with locally injected Cre-dependent vectors encoding excitatory or inhibitory opsins (AAV8-FLEx-ChR2 or Jaws) to achieve directionally selective expression in callosal and frontoparietal pathways. Dual-opsin co-expression enabled precise stimulation or suppression of projection neurons in vivo with minimal off-target labeling. These results establish a scalable framework for projection-specific optogenetic interrogation of distributed circuits in primates, expanding the experimental toolkit for causal studies of higher-order brain function with enhanced anatomical precision and functional specificity.

• Healthy human eyes misaligned optical components: Binocular Listings law
  Authors: Turski, J.
  Published: 2025-08-16 (new results)
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  The healthy human eyes optical components are misaligned. Although important in studying vision quality, it has been overlooked in research on binocular and oculomotor vision. This study presents the construction of ocular torsion in the binocular system that incorporates the fovea displaced from the posterior pole and the lens tilted away from the eyes optical axis. When the eyes binocular posture changes, each eyes torsional position transformations, computed in the framework of Rodrigues vector, are visualized in GeoGebra simulations. Listings law, important in oculomotor control by constraining a single eye redundant torsional degree of freedom, is ab initio formulated for bifoveal fixations in the binocular system with misaligned optical components for the fixed upright head. It leads to the configuration space of binocularly constrained eyes rotations, including the noncommutativity rule. This formulation modifies the Listing plane of the straight-ahead eyes primary position by replacing it with the binocular eyes posture corresponding to the empirical horopters abathic distance fixation, a unique bifoveal fixation for which the longitudinal horopter is a straight frontal line. Notably, it corresponds to the eye muscles natural tonus resting position, which serves as a zero-reference level for convergence effort. Supported by ophthalmology studies, it revises the elusive neurophysiological significance of the Listing plane. Furthermore, the binocular constraints couple 3D changes in the eyes orientation and, hence, torsional positions during simulations with GeoGebras dynamic geometry. The binocular Listings law developed here can support this coupling, which is important in oculomotor control. The results obtained in this study should be a part of the answers to the questions posted in the literature on the relevance of Listings law to clinical practices.

• A systematic protocol to identify 'clinical controls' for pediatric neuroimaging research from clinically acquired brain MRIs
  Authors: Zimmerman, D.; Mandal, A. S.; Jung, B.; Buczek, M. J.; Schabdach, J. M.; Karandikar, S.; Kafader, E.; Gardner, M.; Daniali, M.; Mercedes, L.; Kohler, S.; Abdel-Qader, L.; Gur, R. E.; Roalf, D.; Satterthwaite, T. D.; Williams, R.; Padmanabhan, V.; Seidlitz, J.; White, L. K.; Sotardi, S.; Schmitt, J. E.; Vossough, A.; Alexander-Bloch, A.
  Published: 2025-08-12 (new results)
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  Progress at the intersection of artificial intelligence and pediatric neuroimaging necessitates large, heterogeneous datasets to generate robust and generalizable models. Retrospective analysis of clinical brain magnetic resonance imaging (MRI) scans offers a promising avenue to augment prospective research datasets, leveraging the extensive repositories of scans routinely acquired by hospital systems in the course of clinical care. Here, we present a systematic protocol for identifying "scans with limited imaging pathology" through machine-assisted manual review of radiology reports. The protocol employs a standardized grading scheme developed with expert neuroradiologists and implemented by non-clinician graders. Categorizing scans based on the presence or absence of significant pathology and image quality concerns, facilitates the repurposing of clinical brain MRI data for brain research. Such an approach has the potential to harness vast clinical imaging archives - exemplified by over 250,000 brain MRIs at the Childrens Hospital of Philadelphia - to address demographic biases in research participation, to increase sample size, and to improve replicability in neurodevelopmental imaging research. Ultimately, this protocol aims to enable scalable, reliable identification of clinical control brain MRIs, supporting large-scale, generalizable neuroimaging studies of typical brain development and neurogenetic conditions.

• Neural adolescent pragmatic development mirrors pragmatic differences in adulthood: an fMRI-study
  Authors: Forbes Schieche, C.; Udden, J.
  Published: 2025-08-13 (new results)
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  Pragmatic development is still ongoing during adolescence. However, the developmental trajectory during the adolescent years is understudied and the underlying neural correlates of pragmatic development are unknown. In this study, we used an established fMRI paradigm contrasting indirect and direct speech act processing in a newly acquired adolescent sample (n = 51) and a previously collected adult sample (n = 57). The adolescent sample was split into two groups: Young (ages 13-15) and Mid (ages 16-18); and the adult sample (Old, ages 18-36) into two groups based on pragmatic skill level, established in separate behavioral tests. We observed increased activity with age in the posterior medial prefrontal cortex, and a combination of age-related differences and individual differences in adults in the left posterior intraparietal sulcus (IPS) and the posterior cingulate cortex. These clusters were all located outside of the classical perisylvian language areas ("the language network"). The posterior cingulate cortex cluster overlapped with core nodes of the default mode network. We interpret the IPS finding in terms of its overlap with two relevant networks (one of them is the "multiple demand" network related to cognitive control). The results indicate that young adolescents and adults with low pragmatic skill may be over-interpreting direct speech acts as potentially indirect. The similarity between these two groups across results in turn indicate that a delayed adolescent development may lead to persistent difficulties in adulthood. We have shown that aspects of pragmatic development depend on cognitive abilities other than language and Theory of Mind. By studying adolescence, a presumably uniquely human extended developmental period, we provide a rare empirical angle on the question of which aspects of brain and cultural evolution contributed to the human communicative faculty.

• Reading specific memories from human neurons before and after sleep
  Authors: Ding, Y.; Dunn, S. L. S.; Sakon, J. J.; Duan, C.; Zhang, Y.; Berger, J. I.; Rhone, A. E.; Nourski, K. V.; Kawasaki, H.; Howard, M. A.; Roychowdhury, V. P.; Fried, I.
  Published: 2025-08-12 (new results)
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  The ability to retrieve a single episode encountered just once is a hallmark of human intelligence and episodic memory[1]. Yet, decoding a specific memory from neuronal activity in the human brain remains a formidable challenge. Here, we develop a transformer neural network model[2, 3] trained on neuronal spikes from intracranial microelectrodes recorded during a single viewing of an audiovisual episode. Combining spikes throughout the brain via cross-channel attention[4], capable of discovering neural patterns spread across brain regions and timescales, individual participant models predict memory retrieval of specific concepts such as persons or places. Brain regions differentially contribute to memory decoding before and after sleep. Models trained using only medial temporal lobe (MTL) spikes significantly decode concepts before but not after sleep, while models trained using only frontal cortex (FC) spikes decode concepts after but not before sleep. These findings suggest a system-wide distribution of information across neural populations that transforms over wake/sleep cycles[5]. Such decoding of internally generated memories suggests a path towards brain-computer interfaces to treat episodic memory disorders through enhancement or muting of specific memories.

• Cell-type-specific plasticity in synaptic, intrinsic, and sound response properties of deep-layer auditory cortical neurons after noise trauma
  Authors: Zhao, Y.; Kouvaros, S.; Schneider, N. A.; Krall, R. F.; Lam, S.; Arnold, M. P.; Williamson, R. S.; Tzounopoulos, T.
  Published: 2025-08-15 (new results)
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  Peripheral damage drives auditory cortex (ACtx) plasticity, but the underlying synaptic and cellular mechanisms remain poorly understood. We used a combination of in vitro slice electrophysiology, optogenetics, and in vivo two-photon imaging to investigate layer 5 extratelencephalic (ET) and layer 6 corticothalamic (CT) neuronal plasticity in mice, following noise-induced hearing loss (NIHL). Thalamocortical (TC) input was initially balanced between CTs and ETs but shifted to CT-dominant one day post-NIHL and then normalized by day seven. This transient shift was accompanied by increased quantal size and suprathreshold excitability in CTs, with minimal changes in ETs. In vivo, CTs exhibited persistent elevation in sound intensity thresholds, while ETs showed a transient shift in frequency tuning and reduced high-frequency responsiveness that recovered within a week. These findings reveal distinct, cell-type-specific plasticity mechanisms in deep-layer ACtx neurons following peripheral damage and highlight potential targets for treating hearing loss-related disorders such as tinnitus and hyperacusis.

• A Developmental Atlas of the Drosophila Nerve Cord Uncovers a Global Temporal Code for Neuronal Identity
  Authors: Cachero, S.; Mitletton, M.; Beckett, I. R.; Marin, E. C.; Serratosa Capdevila, L.; Gkantia, M.; Lacin, H.; Jefferis, G. S. X. E.; Dona, E.
  Published: 2025-08-13 (new results)
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  The assembly of functional neural circuits relies on the generation of diverse neural types with precise molecular identity and connectivity. Unlocking general principles of neuronal specification and wiring across the nervous system requires a systematic and high-resolution characterisation of its diversity, recently enabled by advances in single-cell transcriptomics and connectomics. However, linking the molecular identity of neurons to circuit architecture remains a key challenge. Here, we present a high-resolution developmental transcriptional atlas for the Drosophila melanogaster nerve cord, the central hub for sensory-motor circuits. With an unprecedented 38x coverage relative to its reference connectome1,2, our atlas captures extensive molecular diversity and enables robust alignment to the adult connectome. We identified three developmental principles underlying neuronal diversity in the nerve cord. First, timing of neurogenesis shapes molecular identity: embryonic-born neurons adopt discrete molecular identities, while larval-born neurons form continuous identities within lineages, a distinction we also found in the adult connectome. Second, we discovered that the continuous molecular progression is mirrored by the expression dynamics of 17 transcription factors. These factors are common to neurons from all lineages and provide a global molecular identity code based on birth order. Lastly, by mapping sex-specific transcriptional profiles to the connectome, we uncovered female-specific apoptosis and transcriptional divergence as key global drivers of sex-specification. By revealing key organisational axes of molecular identity, this atlas opens new avenues to dissect the molecular mechanisms underpinning the development and evolution of neural circuits. HighlightsA developmental transcriptional atlas of the Drosophila melanogaster ventral nerve cord (VNC) with 38x coverage Birth order, segment and lineage annotation enables the assignment of transcriptional signatures to 122 cell type groups in the connectome 17 transcription factors (TFs) are expressed in a conserved temporal sequence within lineages across the nervous system defining a persistent molecular correlate of birth order Matching sex differences in the developmental atlas and adult connectomes reveals the molecular logic of sexual dimorphism

• In vivo and in silico alpha-synuclein propagation dynamics: The role of genotype, epicentre, and connectivity
  Authors: Tullo, S.; Park, J. S. H.; Rahayel, S.; Gallino, D.; Park, M.; Mar, K.; Zheng, Y.-Q.; del Cid-Pelliter, E.; Fon, E. A.; Luo, W.; Shlaifer, I.; Durcan, T. M.; Misic, B.; Dagher, A.; Devenyi, G. A.; Chakravarty, M. M.
  Published: 2025-08-12 (new results)
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  Synucleinopathies, like Parkinsons disease (PD) are characterized by progressive accumulation and spread of misfolded alpha-synuclein (aSyn) throughout the brain. To improve understanding of disease mechanisms we studied the generalizability of aSyn-mediated atrophy. First, we examined wild-type and M83 A53T hemizygous transgenic mice receiving striatal inoculation with human or mouse preformed fibrils (PFFs). Using magnetic resonance imaging, we demonstrate network-like atrophy and motor deficits, regardless of genotype or PFF species; atrophy was most prominent in M83 mice with mouse PFFs, while human PFFs or wild-type hosts showed attenuated effects. Changing the inoculation site (disease epicentre) to the hippocampus, a major connectivity hub, resulted in localized atrophy. Computational models previously validated in clinical PD predict atrophy patterns associated with striatal but not hippocampal inoculation. Our findings reveal atrophy resulting from aSyn spreading is generalizable across genotype and PFF species, but not disease epicentres, emphasizing the role of regional vulnerability in disease progression.

• Learning the bistable cortical dynamics of the sleep-onset period
  Authors: Hu, Z.; Aravind, M.; Lei, X.; Kutz, J. N.; Aucouturier, J.-J.
  Published: 2025-08-15 (new results)
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  Humans just don't fall asleep like a log -- or step-function. Rather, the sleep-onset period (SOP) exhibits dynamic and non-monotonous changes of electroencephalogram (EEG) with high, and so far poorly understood, intra- and inter-individual variability. Computational models of the sleep regulation network have suggested that the transition to sleep can be viewed as a noisy bifurcation at a saddle point which is determined by an underlying control signal or ``sleep drive''. However, such models do not describe how internal control signals in the SOP can produce rapid switches between stable wake and sleep states, nor how these state-space changes are translated in the macroscopic EEG. Here, we propose a minimally-parameterized stochastic dynamical model, in which one slowly-varying control parameter drives the wake-to-sleep transition while exhibiting noise-driven bistability. We provide a procedure for estimating the parameters of the model given single observations of experimental sleep EEG data, and show that it can reproduce a wide variety of SOP phenomenology. Using the model to analyze a pre-existing sleep EEG dataset, we find that the estimated model parameters correlate with subjective sleepiness reports. These results suggest that the bistable characteristics of the SOP can serve as biomarkers for tracking intra- and inter-individual variability of sleep-onset disorders.

• Visual stimulus-evoked blood velocity responses in individual human posterior cerebral arteries measured with dynamic phase-contrast functional MR angiography
  Authors: Hu, Z.; Proulx, S.; Hartung, G. A.; Gomez, D. E. P.; Chen, J. E.; Varadarajan, D.; Gökcal, E.; Bollmann, S.; Tan, C. O.; Gurol, M. E.; Polimeni, J. R.
  Published: 2025-08-15 (new results)
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  Functional MRI (fMRI) tracks brain activity through the associated hemodynamic changes via neurovascular coupling. Neurons communicate with the microvessels of the parenchyma to initiate a hemodynamic response, and these microvessels then communicate with upstream arterioles and arteries. The role of the larger feeding arteries--far upstream from the site of neuronal activity--in coordinating this response is incompletely understood, yet is important for the interpretation of fMRI. Functional Transcranial Doppler (fTCD) can noninvasively measure blood velocity changes in a subset of the largest macrovessels, albeit with poor spatial resolution, whereas existing functional MR angiography (fMRA) methods can assess blood velocity in mid-sized macrovessels but still lack the temporal resolution required to capture dynamic responses. This study aims to propose a new, quantitative fMRA method for measuring blood velocity responses in individual vessels in humans at high spatiotemporal resolution. A dynamic functional phase-contrast MRA approach was developed to quantify responses evoked by visual stimuli in the ''P2'' segment of the posterior cerebral artery (PCA), located ~6 cm away from primary visual cortex. The achieved temporal resolution is comparable to that of conventional blood-oxygenation-level-dependent (BOLD) fMRI, enabling block-design stimulation paradigms similar to those used in conventional fMRI studies. The temporal and spatial properties of the blood velocity responses were evaluated using both long- and short-duration visual stimuli presented to either the full visual field or a single hemifield. Robust responses were measured on both 3T and 7T clinical MRI scanners, and an approximately 3.3 {+/-} 1.2 cm/s increase in the blood velocity in the targeted segment was observed, which is roughly a 10% increase from baseline. Visual hemifield stimulation generated a measurable blood velocity response only in the contralateral cerebral hemisphere, indicating that systemic physiological changes occurring with stimulation cannot account for the observed response, suggesting that they instead reflect neurovascular coupling initiated in the visual cortex. The observed arterial blood velocity response is consistent with a downstream reduction in microvascular resistance and may represent a passive response rather than an active vessel dilation at the targeted arterial segment. The proposed method has the potential to extend the capability of commonly used approaches, such as fTCD, in clinical applications.

• Extracting Value Coding Features from Individual Serotonin Neurons
  Authors: Harkin, E.; Beique, J.-C.; Naud, R.
  Published: 2025-08-12 (new results)
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  Adaptive behaviour requires animals to continually reevaluate the appetitive or aversive quality of their surroundings. Dorsal raphe serotonin neurons, the main source of serotonergic input to the forebrain, have been implicated in both signaling the quality of an animals environment and regulating reward-seeking and punishmentavoiding behaviour, but the precise quantity signaled by these neurons has remained unclear, as well as how these neurons relate with behaviour. Using open-access recordings of serotonergic neurons of the dorsal raphe nucleus while animals perform a dynamic Pavlovian task, we compare firing rate and behavioral data with a model that considers reward history accumulated over a tunable timescale. Our Bayesian parameter estimation supports that serotonergic neurons are consistent with reward history being estimated over about a hundred trials on average, with a heterogeneity across individual neurons spanning 30 to 300 trials. Anticipatory licking also correlated with reward history at multiple timescale, but could not be dissociated from that of a time/thirst nuisance variable and otherwise mostly on a timescale faster than seen in serotonergic cells. These results provide a more precise picture of the dynamics of serotonergic cells under a dynamic Pavlovian task.

• Slow synaptic plasticity from the hippocampus underlies gradual mapping and fragmentation of novel spaces by grid cells
  Authors: chen, l.; Dong, L. L.; Shin, J. H.; Shahid, F.; Malone, T.; Ma, Y.; Vasu, S. O.; Tien, N.-W.; Cekada, K.; Anderson, L.; Chandra, S.; Fiete, I.; Alvarez, V. A.; Gu, Y.
  Published: 2025-08-12 (new results)
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  Animals construct internal "cognitive maps" of the world during navigation in spatial and non-spatial domains, with grid cells in the medial entorhinal cortex (MEC) playing a key role. This requires associating internal position estimates with external cues to reduce spatial uncertainty over time. However, how grid cell representations evolve in novel spaces to support map formation is unclear. To address this question, we longitudinally record grid cells with two-photon calcium imaging over 10 days as mice learn operant tasks in novel virtual linear tracks. We observe that spatial tuning of grid cells is present immediately in novel tracks but evolves as a significant fraction of spatial fields shift backward on a run-by-run basis, within and across days. Backward shifts are more prevalent and persistent in successful learners. The fields gradually stabilize across days, anchored by landmarks, suggesting a slow plasticity mechanism that results in an increasingly fragmented and stable map. The backward shifts partially reset daily, reflecting a slower consolidation timescale. We show that though individual fields of a cell shift differentially, co-active fields of co-modular grid cells shift together, indicating their coupled dynamics keep them on the same two-dimensional torus during this plastic period. Next, we build an entorhinal-hippocampal model that provides a mechanistic explanation of the diverse phenomena - grid field shifts, fragmentation, and increasing fidelity of the spatial map - and predicts slow Hebbian plasticity in the return hippocampus-to-entorhinal pathway. Finally, using ex vivo slice electrophysiology, we show that plasticity in an indirect hippocampus-to-MEC pathway correlates with spatial learning performance and could account for the hypothesized slow plasticity of the model. Together, our study provides multifaceted evidence of slow plasticity in synapses from the hippocampus to the MEC, elucidating the formation of stable and fragmented maps that combine internal and cue-driven positional estimates in rich environments, elucidating cognitive map formation during spatial learning.

• The Crunchometer: A Low-Cost, Open-Source Acoustic Analysis of Feeding Microstructure
  Authors: Gil-Lievana, E.; Arroyo, B.; Perez-Ortega, J. E.; Lopez, A.; Rodriguez-Blanco, L. A.; Diaz, X.; Hernandez, G.; Coss, A.; Alway, E.; Reicher, N.; Hernandez-Lemus, E.; Kaelberer, M.; Bohorquez, D. V.; Gutierrez, R.
  Published: 2025-08-14 (new results)
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  Elucidating the neuronal circuits that govern appetite requires a detailed analysis of the microstructure of solid food consumption. A significant barrier in this field is that existing techniques for monitoring feeding are either prohibitively expensive, limiting their use, or lack the high temporal resolution necessary to align feeding events with neuronal activity. To overcome this, we developed the Crunchometer, a low-cost, open-source acoustic system that uses computational algorithms to create high-resolution feeding ethograms. We validated the system by monitoring feeding across different energy states (hunger/satiety) and by demonstrating that the anti-obesity drug semaglutide suppresses food intake and reduces preference for a high-fat diet. Crucially, the Crunchometer integrates seamlessly with in vivo neural recordings in freely behaving mice. By pairing our system with electrophysiology in the Lateral Hypothalamus (LH), we identified novel "meal-related" neurons that track entire meals rather than individual feeding bouts. Using calcium imaging, we further revealed that solid food consumption strongly modulates LH GABAergic neurons, but not glutamatergic neurons. We also found that distinct LH neuronal ensembles encode the consumption of solid food versus liquid sucrose. The Crunchometer is thus a powerful and accessible tool for precisely dissecting the neural correlates of naturalistic feeding behavior. Significance statementThe Crunchometer is a low-cost, open-source technology that democratizes feeding analysis, enabling the precise dissection of appetite neuronal circuits to advance therapies for obesity and eating disorders.

• Decision signals in the absence of spiking activity in primate visual cortex
  Authors: Hou, Y. S.; Liu, L. D.; Pack, C. C.
  Published: 2025-08-14 (new results)
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  Fluctuations in single-neuron activity in sensory cortex often correlate with perceptual decisions. This kind of correlation has been hypothesized to reflect a causal influence of sensory signals on decisions, a feedback influence of decisions on sensory signals, and various other factors as well. To disentangle these different possibilities, we have examined local field potentials (LFPs) recorded from the middle temporal (MT) area of non-human primates performing a motion discrimination task. Compared to single-neuron spiking, LFPs have the advantage of being decomposable into different frequencies that are associated with different anatomical sources of input. More importantly, they persist when spiking activity is inactivated, which precludes a causal influence of the corresponding neural activity on behavior. We found that high frequency (70-150 Hz) LFP power was correlated with perceptual decisions and that this correlation disappeared when spikes were inactivated, consistent with a causal role for this frequency band in decision making. These signals overlapped in time with decision signals in lower gamma-band power (30-50 Hz), which persisted after spiking inactivation, suggesting a non-causal, feedback input. Interestingly, lower-frequency LFP signals (5-30 Hz) reflected both impending perceptual decisions and the outcome of previous trials. Our results therefore reveal that neural activity multiplexes different sources of information about perceptual decisions and that these types of information can be estimated reliably from different LFP frequencies.

• Musical complexity governs a tradeoff between reliability and dimensionality in the neural code
  Authors: Mouawad, P.; Sabesan, S.; Greasley, A. E.; Lesica, N. A.
  Published: 2025-08-14 (new results)
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  The rich experience of listening to music depends on the neural integration of its constituent elements within the early auditory pathway. Here, we performed the first large-scale study of neural responses to complex music to characterize the neural coding of individual instruments and mixtures with both normal hearing and mild-to-moderate hearing loss. Using coherence and manifold analyses along with deep learning, we identified strong nonlinear interactions in mixed music that impacted the fidelity and geometry of the neural code. We found that increasing musical complexity resulted in the creation of new neural modes, but this increased dimensionality was associated with decreased reliability. This tradeoff persisted even after hearing loss, the effects of which were largely corrected with suitable amplification. These results suggest that the neural coding of music is governed by an inherent tradeoff and highlight a fundamental challenge in maintaining fidelity while processing sensory inputs with increasing complexity.

• Walking Selectively Modulates Behaviorally Relevant Auditory Responses According to Stride Cycle Phase
  Authors: mehmood, I.; Xu, H.; Song, P.; Zhai, Y.; Chang, C.; Bao, X.; Ye, H.; Guo, S.; Wang, Y.; Zhang, L.; Chen, P.; Wen, W.; Zhao, X.; Chen, G.; Yu, X.
  Published: 2025-08-11 (new results)
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  Human perception operates in dynamic environments, requiring sensory processing to continuously adapt to ongoing motor activity. Here, we investigated how natural walking modulates auditory change detection by recording EEG while participants performed a transitional click train task during sitting and walking. Behaviorally, walking significantly elevated auditory change detection thresholds, reflecting reduced perceptual sensitivity. Electrophysiologically, three distinct auditory responses onset, change, and offset were evoked; both the onset and change responses were attenuated during walking, with the most pronounced effect observed for the cognitively demanding change response. Notably, this modulation was further amplified for the change response during active engagement compared to passive listening, implicating attentional resource allocation. Strikingly, both behavioral performance and change-related neural responses fluctuated rhythmically with the gait cycle, while onset and offset responses remained comparatively stable. Together, these findings reveal a stride-phase-dependent gating mechanism that selectively modulates perceptually relevant auditory signals, illustrating how the brain rhythmically reallocates sensory resources to optimize perception during locomotion.

• Inhibiting the right dorsolateral prefrontal cortex selectively enhances unsupervised statistical learning
  Authors: Pesthy, O.; Pesthy, Z. V.; Vekony, T.; Janacsek, K.; Fabo, D.; Nemeth, D.
  Published: 2025-08-11 (new results)
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  The brain must balance the automatic extraction of environmental regularities with top-down cognitive control, yet the causal neural mechanisms governing this interplay are debated. In particular, the hemispheric contributions of the dorsolateral prefrontal cortex (DLPFC) remain unresolved. Here, we applied inhibitory repetitive transcranial magnetic stimulation (rTMS) to the left, right, or bilateral DLPFC in 95 healthy adults during a probabilistic sequence learning task. We found that inhibiting the right and bilateral DLPFC significantly enhanced statistical learning compared to sham and left DLPFC stimulation. Contrary to the hypothesis that this competition is mediated by the suppression of existing knowledge, episodic memory performance was unaffected across all stimulation groups. These findings challenge a direct episodic gating mechanism and suggest the DLPFCs influence on statistical learning is hemisphere-dependent. As an alternative, we propose that right DLPFC inhibition shifts cognitive processing toward a more exploratory information-sampling strategy, a view supported by our finding of significantly greater reaction time variability in the right and bilateral stimulation groups. Together, our results provide causal evidence for a right-lateralized suppressive influence of the DLPFC on unsupervised learning and suggest its modulatory role is linked to information processing style rather than direct competition with episodic memory systems.

• view larger version (64k): org.highwire.dtl.dtlvardef@ab83b4org.highwire.dtl.dtlvardef@53cefaorg.highwire.dtl.dtlvardef@39a742org.highwire.dtl.dtlvardef@1140f68_hps_format_figexp m_fig o_floatnographical abstract:c_floatno trem2 dual actions on microglia-motoneuron interactions after axotomy. trem2 regulates two types of microglia interactions with axotomized motoneurons. in some situations, trem2 facilitates their regeneration while in other regulates their deletion and phagocytosis, the latter more strongly in females than in males. c_fig" data-authors="pottorf, t. s.; lane, e. l.; haley-johnson, z.; amores-sanchez, v.; ukmar, d. n.; correa-torres, p. m.; alvarez, f. j."> Dual Role of Microglial TREM2 in Neuronal Degeneration and Regeneration After Axotomy
  Authors: Pottorf, T. S.; Lane, E. L.; Haley-Johnson, Z.; Amores-Sanchez, V.; Ukmar, D. N.; Correa-Torres, P. M.; Alvarez, F. J.
  Published: 2025-08-14 (new results)
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  After nerve injuries, spinal cord microglia proliferate and migrate towards injured motoneurons surrounding their cell bodies. The significance of microglia enwrapping motoneurons remains unclear. Within the same motor pools some motoneurons degenerate while others regenerate, and each associate with different microglia phenotypes. Microglia surrounding degenerating motoneurons form tight cell clusters ("death clusters") that fully envelop the cell body and express high TREM2 and large CD68 granules, suggesting a macrophagocyte phenotype for motoneuron removal. Microglia surrounding motoneurons undergoing regeneration remain individualized and also upregulate TREM2 and CD68, although to a lower extent, and CD68 granules are smaller. Microglia on regenerating motoneurons extend processes that scan the cell body surface through sweeping motions, likely sampling contents and endocytosing motoneuron-derived material through microphagocytosis. Removal of TREM2, either globally throughout development or specifically in microglia prior to nerve injuries, reduces p-SYK signaling and CD68 expression in all activated microglia, but particularly inside death clusters. There are also pronounce sex differences: CD68 upregulation and downregulation was more significant in females. TREM2 depletion on microglia over regenerating motoneurons prevented the cell body swelling (in both sexes) characteristic of the chromatolytic reaction at the start of regeneration. This correlated with muscle reinnervation delays. We conclude that within the same motor pools, TREM2 facilitates microglia removal of degenerating motoneurons while it facilitates regeneration on other motoneurons. The signals that direct these different microglia phenotypes over degenerating and regenerating motoneurons, as well as the mechanisms that induce degeneration in some motoneurons while most others regenerate, remain to be investigated. Main PointsTREM2 in activated microglia has a dual function around axotomized motoneuron cell bodies after peripheral nerve injuries. Within different microglia-motoneuron interactions, TREM2 is involved in the removal of degenerating motoneurons or facilitating regeneration. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=188 SRC="FIGDIR/small/668924v2_ufig1.gif" ALT="Figure 1"> View larger version (64K): org.highwire.dtl.DTLVardef@ab83b4org.highwire.dtl.DTLVardef@53cefaorg.highwire.dtl.DTLVardef@39a742org.highwire.dtl.DTLVardef@1140f68_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical Abstract:C_FLOATNO TREM2 dual actions on microglia-motoneuron interactions after axotomy. TREM2 regulates two types of microglia interactions with axotomized motoneurons. In some situations, TREM2 facilitates their regeneration while in other regulates their deletion and phagocytosis, the latter more strongly in females than in males. C_FIG

• Circuit inhibition promotes the dynamic reorganization of prefrontal task encoding to support cognitive flexibility
  Authors: Johnson-Cruz, C.; Cho, K. K. A.; Sohal, V. S.
  Published: 2025-08-11 (new results)
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  The mammalian prefrontal cortex encodes variables related to goal-directed behavior, and enables flexibility during environmental changes, making it critical to understand how the dynamic updating vs. stable maintenance of different encodings contribute to behavioral adaptation. We addressed this by comparing prefrontal encoding during successful adaptation vs. maladaptive perseveration. Specifically, we studied mutant (Dlx5/6+/-) mice, which have dysfunctional parvalbumin-expressing inhibitory interneurons and perseverate in a rule shifting task. We measured mPFC activity patterns using microendoscopic calcium imaging, then used linear classifiers and neural networks to compare representational geometries in wild-type mice and Dlx5/6+/- mutants before, during, and after benzodiazepine treatment, which persistently rescues their rule shift learning. The encoding of correct vs. incorrect trial outcomes rapidly shifts as mice successfully learn new cue-reward associations, but becomes more stable when mutant mice perseverate. We also find activity patterns that normally distinguish learning of the initial association vs. rule shift, but become diminished during perseveration. Finally, during perseveration, outdated representations are inappropriately reinstated, not just passively maintained. These results reveal prefrontal contributions to flexible behavior driven by the dynamic reorganization of abstract rule representations, rather than stable reinforcement signals.

• Tau drives cell specific functional isolation of the hippocampal formation
  Authors: Zwang, T. J.; Jasen, Z.; Gelb-Bicknell, R.; Wolf, N.; Chanchykov, V.; Zhu, H.; Agastra, E.; Devine, A.; Holbrook, A. J.; Bennett, R. E.; Hyman, B. T.
  Published: 2025-08-11 (new results)
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  A major challenge in understanding Alzheimers disease is linking changes that occur across different biological scales. For example, how do changes in individual neurons build into widespread network disruptions? To address this, we used flexible mesh electronics to record neuronal activity for six months in ThyTau22 mice, a model of tauopathy that accumulates mutant human tau with age. Electrophysiology was recorded simultaneously from the hippocampus and entorhinal cortex of awake, behaving mice. At all ages we observed neuron-level, tau-driven silencing including ages without detectable tangles or cell-death. We found an unexpected phenomenon: neurons silenced by tau spontaneously recover individual firing patterns, yet these neurons fail to regain normal network interactions. Thus, as the animals age, disrupted network-level activity emerges. Specifically, we observe a global decrease in excitatory interactions and a breakdown in gamma-band coherence, which is particularly disrupted between the entorhinal cortex and hippocampus. These observations reveal a temporal relationship between neuronal silencing and impaired network connectivity, which also contributes to a progressive disruption in the excitatory/inhibitory balance. This ultimately disconnects viable entorhinal-hippocampal connections, physiologically isolating the hippocampus. Importantly, this network dysfunction is not driven by neuron loss, but by the failure of neurons to re-establish proper network interactions after silencing. This reveals a previously unrecognized mechanism by which mutant tau can destabilize neural systems. Further, these experiments indicate that a therapeutic window may exist where neuronal function and network activity might still be restored prior to irreversible degeneration.

• Modulation of repopulating microglia in multiple sclerosis models with implications for neuroprotection
  Authors: Heitmann, N.; Fiene, S.; Rambuscheck, L.; Eggers, B.; Valdes Michel, M. F.; Gude, A.-C.; Hendek, H. H.; Oberhagemann, S.-M.; Klöster, K.; Hoffrogge, R.; Karachunskaya, A.; Märte, H.; Adam, K.; Rozanova, S.; Bader, V.; Reinehr, S.; Plaza-Sirvent, C.; Tandon, G.; Eisenacher, M.; Plemel, J. R.; Joachim, S. C.; Winklhofer, K. F.; Gramlich, O.; Marcus-Alic, K.; Schmitz, I.; Yong, V. W.; Gold, R.; Faissner, S.
  Published: 2025-08-11 (new results)
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  Microglia play a critical role in central nervous system (CNS) pathologies including multiple sclerosis (MS), and their modulation offers therapeutic potential especially during progressive disease courses. Using cell culture and experimental autoimmune encephalomyelitis (EAE) models, we investigated microglial dynamics during depletion and repopulation (MGrepo) and their modulation using siponimod (sipo), an established CNS penetrating MS medication. Repopulating microglia exhibited a transient reactive state (CD86, MHC-II, Il1b, Tnf). Sipo modulated microglia populations, increasing CD163+, CD206+, and CX3CR1+ while reducing CD86+MHC-II+ cells accompanied by a reduction of neuronal damage. Proteomic spinal cord analysis revealed protein expression alterations by MGrepo and sipo linked to inflammation, myelination, and neuronal structural organization, supported by RNA sequencing of the spinal cord. The neuroinflammation attenuating role of sipo could be linked to cell maintenance and myelin formation associated processes. These findings highlight the capacity of pharmacological interventions to modulate microglia, offering new insights into therapeutic strategies targeting microglial activity in neuroinflammatory diseases.

• view larger version (64k): org.highwire.dtl.dtlvardef@19067aorg.highwire.dtl.dtlvardef@f85eb8org.highwire.dtl.dtlvardef@129e39org.highwire.dtl.dtlvardef@51e79d_hps_format_figexp m_fig c_fig male and female appnl-f mice exhibited distinct visceral fat responses to ad progression. in males, early disease stages were marked by vwat lipolysis and hepatic lipid accumulation with metabolic dysfunction, while symptomatic stages showed a metabolic shift that improved insulin sensitivity and nor performance. in contrast, females displayed progressive vwat reaccumulation, reduced hepatic metabolism, and persistent hippocampal senescence and inflammation from early stages onward." data-authors="mcfadden, s. a.; fang, y.; quinn, k.; peck, m. r.; chapman, j. e.; hill, t.; bartke, a.; hascup, e. r.; hascup, k. n."> Surgical Removal of Visceral Adipose Tissue has Therapeutic Benefit in Male APPNL-F Mice
  Authors: McFadden, S. A.; Fang, Y.; Quinn, K.; Peck, M. R.; Chapman, J. E.; Hill, T.; Bartke, A.; Hascup, E. R.; Hascup, K. N.
  Published: 2025-08-11 (new results)
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  PurposeVisceral white adipose tissue (vWAT) accumulation causes systemic inflammation, insulin resistance, metabolic syndrome, and senescent cell accumulation that are risk factors for Alzheimers disease (AD). Visceral fat removal (VFR) improves metabolism and reduces proinflammatory cytokines. We hypothesized that VFR removal in AD mice would improve metabolism and cognition. MethodsMale and female APPNL-F mice underwent sham or vWAT surgical resection (epididymal and perirenal) at 4 (pre-symptomatic) and 16 (symptomatic) months of age to understand interventional and therapeutic effects, respectively. At 18 months of age, glucose metabolism and novel object recognition (NOR) memory were assayed followed by assessment of body composition and tissue-specific markers of metabolism, cell senescence, inflammation, or amyloid accumulation. ResultsMale and female APPNL-F mice showed distinct VFR responses. In pre-symptomatic males, increased vWAT lipolysis and hepatic lipogenesis led to ectopic liver lipid accumulation, with reduced adiponectin and leptin, elevated visfatin, and impaired glucose metabolism. Symptomatic males showed reduced vWAT lipogenesis, enhanced hepatic lipolysis, glycolysis, and glycogenesis, lowering liver lipids and improving insulin sensitivity. Only symptomatic males improved NOR, linked to elevated hippocampal learning and memory markers. Female vWAT reaccumulation was due to increased lipogenesis and lower lipolysis. Pre-symptomatic females had lower hepatic lipogenesis, while glycolysis and glycogenesis declined with disease progression. Hippocampal senescence and inflammation were elevated early in the disease that persisted symptomatically. ConclusionsSex-specific differences in glucose and lipid metabolism and lipid accumulation underlie the divergent responses to VFR in APPNL-F mice, with symptomatic males showing the only beneficial outcomes in metabolism and cognition. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/669175v1_ufig1.gif" ALT="Figure 1"> View larger version (64K): org.highwire.dtl.DTLVardef@19067aorg.highwire.dtl.DTLVardef@f85eb8org.highwire.dtl.DTLVardef@129e39org.highwire.dtl.DTLVardef@51e79d_HPS_FORMAT_FIGEXP M_FIG C_FIG Male and female APPNL-F mice exhibited distinct visceral fat responses to AD progression. In males, early disease stages were marked by vWAT lipolysis and hepatic lipid accumulation with metabolic dysfunction, while symptomatic stages showed a metabolic shift that improved insulin sensitivity and NOR performance. In contrast, females displayed progressive vWAT reaccumulation, reduced hepatic metabolism, and persistent hippocampal senescence and inflammation from early stages onward.

• Increased neuronal activity restores circadian functionin Drosophila models of C9orf72-ALS/FTD
  Authors: Inami, S.; Jenny, B. P.; Akpoghiran, O.; Gallagher, S. I.; Strich, A. K.; Tonoki, A.; Trotti, D.; Haeusler, A. R.; Koh, K.
  Published: 2025-08-11 (new results)
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  Circadian rhythm disruptions are common across neurodegenerative diseases, but their link to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) remains unclear. The C9orf72 hexanucleotide repeat expansion is the most prevalent genetic cause of ALS/FTD. Here, we used Drosophila models expressing toxic arginine-rich dipeptides (PR or GR) or GGGGCC hexanucleotide repeats to investigate circadian deficits in C9orf72-ALS/FTD. We found that circadian rhythmicity and period length were disrupted in a repeat number-, dosage-, and age-dependent manner. Additionally, we observed lower levels of the neuropeptide PDF, a key regulator of free-running circadian rhythms, as well as decreased projection complexity and reduced neuronal activity in PDF-expressing neurons. Importantly, increases in neuronal activity significantly restored circadian function under select conditions. These results implicate reduced neuronal activity in C9orf72-ALS/FTD circadian deficits, underscoring the importance of precisely tuned, circuit- and stage-specific interventions. HighlightsO_LIC9orf72 dipeptide and nucleotide repeats disrupt circadian rhythms in Drosophila C_LIO_LICircadian dysfunction with reduced PDF and neurites emerges before neuron loss C_LIO_LIIncreased neuronal activity rescues mild circadian dysfunction C_LIO_LIActivity-based rescue is effective across ages and models when precisely tuned C_LI

• Very low amplitude muscle activity increases probability of motor evoked potentials in healthy individuals and in ALS
  Authors: O'Sullivan, S.; Tadjine, Y.; Suleyman, N.; Woods, E.; Fasano, A.; Walsh, C.; Awiszus, F.; Hardiman, O.; Carson, R. G.; McMackin, R.
  Published: 2025-08-11 (new results)
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  IntroductionIn many clinical and research settings, transcranial magnetic stimulation (TMS) intensities are standardised based on resting motor threshold (RMT). It is well-established that contraction of the target muscle increases motor evoked potential (MEP) amplitude and correspondingly decreases RMT. As such, when estimating RMT it is crucial to ensure the target muscle is relaxed. Typically trials in which baseline electromyographic (EMG) amplitude exceeds a specified threshold are rejected. The influence of motor activity below typical rejection thresholds on MEP amplitudes has yet to be established. MethodsWe retrospectively analysed TMS-EMG data collected during RMT measurement in 45 healthy controls (1761 datapoints) and 35 people with amyotrophic lateral sclerosis (ALS, 1238 datapoints). Trials where root mean squared (RMS) baseline EMG amplitude exceeded 10{micro}V were rejected. Generalised linear mixed-effects models were used to assess effects of muscle activity below this rejection threshold on probability of evoking an MEP with peak-to-peak amplitude [≥]50{micro}V. ResultsGreater sub-rejection-threshold activity significantly increases MEP probability in controls (p<0.0004) and people with ALS (p=0.0010). Models predicted a 31-38% increase in MEP probability when baseline RMS-EMG amplitude increased from 1{micro}V to 9{micro}V. Sub-rejection- threshold baseline activity was significantly greater in ALS than controls (p=0.0055). DiscussionWe have shown for the first time that higher EMG amplitudes below a typical rejection threshold markedly increase probability of evoking an MEP with peak-to-peak amplitude [≥]50{micro}V. Researchers should take measures to account for effects of sub-rejection-threshold activity on RMT, particularly in populations where baseline activity may be elevated, such as in ALS.

• Inflammation increases the penetrance of behavioral impairment in Shank3 haploinsufficiency mice -- can it explain the behavioral regression in Autism?
  Authors: Qiao, S.-N.; Wang, S. E.; Kim, K.-Y.; Jo, S.; Jiang, Y.-H.
  Published: 2025-08-11 (new results)
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  Behavioral regression occurs in [~]40% of SHANK3-associated autism spectrum disorder (ASD). We previously reported that significant behavioral regression in a small cohort with SHANK3 haploinsufficiency patients, triggered by subclinical infections, responded to immunomodulator treatments. We hypothesize that behavioral regression results from the interplay between SHANK3 deficiency and neuroinflammation. Using Shank3 exon 4-22 deletion heterozygous mutant (Sh3+/-) mouse, which shows no significant behavior impairments, we established a preclinical model - Shank3 haploinsufficiency mouse undergoing systemic inflammation challenge via intraperitoneal injection of lipopolysaccharides (LPS). We found that, two weeks after LPS challenge, wild-type mice (WT) recovered but Sh3+/- mice exhibited motor impairment, anxiety-like behaviors, and excessive grooming, similar to Shank3 exon 4-22 deletion homozygous mutants. Anti-inflammatory treatment partially reversed LPS-induced behavioral changes. Transcriptomic analysis revealed upregulation of neuroinflammation-related genes and downregulation of synaptic function-related genes in Sh3+/- mice in response to LPS. Especially, pro-inflammatory genes and microglia markers were overly activated that may result from the increased Toll-Like Receptor 4 (TLR4) expression in microglia in Sh3+/-mice. Our findings indicate that neuroinflammation increases the penetrance of behavioral impairment in Shank3 haploinsufficiency mice and support a potential mechanism for the behavioral regression in human SHANK3 disorders for future investigations.

• A Cell-Autonomous Role for the Vitamin B6 Metabolism Gene PNPO in Drosophila GABAergic Neurons
  Authors: Fu, W.; Landaverde, S.; Zhuang, X.; Iyengar, A.
  Published: 2025-08-11 (new results)
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  In animals, the enzyme pyridox(am)ine 5-phosphate oxidase (PNPO) is critical for synthesizing the active form of vitamin B6 (VB6), pyridoxal 5-phosphate (PLP), from inactive vitamers. PLP is a required cofactor for many enzymatic reactions, including the synthesis of GABA and the monoamines. PNPO disruption in humans is associated with an array of epilepsy syndromes, while Drosophila harboring mutations in the sole PNPO ortholog, sugarlethal (sgll), display spontaneous seizures and short lifespans. These phenotypes are suppressed by PLP supplementation and are exacerbated by restriction of dietary B6 vitamers. In the context of PNPO deficiency, it remains to be resolved what the specific contributions by cellular subpopulations in the nervous system are to neurological phenotypes. We addressed this question in sgll mutants by expressing human PNPO (hPNPO) cDNA in cholinergic, glutamatergic, and GABAergic neurons as well as glia and measuring changes in survival and seizure phenotypes. We found hPNPO expression in GABAergic neurons largely restored lifespan and attenuated seizure activity, while glial expression also improved sgll phenotypes albeit to a lesser degree. In contrast, hPNPO expression in either cholinergic or glutamatergic neurons, accounting for most neurons in the fly brain, did not appreciably alter sgll phenotypes. We contrasted these observations with changes in sgll mutants induced by feeding GABA receptor modulators. The GABAB agonist SKF-97541 reduced mortality, while GABA or GABAA receptor modulators did not improve survival. Together, our data establish a cell-autonomous role for PNPO in GABAergic neurons to support brain function, especially under VB6-restricted conditions.

• Sound-evoked auditory neurophysiological signals are a window into prodromal functional differences in a preclinical model of Alzheimer's Disease
  Authors: Aydin, A. G.; Manoj, P.; Ramadan, F.; Youssef, E.; Rajan, S.; Torres, E.; Bieszczad, K. M.
  Published: 2025-08-11 (new results)
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  Hearing has been identified as the largest modifiable mid-life risk factor for Alzheimers Disease (AD), despite that its link to dementia remains unclear. Here we identify a biomarker of AD risk in an auditory neural signal using the non-invasive, rapidly acquired, and clinically translatable auditory brainstem response (ABR) in normal hearing knock-in rats (Swedish familial AD risk variant to Amyloid precursor protein, AppS; male and female). While ABR morphology has been proposed as a biomarker for AD, we report a novel biomarker derived from multidimensional parametric feature extraction on the distribution statistics of repeated single traces of the ABR that increases its potential for clinical utility with sensitivity and specificity. We report accurate prediction of AD genetic risk in both young and aged animals: AppS rats separate clearly from humanized controls in both sex- and age-dependent manners. Notably, auditory learning in young adulthood normalized the ABR signature in AppS rats with maintained effects into older age, altogether supporting a central neural generator of auditory dysfunction related to AD risk. These preclinical findings show how ABRs could provide a very early biomarker for detection of AD risk and lay the groundwork to test the synergy of auditory and cognitive functions in human dementia.

• Neural Circuit Remodeling Underlying Enhanced Feeding During Pregnancy in Mice
  Authors: Inada, K.; Tasaka, G.-i.; Hagihara, M.; Kobayashi, K.; Miyamichi, K.; Yukinaga, H.
  Published: 2025-08-11 (new results)
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  Pregnancy represents a unique physiological state marked by substantial adaptations influencing both behavior and metabolism1. Alterations have been observed across multiple levels--from changes in cellular morphology, synaptic density, and neuroglial interactions to a brain-wide reduction in gray matter volume2-7. While these adaptations are thought to support offspring survival and promote maternal physiological and psychological well-being8, their functional significance remains largely unresolved. In particular, linking localized synaptic plasticity to a broader brain-wide circuit dynamics has posed a major challenge. Using virus-mediated screening in mice, we investigated the pregnancy-induced remodeling of the presynaptic landscape of paraventricular hypothalamic (PVH) oxytocin neurons, a central hub of maternal physiology9,10. Here we show a selective and reversible elimination of excitatory synaptic inputs from the medial preoptic nucleus to PVH oxytocin neurons, displaying region-, cell-type-, and pathway-specificity. This reduction in excitatory drive attenuated the anorexigenic activity of oxytocin neurons during feeding, thereby promoting the increased food intake characteristic of pregnancy. These data demonstrate that the selective suppression of anorexigenic PVH oxytocin neuron activity plays a critical role in appetite regulation during pregnancy. More broadly, our data identify a pregnancy-associated remodeling of hypothalamic neural circuits with direct physiological relevance.

• Reverse Predictivity: Going Beyond One-Way Mapping to Compare Artificial Neural Network Models and Brains
  Authors: Muzellec, S.; Kar, K.
  Published: 2025-08-11 (new results)
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  A major goal in systems neuroscience is to build computational models that capture the primate brains internal representations. Standard evaluations of artificial neural networks (ANNs) emphasize forward predictivity--how well model features predict neural responses--without testing whether model representations are themselves recoverable from neural activity. Here we develop the reverse predictivity metric, which quantifies how well macaque inferior temporal (IT) cortex responses predict ANN unit activations. This two-way framework reveals a striking asymmetry: models with high forward predictivity ([~]50% variance explained) often contain units unpredictable from neural activity, reflecting biologically inaccessible dimensions. In contrast, monkey-to-monkey mappings are symmetric, confirming that the asymmetry reflects genuine representational mismatch. Reverse predictivity isolates "common" ANN units--shared with IT, behaviorally relevant, and generalizing across species--and "unique" units lacking such alignment. Influenced by feature dimensionality, training objectives, and adversarial robustness, reverse predictivity offers a principled benchmark for guiding next-generation ANNs toward both high task performance and genuine biological plausibility.

• Pause characteristics of sentence production in Parkinson's disease: insights from sentence complexity and length
  Authors: Mollaei, F.; Evans, H.; Pool, A.
  Published: 2025-08-11 (new results)
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  PurposeParkinsons disease (PD) affects forward flow of speech including fluency disruptions in 90% of individuals. One of the main parameters affecting flow and fluency of speech is pause behaviour. However, the precise language characteristics of pauses, including sentence complexity and length, and how they contribute to the fluency disruptions of PD are not fully understood. This study examined how sentence complexity and length affect pause behaviour in PD. MethodSeventy-one participants, comprising individuals with PD (n = 32) and neurotypical controls (n = 39), read a speech passage aloud. The number and duration of pauses, categorised by location (between, within sentences), sentence complexity (simple, complex), and sentence length (short, long) were analysed. Cognitive ability, assessed using the Montreal Cognitive Assessment (MoCA), and motor speech deficits (i.e., dysarthria) severity, assessed using a speech perceptual ranking, were evaluated and correlated with pause characteristics. ResultsIndividuals with PD produced significantly more pauses across all categories compared to controls. However, only between-sentence and long-sentence pauses were significantly longer in duration. Pause frequency and duration in both groups were higher in more complex and longer sentences. Significant negative correlations were found between MoCA scores and number of pauses. Significant positive correlations were observed between dysarthria severity and duration of pauses. ConclusionThese findings suggest that increased cognitive-linguistic demands--indexed by sentence complexity and length--may underlie pausing behaviour and contribute to fluency disruptions in individuals with PD. The results extend previous research by highlighting the potential cognitive-linguistic basis of motor speech dysfunction in PD.

• Revisiting Amplitude of Low-Frequency Fluctuations (ALFF) in Resting-state fMRI: Clarifications and Improvements
  Authors: Huang, L.; Jabakhanji, R.; Vigotsky, A. D.; Branco, P.; Baliki, M. N.; Apkarian, A. V.
  Published: 2025-08-11 (new results)
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  The amplitude of low-frequency fluctuations (ALFF) and its related measure, fractional ALFF (fALFF), are widely used resting-state fMRI techniques for quantifying spontaneous neural activity within specific frequency bands. However, inconsistencies in the definition and implementation of ALFF have led to confusion in the field. In this study, we provide a mathematical clarification of ALFF and fALFF by introducing two variants: the arithmetic mean-defined ALFF/fALFF (amALFF/amfALFF) and the quadratic mean-defined ALFF/fALFF (qmALFF/qmfALFF). We examine the relationships between mean BOLD intensity (MBI), amALFF, and qmALFF across both subjects and voxels using two independent datasets mapped onto different brain templates. Additionally, we investigate the impact of z-scoring the original BOLD signal on ALFF and fALFF metrics. Our key findings include: (1) MBI is positively correlated with both amALFF and qmALFF, highlighting the need for normalization to subject-level means; (2) normalized qmALFF and qmfALFF are highly correlated with normalized amALFF and amfALFF, respectively, at both the subject and voxel levels; (3) z-scoring the BOLD signal does not affect amfALFF or qmfALFF, but it substantially alters amALFF and qmALFF. Based on these findings, we present a comprehensive flowchart of the (f)ALFF algorithm implemented in the temporal domain. The full procedure is implemented in R, and the corresponding script is available at: https://github.com/lejianhuang/ALFF.

• Adaptive behavior is guided by integrated representations of controlled and non-controlled information
  Authors: Huang, B.; Ritz, H.; Jiang, J.
  Published: 2025-08-11 (new results)
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  Understanding how task knowledge is encoded neurally is crucial for uncovering the mechanisms underlying adaptive behavior. Here, we test the theory that all task information is integrated into a conjunctive task representation by investigating whether this representation simultaneously includes two types of associations that can guide behavior: stimulus-response (non-controlled) associations and stimulus-control (controlled) associations that inform how task focus should be adjusted to achieve goal-directed behavior. We extended the classic item-specific proportion congruency paradigm to dissociate the electroencephalographic (EEG) representations of controlled and non-controlled associations. Behavioral data replicated previous findings of association-driven adaptive behaviors. Decoding analyses of EEG data further showed that associations of controlled and non-controlled information were represented concurrently and differentially. Brain-behavioral analyses also showed that the strength of both associations was associated with faster responses. These findings support the idea that controlled and non-controlled associations are governed by an integrated task representation to guide adaptive behaviors simultaneously.

• Optimal colors can predict luminosity thresholds in natural scenes
  Authors: Duay, K.; Nagai, T.
  Published: 2025-08-11 (new results)
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  Luminosity thresholds define the luminance boundary at which a surface color shifts in appearance from being perceived as an illuminated surface to appearing self-luminous. Previous research suggests that the human visual system infers these thresholds based on internal references of physically realizable surface colors under a given illumination, referred to as the physical gamut. A surface is perceived as self-luminous when its luminance exceeds the upper limit of this empirically internalized gamut. However, the precise structure and boundaries of these gamuts remain uncertain. Optimal colors, which represent theoretical surface reflectances under specific illuminants, have been shown to provide an effective model for visualizing and computing the physical gamuts. In prior studies, optimal colors have successfully predicted luminosity thresholds; however, these findings were limited to highly simplified, abstract stimuli. Whether this framework generalizes to more naturalistic viewing conditions has remained an open question. In the present study, we demonstrate that the theory of an internal reference in the form of an empirically constructed physical gamut, visualized through optimal colors, remains valid under more natural conditions. Our results confirm that optimal colors can still accurately predict luminosity thresholds in such settings. Moreover, our findings suggest that the luminosity thresholds encompass both self-luminosity and naturalness concepts. Subsequently, this may imply that the notion of physical gamut could envelope both concepts as well and could be defined as "all physically possible colors in a scene for an object that does not emit light." These insights can have profound potential implications for both applied fields (i.e., XR or projection mapping) and fundamental science (e.g., understanding human visual processing mechanisms).

• The Semantic Underpinnings of Speech Disorganization in Schizophrenia
  Authors: Fradkin, I.; Moran, R.; Adams, R. A.; Jefferies, E.; Dolan, R. J.
  Published: 2025-08-12 (new results)
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  Effective communication relies on shared semantic representations and their context-sensitive retrieval. Accordingly, difficulties in communicating coherently, as seen in some patients with schizophrenia, may reflect impairments at the level of semantic structure or the retrieval process operating on this structure. Disentangling these components is challenging. Here, we address this problem using a word association task and magnetoencephalography (MEG), allowing us to examine behavioral markers of semantic structure and retrieval as well as semantic representation in the brain. For the latter, we detail an approach that contrasts the brains encoding of concepts as predicted by generic versus personalized semantic models. In so doing, we provide converging evidence for semantic structure idiosyncrasy in patients with schizophrenia who also exhibit speech disorganization. The findings advance our understanding of the semantic underpinnings of speech disorganization in schizophrenia, while also revealing the potential of using personalized semantic models to explain neural representation and behavior.

• Dynamic, behavior-dependent interactions between dorsal striatal dopamine and glutamate release predict cognitive flexibility and punishment resistant cocaine use
  Authors: Bortz, D. M.; Obaidi, K.; Deldin, A.; Weber, D. J.; Torregrossa, M. M.
  Published: 2025-08-12 (new results)
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  Cognitive inflexibility covaries with substance use disorder (SUD) risk. To determine if there is a neural relationship between these phenomena, glutamate and dopamine release in the dorsomedial (DMS) and dorsolateral (DLS) striatum were measured as rats performed a discrimination and strategy switching test. Elevations in glutamate release, with reductions in dopamine, at trial initiation (DLS) and prior to choice (DMS and DLS) predicted fast strategy switching and punishment sensitive cocaine seeking. Elevations in DLS and DMS dopamine release at these respective timestamps predicted slow switching and punishment resistance. Orbitofrontal cortex and intralaminar thalamus were significant contributors to DLS and DMS glutamate release, but their relative contributions differed between rats that were fast or slow strategy switchers, and in how they affected behavior. As such, these data describe a neural signature of flexibility and associated circuitry that could be used to predict and treat SUDs in humans.

• Spreading alpha-Synuclein Oligomers Trigger Astrocyte Reactivity and Astrocyte-glutamatergic Neuron system dysfunction in an Age-Dependent Manner
  Authors: LeeBae, J.; Bopp, V.; Goreth, A.; Grozdanov, V.; Kuehlwein, J. K.; Gazzola, E.; Rombach, D.; Meier, L.; Dimou, L.; Danzer, K. M.
  Published: 2025-08-11 (new results)
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  Parkinsons disease (PD) is characterized by the progressive accumulation and spatio-temporal spread of -synuclein (-syn) oligomers and a progressive loss of dopaminergic neurons. To investigate the transcriptional and cellular consequences of -syn oligomer spreading, we employed spatial transcriptomics and single-nucleus RNA sequencing (snRNA-seq) in a transgenic PD mouse model. We identified -syn spreading to the substantia nigra and defined a transcriptional "Spreading Signature" associated with -syn pathology. We found an age specific increase in reactive astrocytes, close interactions between reactive astrocytes and -syn, and transcriptional dysregulation of the astrocyte-glutamatergic neuron network. We further identified two subtypes of glutamatergic neurons that are vulnerable to astrocytic changes. Comparative analysis with human PD snRNA-seq data revealed conserved astrocytic dysfunctions, underscoring the translational relevance of our findings. Based on our results, we propose a revised model of -syn spreading and highlight 36 genes as potential therapeutic targets for mitigating astrocyte-neuron dysfunction in PD.

• Distinct goal location beta frequency dynamics in hippocampus and prefrontal cortex across learning
  Authors: Wang, G.; Zhou, N.; Leveroni, Z. M.; Yu, J.
  Published: 2025-08-11 (new results)
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  Neural activity at goal locations contributes to learning by providing feedback on the success of preceding actions. This period engages neocortical and hippocampal networks, which serve distinct functions in processing reward and forming associations with experience that lead to reward. A neocortical network signature for reward feedback processing is beta oscillations (15-30Hz). Beta oscillations are thought to coordinate distributed neural processes across brain regions. However, it is unknown whether beta oscillations coordinate hippocampal-neocortical networks during the goal period, or how their dynamics relate to learning. Here, we show that beta oscillations occur in both hippocampal CA1 and the prefrontal cortex (PFC) when rats reach goal locations in spatial navigation tasks. Despite the presence of beta oscillations in both regions after goal entry, beta activity in each region differed in spectral and temporal properties. These differences suggest that the hippocampus and PFC are not strongly coupled at the beta frequency. We found the strengths of PFC and CA1 beta oscillations across learning were inversely related: PFC beta activity increasing in strength and CA1 beta activity decreasing in strength. Beta burst properties in PFC also had an inverse relationship to those of hippocampal sharp wave-ripples (SWRs), a prominent hippocampal process required for learning. We found a subset of PFC neurons modulated by both beta and hippocampal SWRs, which had distinct task-related firing patterns. Our results suggest that during outcome processing at goal locations, the neocortex and hippocampus are independently modulated by beta oscillations before becoming coordinated for memory-related processes during SWRs.

• The Microglial TREM2 Receptor Programs Hippocampal Development in a Mouse Model of Childhood Deprivation
  Authors: Ahmed, S.; Bowers, C.; Munoz-Martin, J.; Jamwal, S.; Sanganahalli, B. G.; Giuliano, L.; MacDowell Kaswan, Z. A.; Hyder, F.; Yang, X. W.; Kaffman, A.
  Published: 2025-08-12 (new results)
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  Childhood neglect and deprivation are the most common forms of adversity, yet their biological impact on cognitive development--and how enrichment mitigates these effects--remains unclear. Using limited bedding (LB) as a mouse model of deprivation, we previously showed that abnormal microglial-mediated synaptic pruning during the second and third postnatal weeks leads to impaired synaptic connectivity and hippocampal dysfunction, particularly in males. Here, we demonstrate that LB reduces expression of Triggering Receptor Expressed on Myeloid cells 2 (TREM2) in different mouse strains and that TREM2 deficiency contributes to, but does not fully explain, impaired microglial pruning. Overexpressing TREM2 restored microglial phagocytic function and rescued deficits in hippocampal connectivity and fear learning. Brief postnatal enrichment (P14-P17) also normalized synaptic pruning in a TREM2-dependent manner. Together, our findings identify TREM2 as a key molecular mediator of experience-dependent plasticity, revealing its central role in linking early-life deprivation and enrichment to cognitive outcomes later in life.

• The Relationship between Social Reward Behavior and Mesolimbic Dopamine Release
  Authors: Erickson, T. R.; Franks, H. E.; Young, L. J.; Lester, D. B.
  Published: 2025-08-12 (new results)
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  Deficits in social behavior, such as reduced motivation and social avoidance, are key symptoms in several psychiatric disorders. Distinct modes of reward, such as drug and social, may rely on different dopamine release patterns in the mesolimbic pathway. We investigated the relationship between social reward behaviors and dopamine release elicited by phasic and tonic stimulation patterns in C57BL/6J mice. Social conditioned place preference was used to assess motivation for social interaction, and in vivo fixed potential amperometry was used to measure nucleus accumbens dopamine release before and after cocaine (10 mg/kg, ip). Additional measures included the frequency and duration of social interactions during conditioning sessions, with the first and last session representing novel and familiar social interactions respectively. No relationship was found between baseline (pre-cocaine) dopamine and social place preference in either sex. However, in males, social place preference negatively correlated with cocaine-induced phasic dopamine release, indicating that increased social motivation was associated with a reduced phasic dopaminergic response to cocaine. In contrast, greater novel interaction was associated with increased baseline dopamine elicited by tonic stimulations. These relationships were not observed in females. Overall, these findings suggest distinct, sex-dependent roles for phasic and tonic dopamine release in mediating social reward.

• Distinct Flower signaling domains orchestrate cellular fitness via secreted vesicles in Aβ-induced neurodegeneration
  Authors: Chang, H.-F.; Tu, S.-M.; Lin, C.-H.; Liu, Y.; Hohneck, J.; Jung, M.; Clemenz, A.; Rother, S.; Schirra, C.; Schwarz, Y.; Krause, E.; Schulz-Schaeffer, W. J.; Flockerzi, V.; Yao, C.-K.
  Published: 2025-08-12 (new results)
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  Flower isoforms regulate cellular fitness and are implicated in neurodegeneration and tumor progression, yet their mechanisms remain unclear. Using Flower knockout mice, we identify the N- and C-terminal domains as distinct signaling modules: the C-terminus promotes survival of fitter ( winner) cells via intrinsic signaling, while the N-terminus induces apoptosis of neighboring less-fit ( loser) cells via extrinsic signaling. Notably, Flower signaling operates via secreted extracellular vesicles (EVs), with the win isoform exhibiting [~]25-fold higher secretion than the lose, thereby facilitating intercellular fitness selection. In Alzheimers disease human brain tissue and APP transgenic mice, win isoforms are enriched in astrocytes near amyloid-{beta} plaques, suggesting localized fitness surveillance. In cortical neuron-glia cultures, overexpression of the win isoform or its C-terminal domain enhances astrocytic A{beta} clearance and protects neurons from A{beta} toxicity. These findings uncover a novel Flower signaling pathway controlling cell death, providing new insights into EV-mediated communication with therapeutic potential in neurodegeneration.

• High frequency broadband activity detected noninvasively in infants distinguishes wake from sleep states
  Authors: Holubecki, A. M.; Yarbrough, J. B.; Rangarajan, V.; Kuperman, R.; Knight, R. T.; Johnson, E. L.
  Published: 2025-08-12 (new results)
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  High frequency broadband activity (HFB; 70-150 Hz) indexes local brain activity. It is predominantly studied using invasive measures due to signal drop off from skull attenuation. We hypothesized that HFB is detectable in infants noninvasively through fontanelles and thin skull that have not fully developed. We analyzed scalp electroencephalography (EEG) data during wake and sleep states in 19 channels from 18 infants (1-4 months, both sexes). At the group level, linear mixed-effects models revealed greater HFB power in wake versus sleep states in midline and central channels near fontanelles, as well as in occipital channels over thin skull. These differences were detected with 90% reliability using as few as 25 seconds of data per state in as few as 10 subjects. On the individual level, linear mixed-effects models revealed the same wake > sleep effect with a mean reliability of 60% when using at least 50 seconds of data per state. These findings establish that noninvasive HFB detection in infants is not only possible at sites where the skull has not fully developed, but sufficiently robust to enable systematic investigation of early cognitive development.

• Increased numbers of CD4+ T-cells in hypocretin/orexin region of Narcolepsy Type 1
  Authors: Shan, L.; Fonville, M.; Hoekstra, M.; Smolders, J.; Swaab, D.
  Published: 2025-08-12 (new results)
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  Narcolepsy type 1 (NT1) is proposed to be an autoimmune disorder targeting hypothalamic hypocretin (orexin, Hcrt) neurons. Hcrt reactive T-cells have been identified in blood and cerebrospinal fluid (CSF) of NT1 patients. However, it remains unknown whether T-cells infiltrate the brain. Since T-cells can be retained for a lifetime in tissues as tissue resident memory T-cells after primary antigen exposure, we now systematically assess the presence of CD4+ and CD8+ T-cells in NT1 brains to determine their regional distribution and potential autoimmune involvement in NT1 neuropathology. We immunohistochemically stained and quantified CD4+ and CD8+ T-cells in post-mortem brain tissue of NT1 patients (n=5) and matched controls (n=5) in the Hcrt region, paraventricular nucleus (PVN) and median eminence (ME) as well as in the substantia nigra (SN) and locus coeruleus (LC). To phenotypically characterize CD4+ T-cells, we performed double staining with CD49a or C-X-C chemokine receptor type 6 (CXCR6). Furthermore, we stained for fibrinogen to estimate blood-brain barrier integrity, as well as microglia markers and an astrocyte marker to evaluate acute immune reactivity in the Hcrt region of NT1 brains. In NT1 there was an 11-fold increase in total number of CD4+ T-cells in the Hcrt region, but not in the PVN, ME, nor SN or LC. These CD4+ T-cells exhibited tissue residential memory features with double staining with CD49a or CXCR6. There were no changes in blood-brain barrier integrity, microglia and astrocyte staining intensities between NT1 and controls. In addition, the total number of CD4+ T-cells in the Hcrt region showed significant negative correlations with mean sleep latency in NT1 cases. Our findings suggest an enrichment of CD4+ T-cells specifically in the Hcrt region of NT1 indicating prior local antigen engagement. Moreover, greater CD4+ T-cell presence in the Hcrt region of NT1 was associated with increased symptom severity, as reflected by shorter sleep latency. These data support the hypothesis that CD4+ T-cells infiltrate the Hcrt region, where they may contribute to the autoimmune process that initiates NT1.

• Calcium chelation promotes microtubule regrowth and axonal recovery after laser-induced axonal injury
  Authors: Mishra, A.; Joshi, P.; Pullarkat, P. A.
  Published: 2025-08-12 (new results)
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  Axons that are damaged locally due to stretch or crush injury often undergo widespread and irrecoverable damage. Transient elevation of cytosolic free calcium across extended regions of the axon, and calcium mediated disintegration of cytoskeletal elements is one of the main causes of this neurodegeneration. When axonal damage involves complete transection of axons, any recovery has to be driven by the formation of fresh motile tips (growth-cones). However, axons could also undergo partial damage where the axonal plasma membrane retains its continuity while cytoskeletal elements undergo extensive disintegration triggered by elevated free calcium. We invoke such a condition using a partial laser ablation technique, and we show that complete axonal recovery, mainly mediated by microtubule regrowth, is possible in such cases when extracellular calcium is depleted. This method allows us to explore the dynamics of cytoskeletal damage after injury and the modes of recovery of microtubules and actin filaments. Apart from understanding the mechanisms of cytoskeletal damage and recovery, our results can have significant impact on devising treatment strategies for crush injuries to nerves.

• Effects of Tilia tomentosa on sleep architecture and circadian rhythm
  Authors: Di Soccio, A.; Canova, M.; Rizzo, N.; Lodovichi, C.
  Published: 2025-08-12 (new results)
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  Tilia extract has been used for centuries as a sedative and hypnotic compound. The impact of Tilia on sleep architecture and circadian rhythm remained, however, elusive. Here, we addressed these open questions by analysing the behaviour and the EEG signals recorded in freely moving mice fed an enriched diet with Tilia extracts. We found that Tilia significantly increased the amount of sleep, mostly during the dark hours, which correspond to the most active phase in nocturnal animals, such as mice. Furthermore, in darkness, the length of wake episodes did not increase as in controls. Spectral analyses of the EEG showed that the features of the sleep and wake signals remained unaltered upon Tilia treatment. Interestingly, the power in the gamma band resulted significantly decrease while the theta band power resulted increased in treated mice. Altogether, our data demonstrated a clear effect of Tilia on sleep architecture, highlighting its dependency on the circadian rhythm.

• Parallel and convergent pathways for multifeature visual processing in larval zebrafish sensorimotor decision-making
  Authors: Slangewal, K.; Aimon, S.; Capelle, M. Q.; Kaempf, F.; Naumann, H.; Baier, H.; Slanchev, K.; Bahl, A.
  Published: 2025-08-12 (new results)
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  Animals continuously extract and evaluate diverse sensory information from the environment to guide behavior. Yet, how neural circuits integrate multiple, potentially conflicting, inputs during decision-making remains poorly understood. Here, we use larval zebrafish to address this question, leveraging their robust optomotor response to coherent random dot motion and phototaxis towards light. We demonstrate that animals employ an additive behavioral algorithm of three visual features: motion coherence, luminance level, and changes in luminance. Using brain-wide two-photon imaging, we identify the loci of these computations, with the anterior hindbrain emerging as a multifeature sensory integration hub. Through single-cell neurotransmitter and morphological analyses of functionally identified neurons, we characterize potential connections within and across computational nodes. These experiments reveal three parallel and converging pathways, matching our behavioral results. Our study provides a mechanistic brain-wide account of how a vertebrate brain integrates multiple features to drive sensorimotor decisions, bridging the algorithmic bases of behavior and its neural implementation.

• The olfactory bulb reflects structural plasticity within a genetically stable olfactory network
  Authors: Olsson, T.; Joshi, A.; Schaefer, M.; Arshamian, A.; Hummel, T.; Lundstrom, J.; Darki, F.
  Published: 2025-08-12 (new results)
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  The olfactory bulb (OB), the first central relay of the olfactory pathway, plays a critical role in odor perception and exhibits remarkable structural plasticity shaped by environmental influences. This raises a fundamental question about the extent to which the structure of the OB is genetically determined. While both OB volume and function have been implicated in a range of neurodegenerative and neuropsychiatric disorders, such as Parkinsons disease, schizophrenia, and depression, all of which involve known genetic risk factors, the heritability of the OB structure remains poorly understood. Here, we investigated the heritability of OB volume and the broader olfactory network architecture in a large sample of healthy young adults (n = 941; aged 22-35 years), including monozygotic and dizygotic twin pairs. Using a deep learning-based segmentation model, we first automatically segmented OB volumes and then employed a support vector machine framework to classify zygosity based on within-pair morphological similarity. The OB volume alone showed weak classification performance in distinguishing between monozygotic and dizygotic twins, suggesting limited heritability. However, integrating OB volume with morphometric features from olfactory-associated brain regions, including the hippocampus, parahippocampal gyrus, entorhinal cortex, and medial orbitofrontal cortices, substantially improved classification performance. This effect was specific to the olfactory network, underscoring the distributed nature of genetic influence in this system. These findings suggest that the OB, despite being a highly plastic and environmentally responsive structure, is embedded within a genetically coordinated neural network.

• Two pore domain THIK2 channel is involved in acute and chronic pain signal regulation
  Authors: Gilbert, N.; Chatelain, F. C.; Gibaud, S.; Lorivel, T.; Shen, Y.-L.; kerros, M.-E.; Feliciangeli, S.; Fiore, F.; Chen, C.-C.; Lesage, F.; Delphine, B.
  Published: 2025-08-12 (new results)
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  Two-pore domain potassium channels (K2P) regulate neuronal excitability by acting as hyperpolarizing leak channels. Among them, THIK2 remain poorly characterized. Although no study has yet clearly linked them to excitability or pain, their selective expression in nociceptive neurons of the Dorsal Root Ganglia (DRG) suggests a role in nociception and pain regulation. This project investigates THIK2 channels in pain pathophysiology through molecular, electrophysiological, and behavioral approaches. We mapped THIK expression patterns and in THIK2 knock-out mice, we examined DRG neuron excitability and pain sensitivity. Results reveal thermal hypersensitivity under both naive and inflammatory conditions, indicating that THIK2 normally limits neuronal hyperexcitability. These findings position THIK2 as a potential therapeutic target in chronic inflammatory pain, with peripheral inhibition potentially offering analgesia without central opioid side effects.

• Two pore domain THIK2 channel is involved in acute and chronic pain signal regulation
  Authors: Gilbert, N.; Chatelain, F. C.; Gibaud, S.; Lorivel, T.; Shen, Y.-L.; kerros, M.-E.; Feliciangeli, S.; Fiore, F.; Chen, C.-C.; Lesage, F.; Bichet, D.
  Published: 2025-08-13 (new results)
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  Two-pore domain potassium channels (K2P) regulate neuronal excitability by acting as hyperpolarizing leak channels. Among them, THIK2 remain poorly characterized. Although no study has yet clearly linked them to excitability or pain, their selective expression in nociceptive neurons of the Dorsal Root Ganglia (DRG) suggests a role in nociception and pain regulation. This project investigates THIK2 channels in pain pathophysiology through molecular, electrophysiological, and behavioral approaches. We mapped THIK expression patterns and in THIK2 knock-out mice, we examined DRG neuron excitability and pain sensitivity. Results reveal thermal hypersensitivity under both naive and inflammatory conditions, indicating that THIK2 normally limits neuronal hyperexcitability. These findings position THIK2 as a potential therapeutic target in chronic inflammatory pain, with peripheral inhibition potentially offering analgesia without central opioid side effects.

• view larger version (47k): org.highwire.dtl.dtlvardef@1426b97org.highwire.dtl.dtlvardef@1a5bb77org.highwire.dtl.dtlvardef@1b69f32org.highwire.dtl.dtlvardef@8da416_hps_format_figexp m_fig c_fig" data-authors="houmam, s.; siodlak, d.; pham, k.; salinas, c.; ocanas, s. r.; freeman, w. m.; rice, h. c."> Protocol to isolate oligodendrocytes, microglia, endothelial cells, astrocytes, and neurons from a single mouse brain using magnetic-activated cell sorting
  Authors: Houmam, S.; Siodlak, D.; Pham, K.; Salinas, C.; Ocanas, S. R.; Freeman, W. M.; Rice, H. C.
  Published: 2025-08-12 (new results)
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  The isolation of specific cell types of the brain is essential to study cell-type-specific differences in complex neurological diseases such as Alzheimers disease. This protocol isolates oligodendrocytes, microglia, endothelial cells, astrocytes, and neurons from a single mouse brain. The process involves gentle tissue homogenization, debris removal, and sequential sorting of five distinct cell types. We validate cell purity and viability using flow cytometry and RT-qPCR. This protocol is well-suited for a range of downstream applications, including genomics, transcriptomics, and proteomics. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/666877v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@1426b97org.highwire.dtl.DTLVardef@1a5bb77org.highwire.dtl.DTLVardef@1b69f32org.highwire.dtl.DTLVardef@8da416_HPS_FORMAT_FIGEXP M_FIG C_FIG

• Short-term sensory memory mediates adaptation, habituation, and a paradoxical neural-behavioral transformation in C. elegans
  Authors: White, H.; Mallik, S.; Ching, S.; Albrecht, D. R.
  Published: 2025-08-12 (new results)
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  Repeated exposure to stimuli elicits decreasing sensory neural responses over time (adaptation). However, resulting behavioral responses can either weaken over time (habituation) or remain invariant, indicating that the neural-behavioral link is not fixed. To investigate neural adaptation and its flexible translation into behavioral decision making, we created a mathematical framework hypothesizing (1) that sensory networks optimize the speed and accuracy of encoding exogenous stimuli, and (2) that representations form along two time scales, one embedding immediate information and the other stimulus history. Using experimental recordings of the nematode C. elegans, we validated normative model predictions of this optimal encoding strategy, specifically how neural dynamics and adaptation levels vary with stimulus timing. A parametric Bayesian decoder architecture predicted conditions leading to behavioral habituation or invariance, but also paradoxical inversion, whereby appetitive stimuli elicit aversive responses. Experiments with food odors validated that inversion behavior occurred after several repetitions with a long stimulation time and low odor concentrations. Mechanistically, during sensory neural adaptation, weaker immediate stimulus representations can be compensated by secondary processes through memory effects, with biological origins that remain to be studied.

• Development of a genetically encoded melanocortin sensor for high sensitivity intravital imaging
  Authors: Namkung, Y.; Slutzki, T.; Pedroso, J.; Liu, X.; Sabatini, P.; Kokoeva, M. V.; Laporte, S.
  Published: 2025-08-12 (new results)
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  The central melanocortin system, composed of peptides derived from pro-opiomelanocortin (POMC) such as the melanocyte-stimulating hormones (-, {beta}-, {gamma}-MSH) and melanocortin 4 receptors (MC4R), along with the agouti-related protein (AgRP), plays a pivotal role in controlling energy balance. To elucidate the dynamic role of -MSH release in regulating appetite, specific, sensitive, and spatiotemporally resolved genetic sensors are required. The melanocortin 1 receptor (MC1R) scaffold was leveraged for its robust plasma membrane expression, high affinity for melanocortin peptides and low affinity for AgRP to design a -MSH selective sensor for in vivo use. This was achieved by integrating circularly permuted green fluorescent protein (cpGFP) into the receptor, which we named Fluorescence Amplified Receptor sensor for Melanocortin (FLAREMC). The FLAREMC sensor shows high potency and selectivity in heterologous and homologous expressing cells for -MSH and the synthetic melanocortin agonist MTII but not to the inverse agonist AgRP. The sensor exhibited impaired signaling, with reduced G protein activation, no {beta}-arrestin coupling, and failed to internalize upon agonist stimulation. In vitro, FLAREMC displayed high photostability and reversible photoactivation. These properties suggest that the FLAREMC is suitable for long-term activity recording in the brain without desensitizing or interfering with endogenous melanocortin receptor signaling. When expressed in the paraventricular nucleus (PVN) of the mouse hypothalamus, the primary site of anorexigenic -MSH signaling, FLAREMC demonstrated its effectiveness in detecting changes associated with melanocortin responses in vivo. FLAREMC enables the study of melanocortin system in cultured cells and intravitally. This first of its class highly sensitive melanocortin sensor will serve as a valuable tool to advance our understanding of the complex dynamics governing melanocortin-dependent appetite regulation and related processes in the brain.

• Time-series models can forecast long periods of human temporalEEG responses to randomly alternating visual stimuli
  Authors: Foster, R. R.; Delaney, C. M.; Krusienski, D. J.; Ly, C.
  Published: 2025-08-12 (new results)
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  Visual stimuli changing at constant temporal frequencies induces sharp peaks in the power spectrum of the electroencephalogram (EEG) over the visual cortex at the driving frequency and its harmonics, known as steady-state visual evoked potentials (SSVEPs). Visual stimuli that alternate according to randomized temporal patterns can also result in predictable EEG patterns. While such EEG responses are robust and predictable, the underlying biophysical mechanisms that shape these responses are not fully understood. To better understand the relationship between the stimuli and associated EEG responses, and ultimately inform a biophysical model, we examine these relationships using EEG data from a controlled experiment. We model the EEG using several statistical time series models with components that loosely mimic biophysical mechanics: an autoregressive (AR) model, with an exogenous input (ARX), adding moving average terms (ARMAX), and a seasonality term (SARMAX). We fit these models using the Box-Jenkins methodology and assess EEG forecast performance for a relatively long period of several seconds out-of-sample. We find in-sample fits are good in all models despite the complexities of the visual pathway, and that all models can capture aspects of out-of-sample EEG, including the distribution of values (point-wise in time), the point-wise Pearsons correlation of EEG and model, and the frequency content. Surprisingly, we find little variation in the performance of all models, with the most sophisticated and detailed model (SARMAX) performing comparatively poorly in some instances. Taken together, our results suggest the simplest AR model is valuable because it is easy to understand and can perform just as well as more complicated models. Since these models are relatively simple and more transparent than contemporary predictive models with numerous parameters, our study may provide insights into the biological mechanisms of the temporal dynamics of human EEG response that could generalize to other visual stimuli.

• Manual lymph drainage massage of the head and neck improves cognition and reduces pathological biomarkers in the 5x-FAD mouse model of Alzheimers disease
  Authors: Bartlett, M. J.; Erickson, R. P.; Frye, J.; Doyle, K. P.; Pires, P. W.; Witte, M. H.
  Published: 2025-08-12 (new results)
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  Alzheimers disease (AD) affects 6.9 million people over the age of 65 in the US and is expected to double by 2060. While FDA approved immunotherapies slow cognitive decline in some individuals with AD, they do not improve cognition, are costly, and have significant side-effects. Therefore, new targets, approaches, and treatments for AD are a necessity. There are no FDA approved therapies for AD that target the brains lymphatic system. It is well established that the toxic protein, amyloid-beta (A{beta}), accumulates in the AD brain. Recent studies have shown that A{beta} is cleared via interstitial fluid and cerebrospinal fluid through a pathway involving the glymphatic system--meningeal lymphatic vessels--leading to deep and superficial cervical lymphatic vessels and nodes. Therefore, any blockage along this route can cause inefficient drainage and result in pathological buildup of A{beta}, which can lead to AD. Here, we propose a new approach to treating AD by manual lymph drainage (MLD), which is a light skin massage traditionally used to reduce fluid accumulation in lymphedema. This therapy has also been demonstrated to be safe in individuals with AD, but its effects on cognition and biomarkers of AD has never been investigated. In this study we demonstrate that repeated MLD of the head and neck, including the superficial cervical lymphatic vessels (scLVs), improves cognitive function in AD as measured in both the Y-maze and nest-building tests. We also show that this coincides with a reduction in plasma levels of neurofilament light chain (NfL), a non-specific biomarker for neuronal cell death and axonal damage. MLD was also shown to reduce A{beta} in the hippocampus of these mice. Combined, this data provides compelling proof-of-principle evidence for the potential of MLD as a standalone or adjunct therapy in the treatment of AD.

• Disrupted Transcriptional Networks by Mutant Atrophin-1 in a Cell Culture Model of Dentatorubral-Pallidoluysian Atrophy
  Authors: Nuga, O.; Pourhadi, M.; Rausch, J. P.; Todi, S. V.
  Published: 2025-08-12 (new results)
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  Dentatorubral-Pallidoluysian Atrophy (DRPLA) is a dominant neurodegenerative disease caused by CAG triplet repeat expansion in ATN1, which encodes the transcriptional co-repressor Atrophin-1. DRPLA features motor, cognitive, and epileptic symptoms and shares pathogenic mechanisms with other polyglutamine (polyQ) disorders, including protein misfolding, impaired autophagy, and transcriptional dysregulation. To understand disease mechanisms, we performed RNA-seq on HEK293T cells stably expressing wild-type or polyQ-expanded ATN1. Cells expressing pathogenic ATN1 exhibited a distinct transcriptomic profile, including disruptions in synaptic organization, extracellular matrix remodeling, ion channel expression, and neurotransmission. Several genes tied to neurodevelopmental, neurodegenerative, and oncogenic pathways were fully activated or silenced. Dysregulated pathways also included inflammation, chromatin remodeling, stress responses, and redox imbalance. Heat shock protein expression changes suggested proteotoxic stress and impaired protein quality control, with some findings conserved in a previously reported Drosophila melanogaster model of DRPLA. These transcriptomic signatures expand our understanding of molecular events related to degeneration in DRPLA and may lead to the identification of therapeutic targets.

• Effects of experimentally induced fatigue on motor learning: A scoping review
  Authors: Ghafari Goushe, B.; Youssef, L.; Mangin, T.; Arvisais, D.; Neva, J. L.; Pageaux, B.
  Published: 2025-08-12 (new results)
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  The literature on the effect of fatigue on motor learning is limited and marked by inconsistent findings. This scoping review aimed to explore the available knowledge on the effects of fatigue induced by physical and cognitive exertion on motor learning, and to compile and understand how it is studied. A comprehensive search strategy using relevant index terms and keywords was conducted across MEDLINE, EMBASE, SPORTDiscus, Web of Science, PsycINFO, CINAHL, ERIC, and Dissertations & Theses Global. Twenty-two studies met the inclusion criteria. The findings revealed considerable inconsistencies in how fatigue and motor learning were defined and measured. None of the studies examined the effect of fatigue induced by combined physical and cognitive exertion, and only 27% investigated fatigue induced by cognitive exertion. Acuity tasks were the most frequently used to assess motor learning, employed in 59% of the studies. Notably, all participants were between 19 and 31 years of age, and reporting of key demographic and physiological characteristics such as sex, gender, physical activity level, and body mass index was inconsistent or absent. This review highlights the need for comprehensive definitions of both fatigue and motor learning to improve consistency and reproducibility across studies. Given the limited research on the effects of fatigue induced by cognitive and combined physical and cognitive exertion, future studies should prioritize using these experimental manipulations. Also, future studies should diversify the motor learning tasks used in research to allow both direct and conceptual replication. Additionally, broader age ranges and comprehensive participant profiling should be prioritized.

• Transcutaneous auricular vagus nerve stimulation during short-term motor practice drives cortical plasticity without behavioral improvement
  Authors: Nakagawa, K.; Osu, R.
  Published: 2025-08-12 (new results)
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  Transcutaneous auricular vagus nerve stimulation (taVNS) is emerging as a promising non-invasive neuromodulation technique to augment neurorehabilitation, yet its mechanisms in humans remain poorly understood. Animal studies suggest that VNS delivered during motor skill practice drives task-specific plasticity in the primary motor cortex (M1), but direct evidence in humans has been lacking. Here, we provide the first demonstration that taVNS paired with motor skill practice selectively enhances cortical plasticity without boosting motor performance beyond practice alone during short-term training. Thirty-one healthy right-handed adults practiced a novel implicit motor task, rotating two balls with the non-dominant hand for 15 minutes. Participants were randomized to receive taVNS to the left tragus or sham stimulation during practice. Motor performance, M1 hand representation (TMS mapping), and spinal excitability (F-wave) were assessed pre- and post-practice, while pupil diameter was continuously monitored as an index of noradrenergic activity. Motor performance improved similarly in both groups, whereas cortical map expansion was significantly greater in the taVNS group than in the sham group. F-wave amplitude increased only in the sham group, suggesting that taVNS-driven plasticity was restricted to cortical circuits. Moreover, taVNS uniquely elicited pupil dilation during practice, consistent with noradrenergic system engagement. These findings reveal that taVNS can promote task-specific cortical reorganization in humans independent of immediate behavioral improvement. By linking taVNS-induced plasticity to noradrenergic modulation and dissociating cortical from spinal effects, this study provides novel mechanistic insight into how taVNS may lay the neural groundwork for enhanced motor recovery, with critical implications for neurorehabilitation. Significance StatementMotor recovery after stroke depends on the brains ability to reorganize motor circuits. Vagus nerve stimulation (VNS) has been proposed as a powerful approach to enhance such plasticity, but the underlying mechanisms in humans remain unclear. Here we show that non-invasive transcutaneous auricular VNS (taVNS), when paired with motor practice, selectively enhances reorganization of the primary motor cortex without additional behavioral improvement. Importantly, these effects were observed after only 15 minutes of practice, demonstrating that taVNS can induce rapid plastic changes. This provides the first evidence in humans that taVNS promotes task-specific cortical plasticity, underscoring its promise as a neuromodulatory tool for neurorehabilitation.

• Transcutaneous vagus nerve stimulation reduces total striatal GABA content and facilitates early-phase motor learning
  Authors: Matsumura, K.; Matsuta, H.; Kawasoe, R.; Fumuro, T.; Matsushita, K.; Hata, N.; Asayama, Y.; Fujiki, M.; Sugata, H.
  Published: 2025-08-12 (new results)
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  BackgroundTranscutaneous vagus nerve stimulation (tVNS) has emerged as a promising non-invasive technique for modulating neuroplasticity. Previous studies have suggested that changes in regional brain GABA signaling contribute to these effects, but empirical neurophysiological evidence remains limited. MethodsWe investigated the neurophysiological and behavioral effects of tVNS (200-s pulses at 20 Hz, alternating 30 s ON-1 s OFF cycles, 30 min total duration) in healthy adults using two experimental paradigms. In Experiment 1, GABA levels were measured in the left striatum (STR), dorsolateral prefrontal cortex (DLPFC), and sensorimotor cortex (SM) of 34 participants by magnetic resonance spectroscopy (MRS) before and after ipsilateral tVNS. In Experiment 2, 28 participants performed a right-hand force-control motor learning task before, during, and after tVNS. ResultsAdministration of tVNS significantly reduced GABA levels in the left STR compared to sham stimulation (p < 0.05), and also significantly improved motor task performance compared to the sham group at 10 minutes after stimulus onset (p < 0.05) ConclusionTranscutaneous VNS may facilitate early-phase motor learning by reducing striatal GABA levels and consequently inducing corticobasal circuit disinhibition. These findings support tVNS as a potential noninvasive intervention to enhance motor learning for neurorehabilitation and motor disorder treatment.

• Global and local origins of trial-to-trial spike count variability in visual cortex
  Authors: Li, A.; Lu, Z.; Ladd, A.; Matveev, P.; Shea-Brown, E.; Steinmetz, N. A.
  Published: 2025-08-12 (new results)
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  Sensory neuron spiking responses vary across repeated presentations of the same stimuli, but whether this trial-to-trial variability represents noise versus unidentified signals remains unresolved. Some of the variability can be attributed to correlations between neural activity and arousal, locomotion, and other overt movements. We hypothesized that correlations with global activity factors, i.e., patterns of neural activity observable in other brain regions, may explain additional variability in spike count responses of visual cortical neurons. To test this, we used Neuropixels 2.0 probes to record neural activity in mouse primary visual cortex (V1) while subjects passively viewed images. We recorded videos of behavior alongside neural activity from other brain regions, either spiking activity of neural populations in anterior cingulate area (ACA) or widefield calcium signals from across the dorsal cortex. We then used a model based on reduced rank regression to partition the explainable variability of visual cortical responses by source. Some of the trial-to-trial variability in V1 spike counts was attributable to locally shared patterns of activity uncorrelated with either behavior or global activity patterns. Locally shared activity patterns explained trial-to-trial variability that was in excess of Poisson spike generation. Of the parts of variability attributable to non-local sources, global cortical activity predicted significantly more V1 spike count variability than behavioral factors. Additionally, behavioral factors explained little variability uniquely and comprised a geometric subspace of the globally predictable V1 activity. Finally, optogenetically perturbing ACA directly impacted V1 activity, and ACA activity patterns predicted V1 spike count variability even on trials without overt behaviors. Our data indicate that globally shared factors from other cortical areas contribute substantially to shared spike count variability in V1, with only a minority of shared variability confined to local V1 circuits.

• Function aligns with geometry in locally connected neuronal networks
  Authors: Legare, A.; Ribordy, O.; De Koninck, P.; Allard, A.; Desrosiers, P.
  Published: 2025-08-12 (new results)
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  The geometry of the brain imposes fundamental constraints on its activity and function. However, the mechanisms linking its shape to neuronal dynamics remain elusive. Here, we investigate how geometric eigenmodes relate to functional connectivity gradients within three-dimensional structures using numerical simulations and calcium imaging experiments in larval zebrafish. We show that functional connectivity gradients arising from network activity closely match the geometric eigenmodes of the networks spatial embedding when neurons are locally connected. By systematically varying network parameters such as the connectivity radius and the prevalence of long-range connections introduced via edge swaps, we reveal a robust geometry-function correspondence that progressively deteriorates as local connectivity is disrupted. Additionally, we demonstrate that spatial filtering can artificially impose geometric structure on functional gradients, even at modest levels. To support our computational results, we conduct volumetric calcium imaging experiments at cellular resolution in the optic tectum of zebrafish larvae. We uncover cellular functional gradients that closely align with geometric eigenmodes up to a certain eigenmode wavelength that reflects the spatial extent of neuronal arborizations measured in single-neuron reconstructions, as predicted by our simulations. Our findings highlight the importance of short-range anatomical connectivity in shaping the geometric structure of brain activity.

• Geometry of neural dynamics along the cortical attractor landscape reflects changes in attention
  Authors: Song, H.; Chen, R.; Botch, T. L.; Braver, T. S.; Rosenberg, M. D.; Zacks, J. M.; Ching, S.
  Published: 2025-08-12 (new results)
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  The brain is a complex dynamical system whose activity reflects changes in internal states, such as attention. While prior work has shown that large-scale brain activity reflects attention, the mechanism governing this association in a time-varying and task-dependent manner remains unknown. Here, we tested a hypothesis that the geometry of neural dynamics on the attractor landscape, or the movement along the "hills and valleys", reflects changes in attentional states over time and variations across controlled and naturalistic contexts. We fit a parametric dynamical systems model to fMRI data collected during rest, task performance, and naturalistic movie-watching. The model decomposes neural dynamics into components that are intrinsic versus extrinsically driven by stimuli. Model parameters were biologically meaningful, reflecting both cognitive states and individual differences. Model simulations revealed a set of attractors that mirrored functional brain networks, spanning the canonical gradient from sensorimotor to default mode network regions. The speed and direction of neural trajectories toward these attractors systematically varied across attentional states in a context-dependent manner. When participants were paying attention to effortful tasks, neural dynamics converged directly toward a task-relevant attractor, suggesting that it occupied a steeper region of the attractor landscape. In contrast, when participants were engaged in sitcom episodes, neural dynamics were in a flattened region of the landscape, directed away from the attractors. These findings demonstrate that while the positions of the attractors are largely determined by the cortical organization, the geometry of neural dynamics on the attractor landscape changes systematically across attentional states and situational contexts.

• Mental Imagery abilities affect visual working memory performance: evidence from aphantasic participants
  Authors: Zhao, C.; Vogel, E. K.; Bainbridge, W. A.
  Published: 2025-08-12 (new results)
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  Visual imagery refers to the mental generation of visual representations of stimuli, while visual working memory involves retaining visual information for a short period without external input. Due to the conceptual overlap between these two constructs, successful performance on visual working memory tasks may rely on the use of visual imagery to rehearse items during the retention interval. Consequently, individuals with aphantasia, who lack voluntary visual imagery, may experience difficulties with such tasks. However, prior research has suggested that some individuals with aphantasia might employ non-visual strategies to compensate for this deficit. In two experiments, we examined visual working memory performance in aphantasic and control participants across a range of stimulus types. In Experiment 1, participants completed a change localization task using color squares and complex fractals; in Experiment 2, stimuli included real words, phonologically valid pseudowords, and phonologically invalid pseudowords. Across both experiments, aphantasic participants demonstrated significantly impaired visual working memory compared to controls. Notably, their performance was equally impaired for stimuli that were easily verbalizable (i.e., colors and words) and those that were not (i.e., fractals and pseudowords). Furthermore, individual differences in visual imagery ability, as measured by the Vividness of Visual Imagery Questionnaire (VVIQ), significantly predicted working memory performance across all stimulus types. These findings provide direct evidence for the critical role of visual imagery in supporting visual working memory.

• Heartbeat-evoked responses in M/EEG: A systematic review of methods with suggestions for analysis and reporting
  Authors: Steinfath, T. P.; Azanova, M.; Kapralov, N.; Loesche, T.; Enk, L.; Nikulin, V.; Villringer, A.
  Published: 2025-08-12 (new results)
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  Heartbeat-evoked responses (HER), as measured by electroencephalography (EEG) or magnetoencephalography (MEG), have become widely used as a marker of cardiac interoception in the study of brain-body interactions. However, HER studies report largely variable findings, at least partially due to methodological variability. To achieve consensus on HER processing and improve the reproducibility of findings, the field urgently requires a structured summary of the methods employed so far. To this end, we conducted a systematic review of 132 HER studies using non-invasive M/EEG recordings in humans. Our results reveal substantial heterogeneity across most steps of HER analysis, ranging from data acquisition and preprocessing to HER estimation and statistical approaches. The large diversity in the processing choices is accompanied by considerable proportions of unreported methodological information across reviewed studies, reaching up to 80% for key processing steps. In addition, less than 33% of studies had enough statistical power to reliably detect meta-level HER effects, while their reported spatiotemporal locations varied substantially. We provide a comprehensive reporting and quality control checklist to aid in the development of more standardized procedures, highlighting critical steps for robust HER investigations. Additionally, we share the full extracted dataset, including an interactive version, to support other researchers in answering additional specific questions they may have. We hope that these resources will improve the robustness, reproducibility, and transparency of research in the growing HER field.

• A quantitative framework for predicting odor intensity across molecule and mixtures
  Authors: Pellegrino, R.; Samoilova, K.; Ihara, Y.; Andres, M.; Singh, V.; Gerkin, R. C.; Koulakov, A.; Mainland, J. D.
  Published: 2025-08-12 (new results)
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  In vision and hearing, standardized units such as lumens (for brightness) and decibels (for loudness) allow consistent quantification of stimulus intensity, enabling precise control of sensory experiences. Olfaction, by contrast, currently lacks a robust quantitative framework linking physical stimulus properties directly to perceived odor intensity, complicating efforts to accurately characterize and manipulate aromas. To bridge this gap, we used a precisely controlled odor delivery system combined with deep learning models to predict the intensity of both single molecules and mixtures from physical properties. These models allowed us to develop an automated, quantitative method that accurately identifies which volatile components meaningfully contribute to aroma perception, overcoming the limitations of traditional heuristic approaches such as odor activity values and demonstrating practical utility in complex naturalistic odors.

• Rapid cognitive testing predicts real-world driving risk in commercial and medically at-risk drivers
  Authors: Atkin, A. E.; Scott, D.; Popowich, C.; Singhal, A.
  Published: 2025-08-12 (new results)
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  Road safety is a major public and occupational health issue. Safe driving requires numerous cognitive and sensorimotor skills, and past literature suggests that cognitive testing can predict safe or unsafe driving in both healthy and medically at-risk drivers. However, such testing is often time-consuming and inaccessible. In this study, we designed a modified version of the Trail Making Test (TMT) which can be completed on a smartphone in approximately 5 minutes. We recruited 4405 commercially-licensed drivers and 314 medically at-risk drivers to complete the TMT, plus an on-road test of their driving abilities. We then trained and tested a logistic regression model using 50-50 splits on each dataset. The results of the model showed that the longer it took drivers in both groups to complete the TMT, the more likely they were to fail the on-road driving test. Accuracy for the commercial group was 83.8%, with a positive predictive value (PPV) of 34.4% and a negative predictive value (NPV) of 85.3%. Accuracy for the medically at-risk group was 63.1%, with a PPV of 55.8% and an NPV of 65.8%. Overall accuracy was 82.5%, with a PPV of 43.0% and an NPV of 84.3%. Log-transformed reaction time to targets was significantly associated with on-road failure in both driving groups. The results of this study suggest that a rapid and accessible version of the TMT can predict unsafe driving with comparable accuracy to more time-consuming and administratively burdensome means of testing.

• Online supervised learning of temporal patterns in biological neural networks under feedback control
  Authors: Sono, Y.; Yamamoto, H.; Nishi, Y.; Sumi, T.; Sato, Y.; Hirano-Iwata, A.; Katori, Y.; Sato, S.
  Published: 2025-08-12 (new results)
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  In vitro biological neural networks (BNNs) provide a well-defined model system to constructively investigate how living cells interact with their environment to shape high-dimensional dynamics that could be used to generate a coherent temporal output, such as those required for motor control. Here, we developed a real-time closed-loop BNN system capable of generating periodic and chaotic temporal signals by integrating cultured cortical neurons with microfluidic devices and high-density microelectrode arrays. We show that training a simple linear decoder with fixed feedback weights enables the system to learn and autonomously generate diverse temporal patterns. When feedback was switched on, irregular activity in BNNs is transformed into low-dimensional, structured dynamics, producing coherent trajectories characterized by stable transitions between neural states. BNNs trained on different target frequencies--ranging from 4 to 30 s--could be trained to sustain oscillations at distinct frequencies, demonstrating their adaptability. Importantly, a top-down control of self-organized network formation with microfluidic devices is the key to suppress excessive synchronization and increase dynamical complexity in BNNs, facilitating the training and robust output generation. This work offers a biologically inspired platform for understanding the physical basis of cortical computation and for advancing energy-efficient neuromorphic computation. Significance StatementReservoir computing is a machine learning paradigm that exploits the transient dynamics of high-dimensional nonlinear systems. Although it was originally inspired by the mammalian brain and widely explored in physical systems, its implementations in biological neural networks (BNNs) have been limited due to their excessive connectivity and global synchrony in vitro. Here, we use microfluidic devices to construct modular, nonrandomly connected BNNs and integrate them with microelectrode arrays in a closed-loop reservoir computing environment. We show that the system can be trained to autonomously output various temporal signals, with the modular connectivity that is essential for learning. In vitro BNNs provide unique alternatives for physical reservoirs with dynamic adaptability.

• When Firing Rate Falls Short: Spike Synchrony to Efficiently Disentangle Stimulus Saliency and Familiarity
  Authors: Zemliak, V.; Nieters, P.; Pipa, G.
  Published: 2025-08-12 (new results)
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  The function of temporal coding in the brain remains controversial, with debate centering on the following question: does spike timing information, such as their temporal synchrony, play a meaningful role in neural computation which cannot be attributed to firing rate? We propose the solution to this dilemma: spike synchrony provides crucial information about stimulus familiarity under conditions when the firing rate alone is insufficient - namely, when the input stimulus is varied in saliency. Using simulations of recurrent spiking networks, we show that synchrony is particularly effective in distinguishing familiar stimuli of low saliency from novel stimuli of high saliency - an important distinction for both biological perception and artificial agents navigating dynamic environments. We evaluate familiarity detection across two frameworks: a biologically inspired model of the primary visual cortex (V1) and an abstract associative memory model. We show that in both cases, synchrony is more sensitive to recurrent connectivity, that encodes prior experiences, compared to input firing rate. This highlights the relevance of synchrony for familiarity encoding in a scenario of realistic input variability.

• The Hsp40 co-chaperone DNAJC7 modifies polyglutamine but not polyglycine aggregation
  Authors: Ramani, B.; Ehsani, K.; Kampmann, M.
  Published: 2025-08-12 (new results)
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  Polyglutamine (polyQ) diseases, including Huntingtons disease and several spinocerebellar ataxias, are caused by abnormally expanded CAG nucleotide repeats, which encode aggregation-prone polyQ tracts. Substantial prior evidence supports a pathogenic role for polyQ protein misfolding and aggregation, with molecular chaperones showing promise in suppressing disease phenotypes in cellular and animal models. In this study, we developed a FRET-based reporter system that models polyQ aggregation in human cells and used it to perform a high-throughput CRISPR interference screen targeting all known molecular chaperones. This screen identified as a strong suppressor of polyQ aggregation the Hsp40 co-chaperone DNAJC7, which has previously been shown to modify aggregation of other disease proteins (tau and TDP-43) and has mutations causative for amyotrophic lateral sclerosis. We validated this phenotype and further established a physical interaction between DNAJC7 and polyQ-expanded protein. In contrast, DNAJC7 did not modify aggregation of polyglycine (polyG) in a FRET-based model of neuronal intranuclear inclusion disease. In addition to establishing new inducible, scalable cellular models for polyQ and polyG aggregation, this work expands the role of DNAJC7 in regulating folding of disease-associated proteins.

• Females with epilepsy show abnormal changes to perimenstrual sensory induced long-term potentiation
  Authors: Alshakhouri, M.; Sharpe, C.; Bergin, P.; Shaw, A. D.; Muthukumaraswamy, S. D.; Hamandi, K.; Sumner, R. L.
  Published: 2025-08-12 (new results)
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  IntroductionCatamenial epilepsy refers to a cyclical exacerbation of seizure frequency and/or severity linked to stages of the menstrual cycle. To investigate the contribution of underlying excitatory and inhibitory mechanisms of this exacerbation we induced and measured long-term potentiation (LTP). Oestradiol modulates primarily NMDA receptor driven excitation and would enhance visual LTP. Allopregnanolone modulates GABA receptor mediated inhibition and would suppress visual LTP. MethodA control cohort (n = 25) and a cohort with epilepsy (n = 20) were recruited. Participants took part in a visual LTP task while EEG was recorded. Three study visits were timed to capture the mid-follicular (days +5 to +8), mid-luteal (days -9 to -5) phases, as well as the hormone withdrawal in the perimenstrual phase (days -3 to +2). Blood samples confirmed session timing. Generative computational modelling of thalamocortical changes in the EEG was paired with standard evoked potential analysis. Result17 (age 26 {+/-} 9.40) participants with epilepsy, and a control cohort of 25 (age 30 {+/-} 7.06) without epilepsy completed the study. The P2 visually evoked potential (a positive-going component of the visual event related potential waveform) was significantly more enhanced by LTP induction in the mid-follicular phase than the mid-luteal or perimenstrual phases in the control cohort (F(2, 144) =11.54, p = 0.004 corrected). In contrast, in the epilepsy cohort the P2 was significantly more potentiated in the perimenstrual phase than the mid-follicular or mid-luteal phases (F(2,108) = 12.21, p = 0.005 corrected). The effect of cycle on visual LTP was robust, with only 3/17 participants with epilepsy showing highest P2 modulation in the mid-follicular phase (which is the pattern the healthy cohort showed). The computational modelling showed that in epilepsy, the perimenstrual phase was associated with a decrease in superficial pyramidal grain control as well as decreased LTP driven modulation of feed-forward superficial connections to layer 5 and layer 6 to thalamus. DiscussionOur finding of enhanced visual LTP in the luteal phase and perimenstrual phase of females with epilepsy indicates a breakthrough of glutamatergic excitation. Given the relationship between oestrogen and n-methyl-D-aspartate (NMDA) receptor dependent LTP this is plausibly NMDA receptor driven. Several thalamocortical model parameter changes observed warrant further investigation in studies stratifying participants by catamenial epilepsy type. Overall, while research into allopregnanolone and its inhibitory effects dominate perimenstrual catamenial epilepsy research, this study justifies consideration of the role of seizure exacerbating oestradiol.

• B Cell Tolerance and BCR Signaling Dysregulation in NF155-Mediated Autoimmune Nodopathies
  Authors: Roy, B.; Obaid, A. H.; Wang, Z.; Kovacs, K. G.; Ohashi, S.; Kalayci, F. N. C.; Joo, D.; Masi, G.; Coppola, C.; Das, S.; Hernandez, A. L.; Martin-Aguilar, L.; Lleixa, C.; Querol, L.; Nowak, R. J.; O'Connor, K. C.
  Published: 2025-08-12 (new results)
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  ObjectiveAutoimmune nodopathies (AINs) are a group of rare, acquired autoimmune neuropathies with distinct clinical features and the presence of circulating autoantibodies - often of the immunoglobulin G4 (IgG4) subclass - targeting proteins at the node of Ranvier. Defects in B cell tolerance checkpoints have been implicated in several autoimmune diseases. Prior work identified defective B cell tolerance--reflected by a high frequency of self-reactive naive B cells--in patients with MuSK-positive myasthenia gravis (MG), mediated by IgG4 autoantibodies. Here, we investigated whether tolerance defects exist in neurofascin-155-mediated AIN (NF155-AIN), similar to MuSK+ MG. Additionally, we analyzed B and T cell transcriptomics and interactions at the single-cell level to explore the underlying pathomechanism. MethodsUsing a well-established assay, we assessed B cell tolerance fidelity by generating recombinant antibodies from new emigrant (NE) and mature naive (MN) B cell populations-- directly downstream of key tolerance checkpoints--from three NF155-AIN patients, and testing these antibodies for polyreactivity and autoreactivity, thereby determining the frequency of polyreactive and autoreactive B cells. The transcriptome of peripheral blood mononuclear cells (PBMC) was studied, with a special focus on naive B cells and CD4+ T cells at the single-cell level, along with characterization of cell-cell interactions. ResultsNF155-AIN patients have an elevated frequency of polyreactive B cells in the NE (37.4% compared to 9.7% in healthy controls (HCs), p = 0.03) and MN (31.5% compared to 10.5% in HCs, p = 0.03) compartments with increased B cell clones expressing autoreactive antibodies, consistent with a breach in early tolerance checkpoints. We observed abnormal B cell receptor (BCR) signaling characterized by low CD79B, CSK, BLNK, and BTK expression, which may contribute to a breach in B cell tolerance. We also observed evidence of impaired follicular helper T cells (Tfh) and regulatory T cells (Treg), which may limit the normal development and suppression of autoreactive B cells. Moreover, comparative gene expression analysis of B cells and CD4+ T cells from three patients with chronic inflammatory demyelinating polyneuropathy (CIDP) --a related autoimmune neuropathy-- confirmed that these differences are largely specific to NF155-AIN, supporting a distinct pathophysiology in this subset. ConclusionThese findings demonstrated a breach in early B cell tolerance checkpoints, defective BCR signaling, and disrupted T cell-B cell interactions in NF155-AIN, all of which may contribute to the development of pathogenic autoreactivity. These immunologic abnormalities appear distinct from those seen in CIDP, supporting NF155-AIN as a unique immunopathologic entity.

• Generalized brain-state modeling with KenazLBM
  Authors: Johnson, G. W.; Makhoul, G.; Doss, D.; Hidalgo, B.; Cai, L.; Liao, E.; Paulo, D.; Reda, A.; Withers, C. P.; Cavender, A.; Qian, H.; Obiri-Yeboah, D.; Mensah-Brown, K.; Kerezoudis, P.; Baker, M.; Jensen, M.; Reddy, S.; Roberson, S. W.; Crudele, A.; Naftel, R.; Hermes, D.; Hawkes, M.; Kremen, V.; Bydon, M.; Ali, R.; Lee, K.; Lanzino, G.; Bick, S.; Van Gompel, J.; Constantinidis, C.; Morgan, V.; Marsh, R.; Zadeh, G.; Worrell, G.; Miller, K.; Englot, D.
  Published: 2025-08-12 (new results)
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  The large-scale functional state of a human brain remains difficult to characterize, much less predict. Regardless, humans have engineered techniques to electrically neuromodulate the brain to treat a subset of neurologic and psychiatric diseases with moderate efficacy. Accurate characterization of a brains instantaneous functional state has stymied the development of more effective neuromodulation paradigms. Advanced computational methods are required to address this gap and enable large-scale neuroscience. Here we define the concept of generalized brain-state modeling across humans as Large Brain-State Modeling (LBM) and present KenazLBM as the worlds first example. KenazLBM can instantaneously characterize the functional state of a persons brain with raw iEEG data, and predict future brain-states. KenazLBM was trained on over 17.9 billion unique multichannel tokens from people undergoing intracranial electroencephalography (iEEG) recordings, and has learned to meld brain-states between people into a common interpretable topology. Most importantly, the model generalizes to unseen subject data with significant recording channel heterogeneity from the training set. We offer KenazLBM as a first generalized brain-state model to serve as a new paradigm of basic neuroscience inquiry and potential translation into neuromodulation therapeutics.

• Generalized brain-state modeling with KenazLBM
  Authors: Johnson, G. W.; Makhoul, G.; Doss, D.; Hidalgo, B.; Cai, L.; Liao, E.; Paulo, D.; Reda, A.; Withers, C. P.; Cavender, A.; Qian, H.; Obiri-Yeboah, D.; Mensah-Brown, K.; Kerezoudis, P.; Baker, M.; Jensen, M.; Reddy, S.; Roberson, S. W.; Crudele, A.; Kahoud, R. J.; Naftel, R.; Hawkes, M.; Kremen, V.; Bydon, M.; Ali, R.; Lee, K.; Bick, S.; Van Gompel, J.; Constantinidis, C.; Morgan, V.; Marsh, R.; Zadeh, G.; Worrell, G.; Miller, K.; Englot, D.
  Published: 2025-08-12 (new results)
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  The large-scale functional state of a human brain remains difficult to characterize, much less predict. Regardless, humans have engineered techniques to electrically neuromodulate the brain to treat a subset of neurologic and psychiatric diseases with moderate efficacy. Accurate characterization of a brains instantaneous functional state has stymied the development of more effective neuromodulation paradigms. Advanced computational methods are required to address this gap and enable large-scale neuroscience. Here we define the concept of generalized brain-state modeling across humans as Large Brain-State Modeling (LBM) and present KenazLBM as the worlds first example. KenazLBM can instantaneously characterize the functional state of a persons brain with raw iEEG data, and predict future brain-states. KenazLBM was trained on over 17.9 billion unique multichannel tokens from people undergoing intracranial electroencephalography (iEEG) recordings, and has learned to meld brain-states between people into a common interpretable topology. Most importantly, the model generalizes to unseen subject data with significant recording channel heterogeneity from the training set. We offer KenazLBM as a first generalized brain-state model to serve as a new paradigm of basic neuroscience inquiry and potential translation into neuromodulation therapeutics.

• Comparison and Dynamic interaction between Auditory Cortex and Prefrontal Cortex of Behaving Monkeys during Novelty Detection
  Authors: Xu, H.; Song, P.; Ye, H.; Zhang, Q.; Zhai, Y.; Bao, X.; Mehmood, I.; Tanigawa, H.; Tu, Z.; Zhang, L.; Zhao, X.; Perez-Gonzalez, D.; Malmierca, M. S.; Yu, X.
  Published: 2025-08-12 (new results)
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  The ability to detect deviations from expected sensory input is critical for adaptive behavior. Here, we investigated the neural dynamics of novelty detection in the auditory cortex (AC) and prefrontal cortex (PFC) of macaques performing an auditory oddball task. Using high-density electrocorticography and Granger causality analyses (GCA), we identified distinct repetition-related signals in both regions: the AC showed both suppression and facilitation to repeated stimuli, while the PFC exhibited robust enhancement, particularly in low-frequency (2 Hz) oscillatory activity. These predictive responses were accompanied by bidirectional AC-PFC coupling in the delta band, reflecting a temporally coordinated predictive state. Deviant tones elicited early responses in the AC, followed by PFC activation, and were associated with increased feedforward and feedback connectivity across delta, theta, and gamma bands. Task engagement amplified both prediction and prediction-error signals, enhancing interareal interactions and behavioral selectivity. Our results reveal that the AC encodes early sensory regularities and violations, while the PFC supports integrative and state-dependent prediction, jointly forming a distributed cortical network for hierarchical predictive coding.

• SynAnno: Interactive Guided Proofreading of Synaptic Annotations
  Authors: Lauenburg, L.; Troidl, J.; Gohain, A.; Lin, Z.; Pfister, H.; Wei, D.
  Published: 2025-08-12 (new results)
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  Connectomics, a subfield of neuroscience, aims to map and analyze synapse-level wiring diagrams of the nervous system. While recent advances in deep learning have accelerated automated neuron and synapse segmentation, reconstructing accurate connectomes still demands extensive human proofreading to correct segmentation errors. We present SynAnno, an interactive tool designed to streamline and enhance the proofreading of synaptic annotations in large-scale connectomics datasets. SynAnno integrates into existing neuroscience workflows by enabling guided, neuron-centric proofreading. To address the challenges posed by the complex spatial branching of neurons, it introduces a structured workflow with an optimized traversal path and a 3D mini-map for tracking progress. In addition, SynAnno incorporates fine-tuned machine learning models to assist with error detection and correction, reducing the manual burden and increasing proofreading efficiency. We evaluate SynAnno through a user and case study involving seven neuroscience experts. Results show that SynAnno significantly accelerates synapse proofreading while reducing cognitive load and annotation errors through structured guidance and visualization support. The source code and interactive demo are available at: https://github.com/PytorchConnectomics/SynAnno.

• Geometric Characterization of Pediatric Multiple Sclerosis Lesion Morphology: A Cross-Sectional and Temporal Analysis using Differential Geometry
  Authors: Mittal, P.; Singh, P. P.; Chauhan, J.
  Published: 2025-08-12 (new results)
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  Pediatric-onset multiple sclerosis (POMS) involves aggressive inflammation and large lesions; however, its detailed shapes and structures remain poorly understood. Traditional volumetric metrics often overlook the complex geometry of these lesions. The main objective of this study is to develop a differential geometry-based framework to quantify the shape and structure of lesions in pediatric multiple sclerosis(MS) patients using longitudinal 3D FLAIR MRI. The goal was to identify reproducible lesion morphotypes and to track their evolution over time. Our approach sensitively tracked shape changes over time and revealed consistent progression patterns. Our findings suggest that geometric biomarkers offer a powerful new lens for decoding MS heterogeneity and tracking disease activity in the pediatric population.

• view larger version (35k): org.highwire.dtl.dtlvardef@25d0f5org.highwire.dtl.dtlvardef@b9a5b9org.highwire.dtl.dtlvardef@2f4f86org.highwire.dtl.dtlvardef@e2515_hps_format_figexp m_fig o_floatnographical abstractc_floatno schematic model of our findings: tau phosphorylation is dynamically regulated in specific combinatorial patterns in response to shifting mt growth cycles. c_fig" data-authors="naseri, n. n.; xu, t.; chantarawong, s.; patrie, s. m.; kelleher, n. l.; sharma, m.; shalem, o.; rhoades, e."> Specific Combinations of Physiological Tau Phosphorylation Regulate Tau-Microtubule Interactions in Developing Neurons
  Authors: Naseri, N. N.; Xu, T.; Chantarawong, S.; Patrie, S. M.; Kelleher, N. L.; Sharma, M.; Shalem, O.; Rhoades, E.
  Published: 2025-08-12 (new results)
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  Tau phosphorylation is a defining feature of Alzheimers disease, yet it also plays an essential physiological role in stabilizing microtubules (MTs) during normal neuronal development. While individual phosphorylation sites have been well-studied in pathology, it remains largely unknown how combinatorial phosphorylation is regulated under physiological conditions. Here, we uncover distinct, site-specific phosphorylation patterns on tau in developing human neurons. With top-down mass spectrometry we find that functional, endogenous tau is highly modified, with up to 21 phosphates per molecule. We identify patterns of co-occurrence between phosphorylation sites that are in proximity in the linear protein sequence, such as epitopes S202/T205/T212/T217 and T231/S235/S262. Moreover, these phospho-epitopes define discrete pools of tau and regulate tau-MT interactions in coordination, providing a mechanism for fine-tuning the binding of tau to MTs. Intriguingly, we find that co-occurring phospho-epitopes are dynamically regulated in response to changes in MT integrity; chemical perturbation of neuronal MTs promotes rapid tau dephosphorylation by phosphatase PP2a at most sites to enhance tau-MT interactions and counteract destabilization. We then use the PS19 tauopathy mouse model to demonstrate that developmental and pathological tau phosphorylation patterns partially overlap, and that co-occurring phospho-epitopes exhibit similar associations with the insoluble fraction in aged mice. Our results reveal an isoform-dependence on the effects of site-specific tau phosphorylation on its behavior. Together, these findings define a combinatorial phosphorylation code that modulates taus physiological function in neurons and raises the possibility that MT destabilization precedes tau phosphorylation in disease. This work provides a mechanistic framework for distinguishing functional from pathological tau phosphorylation, with implications for the development of therapies that specifically target disease-associated tau proteoforms. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=196 SRC="FIGDIR/small/669485v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@25d0f5org.highwire.dtl.DTLVardef@b9a5b9org.highwire.dtl.DTLVardef@2f4f86org.highwire.dtl.DTLVardef@e2515_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGRAPHICAL ABSTRACTC_FLOATNO Schematic model of our findings: Tau phosphorylation is dynamically regulated in specific combinatorial patterns in response to shifting MT growth cycles. C_FIG

• Basal ganglia-independent thalamic bursts do not wake cortex during sleep
  Authors: Liu, X.; Guang, J.; Israel, Z.; Wajnsztajn, D.; Raz, A.; Bergman, H.
  Published: 2025-08-12 (new results)
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  The thalamus is a key forebrain structure that gates peripheral, subcortical, and cortico-cortical communication1,2. Awake thalamic bursts provide the cortex with a "wake-up" signal2-4. Paradoxically, thalamic neurons discharge tonically during cellular depolarization and activated brain states (wakefulness, REM sleep) but burst during hyperpolarization and NREM sleep5-9. It has been proposed that NREM thalamic bursts do not awaken the cortex because of their periodic and synchronized nature2-4; however, this has never been tested in vivo during natural sleep. We simultaneously recorded polysomnographic signals, local field potentials, and spiking activity from multiple thalamic neurons in the ventral anterior and centromedian nuclei of two female non-human primates during naturally occurring vigilance states. These nuclei receive GABAergic output from the basal ganglia10,11, with discharge rate and GABA outflow decreasing during NREM sleep12. We found that despite the expected thalamic depolarization, bursting increased significantly. NREM bursts were neither periodic nor highly synchronized. However, EEG activity time-locked to burst onset during NREM sleep differed markedly from that observed during wakefulness and REM sleep. These results support a modulatory, rather than a driving, relationship between the basal ganglia and thalamus. NREM thalamic bursts do not awaken the cortex, probably due to unique state-dependent thalamocortical dynamics.

• Short-term synaptic dynamics in the ventrolateral and dorsomedial periaqueductal gray
  Authors: Romero, A. V. C.; Tyner, K. A.; Carroll, J. N.; Vaaga, C. E.
  Published: 2025-08-12 (new results)
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  The ability to assess and rapidly respond to predator threats in the environment is necessary for survival and requires dedicated neural circuits for threat detection, sensorimotor integration, and execution of ethologically appropriate behavioral responses. Although numerous brain circuits are involved in these processes, the midbrain periaqueductal gray (PAG) serves as an important central hub to generate ethologically appropriate passive and/or active defensive behaviors. Despite its central role in generating defensive behaviors, little is known about the intrinsic and synaptic properties of neurons across columns in the PAG. To address this knowledge gap, we made whole-cell voltage- and current-clamp recordings from unlabeled neurons in the vl- and dmPAG of mice. Consistent with in vivo work, our data highlights the relative importance of synaptic inhibition in both columns. Further, our results suggest that neurons in both the vl- and dmPAG prioritize frequency-invariant coding strategies, showing remarkably stable paired pulse ratios across interstimulus intervals. Despite this common theme, the underlying mechanism each column utilizes to achieve such frequency invariant coding is distinct, reflecting important differences in synaptic processing across columns. More specifically, while the vlPAG is relatively resistant to phasic short-term depression across stimulation frequencies, neurons in the dmPAG show a pronounced buildup of tonic/slow current during high frequency stimulation trains, which counteracts short-term depression of the phasic current amplitude observed during high frequency stimulation trains. This prolonged tonic current observed in the dmPAG prolongs the period of spike elevation, suggesting that high frequency stimulation may drive sustained activity in the dmPAG. Together, these results provide fundamental information of synaptic integration and network properties across columns in the PAG, which ultimately support their distinct roles in threat processing.

• Tactile stimulation transiently disrupts encoding of whisker position by cerebellar molecular layer interneuron ensembles
  Authors: Meyer, E. M. M.; Chadderton, P.
  Published: 2025-08-12 (new results)
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  Molecular layer interneurons (MLIs) within the cerebellar cortex mediate feed-forward inhibition onto Purkinje cells, positioning them as pivotal modulators of cerebellar output. We asked how motor patterns and salient sensory input influence MLI population activity during active whisking and tactile interactions. Utilizing two-photon calcium imaging combined with high-speed videography, we examined MLI population dynamics in awake, behaving mice engaged in voluntary whisker movements. Our results demonstrate that during free whisking, MLI population activity reliably tracks whisker position, yielding uniform graded responses that provide stable and precise representations over time. Tactile contact with external stimuli evokes additional activation in a subset of MLIs. Sensory input transiently disrupts the linear relationship between MLI activity and whisker position and may account for rapid synchronous inhibition of Purkinje cell spiking activity following tactile stimulation. These findings indicate that MLIs in Crus 1 maintain an accurate internal model of whisker position which is perturbed upon encountering obstacles. This disruption likely reflects the integration of sensory feedback, disrupting predictive signals that are subsequently passed forward to Purkinje cells. Such signals can alert the brain to novel happenings and be used to update motor commands, thereby contributing to cerebellar function in response to environmental changes.

• Dynamic Neural Encoding of Prior Expectations and Auditory Evidence Drive Perceptual Decision-Making
  Authors: Tune, S.; Borschke, I.; Obleser, J.
  Published: 2025-08-12 (new results)
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  Perceptual decision-making has been studied extensively as the integration of evidence over time. Yet how moment-to-moment fidelity of sensory encoding interacts with prior expectations in shaping our choices remains poorly understood--particularly in the auditory domain. Here we quantify how priors act at the stage of sensory encoding and how these fluctuations predict behaviour. In a human model-based EEG study, we augmented a canonical click-train evidence accumulation task with probabilistic cues to shape prior expectations and analysed all activity with trial-resolved linear encoding models. Probabilistic cues drove alpha-oscillatory EEG patterns and induced symmetric shifts in response bias but did not change temporal integration dynamics. Neural encoding strength in lateralised auditory cortex uniquely predicted single-trial choice and confidence beyond what was explained by evidence strength or cueing alone. These findings identify sensory encoding fidelity as a mechanistic, behaviourally relevant link between priors and perceptual choice, offering new understanding how neural noise and expectations jointly shape decisions under uncertainty.

• From Wiring to Firing: Collapse of embryonic identities and emergence of functional diversity during motor neuron maturation
  Authors: Chen, Y.; Chi, H.-M.; Tian, A.; Miller, A.; Patel, T.
  Published: 2025-08-12 (new results)
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  Neurons born in the embryo undergo a protracted process of maturation during which time they project axons to their specific targets, integrate into circuits, refine synapses, and acquire unique electrophysiological properties. The molecular strategies that individual neuron types deploy to complete this complex process remain poorly understood. In this work, we used single nucleus multiome sequencing (RNA-seq and ATAC-seq) to track the transition from specification to functional maturation in mouse skeletal motor neurons (SMNs). Our data show that individual SMNs undergo significant transcriptional changes as they mature, but more strikingly, we find that diversity within SMNs fluctuates dramatically as the functional needs of these cells change over time. At embryonic day E15.5, when motor axons are innervating their specific muscle targets, SMNs can be subdivided into dozens of transcriptional subclusters. These embryonic subclusters represent known motor columns and pools, which utilize column- and pool-specific genes to innervate unique muscle targets. About a week later, at postnatal day 3 (P3) many column- and pool-specific genes are downregulated or become broadly expressed and SMNs coalesce on the molecular level into a more homogenous state. These neurons then undergo a second round of diversification during the first two weeks of postnatal life (P3-P13), acquiring gene expression patterns that divide them into the functionally distinct alpha, gamma, and type3 subtypes found in adults. The fluctuations in SMN diversity go hand-in-hand with changes in accessible chromatin regions and transcription factor (TF) expression. Differential ATAC-seq peaks that define embryonic diversity are lost over time while new peaks that control expression in adult subtypes are gained. TFs that are known to regulate embryonic diversity are also downregulated over time, as a separate set of TFs that likely regulate adult subtype identities are upregulated. Our work uncovers a novel maturation trajectory for postmitotic neurons where extensive spatial diversity is first acquired in the embryo to ensure proper circuit wiring; this diversity is then lost as maturing neurons re-diversify into functional identities required for proper circuit firing in postnatal life. Therefore, all aspects of a neurons identity - its morphology, circuitry, and electrophysiologically - may not be fully described by its gene expression program at adulthood, but instead is a culmination of transcriptional events that occur throughout its specification and maturation trajectory as the functional needs of the cells evolve.

• δ-catenin haploinsufficiency is sufficient to alter behaviors and glutamatergic synapses in mice
  Authors: Hinchliffe, E. S.; Aragon, V.; Mai, V. T.; Shah, S. A.; Lee, R.; Arikkath, J.; Kim, S.
  Published: 2025-08-12 (new results)
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  {delta}-catenin (also known as CTNND2) functions as an anchor for the glutamatergic AMPA receptor (AMPARs) to regulate synaptic activity in excitatory synapses. Alteration in the gene coding {delta}-catenin has been implicated in many neurological disorders. Some of these genetic alterations exhibit a profound loss of {delta}-catenin functions in excitatory synapses. We have shown that {delta}-catenin deficiency induced by the homozygous {delta}-catenin knockout (KO) and autism-associated missense glycine 34 to serine (G34S) mutation significantly alters AMPAR-mediated synaptic activity in cortical neurons and disrupts social behavior in mice. Importantly, many genetic disorders are caused by haploinsufficiency. Indeed, {delta}-catenin haploinsufficiency contributes to severe autism and learning disabilities in humans. However, previous studies have used only homozygous {delta}-catenin deficiency models. Therefore, it is important to examine the effects of {delta}-catenin haploinsufficiency on animals behaviors and excitatory synapses. Here, we use heterozygous {delta}-catenin KO and G34S mice as a {delta}-catenin haploinsufficiency model to examine this idea. Multiple behavioral assays, a social behavior test, contextual fear conditioning, and an open field test, reveal that both {delta}-catenin KO and G34S haploinsufficiency significantly disrupt animals social behavior and fear learning and memory. Interestingly, only KO haploinsufficiency mice show anxiety-like behavior. A biochemical assay using brain extracts demonstrates that {delta}-catenin haploinsufficiency significantly affects the levels of synaptic {delta}-catenin and AMPARs. Our findings thus suggest that {delta}-catenin haploinsufficiency affects animals behaviors via altering glutamatergic synaptic activity.

• Acetylcholine Enhances Deviance Detection in Hodgkin-Huxley Neuronal Networks
  Authors: Fang, F.; Huang, Z. G.; Chao, Z. C.
  Published: 2025-08-12 (new results)
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  The brains ability to detect unexpected events, deviance detection (DD), is critical for survival. While DD has been computationally explained by synaptic plasticity, the role of neuromodulators like acetylcholine (ACh) remains less understood. Here, we examine how ACh modulates DD without invoking additional plasticity mechanisms. Using a cholinergic-sensitive Hodgkin-Huxley network of 200 neurons arranged in 2D space and stimulated via five spatially distinct inputs (A-E), we implemented an oddball paradigm with three conditions: standard (80% A, 20% B), deviant (20% A, 80% B), and a multi-standard control (20% each of A-E). ACh levels were controlled by the conductance of the slow K+ current. In the absence of ACh, the network already exhibited DD, responding more strongly to deviant A compared to control A. Notably, introducing a small amount of ACh amplified DD, while further increases suppressed it. Maximal DD occurred when strong spike frequency adaptation to standard B reduced competition, and enhanced phase-locking synchronized the networks response to deviant A. These findings reveal how neuromodulation can shape context-sensitive neural computation, optimizing detection of salient events through a dynamic balance of suppression and synchronization.

• A Computational Model of Action Specification in the Basal Ganglia
  Authors: Bartlett, M.; Furlong, P. M.; Stewart, T.; Orchard, J.
  Published: 2025-08-12 (new results)
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  The basal ganglia has traditionally been modelled as a system that represents the available, discrete action space using a finite set of distinct and non-overlapping representational units. This limits these models from addressing questions around how the basal ganglia is involved in action specification: the selection of continuously valued action dynamics such as speed and vigor. In this article we present a novel computational model of the basal ganglia which incorporates vector-symbolic algebras in order to represent continuous action spaces. The stages of model development are presented along with simulation experiments to test the basic properties of the model. This work represents a promising foundational step in providing a mechanistic account for neuroscientific and behavioural evidence implicating the basal ganglia in action specification, thereby filling a gap in the literature.

• Evaluating scientific theories as predictive models in language neuroscience
  Authors: Singh, C.; Antonello, R. J.; Guo, S.; Mischler, G.; Gao, J.; Mesgarani, N.; Huth, A. G.
  Published: 2025-08-12 (new results)
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  Modern data-driven encoding models are highly effective at predicting brain responses to language stimuli. However, these models struggle to explain the underlying phenomena, i.e. what features of the stimulus drive the response? We present Question Answering encoding models, a method for converting qualitative theories of language selectivity into highly accurate, interpretable models of brain responses. QA encoding models annotate a language stimulus by using a large language model to answer yes-no questions corresponding to qualitative theories. A compact QA encoding model that uses only 35 questions outperforms existing baselines at predicting brain responses in both fMRI and ECoG data. The model weights also provide easily interpretable maps of language selectivity across cortex; these maps show quantitative agreement with meta-analyses of the existing literature and selectivity maps identified in a follow-up fMRI experiment. These results demonstrate that LLMs can bridge the widening gap between qualitative scientific theories and data-driven models.

• Disentangling the influences of pre- and postnatal periods on human cortical microstructure
  Authors: Tsigaras, T.; Dukart, J.; Oldham, S.; Eickhoff, S. B.; Paquola, C.
  Published: 2025-08-13 (new results)
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  During late gestation and early postnatal development a combination of intrinsic and extrinsic factors drive the maturation of the human cortex. This process is regionally heterogeneous, with cortical areas developing at different paces and trajectories. Leveraging submillimetre T1-weighted/T2w-weighted (T1w/T2w) magnetic resonance imaging (MRI) from pre- and full-term neonates (n = 599, 0-7 weeks), we sampled intracortical microstructure profiles across the cortex and characterised the profiles shapes according to their central moments. We found that gestational age at birth dominated the effects on early cortical development, with significant, global increases in microstructural density, increasing intracortical homogeneity and a bimodal change of the microstructural balance between superficial and deeper cortical layers. On the other hand, weeks since birth (i.e. postnatal age) exhibited different effects on microstructure, with density increasing at a slower pace, increasing intracortical heterogeneity, and intracortical balance only shifting towards deeper layers in posterior temporal, occipital, medial parietal areas and some prefrontal areas. These effects align with low spatial-frequency geometric eigenmodes of the human cortex, specifically the anterior-posterior, superior-inferior and central-polar axes. Our findings demonstrate that separating prenatal from postnatal influences, and analysing intracortical profiles rather than macroscale features, provides finer-grained insights into how human cortical microstructure changes during perinatal development and lays the groundwork for investigating the biological underpinnings that govern normative cortical maturation.

• Decoding intended speech with an intracortical brain-computer interface in a person with longstanding anarthria and locked-in syndrome
  Authors: Jude, J. J.; Haro, S.; Levi-Aharoni, H.; Hashimoto, H.; Acosta, A. J.; Card, N. S.; Wairagkar, M.; Brandman, D. M.; Stavisky, S. D.; Williams, Z. M.; Cash, S. S.; Simeral, J. D.; Hochberg, L. R.; Rubin, D. B.
  Published: 2025-08-13 (new results)
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  Intracortical brain-computer interfaces (iBCIs) for decoding intended speech have provided individuals with ALS and severe dysarthria an intuitive method for high-throughput communication. These advances have been demonstrated in individuals who are still able to vocalize and move speech articulators. Here, we decoded intended speech from an individual with longstanding anarthria, locked-in syndrome, and ventilator dependence due to advanced symptoms of ALS. We found that phonemes, words, and higher-order language units could be decoded well above chance. While sentence decoding accuracy was below that of demonstrations in participants with dysarthria, we are able to attain an extensive characterization of the neural signals underlying speech in a person with locked-in syndrome and through our results identify several directions for future improvement. These include closed-loop speech imagery training and decoding linguistic (rather than phonemic) units from neural signals in middle precentral gyrus. Overall, these results demonstrate that speech decoding from motor cortex may be feasible in people with anarthria and ventilator dependence. For individuals with longstanding anarthria, a purely phoneme-based decoding approach may lack the accuracy necessary to support independent use as a primary means of communication; however, additional linguistic information embedded within neural signals may provide a route to augment the performance of speech decoders.

• Guided by Noise: Correlated Variability Channels Task-Relevant Information in Sensory Neurons
  Authors: Srinath, R.; Xu, Y.; Ruff, D. A.; Ni, A. M.; Doiron, B.; Cohen, M. R.
  Published: 2025-08-13 (new results)
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  Shared trial-to-trial variability across sensory neurons is reliably reduced when perceptual performance improves, yet this variability is low-dimensional, so it could be ignored by an optimal readout mechanism. Why then is it so consistently related to behavior? We propose that shared variability reflects the information communicated to downstream areas, rather than noise to be avoided. Using a circuit model, we show that when sensory signals align with shared variability, behaviorally relevant information is amplified without compromising coding fidelity. Analyses of neural population recordings from multiple brain areas and tasks reveal that the dominant axis of shared variability consistently aligns with task-relevant stimulus features and action plans. Finally, the behavioral impact of microstimulation can be explained by the extent to which it changes projections onto the shared variability axis. These findings suggest that shared variability may illuminate, rather than obscure, the neural dimensions that guide behavior.

• BIOPHYSICAL MECHANISMS UNDERLYING THE GENERATION AND MAINTENANCE OF RULE-LEARNING ENGRAM
  Authors: Kundu, S.; Keren, D.; Zidan, S.; Kumar, A.; Schiller, J.; Barkai, E.
  Published: 2025-08-13 (new results)
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  Training rodents in a particularly difficult olfactory-discrimination task results with acquisition of high skill to perform the task superbly, termed rule-learning. We show that rule-learning occurs abruptly, in a "light bulb moment". Using whole-cell patch-clamp recordings in the piriform cortex of Fos2A-iCreER/TRAP2 mice, we targeted activated neurons, expressing immediate early genes (IEG). From the onset of training, IEG-positive neurons from trained animals display enhanced intrinsic excitability. Subsequently, synaptic excitation and inhibition is enhanced in these neurons, in a coordinated, cell-wide process. In parallel, the density of IEG-expressing neurons sharply declines. Double labeling with TRAP and c-Fos reveals that nearly two-thirds of the rule-memory engram neurons were engaged from the beginning of training. Silencing TRAP-expressing neurons using DREADDs leads to a complete loss of rule memory. We propose that rule learning occurs at a discrete moment, and is developed through a gradual process that stabilizes the memory of the rule.

• Rethinking synthesis and function of neuro-estrogen and neuro-androgen in the hippocampus: some methodological problems and possible solutions
  Authors: Kawato, S.; Ogiue-Ikeda, M.; Soma, M.; Horie, S.; Saito, M.; Minato, K.
  Published: 2025-08-13 (new results)
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  Local synthesis and action of neuro-estrogen and neuro-androgen (including neuro-estradiol (nE2) and neuro-testosterone (nT) have become recognized as key mechanisms in modulation of neural plasticity and cognitive performance, in addition to the contribution of circulating sex steroids. However, still several methodological problems are left to be solved in order to get an better understanding of functions of neural sex steroids in the brain. Here we describe and discuss important improvements in the methods for determination of accurate concentrations of nE2 and nT in rat hippocampus (Section 1), and in methods for analysis of the dendritic spine density in castrated male rat hippocampus (Section 2). The improvements are discussed in order to solve the following two problems. One problem is that the previously reported nE2 concentrations in the hippocampus were widely distributed between [~]3 pg/g tissue and [~]2 ng/g tissue (i.e., between [~]11 pM and [~]7 nM) (Section 1). The other problem is that the degree of decrease in hippocampal spine density by castration in male rat hippocamps was strongly dependent on surgical skills of operators (surgeons) (Section 2).

• Neural Oscillations during Perceptual Grouping: Insights from Alpha and Theta Bands in Visual Perception Tasks
  Authors: Gupta, S.; Gandhi, T.
  Published: 2025-08-13 (new results)
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  Perceptual grouping, the brains ability to organize visual stimuli into coherent objects and patterns, is thought to rely on distinct neural oscillations across various frequency bands. However, the specific contributions of these frequency bands to perceptual grouping remain a central question in cognitive neuroscience. Our study employs spectral analysis and time-frequency analysis techniques to analyze EEG data collected during visual perception tasks. By examining the temporal dynamics and frequency-specific activity, particularly focusing on the alpha and theta bands immediately following stimulus onset, our goal is to uncover the neural processes underlying perceptual grouping. Our findings indicate significant changes in alpha and theta band activity associated with perceptual grouping in the brain. These results suggest that alpha band oscillations may play a role in directing attention and filtering relevant visual information, while theta band oscillations might facilitate the integration of visual elements into coherent percepts by engaging memory processes and enhancing neural communication across brain regions. This research contributes to a deeper understanding of how neural oscillations coordinate to support perceptual organization, potentially informing future studies and therapeutic approaches aimed at enhancing visual perception and cognitive function.

• Astrocytic Regulation of aberrant perineuronal net formation in Mecp2-null Neocortex
  Authors: Sinha, A.; Kowalchuk, A. M.; Khatibi, N.; Matthews, R. T.; MacDonald, J. L.
  Published: 2025-08-13 (new results)
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  Rett syndrome (RTT), caused by mutations in MECP2, is a complex neurological disorder characterized by myriad physiological disruptions, including early closure of the critical period of developmental plasticity and precocious formation of perineuronal nets (PNNs). PNNs are lattice-like substructures of extracellular matrix (ECM) that enwrap specific subpopulations of neurons. PNNs are essential in the modulation of neuronal plasticity and brain maturation, and their enzymatic disruption can partially restore plasticity in adults and improve memory. Although precocious PNN formation is well-established in RTT, little is known of the cellular, molecular, or biochemical underpinnings of their precocious formation, or whether precocious PNN formation is due to cell-autonomous or non-cell-autonomous mechanisms. While PNNs form on subsets of neurons throughout the brain, astrocytes secrete many ECM components that form PNNs, and they play a central role in controlling closure of the critical period. We find that Mecp2-null astrocyte conditioned media induces the expression of the key PNN component Hapln1 and causes enhanced PNN formation on wildtype neurons, suggesting that Mecp2-null astrocytes play a key role in the precocious formation of PNNs in RTT. Further, we identify increased expression of HAPLN1 and other PNN / ECM components in the developing Mecp2-null cortex, and demonstrate that PNNs are structurally and biochemically mature at an earlier developmental stage. These results provide essential insight into the mechanisms and structure of aberrant PNNs in Mecp2-null cortex and identify potential new avenues for targeted rescue or reversal of the precocious closing of the critical period in RTT.

• Experience-dependent reconfiguration of receptors at a sensory compartment regulates neuronal plasticity
  Authors: Harris, N.; Dutta, P.; Krishnan, N.; Nurrish, S.; Sengupta, P.
  Published: 2025-08-13 (new results)
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  Neurons continuously adjust their properties as a function of experience. Precise modulation of neuronal responses is achieved by multiple cellular mechanisms that operate over a range of timescales. Primary sensory neurons rapidly adapt their sensitivities via posttranslational mechanisms including regulated trafficking of sensory molecules1-4 but also alter their transcriptional profiles on longer timescales to adapt to persistent sensory stimuli5-8. How diverse transcriptional and posttranscriptional pathways are coordinated in individual sensory neurons to accurately adjust their functions and drive behavioral plasticity is unclear. Here we show that temperature experience modulates both transcription and trafficking of thermoreceptors on different timescales in the C. elegans AFD thermosensory neurons to regulate response plasticity. Expression of the PY motif-containing adaptor protein (PYT-1) as well as the GCY-18 warm temperature-responsive guanylyl cyclase thermoreceptor9 is transcriptionally upregulated in AFD upon a temperature upshift5,10. We find that as GCY-18 begins to accumulate at the AFD sensory endings, the GCY-23 cooler temperature-responsive thermoreceptor9 exhibits altered subcellular localization and increased retrograde trafficking, thereby increasing the functional GCY-18 to GCY-23 ratio in the AFD sensory compartment. Altered GCY-23 localization and trafficking requires PYT-1-dependent endocytosis, and we show that PYT-1-mediated modulation of the GCY-18 to GCY-23 protein ratio at the AFD sensory endings is necessary to shift the AFD response threshold towards warmer values following the temperature upshift. Our results describe a mechanism by which transcriptional and posttranscriptional mechanisms are temporally coordinated across sensory receptors to fine tune experience-dependent plasticity in the response of a single sensory neuron type.

• Tunneling Nanotube-like Connections in the Developing Cerebellum: Distinct from Cytokinetic and Intercellular Bridges
  Authors: RAKOTOBE, M.; Virmani, G.; Liu, S.; Kaddour, G.; Mendoza, N. D.; Livet, J.; Cathala, L.; Zurzolo, C.
  Published: 2025-08-14 (new results)
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  Intercellular communication is essential for brain development. While classical communication modes-such as paracrine, juxtacrine and synaptic signaling-are well characterized, emerging evidence suggests that tunneling nanotubes (TNTs), membranous bridges primarily observed in vitro, may also contribute. However, their presence and function in vivo remain unclear, partly due to the challenge of distinguishing them from other types of intercellular connections (ICs). Building on prior evidence of ICs in the external granule layer (EGL) of the developing cerebellum, we investigated their nature in postnatal day 7 (P7) mice. Using immunofluorescence and genetically sparse labeling, we distinguished cytokinetic bridges (CBs), transient connections formed between daughter cells during the final stage of cell division, and intercellular bridges (IBs), more stable connections that persist after division, from TNT-like structures, which form independently of cell division. We observed CBs but not IBs in the EGL. We also observed TNT-like connections throughout the EGL, which appeared to connect both clonally and non-clonally related cells. The presence of these TNT-like structures in the developing EGL suggests that TNT-like connections may contribute to intercellular communication, paving the way for further study of a previously unrecognized mechanism that could influence neuronal fate, migration, and network formation during cerebellar development.

• ROSMAP-Compass: A data-harmonised, AI-ready atlas of 22 million single nuclei from the ROSMAP cohort
  Authors: Flotho, M.; Diks, I. F.; Flotho, P.; Hirsch, P.; Wagner, V. P.; Grandke, F.; Keller, A.
  Published: 2025-08-14 (new results)
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  The Religious Orders Study and Memory and Aging Project (ROSMAP) cohort has generated the world's most comprehensive single-cell transcriptomic resource for Alzheimer's disease research. Naturally, in a project spanning multiple years with dozens of research groups involved, the resulting data landscape shows fragmentation across sequencing chemistries, protocols, and pipelines. This presents both a challenge and a unique opportunity for harmonized, collaborative analysis. Following an early data integration strategy and complete realignment of all single nucleus RNA sequencing data, we generated a fully harmonized resource: ROSMAP-Compass, comprising more than 22 million high-quality nuclei from 2,058 donors in multiple brain regions from the ROSMAP and Neuro Psychiatric Symptoms (NPS-AD) cohorts. Through systematic curation and unified reprocessing, we addressed substantial technical challenges including chemistry-specific biases, cross-study batch effects, and sample redundancies across multiple studies spanning different time periods and research groups. ROSMAP-Compass demonstrates the critical importance of systematic data harmonization when integrating large-scale single-cell datasets from multiple sources. By combining open science principles with cutting-edge AI integration, we provide both a critical resource for understanding Alzheimer's disease heterogeneity and a blueprint for making complex biomedical data accessible to the global research community. The full resource, interactive web portal, and LLM compatible API are freely available, empowering researchers worldwide to accelerate discovery in neurodegenerative diseases.

• Obsessive-Compulsive Tendencies Shift the Balance Between Competitive Neurocognitive Processes
  Authors: Brezoczki, B.; Vekony, T.; Farkas, B. C.; Hann, F.; Nemeth, D.
  Published: 2025-08-15 (new results)
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  Theoretical models of Obsessive-Compulsive Disorder (OCD) propose that its symptoms stem from an imbalance between habitual and goal-directed processes, marked by a bias toward habitual behavior and deficits in goal-directed control. While much of the existing research has focused on reward-based learning, the contribution of reward-independent learning processes to this imbalance remains unclear. To address this gap, the present study investigated the interaction between statistical learning (SL), a form of reward-free learning, and cognitive flexibility, a key goal-directed function, in a non-clinical population. By adopting a dimensional approach to obsessive-compulsive (OC) tendencies, this work aims to overcome the limitations of categorical diagnoses and better capture the continuous, nuanced variability of symptoms, while clarifying how specific neurocognitive processes relate to OC tendencies. A total of 402 participants from the non-clinical population completed an online study involving the Alternating Serial Reaction Time (ASRT) task to assess SL and a Card Sorting Task to measure cognitive flexibility. Our findings revealed a competitive relationship between SL and cognitive flexibility. Critically, this inverse association weakened as OC tendencies increased, suggesting that even at non-clinical levels, OC tendencies may interfere with the typical interplay between automatic and goal-directed processes. Notably, SL performance remained intact, and the observed effects were not attributable to reward sensitivity, as learning occurred without external feedback. These findings emphasize the value of examining non-clinical OC tendencies and highlight the importance of investigating neurocognitive system interactions, rather than isolated functions, in advancing our understanding of OCD.

• A unified derivative-like dopaminergic computation across valences
  Authors: Park, M.; Yun, J.; Choi, H.; Kim, H. R.
  Published: 2025-08-15 (new results)
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  Dopamine activity in the brain affects decision-making and adaptive behaviors. A wealth of studies indicate that dopamine activity encodes discrepancy between actual and predicted reward, leading to the reward prediction error (RPE) hypothesis. Specifically, it has been claimed that mesolimbic dopamine activity conforms to temporal-difference reward prediction error (TD RPE), a teaching signal in machine learning algorithms. Recently, there is growing evidence suggesting that dopamine is also involved in learning during aversive situations. However, the fundamental computation of dopamine activity in aversive situations is still unknown. A plausible but untested hypothesis is that dopamine activity in aversive situations also encodes TD RPE. Here, we tested this hypothesis by using mice in virtual reality. Mice were trained to avoid electrical tail shocks by running out of a virtual shock zone. Using probe conditions with speed manipulation or teleportation, we revealed that the dopamine signal in the ventral striatum follows the temporal derivative form of a value function. Delivering a reward at the end of the track enabled us to observe the integration of aversion and reward in a derivative form. Moreover, the value functions unbiasedly estimated from the recorded signal is consistent with the initial hypothetical form, with a realistic reflection of a received shock distribution. Taken together, our results show that mesolimbic dopamine activity can operate as a unified teaching signal in natural situations with positive and negative valences.

• Unveiling the neuro-vascular interplay in the skeletal muscle in health, injury and disease
  Authors: Fuertes-Alvarez, S.; Ascension, A. M.; Pelaez-Poblet, N.; Elicegui-Aguirre, A.; Gonzalez-Granero, S.; Gomez-Sanchez, J.-A.; Osta, R.; Garcia-Verdugo, J.-M.; Alonso-Martin, S.; Izeta, A.
  Published: 2025-08-15 (new results)
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  Neuromuscular junctions (NMJs) are complex multicellular structures that convey motor neuron-induced responses in the skeletal muscle. Their cellular composition is well characterized, but interactions between the different cell types and with the surrounding microenvironment remain underexplored. Here, by using a panel of newly discovered mouse cell lineage markers, single-cell RNA sequencing analyses and iDisco tissue clarification, we demonstrate the existence of contacts between adjacent NMJs through their kranocytes, assembling kranocyte network-like structures within the muscle interstitium, which is essential for regulating blood flow and supporting muscle regeneration. Indeed, kranocytes do contact with the surrounding microvasculature as well, both of them uncovering a previously unexplored, expansive interactive system. Moreover, unlike the robustness shown by their counterparts, the terminal Schwann cells, we strikingly observed that kranocytes rapidly detected stressful conditions, leading to structural changes and even the loss of their connections in response to acute damage, such as muscle injury or neuromuscular disease-induced denervation. Therefore, we propose kranocytes as the interactive sensory platforms of the NMJs, working in a perpendicular axis of nerve-transmission, as key NMJ-connectors by, interconnecting adjacent NMJs and interacting with the microvasculature and the microenvironment, and also as NMJ-sensors by detecting microenvironmental inputs. Together, our data postulate kranocytes as triple connectors of the nervous, musculoskeletal and vascular systems.

• Interval Timing is altered in male Nrxn1+/- mice: A Model of Autism Spectrum Disorder
  Authors: Roddick, K. M.; Habib, E. B.; Brown, R. E.; Balcı, F.
  Published: 2025-08-15 (new results)
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  Autism spectrum disorder (ASD) is characterised by impaired social interactions and communication and increased repetitive and stereotypical behaviour. Neuroimaging shows functional abnormalities in brain areas involved in temporal processing of autistic individuals, and autistic individuals show deficits in interval timing. Neurexin (NRXN) mutations have been identified in a wide variety of neuropsychiatric disorders, including ASD, and Nrxn1+/- mice possess a mutation that disrupts the , {beta}, and {gamma} isoforms of Nrxn1, a gene involved in synapse structure. We investigated the interval timing abilities of the Nrxn1+/- mouse model of ASD in the peak interval procedure using a 15-second target interval and compared their performance with that of Nrxn1+/+ and Nrxn1{Delta}S5/- rescue mice. Two-month-old male Nrxn1+/+ (C57BL/6J), Nrxn1+/-, and Nrxn1{Delta}S5/-, mice were trained to obtain sucrose liquid rewards 15s after the onset of a discriminative stimulus (discrete fixed-interval training), and their timing responses were tested in non-reinforced probe trials. Our analysis of responses in individual trials revealed that Nrxn1+/- mice had overall earlier timing responses. This difference was manifested as earlier termination of responding in terms of the response curves. These findings are consistent with leftward shifts observed with experimental animal models of ASD. In conclusion, we believe that these results are indicative of a biased long-term memory in the Nrxn1+/- mouse model of ASD and may capture the timing deficit observed in autistic individuals. Lay Summary: Neurexins help nerve cells connect and communicate with each other, and changes in these genes are often seen in people with autism. Mice with a change in their neurexin 1 gene, called Nrxn1+/- mice, show autism-like behaviours. In a test that involves judging time, these mice respond early, similar to some people with autism. This study helps develop our understanding of how interval timing is affected in ASD.

• CD11b Activation Reduces Myeloid Brain Infiltration and Mitigates Synucleinopathy in a Model of Parkinson's Disease
  Authors: Shaw, A. M.; Jimenez, V.; Nguyen, B.; Duvernay, J.; Choi, S.; Cameron, M.; Killinger, B. A.; Gupta, V.
  Published: 2025-08-15 (new results)
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  The pathology of Parkinson's disease is defined by -synuclein (-syn) aggregation into neuronal Lewy bodies, which may lead to chronic neuroinflammation and dopaminergic neurodegeneration. Misfolded -syn activates Toll-like receptor signaling in microglia, leading to downstream activation of NF-{kappa}B and subsequent release of pro-inflammatory cytokines. These cytokines recruit pro-inflammatory myeloid cells from circulation, thereby amplifying neuroinflammation. Thus, reducing microglial activation and myeloid cell infiltration has the potential to reduce neuroinflammation and PD pathology. Here, we investigated a targeted immunomodulatory strategy using LA1, a novel, small-molecule agonist of CD11b, a {beta}2 integrin receptor highly and selectively expressed on myeloid cells and microglia. CD11b has key roles in cell adhesion, migration, and phagocytosis. Previous work has demonstrated that CD11b agonism via LA1 transiently enhances integrin-mediated adhesion that limits immune cell transmigration and tissue infiltration. CD11b agonism also suppresses TLR-driven inflammatory signaling and myeloid cell activation. To evaluate its efficacy in vivo, we utilized pre-clinical Parkinson's disease model by stereotaxically delivering AAV2-SYN to induce -synuclein overexpression in the murine midbrain. Mice were treated with oral LA1 for four or eight weeks and analyzed. LA1 treatment significantly reduced microglial activation and decreased brain infiltration of peripheral immune cells, thereby attenuating -synuclein-induced neuroinflammation. These findings suggest that CD11b agonism may offer a dual-action therapeutic approach in Parkinson's disease by dampening pro-inflammatory responses by central and peripheral myeloid cells.

• BIN1 expression in the presynaptic compartment leads to isoform-specific synaptotoxicity
  Authors: Lambert, E.; Gelle, C.; Leclerc, V.; Freire-Regatillo, A.; Barois, N.; Malfoi, T.; Hermant, X.; Demiautte, F.; Lafont, F.; Amouyel, P.; Blary, K.; Kuenen, S.; Najdek, C.; Verstreken, P.; Siedlecki-Wullich, D.; Yger, P.; Lambert, J.-C.; Kilinc, D.; Dourlen, P.
  Published: 2025-08-15 (new results)
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  Alzheimer's disease (AD) is characterized by a strong genetic predisposition and by an early loss of synaptic connectivity that strongly correlates with cognitive deficit. Some genetic determinants could contribute to synapse frailty toward AD pathology. However, the role of genetic determinants in AD pathogenesis remains poorly understood at the synaptic level. Here, we show that the expression of an isoform of the major AD susceptibility gene BIN1 in the presynaptic compartment results in synaptic loss. Using electrophysiology, we observed an early loss of synaptic transmission upon BIN1 isoform 1 (BIN1iso1) expression in Drosophila retinal photoreceptor neurons. This was not observed for the other human BIN1 isoforms tested, isoform 8 and isoform 9. Structural analysis of photoreceptor neuron synapses shows a strong accumulation of abnormally large vesicles in the presynaptic compartment, reminiscent of this same isoform-induced endosome defects in cell bodies. In addition, the expression of BIN1iso1 in motoneurons of the Drosophila neuromuscular junction alters the morphology of synaptic boutons, with a greater number and a smaller size of synaptic boutons, and the appearance of satellite boutons. As opposed to endosomal defects in cell body, modulating the Rab11 recycling endosome regulator did not prevent BIN1iso1 synaptotoxicity. To test if synaptic deficits are conserved in a mammalian model and to assert a presynaptic vs postsynaptic role for BIN1, we used rat primary neurons cultured in microfluidic devices that restrict gene expression modulation in particular neuron populations. We found a loss of synaptic connectivity only when expressing BIN1iso1 in the presynaptic compartment, which was confirmed by microelectrode array analysis. Together, our results suggest that BIN1 expression in the presynaptic terminal, but not the postsynaptic terminal leads to an isoform-specific, deleterious effect on synaptic integrity. BIN1 synaptotoxicity could contribute to the synapse loss observed early in AD. This supports the idea that genetic determinants could make synapses prone to failure in AD.

• PU.1-driven enrichment enables microglia profiling from frozen brain tissue using the high-throughput Smart-seq3xpress method
  Authors: Dostalova, D.; Abaffy, P.; Rohlova, E.; Kriska, J.; Knotek, T.; Tureckova, J.; Kirdajova, D.; Anderova, M.; Valihrach, L.
  Published: 2025-08-15 (new results)
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  Single-cell transcriptomics has revealed the central role of microglia in brain development, homeostasis, and disease, particularly in the context of neuroinflammation. While single-cell RNA-sequencing enables targeted microglial analysis from fresh tissue, studying these cells in cryopreserved or archival samples remains challenging due to the lack of protocols for their specific enrichment. We introduce a method for the selective isolation of microglial nuclei from fresh-frozen brain tissue using the transcription factor PU.1 as a nuclear marker. To stabilize PU.1 for reliable detection, a brief formaldehyde fixation step is applied. The protocol is fully compatible with Smart-seq3xpress, a high-sensitivity, full-length transcriptomic method offering isoform- and allele-level resolution, making the workflow scalable and cost-efficient. We benchmarked the method in a mouse model of ischemic stroke, evaluating both technical performance and its ability to capture biologically meaningful microglial states. Compared to standard single-nucleus protocols, our approach yielded higher gene and UMI counts and a greater proportion of coding reads. Transcriptomic profiles closely matched those from whole-cell RNA- sequencing including the detection of activation markers and diverse microglial subpopulations. This approach addresses key limitations of single-nucleus RNA - sequencing and opens new possibilities for studying microglial states in cryopreserved and archival brain tissue, broadening access to cellular insights in both basic and translational research. Key words: Enrichment, Frozen tissue, Microglia, PU.1, Smart-seq3xpress, single-nucleus RNA - sequencing, Stroke, Transcriptomics

• Inverse expression of Ten3 and Lphn2 across the developing mouse brain reveals a global strategy for circuit assembly
  Authors: Chon, U.; Pederick, D. T.; Song, J. H.; Zhang, Y.; Rana, I.; Luo, L.
  Published: 2025-08-15 (new results)
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  Precise wiring of neural circuits requires molecular strategies that ensure accurate target selection across diverse brain regions. Here, we identify inverse expression between a ligand-receptor pair, Teneurin-3 (Ten3) and Latrophilin-2 (Lphn2), throughout the developing mouse brain. Ten3 and Lphn2 exhibit inverse expression gradients along a retinotopic axis orthogonal to the ephrin-A and EphA gradients; along the tonotopic axis across multiple brainstem auditory nuclei; and along the dorsomedial-ventrolateral axis in striatum and pallidum. Their inverse expression also creates discrete domains of cerebellar Purkinje cells and cerebellar nuclei along the mediolateral axis. Using conditional tag mice, we show that inverse Ten3 and Lphn2 expression patterns predict connectivity, following a 'Ten3 [->] Ten3, Lphn2 [->] Lphn2' rule in all above circuits. We further demonstrate a functional role for Lphn2 in executing this rule in Purkinje cells [->] cerebellar nuclei projection. Our findings reveal a global strategy of coordinating gene expression of key wiring molecules with circuit connectivity across the developing brain.

• Distributed theta networks support the control of working memory: Evidence from scalp and intracranial EEG
  Authors: Shi, L.; Chattopadhyay, K.; Gray, S. M.; Yarbrough, J. B.; King-Stephens, D.; Saez, I.; Girgis, F.; Shaikhouni, A.; Schuele, S. U.; Rosenow, J. M.; Asano, E.; Kim-McManus, O.; Sattar, S.; Knight, R. T.; Johnson, E. L.
  Published: 2025-08-15 (new results)
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  We combined scalp EEG and intracranial EEG (iEEG) to identify spectral and network-level signatures of executive control during a delayed match-to-sample task working memory task. To isolate executive processes, we contrasted test and sample phases, matched in perceptual input but differing in cognitive demand. Scalp EEG revealed increased frontal midline theta event-related spectral perturbations (ERSPs), dynamic increases and decreases in posterior theta-alpha ERSPs, and decreased central alpha-beta ERSPs during the test phase. These local spectral changes were accompanied by enhanced frontoposterior theta phase synchrony and network hub strength, predicting higher behavioral accuracy. Using a novel cross-modal scalp EEG-iEEG ERSP similarity approach, we localized the sources of scalp-derived frontal midline, posterior, and central control effects to medial frontal, parietal, temporal, and occipital regions. Our results integrate power and connectivity measures across scalp and iEEG, linking local spectral fluctuations to broader network organization. Together, they support a model in which executive control emerges from flexible, temporally precise coordination between medial frontal control hubs and posterior representational systems.

• An astrocytic AMPK clock drives circadian behaviour
  Authors: Luengo-Mateos, M.; Gonzalez-Vila, A.; Silveira-Loureiro, M.; Abreu, D. S.; Azkargorta, M.; Ibrahim-Alasoufi, A. M.; Pardo-Garcia, V.; Lopez-Goldar, H.; Covelo-Molares, H.; Dragano, N. R. V.; Fernandez-Sanmartin, P.; Estevez-Salguero, A. M.; Astiz, M.; Cavadas, C.; Dieguez, C.; Fidalgo, M.; Guallar, D.; Elortza, F.; Oliveira, J.; Lopez, M.; Barca-Mayo, O.
  Published: 2025-08-15 (new results)
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  Circadian clocks coordinate behaviour and physiology with daily cycles of light and nutrient availability, yet how metabolic signals tune brain timing remains unclear. Astrocytes integrate metabolic and hormonal cues and sustain cell-autonomous rhythms, implicating them as candidate links between energy state and central circadian control. Here we show that AMP-activated protein kinase (AMPK) in hypothalamic astrocytes exhibits intrinsic, calcium-dependent rhythmicity that persists under constant darkness and without feeding cues. This glial rhythm sustains time-of-day phosphorylation programmes in the hypothalamus and stabilises the clock protein PER2 via phosphorylation at a conserved serine residue, thereby linking metabolic state to period control beyond the canonical transcription-translation feedback loops. In the ventromedial hypothalamus, astrocytic AMPK-PER2 signalling is required for food-anticipatory activity, identifying a glial node within the food-entrainable timing system. Disrupting astrocytic AMPK rhythmicity alters circadian behaviour and energy homeostasis and shortens lifespan in a sex-dependent manner. These findings recast AMPK as a metabolically adaptive glial timekeeper that connects calcium signalling and phosphorylation rhythms to behaviour and metabolism. They also reveal a phosphorylation-based timing layer in central metabolic circuits, with implications for circadian-metabolic misalignment in contexts such as shift work and metabolic disorders.

• Teneurin-3 and latrophilin-2 are required for somatotopic map formation and somatosensory topognosis
  Authors: Sangster, K. T.; Zhang, X.; del Toro, D.; Sarantopoulos, C.; Moses, A. M.; Mahasenan, S.; Pederick, D. T.; Perreault, S.; Fallet-Bianco, C.; Roome, R. B.; Seiradake, E.; Luo, L.; Kania, A.
  Published: 2025-08-15 (new results)
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  Somatotopy is a recurring organizational feature of the somatosensory system where adjacent neurons and their connections represent adjacent regions of the body. The molecular mechanisms governing the formation of such "body maps" remain largely unknown. Here we demonstrate that the cell surface proteins teneurin-3 and latrophilin-2 are expressed in opposing gradients in multiple somatotopic maps in the mouse, including within the dorsal horn of the spinal cord. Genetic manipulation of these proteins in spinal dorsal horn or sensory neurons distorts the somatotopy of neuronal connections and impairs accurate localisation of a noxious stimulus on the surface of the body. Our work provides the foundation for a molecular model of somatotopic map formation and insights into their function in localisation of somatosensory stimuli or topognosis.

• Exploring Cerebellar Hippocampal Dynamics in Temporal Lobe Epilepsy: A Multivariable Synthetic Modeling Study of Purkinje Cell Degeneration and Stimulation Timing
  Authors: Ibrahim, M.; Hu, B.
  Published: 2025-08-15 (new results)
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  Objective: To determine whether Purkinje cell degeneration precedes or follows seizure onset in temporal lobe epilepsy (TLE), identify shared cerebello-hippocampal pathways, and evaluate the influence of stimulation timing on modeled seizure outcomes. Methods: We constructed a 50-variable evidence model integrating structural, molecular, and circuit-level data from published literature. This framework generated a PASS-validated synthetic cohort of 10,000 virtual subjects, with validation details in the Appendix. Analyses employed causal inference with inverse probability of treatment weighting (IPTW), mediation analysis, factorial ANOVA, and the Two One-Sided Test [TOST] for equivalence. The model predictive fit was deliberately modest (RMSE = 0.499; R square = -0.010), focusing on causal insights rather than precise prediction. Evaluations were stratified by timing and circuit integrity. Results: Causal analysis revealed a weak, nonsignificant direct effect of Purkinje cell density on seizure burden (ATE = +0.0045, 95% CI: -0.0053 to +0.0143) [Table 1, row 1]. Mediation via GABAergic pathways was negligible. Early stimulation ([≤]4 days post-onset) significantly reduced seizure burden (p = 0.045, mean Delta; = -0.020), with a timing x integrity interaction [Table 1, row 3]. Factorial ANOVA confirmed this interaction (F = 3.30, p = 0.019, partial eta square= 0.001), with Tukey HSD emphasizing timing role. TOST with a +/-0.015 margin did not confirm equivalence for Purkinje effects (P1; = 0.0019, ;P2;= 0.136), suggesting minimal impact. Sensitivity and perturbation tests across 10,000-subject cohorts ensured robustness. Interpretation: This model suggests cerebellar stimulation mitigates seizure burden through timely intervention rather than Purkinje integrity. Recent studies support cerebellar changes in TLE and rTMS-induced vermis volume increases linked to seizure reduction.Trials of transcranial alternating current stimulation in refractory TLE align with our findings. Results from synthetic data propose translational validation. Conclusion: Optimizing stimulation timing offers a testable strategy to modulate hippocampal excitability in TLE, independent of Purkinje status, highlighting synthetic model utility in exploring dynamic interventions.

• Striatal neuron excitability is regulated by huntingtin in the adult brain
  Authors: Barron, J. C.; Greenland, M. L.; Ashrafganjoie, F.; Hurley, E. P.; Nafar, F.; Moore, C. S.; Parsons, M. P.
  Published: 2025-08-15 (new results)
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  Huntington disease (HD) is a hereditary neurodegenerative disease that typically presents during midlife and is characterized by a combination of motor, cognitive and psychiatric symptoms. HD is fatal and arises from a mutation in the huntingtin (HTT) gene, which results in decreased neuronal health followed by brain atrophy, with spiny projection neurons (SPNs) of the striatum being especially vulnerable to degeneration. HTT loss-of-function, caused by haploinsufficiency of the wild type HTT gene (wtHTT), is an important feature of HD pathophysiology that has previously been understudied compared to mutant HTT gain-of-function mechanisms. wtHTT is essential for nervous system development and functions as a scaffolding protein to support many vital cellular functions including axonal transport, autophagy and synaptic plasticity. Here, we examined the consequences of wtHTT deletion in the adult striatum by conditionally inactivating wtHTT in 2-4 month old male and female Httfl/fl mice. wtHTT loss of function in mature SPNs decreased intrinsic neuronal excitability and produced a neuroinflammatory response in these mice, while tissue organization, spine morphology and motor behaviour remained unaffected. Results presented here provide additional evidence that wtHTT is vital for maintaining neuronal health in the adult brain and highlight some potential adverse consequences of non-selective HTT-lowering for the treatment of HD.

• Ten3-Lphn2-mediated target selection across the extended hippocampal network demonstrates a repeated strategy for circuit assembly
  Authors: Gingrich, E. C.; Pederick, D. T.; Zhang, Y.; Luo, L.
  Published: 2025-08-15 (new results)
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  How do a limited number of wiring molecules specify trillions of connections in developing brains? We previously found that inverse expression of a ligand-receptor pair, Teneurin-3 (Ten3) and Latrophilin-2 (Lphn2) in CA1 and subiculum instructs CA1[->]subiculum target selection through Ten3-Ten3 homophilic attraction and Ten3-Lphn2 heterophilic reciprocal repulsion. Here, we leveraged conditional knockouts to systematically demonstrate that these mechanisms generalize to extended hippocampal connections, including entorhinal cortex and hypothalamus. Cooperation between attraction and repulsion differs depending on the order developing axons encounter the attractant and repellent subfields. Strikingly, Ten3 and Lphn2 can serve both as ligands for incoming axons and receptors for their own target selection, within the same neuron; Ten3 can be repulsive or attractive as ligand or receptor. Thus, multifunctionality and repeated use, together with the recurrent circuit motifs prevalent in the brain, enable one ligand-receptor pair to instruct target selection of many more neurons.

• Pharmacological Depletion of Retinal Mononuclear Phagocytes is Neuroprotective in a Mouse Model of Mitochondrial Optic Neuropathy
  Authors: Okrent, A. L.; Viswanath, R.; Bomze, H. M.; Hao, Y.; Gospe, S. M.
  Published: 2025-08-15 (new results)
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  Purpose: The Vglut2-Cre;ndufs4loxP/loxP mouse strain with retinal ganglion cell (RGC)-specific mitochondrial complex I dysfunction develops severe RGC degeneration by postnatal day 90 (P90), with accompanying retinal mononuclear phagocyte (MNP) accumulation. We have reported that continuous exposure to hypoxia partially rescues RGC death in these mice, with minimal effect on MNP abundance. We hypothesized that pharmacological depletion of MNPs with the colony-stimulating factor-1 receptor inhibitor pexidartinib would enhance RGC neuroprotection by hypoxia. Methods: Iba1+ retinal MNP depletion was assessed in C57Bl/6J mice fed control or pexidartinib-infused chow beginning at P25. Subsequently, Vglut2-Cre;ndufs4loxP/loxP mice and control littermates were raised under normoxia or hypoxia and fed control or pexidartinib chow from P25 to P90. The neuroprotective effect of pexidartinib and hypoxia alone and in combination was assessed by quantifying RGC soma and axon survival in retinal flat mounts and optic nerve cross sections. Results: Pexidartinib completely depleted retinal MNPs within one week of treatment. Untreated Vglut2-Cre;ndufs4loxP/loxP mice exhibited the expected ~50% reduction of RGC soma and axon survival at P90 (p<0.0001 for both). Hypoxia or pexidartinib monotherapy each reduced RGC degeneration by more than one-half, while their combination resulted in complete RGC neuroprotection (p<0.001 for all three treatments). Normal myelination patterns were restored in mice receiving dual therapy. Conclusions: Pexidartinib effectively depletes retinal MNPs and is neuroprotective in the setting of severe RGC mitochondrial dysfunction. This therapeutic effect is additive to that of hypoxia. Combating retinal neuro-inflammation may therefore be a useful adjunct therapy in mitochondrial optic neuropathies like Leber hereditary optic neuropathy.

• Analysis of human visual experience data
  Authors: Zauner, J.; Nicholls, A.; Ostrin, L. A.; Spitschan, M.
  Published: 2025-08-15 (new results)
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  Exposure to the optical environment, often referred to as visual experience, profoundly influences human physiology and behavior across multiple time scales. In controlled laboratory settings, stimuli can be held constant or manipulated parametrically. However, such exposures rarely replicate real-world conditions, which are inherently complex and dynamic, generating high-dimensional datasets that demand rigorous and flexible analysis strategies. This tutorial presents an analysis pipeline for visual experience datasets, with a focus on reproducible workflows for human chronobiology and myopia research. Light exposure and its retinal encoding affect human physiology and behavior across multiple time scales. Here we provide step-by-step instructions for importing, visualizing, and processing viewing distance and light exposure data using the open-source R package LightLogR. This includes time-series analyses for working distance, biologically relevant light metrics, and spectral characteristics. By leveraging a modular approach, the tutorial supports researchers in building flexible and robust pipelines that accommodate diverse experimental paradigms and measurement systems.

• Characterizing Surround Suppression with Dynamic Natural Scenes
  Authors: Kiniklioglu, M.; Kaiser, D.
  Published: 2025-08-15 (new results)
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  Surround suppression refers to the reduction in perceptual sensitivity to a central stimulus caused by its surrounding context. Previous studies have examined this phenomenon mainly with simple stimuli varying only in low-level visual features, leaving it unclear whether the same principles apply to natural scenes. To address this, we investigated surround suppression in complex and dynamic scenes by systematically manipulating categorical similarity and motion congruence between the center and surrounding scenes. Categorical similarity was examined across four levels: identical exemplars, different exemplars of the same basic-level category, different basic-level categories, and different superordinate categories. Motion direction was manipulated by center and surround drifting either in the same or opposite directions. In two experiments, we measured contrast sensitivity for the center scene during a categorization task. We found that the suppression increased as the categorical similarity between the center and the surround decreased, with the strongest suppression observed for different superordinate categories. This contrasts with results for simple stimuli, where increasing center-surround similarity increases suppression. Yet, consistent with the findings from simple stimuli, suppression was stronger when the center and surround moved in the same direction. These findings show that contextual modulation in natural vision is governed not only by low-level feature similarity but also by high-level categorical structure. Context-dependent suppression may therefore help the visual system prioritize coherent, task-relevant information while filtering incongruent input.

• Mobile Eye Tracking in the Real World: Best Practices
  Authors: Nolte, D.; Walter, J. L.; von Bassewitz, L.; Scherer, J.; Müller, M. M.; König, P.
  Published: 2025-08-15 (new results)
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  As research on human behavior, such as spatial navigation, increasingly adopts naturalistic settings, establishing best practices for such experiments becomes essential. While virtual reality (VR) offers a bridge between laboratory control and real-world complexity, it does not fully capture the experiential richness of real-world environments. Here, we present a demonstration of a mobile eye-tracking study conducted in a large-scale, outdoor urban environment, featuring unconstrained, long-duration free exploration and outside-pointing tasks. Using the city of Limassol, Cyprus as our testbed, we showcase the feasibility of collecting high-quality mobile eye-tracking, head orientation, and GPS data "in the wild," capturing a wide range of natural behavior with minimal experimental constraints. Based on this experience, we provide a set of best practices tailored to the logistical and methodological challenges posed by complex, real-world urban settings, challenges unlikely to arise in traditional indoor or highly controlled environments. While these recommendations have general relevance, we exemplify them in the context of spatial navigation research. By establishing methodological standards for studies at this scale, we aim to encourage and inform future research into naturalistic human behavior outside the laboratory.

• DynVision: A Toolbox for Biologically Plausible Recurrent Convolutional Networks
  Authors: Gutzen, R.; Lindsay, G. W.
  Published: 2025-08-15 (new results)
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  Convolutional Neural Networks (CNNs) have demonstrated remarkable success in image recognition and exhibit conceptual similarities to the primate ventral visual pathway. Adding recurrence opens the door to exploring temporal dynamics and investigating mechanisms underlying recognition robustness, attentional modulation, and rhythmic perception phenomena. However, modeling spatiotemporal dynamics of biological vision using CNN-based architectures remains challenging. Incorporating functionally beneficial recurrence, capturing biologically plausible temporal phenomena such as adaptation and subadditive temporal summation, and maintaining topographic organization aligned with cortical structure require significant computational considerations. Although recent advances have incorporated neurobiological constraints, the field lacks accessible tools for efficiently integrating, testing, and comparing these approaches. Here, we introduce DynVision, a modular toolbox for constructing and evaluating recurrent convolutional neural networks (RCNNs) with biologically inspired dynamics. Our approach facilitates the incorporation of key visual cortex properties, including realistic recurrent architectures, activity evolution governed by dynamical systems equations, and structured connectivity reflecting cortical arrangements, while maintaining computational efficiency. We demonstrate the framework's utility through systematic analysis of emergent neural dynamics, highlighting how different biologically motivated modifications shape scientifically-relevant response patterns. Code can be found at: https://github.com/Lindsay-Lab/DynVision/

• A Coupling Model of Transcranial Magnetic Stimulation Induced Electric Fields to Neural State Variables
  Authors: Miller, A.; Knösche, T. R.; Weise, K.
  Published: 2025-08-15 (new results)
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  Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique used to modulate neural activity, with applications in clinical treatment, diagnostics, and neuroscientific research. TMS targeting the human primary motor cortex (M1) is well studied, aided by experimental readouts from the cerebral cortex, the spinal cord, and activated muscle targets. One key readout is a series of pulses that descend the spinal cord following TMS, called DI-waves. These reflect the output of M1 to the spinal cord and are influenced by TMS parameters such as orientation, strength, and waveform. Previous modeling studies have deployed numerous strategies to explain DI-wave generation, but generally approximate TMS inputs as semi-arbitrary current or synaptic inputs. A consistent missing piece to these models is a biophysically motivated coupling between TMS and the neural states of cells and cell populations. This study aims to leverage cable simulations of realistic neuron morphologies to couple TMS induced electric fields to average state variables of cortical cell populations. This coupling model quantifies the spatial-temporal activation function of directly stimulated axonal fibers and the average input current that downstream cells receive due to synaptic inputs from directly stimulated cells. An example M1 cortical circuit is studied, in which TMS stimulates layer 2/3 excitatory and inhibitory neurons that project synapses onto layer 5 corticospinal neurons. Results indicate that TMS induces unique directionally sensitive distributions of synaptic outputs in time and space for each cell type. Directional and dosage sensitivity carries forward to the dendritic current flowing into layer 5 cells. Ultimately, the coupling model provides a novel architecture to translate electric fields from TMS into activation functions that alter neural states and serve as inputs to cortical circuit modeling. The study of other brain regions is achievable through an alternate choice of cell morphologies, cell locations, and circuit design.

• Your Emotions, My Brain: Generalizable Neural Signatures of Emotional Memory Reactivation During Sleep
  Authors: Abdellahi, M. E.; Tsimpanouli, M. E.; Lewis, P.
  Published: 2025-08-15 (new results)
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  Reactivation in sleep alters the structure of memories and can potentially be used to restructure upsetting representations. Reactivation can be triggered with auditory cues and then detected using machine learning and electroencephalography (EEG), but can we also detect the emotionality of reactivated memories? We examined this by presenting auditory cues that had been associated with negative or neutral stimuli in wake during subsequent NREM sleep and training a classifier to detect the emotionality of subsequent EEG responses. We were able to detect the reinstatement of emotionality 0.4-0.6 seconds after cue presentation. Importantly, we used a between-participant machine learning pipeline to identify shared neural signatures of emotionality across individuals without fine-tuning the model on testing participants. This approach eliminates the need for individualized wake localizer sessions, establishing a methodologically efficient framework for investigating emotional processing during sleep. Detection of emotional reactivation in sleep will help us to understand how such reactivation impacts upon the emotionality of the memories in the long term, potentially facilitating development of treatments for PTSD and depression through memory restructuring in sleep.

• Normative neural and physiological correlates of parent-child observational threat extinction
  Authors: Heyn, S. A.; Herringa, R. J.
  Published: 2025-08-15 (new results)
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  The dyadic relationship between a parent and child is a critical facilitator of social learning, particularly in the management of fear. Vicarious extinction, the process of learning by observing a parent extinguish learned threat responses, holds critical translational potential in understanding adolescent psychopathology involving aberrant threat responses. However, normative biological profiles of vicarious extinction have yet to be uncovered. Here, a community sample of 97 parent-child dyads, enriched for trauma-exposure, completed a validated vicarious extinction paradigm. Youth completed all phases during functional magnetic resonance imaging, while caregivers simultaneously completed the behavioral task. Linear models interrogating normative behavioral, physiological, and neural correlates of acquisition and direct and vicarious extinction, controlled for trauma and symptom severity. The degree of parent-child autonomic synchrony was used to predict the strength of extinction learning. Youth behavioral and skin conductance response markers suggest successful threat acquisition and direct and vicarious extinction. Autonomic arousal during active vicarious extinction learning processes was significantly associated with the strength of parent-child synchrony. Neural activation analyses reveal patterns of early encoding of threat and safety discrimination that were reactivated during later threat reinstatement. Finally, results corroborate and expand known models of direct and vicarious extinction, respectively involving the ventromedial and ventrolateral prefrontal cortex. Altogether, this data confirms that youth can directly and vicariously modify learned threat associations with distinct neurobiological profiles. This delineation of vicarious extinction neural circuitry within a normative population is pivotal for understanding how these processes may be altered by the environment and/or psychopathology during adolescence.

• Tactile Pressure Evokes a Biphasic BOLD Response in Ipsilateral Primary Somatosensory Cortex
  Authors: Feldbush, A. C.; Kalantaryardebily, N.; Reddy, N. A.; Faubion-Trejo, R.; Soldate, J.; Lisinski, J.; Bright, M. G.; Gurari, N.; LaConte, S. M.
  Published: 2025-08-15 (new results)
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  Tactile perception is fundamental to how we engage with and interpret our surroundings. While the contralateral primary somatosensory cortex (S1) is thought to be generally responsible for processing tactile information, simultaneous responses in the ipsilateral hemisphere have been observed. This work aims to characterize the blood-oxygen-level-dependent (BOLD) response pattern of ipsilateral S1 to unilateral tactile stimuli. In this study, tactile stimuli were applied using a custom pneumatically actuated stimulator designed and built in house (KalantaryArdebily et al., 2024). Three stimulus force levels were applied in an event-related design. As expected we observed an apparent difference in BOLD responses between the contralateral and ipsilateral hemispheres. We found differing response patterns between the Brodmann's areas (BA) within ipsilateral S1. Ipsilateral BA2 had a positive BOLD response similar to that of the contralateral hemisphere. In contrast, ipsilateral BA1 and BA3b appeared to have a biphasic response. That is, those regions had an initial negative response, followed by a secondary positive one. Using multi-echo analysis, we verified that this biphasic response pattern is BOLD-related. In addition, the secondary (positive) phase was more sensitive to tactile stimulus force than the initial "negative" BOLD phase. The ipsilateral BA1 and BA3b responses support a previous hypothesis of bilateral sensory gating (Blatow et al., 2007; Chung et al., 2014; Hamalainen et al., 2000; Kastrup et al., 2008; Klingner et al., 2016; Schafer et al., 2012; Tame et al., 2015). This study extends previous research reporting negative responses in ipsilateral S1, suggesting that the response is BOLD-related, biphasic, and that the previously overlooked secondary positive phase is actually more sensitive to stimulus intensity.

• The Social Switchboard: Context and Rank Shapes Behavioural and Neural Responses During Macaque Decision-Making
  Authors: Zarei, S. A.; Tu, J.; Wang, X.; Andolina, I. M.
  Published: 2025-08-15 (new results)
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  Social interactions shape many of our most ethologically relevant decisions and require considerable cognitive sophistication. Factors such as immediate needs, social bonds, hierarchical status, and reciprocity norms impact decision-making. Yet most laboratory paradigms examine individuals in isolation. We developed a face-to-face cognitive testing platform using a transparent touchscreen that allowed pairs of adult male Macaca fascicularis (n = 6) with established dominance relationships to perform a decision-making task across six social contexts: audience, co-action, envy, cooperation, competition, and altruism. We recorded eye movements simultaneously from both subjects (gaze position and pupil diameter), synchronised behavioural video, and task performance. Across social contexts, macaques performed better in the presence of a conspecific than when tested alone, but performance declined under altruistic and competitive conditions. Dominance substantially modulated motivation: dominant subjects were less willing to engage when rewards were shared (envy), when only the partner was rewarded (altruism), or when contingent action with a subordinate was required (cooperation). Eye-tracking revealed greater pre-choice arousal and social attention during social sessions, indexed by larger pupils, longer fixations on the partner's face, and more saccades before (but not during or after) choices. Pupil dilation was larger in dyads where both individuals were dominant than in dyads where one was subordinate. Finally, noninvasive functional near-infrared spectroscopy (fNIRS) showed increased cortical engagement relative to baseline in audience, altruism, competition, and cooperation conditions. These findings demonstrate that social context and hierarchical dominance systematically shape choices, attentional allocation, autonomic arousal, and cortical engagement in macaques, and provide a tractable platform for further dissecting the neural bases of contextual social decision-making.

• Structural connectome architecture and biological vulnerability shape cortical atrophy in cocaine use disorder
  Authors: Han, Z.; Liu, T.; Wang, K.; yang, G.; Yan, T.
  Published: 2025-08-15 (new results)
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  Cocaine use disorder (CUD) is prevalent and characterized by widespread gray matter atrophy across the cerebral cortex. However, it remains unclear whether and how connectome-based circuits and biological features shape these structural abnormalities. Here, we show that CUD-associated regional atrophy is constrained by the white matter (WM) structural connectome. Along these WM pathways, regions that share similar haemodynamic activity and molecular profiles are more likely to exhibit analogous atrophy patterns. By integrating the structural connectome with these multiple connectivity blueprints, we subsequently identify CUD epicenters and reveal that the prefrontal and visual cortices serve as core systems. Furthermore, we link these epicenters to cortical gene expression patterns and delineate CUD-related transcriptomic enrichment in biological processes, including inter-neuronal communication, synaptic function and neural homeostasis. Finally, we demonstrate that the spatial distribution of these epicenters correlates with cocaine craving-response maps derived from repeated transcranial magnetic stimulation and can track individual variations in clinical behavioural representations, suggesting their potential as key targets for therapeutic intervention. Together, our findings establish a structurally constrained framework for the spread of pathology underlying cortical atrophy in CUD, where initial perturbations propagate via structural connectome pathways to vulnerable regions shaped by neural activity and molecular landscapes.

• Modeling presynaptic inhibition by the amyloid precursor protein demonstrates one potential mechanism for preventing runaway synaptic modification in Alzheimers disease
  Authors: Barber, D.; Hasselmo, M. E.; Rice, H. C.
  Published: 2025-08-15 (new results)
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  INTRODUCTION Previous simulations of Hebbian associative memory models inspired the malignant synaptic growth hypothesis of Alzheimers disease (AD), which suggests that cognitive impairments arise due to runaway synaptic modification resulting from poor separation between encoding and retrieval. METHODS We computationally model presynaptic inhibition by the recently identified interaction of soluble amyloid precursor protein (sAPPalpha) with the gamma-aminobutyric acid type B receptor (GABABR) as one potential biological mechanism which can enhance separation between encoding and retrieval. RESULTS Simulations predict that the dual effect of sAPPalpha on long-term potentiation and presynaptic inhibition of glutamatergic synapses maintains effective associative memory function and prevents runaway synaptic modification. Moreover, computational modeling predicts that sAPPalpha, which interacts with the 1a isoform of GABABR, is more effective at stabilizing associative memory than the GABABR agonist Baclofen. DISCUSSION Molecular mechanisms that enhance presynaptic inhibition, such as sAPPalpha-GABABR1a signaling, are potential therapeutic targets for preventing cognitive impairments in AD.

• Epigenetic Shifts Reveal Alzheimer's Origins after Sustained Picomolar Aβ Exposure
  Authors: Paquola, A.; Acquarone, E.; Staniszewski, A.; Teich, A. F.; Arancio, O.
  Published: 2025-08-15 (new results)
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  Recent advances in sequencing have identified genetic risk factors for Alzheimer's disease (AD), but the molecular mechanisms triggering disease onset remain unclear. While high brain levels of amyloid-beta (A{beta}) impair synaptic function and memory, exposure to low picomolar (pM) A{beta} ; concentrations - typical of healthy brains - enhances these functions, while sustained exposure results in impairment. To investigate this transition from physiological to pathological A{beta} ; activity, we profiled DNA methylation and gene expression in C57B16 mice subjected to prolonged pM A{beta}42 exposure. We identified differentially methylated and expressed genes, including those involved in synaptic function, associated with three phases: memory enhancement (brief exposure), a transitional state with intact memory (intermediate), and memory decline (prolonged). These gene sets may represent early molecular drivers of AD pathogenesis.

• ATHENA: Automatically Tracking Hands Expertly with No Annotations
  Authors: Mulla, D. M.; Costantino, M.; Freud, E.; Michaels, J. A.
  Published: 2025-08-15 (new results)
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  Studying naturalistic hand behaviours is challenging due to the limitations of conventional marker-based motion capture, which can be costly, time-consuming, and encumber participants. While markerless pose estimation exists - an accurate, off-the-shelf solution validated for hand-object manipulation is needed. We present ATHENA (Automatically Tracking Hands Expertly with No Annotations), an open-source, Python-based toolbox for 3D markerless hand tracking. To validate ATHENA, we concurrently recorded hand kinematics using ATHENA and an industry-standard optoelectronic marker-based system (OptiTrack). Participants performed unimanual, bimanual, and naturalistic object manipulation and we compared common kinematic variables like grip aperture, wrist velocity, index metacarpophalangeal flexion, and bimanual span. Our results demonstrated high spatiotemporal agreement between ATHENA and OptiTrack. This was evidenced by extremely high matches (R2 > 0.90 across the majority of tasks) and low root mean square differences (< 1 cm for grip aperture, < 4 cm/s for wrist velocity, and < 5-10 degrees for index metacarpophalangeal flexion). ATHENA reliably preserved trial-to-trial variability in kinematics, offering identical scientific conclusions to marker-based approaches, but with significantly reduced financial and time costs and no participant encumbrance. In conclusion, ATHENA is an accurate, automated, and easy-to-use platform for 3D markerless hand tracking that enables more ecologically valid motor control and learning studies of naturalistic hand behaviours, enhancing our understanding of human dexterity.

• Altered molecular signaling pathways in the hippocampus of rhesus monkeys following chronic alcohol use
  Authors: Pareek, T.; Vergis, J. M.; Zhang, X.; Platt, D. M.; Grant, K. A.; McCullumsmith, R.; Gisabella, B.; O'Donovan, S. M.; Pantazopoulos, H.
  Published: 2025-08-15 (new results)
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  Context-induced relapse is a significant factor limiting recovery from alcohol use disorder (AUD). However, the molecular processes in the hippocampus, a critical region for contextual memory impacted by chronic alcohol use, remain poorly understood. We used a non-human primate model to test the hypothesis that chronic alcohol use impacts hippocampal molecular pathways that may serve as therapeutic targets for context-induced relapse and memory processing issues associated with chronic alcohol use. We conducted RNAseq profiling on hippocampal samples from adult male rhesus monkeys with chronic alcohol use (n=7) and controls (n=5) from the Monkey Alcohol Tissue Research Resource (MATRR). We identified 2,575 differentially expressed genes (DEGs) in subjects with chronic alcohol use, including genes implicated in genome-wide association studies (GWAS) of alcohol dependence, such as GLP2R and GABBR2. Downregulated pathways included chemical synaptic transmission, trans-synaptic signaling, and neuron development, and upregulated pathways involved mitochondrial function. Targeted pathway analysis highlighted significant downregulation of synaptic signaling (e.g., axonal fasciculation) and upregulation of mitochondrial processes (e.g., electron transport). Leading-edge gene analysis revealed several downregulated genes involved in synaptic signaling including GRIN2B, CACNA1C, and NLGN1 as well as upregulated genes such as NDUFS3 and MT-ND1 involved in mitochondrial processes. Drug repurposing analysis identified several targets including epidermal growth factor receptor (EGFR) inhibitors, and L-type calcium channel blockers as potential therapeutic targets. Our results provide critical insights into molecular pathways underlying hippocampal pathology in chronic alcohol use, emphasizing the roles of mitochondrial function, synaptic regulation and calcium channels, and offering potential novel therapeutic targets.

• Functional recovery by transplantation of human iPSC-derived A2B5 positive neural progenitor cell after spinal cord injury in mice
  Authors: Zheng, Y.; Chen, X.; Bu, P.; Xue, H.; Kim, D. H.; Zhou, H.; Xia, X.; Liu, Y.; Cao, Q.
  Published: 2025-08-15 (new results)
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  Human induced pluripotent stem cells (hiPSCs) hold great potential for patient-specific therapies. Transplantation of hiPSC-derived neural progenitor cells (NPCs) is a promising reparative strategy for spinal cord injury (SCI), but clinical translation requires efficient differentiation into desired neural lineages and purification before transplantation. Here, differentiated hiPSCs, reprogrammed from human skin fibroblasts using Sendai virus-mediated expression of OCT4, SOX2, KLF4, and C-MYC, into neural rosettes expressing SOX1 and PAX6, followed by neuronal precursors ({beta}-tubulin III+/NESTIN+) and glial precursors (GFAP+/NESTIN+). Both neuronal and glial precursors expressed the A2B5 surface antigen. A2B5+ NPCs, purified by fluorescence-activated cell sorting (FACS), proliferated in vitro with mitogens and differentiated into mature neurons and astrocytes under lineage-specific conditions. NOD-SCID mice received a T9 contusion injury followed by transplantation of A2B5+ NPCs, human fibroblasts, or control medium at 8 days post-injury. At two months, grafted NPCs showed robust survival, progressive neuronal maturation ({beta}-tubulin III+ to doublecortin+ to NeuN+), and astrocytic differentiation (GFAP+), particularly in spared white matter. Transplantation significantly increased spared white matter volume and improved hindlimb locomotor recovery, with no teratoma formation observed. These results demonstrate that hiPSC-derived, FACS-purified A2B5+ NPCs can survive, differentiate into neurons and astrocytes, and enhance functional recovery after SCI. This approach offers a safe and effective candidate cell source for treating SCI and potentially other neurological disorders.

• Temporal confounds emulate multivariate fMRI measures of perceptual learning
  Authors: Milne, G. A.; Staeubli, K.; Chow-Wing-Bom, H. T.; Greenwood, J. A.; Kok, P.; Maimon-Mor, R. O.; Dekker, T. M.
  Published: 2025-08-15 (new results)
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  Human perception inherently involves learning. We can experience the same stimulus completely differently depending on our prior knowledge. Understanding the neural basis of perception therefore requires measurements that capture these temporal dynamics. Multi-voxel pattern analysis (MVPA) approaches are widely used to characterise changes in neural representations over time. A popular example is the perceptual reorganisation paradigm, which investigates the neural correlates of enhanced recognition of distorted images after cueing with the undistorted version. Studies typically report increased representational similarity of these two images in early visual cortex. However, as these paradigms include an inherent ordering of stimuli that precludes trial randomisation or counterbalancing, they are vulnerable to temporal confounds common to fMRI. Here, we investigate how these confounds could influence current understanding of perceptual reorganisation. We tested different perceptual reorganisation paradigm designs derived from published fMRI studies, and found substantial design-driven order effects at the single-subject level for all paradigms. For certain designs, these effects artificially amplified neural indices of perceptual reorganisation at both the single-subject and group levels, emulating widespread signatures of perceptual reorganisation across the brain. To disentangle perceptual learning processes from measurement artefacts, we recommend (i) selecting designs that minimise the effect of stimulus order confounds on contrasts of interest, (ii) correcting for these confounds, and (iii) confirming results are perceptually driven via negative controls, e.g., stimuli or brain areas not expected to produce perceptual effects. Our work demonstrates how current understanding of perceptual learning mechanisms based on multivariate neuroimaging approaches could be influenced by non-obvious design confounds that misdirect interpretations towards distributed neural processing, and offers practical solutions to address this.

• Targeting intracellular tau with a gene-encoded single-chain antibody promotes neuronal homeostasis and ameliorates tau pathology
  Authors: Caruso, A. C.; Kavanagh, T.; van Waardenberg, A. J.; Graham, M. E.; Götz, J.; Drummond, E.; Nisbet, R. M.
  Published: 2025-08-15 (new results)
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  The intraneuronal aggregation of tau is a key driver of pathogenesis in tauopathies such as Alzheimer's disease. Passive immunotherapy is a promising strategy for targeting tau, with several tau-specific antibodies having demonstrated the ability to reduce tau pathology and improve behavioural deficits in tau transgenic mouse models. Despite preclinical promise, however, conventional antibodies have limited access to the cell cytoplasm where tau pathology itself originates and accumulates to cause downstream neuronal dysfunction. As such, conventional antibodies are typically limited to targeting extracellular tau, failing to address the primary site of tau pathogenesis. This challenge can be overcome by intracellular antibodies or intrabodies, small antibody fragments that can be expressed within cells to target intracellular antigens like tau. Here, we have generated a single-chain variable fragment (scFv) derived from the N-terminal tau-specific antibody, RNJ1, and investigated its potential as an intrabody to reduce tau pathology and restore neuronal function in a tau transgenic mouse model. The RNJ1 intrabody successfully engaged intracellular tau and reduced total tau and phosphorylated tau inclusions in brains of tau transgenic mice. Furthermore, treatment with the RNJ1 intrabody in female tau transgenic mice induced restoration of various protein pathways important for cellular homeostasis, thus promoting the restoration of neuronal function. Our findings underscore the therapeutic utility of targeting intracellular tau in disease, providing novel insights into the potential mechanisms by which intrabodies ameliorate tau pathology.

• Microcephaly-like phenotype triggered by novel reassortant and prototypic Oropouche Virus strains in brain organoids
  Authors: Da Silva, G. B. L.; Rocha, V. G.; Monteiro, F. L. L.; Guimaraes, B. L. d. M. L.; Silva, L. G.; Delou, J. M. d. A.; Mourao, P. J. P.; Gomes, I. C. d. S.; Barone, E. O.; Andrade, M. V.; Lima, R. F.; Mamede, I.; Reis, C. R.; Marim, F. M.; Geddes, V. E. V.; Aguiar, R. S.; Tanuri, A.; Voloch, C. M.; Rehen, S. K.
  Published: 2025-08-15 (new results)
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  Oropouche virus (OROV) is an emerging arbovirus currently spreading across South America, with increasing reports of neurological manifestations, severe systemic disease, and congenital abnormalities. Although traditionally associated with mild febrile illness, the recent geographic expansion and surge in OROV outbreaks have prompted attention to its neurotropic potential. Here, we investigated the impact of OROV infection on human neural development using neural stem cells (NSCs) and brain organoids derived from induced pluripotent stem cells. Recent OROV isolates exhibiting genomic reassortment and associated with increased neurological manifestations were compared with a prototypical strain for the ability to infect NSCs, early-stage organoids, and more mature cortical-like tissues. OROV infected NSCs efficiently, leading to widespread cell death, depletion of proliferative progenitors, and disruption of neuroepithelial organization. Transcriptomic profiling of infected NSCs revealed a robust reduction of antiviral response genes and an enrichment of pathways related to viral replication, apoptosis, and the inhibition of stem cell maintenance and neuronal differentiation. These molecular signatures aligned with the phenotypic collapse of progenitor pools and cortical structure observed in organoids. OROV antigens were detected in both astrocytes and neurons, with associated structural degeneration. Although a substantial overlap in differentially expressed genes was observed between the two viral strains, some strain-specific transcriptional responses were detected. However, these modest differences did not translate into distinct cytopathogenic effects between the two viral strains. These phenotypes, including the reduced growth of infected organoids, resemble those previously described with Zika virus in the same cellular models, supporting the hypothesis that OROV may impair brain development. Together, these results reveal a previously unrecognized neuroteratogenic potential of OROV strains and provide mechanistic insight into the potential of OROV to induce microcephaly-like phenotypes, highlighting its relevance as a significant threat to maternal-fetal health.

• GIP receptor agonism suppresses inflammation-induced aversion and food intake via distinct circuits
  Authors: Province, H. S.; Hayes, N. W.; Leong, N. A.; Lorch, C. M.; Pekerman, A.; Xia, J. L.; Beutler, L. R.
  Published: 2025-08-15 (new results)
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  Glucose-dependent insulinotropic polypeptide (GIP) is a gut-derived incretin hormone, and pharmacologic modulation of central GIP receptors (GIPR) improves energy homeostasis. Recent reports have demonstrated that GIPR agonism is also anti-aversive. However, the mechanisms by which GIPR signaling impact food intake and aversion are incompletely understood. Here, we show that GIPR agonism abrogatesthe aversive and enhances the anorexigenic effects of the pro-inflammatory cytokine interleukin-1{beta} (IL-1{beta}). Aversion-encoding parabrachial calcitonin-gene related peptide (CGRP) neurons were required for IL-1{beta}-induced conditioned taste avoidance (CTA) but not anorexia. Moreover, systemic IL-1{beta} increased in vivo CGRP neural activity, and this was significantly attenuated by co-administration of a GIPR agonist. By contrast, GIPR in the dorsal vagal complex were required for the acute anorectic effect of GIPR agonism but not its anti-aversive effect. Taken together, our data suggest that GIPR agonism reduces food intake and prevents aversion via distinct circuits, and that GIPR agonism may represent an effective approach to alleviate inflammation-induced aversion.

• Circular continuum of alpha motoneuron types
  Authors: Garrett, T. L.; Wintermute, L.; Armitage, M.; Ward, S.; Abdul Halim, I.; Mousa, M. H.; Gerber, K.; Elbasiouny, S. M.
  Published: 2025-08-15 (new results)
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  Alpha-motoneurons ( - MNs) are traditionally classified into slow (S), fast fatigue-resistant (FR), and fast-fatigable (FF), which exist along a continuum of properties between slow and fast, enabling the generation of graded force and seamless movement. Using combinations of markers, we developed novel immunohistochemistry protocols that enabled co-labeling of six major and transitional - MN types throughout the mouse lumbar spinal cord with unprecedented detail. Intriguingly, our protocols labeled for the first time: - MNs of the fast fatigue intermediate (FI) type; a previously undescribed transitional - MN subtype (FR/FI); and a novel subtype of - MNs exhibiting hybrid characteristics of both S and FF types -- termed S/FF -- which resist ALS degeneration. Electrophysiological recordings confirmed FR/FI and S/FF subtypes, both exhibiting mixed traits. The discovery of S/FF subtype reveals that - MNs exist along a circular continuum between slow and fast types, challenging the traditional linear model and reshaping our understanding of their role in motor control.

• Longitudinal three-photon imaging for tracking amyloid plaques and vascular degeneration in a mouse model of Alzheimer's disease
  Authors: Stas, E.; Yang, M.; Go, M. A.; Schultz, S. R.
  Published: 2025-08-15 (new results)
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  Significance: Vascular abnormalities may contribute to amyloid-beta accumulation and neurotoxicity in Alzheimer's disease (AD). The ability to monitor vascular degeneration as AD progresses is essential. Three-photon fluorescence microscopy (3PM) enables high-resolution deep tissue imaging with minimal invasiveness and photodamage. Aim: This study established a longitudinal 3P imaging pipeline to quantify vascular degeneration and amyloid plaque formation in the APP NL-G-F mouse model. Approach: A cranial window allowed repeated 3P imaging at four-week intervals beginning at five weeks after surgery. Vessels labelled with Texas-Red were segmented using DeepVess, while plaques labelled with methoxy-XO4 were segmented using custom scripts. Quantitative analyses assessed vascular parameters (diameter, density, tortuosity, length, inter-vessel distance) and plaque metrics (radius, nearest plaque-to-vessel distance). Results: We imaged the same field over 4 weeks quantifying a decrease in vasculature and increase in amyloid plaque formation with age. Significant decreases in vessel diameter, increases in inter-vessel distance, and alterations in vessel length were observed. Changes in vessel tortuosity, plaque radius, and plaque proximity to vessels were not significant. Conclusions: This pipeline tracks vascular remodeling and amyloid pathology in deep cortical structures. It offers a tool for studying the interplay between vascular and amyloid pathologies in AD, supporting future research into disease mechanisms and therapeutic strategies.

• Semaglutide drives weight loss through cAMP-dependent mechanisms in GLP1R-expressing hindbrain neurons
  Authors: Gao, C.; Geneve, I. C.; Li, C.; McElhern, K.; Reitman, M.; Lutas, A.; Krashes, M. J.
  Published: 2025-08-15 (new results)
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  Glucagon-like peptide 1 receptor (GLP1R) agonists like semaglutide drive weight loss through the brain, but insights into their intracellular signaling mechanisms are lacking. Although canonically GLP1Rs signal through the stimulatory alpha Gs protein, we find that semaglutide utilizes both Gs- and Gq-signaling pathways in GLP1Rs in the area postrema (AP)--the primary site of semaglutide action in the brain--to differentially regulate neuronal activation across distinct neuronal clusters. Semaglutide also drives graded increases of the essential secondary messenger cyclic adenosine monophosphate (cAMP) in Glp1r-expressing AP neurons (APGlp1r) through Gs-dependent and -independent manners. Inhibition of the cAMP-degradation enzyme phosphodiesterase 4 (PDE4) can enhance and sustain these cAMP responses, whereas disruption of Gs or cAMP signaling in APGlp1r neurons abolishes semaglutide-induced weight loss and downstream brain-wide activation. Our systematic characterization of semaglutide's signaling mechanisms in the brain provides avenues for improving the performance of obesity therapeutics.

• Extreme Small-World, Modular, and Rich-Club Topology of Single-Neuron Networks in Mouse Primary Visual Cortex
  Authors: Tu, S.; Li, X.; Jiang, L.; Xiao, G.; Liu, J.
  Published: 2025-08-15 (new results)
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  Understanding whether the canonical topologies of macroscale connectomes, such as small-world architecture, hub dominance, rich-club cores, and modularity, extend to local cortical microcircuitry has remained challenging due to limitations in simultaneously recording large neuronal populations in vivo. Here, using ultra-large-scale, high-resolution calcium imaging, we tracked spontaneous activity from approximately 2,000 neurons across the mouse primary visual cortex (V1). Across multiple mice and correlation thresholds, V1 neuronal networks exhibited hallmark characteristics of efficient brain organization, but in a markedly intensified form compared to macroscopic brain networks. Local clustering coefficients remained an order of magnitude above random levels, while characteristic path lengths approached those observed in random networks, yielding an exceptionally high small-world index that substantially exceeded typical values previously reported at macroscopic scales. Degree distributions followed a power-law, identifying highly connected hub neurons whose interconnections formed a robust rich-club integrative core. Community detection analyses showed robust modularity upon pruning weak connections, indicating functionally specialized neuronal clusters interconnected predominantly through hubs. These findings provide one of the first direct in vivo evidence that single cortical microcircuits not only recapitulate but intensify network topologies observed at macroscopic scale, implying evolutionarily conserved design principles underlying brain organization from neurons to systems.

• PHA-4/FoxA controls the function of pharyngeal and extrapharyngeal enteric neurons of C. elegans
  Authors: Walker, Z.; Cao, W. X.; Leyva-Diaz, E.; Rahman, M.; Sural, S.; Attner, M. A.; Hobert, O.
  Published: 2025-08-15 (new results)
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  FoxA transcription factors pattern gut tissue across animal phylogeny. Beyond their early patterning function, little is known about whether they control the terminal differentiation and/or function of the fully mature enteric nervous system, the intrinsic nervous system of the gut. We show here that the expression and function of the sole C. elegans FoxA homolog, PHA-4, reaches beyond its previously described pioneer factor roles in patterning the foregut. Through the engineering of neuron-specific cis-regulatory alleles, Cre-mediated cell-specific knockouts and degron-mediated, temporally controlled PHA-4/FoxA removal in postmitotic neurons, we found that PHA-4/FoxA is required not only to initiate the terminal differentiation program of foregut-associated enteric neurons, but also to maintain their functional properties throughout the life of the animal. Moreover, we discovered novel sites of expression of PHA-4/FoxA in extrapharyngeal enteric neurons that innervate the hindgut (AVL and DVB), a GABAergic interneuron that controls foregut function during sleep (RIS), and a peptidergic neuron, PVT, which we implicate here in controlling defecation behavior. We show that while PHA-4/FoxA is not required for the developmental specification of AVL, DVB, RIS, and PVT, it is required to enable these neurons to control enteric functions. Taken together, pha-4 is the only transcription factor known to date that is expressed in and required for the proper function of all distinct types of enteric neurons in a nervous system.

• Indirect pathway neurons in the tail of the striatum regulate inhibitory control over sensory driven behavior
  Authors: Ferrigno, S. M.; Zhang, N.; Iliakis, E.; Pandey, S.; Galanaugh, J.; Fuccillo, M. V.
  Published: 2025-08-15 (new results)
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  Inhibitory control, or the ability to withhold action in certain situations, is behaviorally essential. Disrupted inhibitory control is linked to various neuropsychiatric symptoms, making it critical to understand the underlying neural basis. We examined how the tail of the striatum (TS), a major basal ganglia sensory hub, regulates actions to sensory stimuli. Mice performed an auditory Go/NoGo task where we recorded cell-specific activity of TS neurons. Both major striatal types were active during target sounds, but non-target sounds preferentially engaged indirect pathway neurons. Temporarily silencing this activity increased errors to non-target stimuli, indicating a role in suppressing inappropriate action. In mice deficient for the synaptic adhesion molecule Neurexin1, a gene linked to autism spectrum disorder and ADHD, TS indirect pathway recruitment was reduced, and these mice demonstrated auditory-specific inhibitory control deficits. Altogether, these findings highlight a subcortical target to potentially improve attentional and behavioral regulation in neurodevelopmental disorders.

• Neural correlates of motor sequence learning and enhanced offline consolidation in 7- to 11-year-old children
  Authors: Van Roy, A.; Temudo, A.; Koppelmans, V.; Hödlmoser, K.; Albouy, G.; King, B. R.
  Published: 2025-08-15 (new results)
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  Intro: Many daily activities involve series of interrelated movements and thus the capacity to learn new motor sequences is vital for everyday functioning. Although learning new skills is especially prominent throughout childhood, remarkably few studies have examined the neural underpinnings of motor sequence learning (MSL) in children. Methods: Twenty-two children (7-11 years) and 23 adults (18-30 years) underwent functional magnetic resonance imaging while completing two sessions of a MSL task, separated by a 5-hour offline period of wakefulness. Results: Analyses of the behavioral data revealed comparable initial learning in children and adults. However, and consistent with previous research, children exhibited superior motor memory consolidation over the 5-hour offline epoch. Neuroimaging analyses revealed that children exhibited smaller modulations in brain activity between task and rest epochs in a widespread network of areas, including the sensorimotor cortex, supplementary motor area, cerebellum, putamen and regions associated with the default mode network. Similar levels of activity during task and rest epochs in the hippocampus, dorsolateral prefrontal cortex and somatosensory cortex were associated with better motor memory consolidation in children. Conclusion: Results potentially suggest that the continued engagement of the developing brain during interleaved rest contributes to the childhood advantage in motor memory consolidation.

• E/I ratio and net E+I strength are differentially affected across brain disorders
  Authors: Avramiea, A.-E.; Diachenko, M.; Westbrook, A.; Hardstone, R.; Mansvelder, H. D.; Bruining, H.; Linkenkaer-Hansen, K.
  Published: 2025-08-15 (new results)
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  Neuronal oscillations wax and wane near criticality, switching between high- and low-power states. However, the link between this bistability and excitation-inhibition balance is not well understood. Using a computational model, we demonstrate that bistability is influenced by two key factors: the excitatory-inhibitory (E/I) ratio and the combined strength of excitatory and inhibitory activity (E+I). We developed algorithms to infer both metrics from electrophysiological data and validated them in vivo. In intracranial recordings from epilepsy patients, both E/I and E+I increased during seizures, while interictally, E+I remained elevated in seizure zones as E/I decreased, consistent with compensatory inhibition. Extending the framework to scalp EEG from eight disorders, we found that Alzheimer's disease is better classified by E/I changes, whereas autism spectrum disorder and ADHD are distinguished by E+I alterations. Our findings highlight the importance of bistability in understanding EI regulation and offer handles for diagnostic and treatment decision support.

• O-GlcNAcase promotes dendritic spine morphogenesis while downregulating their GluA2-containing AMPA receptors
  Authors: Han, L.; Galizia, S.; Pan, J.; Lagerlöf, O.
  Published: 2025-08-15 (new results)
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  Dendritic spines are essential for synaptic transmission, neural circuit organization, and cognitive function. Their morphology and density influence synaptic plasticity, learning, and memory. Many proteins in dendritic spines are modified with O-GlcNAc, a monosaccharide that can be attached and removed from serines and threonines. O-GlcNAc has been implicated in multiple brain disorders, yet the role of O-GlcNAcase (OGA), the enzyme that removes O-GlcNAc modification from proteins, in dendritic spine regulation remains unclear. This study examines the role of OGA in spine and synapse morphogenesis. Immunohistochemical and biochemical analyses reveal OGA present in dendritic spines. Functional assays show that OGA promotes spine maturation, increases spine density, and alters synapse size. Additionally, OGA modulates the -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), down-regulating GluA2-containing receptors in developing and mature neurons. These findings highlight OGA as a key regulator of excitatory synaptic remodeling and a therapeutic target for synapse-related pathologies such as Alzheimer's disease and autism.

• Mapping social relevance in affective scenes: A large-scale multidimensional rating study
  Authors: Mitschke, V.; Grassi, F.; Doganer, A.; Schacht, A.
  Published: 2025-08-16 (new results)
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  Understanding how individuals evaluate social content in affective scenes is crucial for research in emotion, social cognition, and decision-making. However, standardized image databases often lack fine-grained ratings of social dimensions beyond basic emotional content. We present a normative dataset of 296 affective scenes rated by 424 adult participants across six social-affective dimensions: social relevance, emotion sharing, action sharing, interpersonal equality, scene pleasantness, and participatory arousal. Each image was independently coded for objective features such as number of people, face visibility, and gaze direction. All rating dimensions showed excellent interrater reliability. Pleasantness ratings demonstrated strong convergent validity with established valence norms from the International Affective Picture System (IAPS), while arousal ratings differentiated between experienced and participatory arousal, suggesting that the latter captures a distinct affective component. Correlation analyses revealed that social relevance was strongly predicted by scene pleasantness and a composite "engagement" factor combining emotion sharing, action sharing, and equality. Notably, the association between pleasantness and social relevance was especially pronounced in scenes depicting single individuals. Linear mixed models further indicated that extraversion modestly amplified the relationship between engagement and social relevance, while other personality traits and empathy did not significantly affect ratings. This open-access dataset provides a reliable, multidimensional tool for selecting affective scenes based on both emotional and social-interpersonal features. It supports improved stimulus control and design in a wide range of behavioral and neurocognitive research. By systematically mapping social meaning in static affective scenes, our study advances existing methodological resources and offers empirical insight into the structure of social-affective appraisals. All image codes, mean ratings, and analysis scripts are publicly available via the Open Science Framework.

• Comparison of the effects of lithium orotate and lithium carbonate on locomotion and memory in a Drosophila melanogaster model of Alzheimer's disease
  Authors: Alla, I. R.; Chung, R.
  Published: 2025-08-16 (new results)
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  Alzheimer's disease (AD) is a terminal neurodegenerative disease characterized by cognitive decline and memory loss resulting from the buildup of amyloid-beta plaques and tau protein tangles. Lithium salts, particularly lithium carbonate (Li2CO3), inhibit the enzyme Glycogen Synthase Kinase-3, which is upregulated in AD, reducing tau and amyloid-beta accumulation, inflammation, and oxidative stress. However, Li2CO3 has declined in use due to long-term neurotoxicity. Lithium orotate (LiOr), an alternative lithium salt, has greater bioavailability--delivering more ions to the brain--but was discontinued in the 1970s due to toxicity concerns at equivalent doses. It was hypothesized that LiOr would be more effective than Li2CO3 at lower doses (5 mM) due to higher lithium ion transfer, while Li2CO3 may outperform LiOr at higher doses (10 mM) due to LiOr's toxicity. This study compares LiOr and Li2CO3 in treating locomotion and memory in a Drosophila melanogaster model produced by crossing UAS amyloid-beta 42 and Act5c GAL4 flies via the GAL4/UAS system. Once aged to 25 days, flies were assessed for locomotion using the negative geotaxis assay and for short-term memory using the aversive phototaxic suppression (APS) assay. These behavioral assays aim to quantify changes in cognitive and motor function resulting from treatment. Results suggest Li2CO3 improves cognitive and motor performance in healthy flies, but LiOr was not found to be significantly more effective. This study offered a novel comparison of two lithium compounds in an Alzheimer's model and may guide research into safer, more effective AD and lithium treatments.

• Blunted response of caudal locus coeruleus to arousing stimuli in Parkinson's Disease
  Authors: Lund, A. E.; Madelung, C. F.; Madsen, K. H.; Thomsen, B. L. C.; Lokkegaard, A.; Meder, D.; Siebner, H. R.
  Published: 2025-08-16 (new results)
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  Parkinson's disease (PD) causes progressive degeneration of noradrenergic neurons in the locus coeruleus (LC), contributing to non-motor symptoms. Using neuromelanin-sensitive ultra-high field (7T) MRI, we previously identified a reduction in neuromelanin signal in the caudal LC, indicating a rostro-caudal gradient of noradrenergic cell loss. Caudal LC degeneration was associated with greater severity of non-motor symptoms such as orthostatic hypotension and apathy. In the current study, we expanded the PD cohort to further validate the structure-symptom relationships within the LC and investigate how degeneration along the rostro-caudal LC axis affects arousal-related functional responsivity. To this end, 71 people with PD in the ON-medication state and 40 age- and sex-matched healthy controls underwent clinical assessments and 7T magnetization transfer-weighted (MTw) MRI to quantify structural changes along the rostro-caudal LC axis. A subgroup of 30 people with PD and 27 controls underwent 7T fMRI to assess LC responsivity to arousing auditory and visual stimuli in two fMRI sessions on separate days. Healthy controls were scanned twice without medication, while people with PD were studied on and off dopaminergic medication in counterbalanced order. In the PD group, MTw MRI confirmed a significant reduction of the regional neuromelanin signal in caudal LC relative to the control group (P = 0.0099). This structural disintegration correlated with orthostatic hypotension (P = 0.0087) and cognitive impairment (P = 0.036), corroborating its clinical relevance. Functional MRI revealed reduced activation of the caudal LC to arousing visual and auditory stimuli in people with PD relative to controls (P = 0.012). This difference reached statistical significance only in the ON-medication state, with a similar but non-significant trend in the OFF-medication state (P = 0.10). In an exploratory analysis of a smaller sub-sample, structural and functional caudal LC signals were significantly correlated in both people with PD and healthy controls (P = 0.0069). Together, the findings provide evidence for a rostro-caudal gradient of LC pathology in PD at both structural and functional levels. While structural MRI provides fine-grained insights into spatial gradients of disease-related pathology, functional MRI captures impaired functional responsivity of caudal LC. The presence of arousal-induced hypoactivation of caudal LC in the ON-medication state indicates that LC dysfunction extends beyond dopamine deficits in PD, highlighting complex interactions between dopaminergic and noradrenergic systems.

• Deep Brain Stimulation rescues the homeostasis disruption of circulating D- and L-amino acids level in men with Parkinson's Disease.
  Authors: Nuzzo, T.; Carrillo, F.; Serra, M.; Gentile, C.; Di Maio, A.; Pizzella, A.; Pietracupa, S.; Modugno, N.; Errico, F.; Esposito, T.; Usiello, A.
  Published: 2025-08-16 (new results)
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  In a comprehensive study of genetically and clinically characterized male and female Parkinson's disease (PD) patients and healthy controls, we recently reported a marked downregulation in blood D- and L-amino acids level that regulate glutamatergic NMDAR function, particularly in idiopathic male cases. However, the extent to which disease progression and antiparkinsonian therapies contribute to this systemic dysregulation remains unclear. To address these issues, in the present study we measured by High Performance Liquid Chromatography the concentrations of glutamatergic system-related D- and L-amino acids and their precursors in the plasma of male and female healthy controls (HC) and PD patients across three distinct clinical stages and treatment conditions: (1) early stage L-DOPA naive patients treated with MAO-B inhibitors; (2) mid-stage patients treated with L-DOPA; and (3) advanced stage patients receiving Deep Brain Stimulation in the subthalamic nucleus (STN-DBS) plus L-DOPA. Our results reveal notable reduction of circulating neuroactive D- and L-amino acids exclusively in male PD patients, while female patients remain unaffected regardless of disease stage or treatment. In male patients, this dysregulation manifests early, with L-DOPA-naive individuals showing decreased plasma levels of L-glutamate and L-aspartate. In mid stage L-DOPA-treated PD patients, amino acid reductions extend to L-alanine, L-serine, L-glutamine, L-asparagine, and L-threonine. Remarkably, in advanced PD patients, with a median disease duration of ~23 years, STN-DBS normalizes the blood concentrations of these amino acids to those observed in HC. In conclusion, our study highlights the potential of circulating D- and L-amino acid dysregulation as an early biomarker of PD and demonstrates that, in contrast to L-DOPA therapy, the STN-DBS confers systemic metabolic benefits even at advanced stages of the disease.

• Age-related cognitive decline in house crickets reveals conserved patterns of sensory and learning deficits across the lifespan
  Authors: Liao, G. Y.; Klug, J.; Ladiges, W. C.
  Published: 2025-08-16 (new results)
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  Cognitive decline with age is characterized by impairments in learning, sensory discrimination, and decision-making. While mammalian models have advanced understanding of the neural substrates of aging, their use in large-scale behavioral studies is limited. Invertebrate models, such as the house cricket (Acheta domesticus), offer short lifespans, high throughput, and conserved neurobiological pathways but remain underexplored in geroscience. We developed a dual behavioral paradigm integrating an olfactory discrimination Y-maze and an escape learning task requiring crickets to override innate odor preferences. Adult, mid-age, and geriatric crickets were tested for sensory discrimination, associative learning, and decision speed. Morphological traits, including antennal and femoral metrics, were quantified to evaluate their influence on cognitive outcomes. Data were analyzed using ANOVA, ANCOVA, and logistic regression models. Aging impaired olfactory preference and learning success, with geriatric crickets showing reduced task acquisition and memory retention. Mid-age individuals exhibited the slowest decision-making, suggesting an early onset shift in behavioral strategy. Morphological traits predicted aspects of sensory performance and physiological resilience, such as reduced weight loss in crickets with larger femoral dimensions but did not explain age-related cognitive deficits. Olfactory decline was particularly pronounced in males, mirroring sex differences observed in human cognitive aging. House crickets exhibit hallmark features of cognitive aging, including sensory decline, learning impairments, and reduced resilience, independent of morphological deterioration. These findings establish the house cricket as a scalable invertebrate model for dissecting conserved mechanisms of neural aging and testing interventions to promote cognitive health.

• An interneuronal CRH and CRHBP circuit stabilizes birdsong performance
  Authors: Colquitt, B. M.; Brainard, M.
  Published: 2025-08-17 (new results)
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  The performance of skilled behaviors requires a balance between consistency and adaptability. Although the neural mechanisms that regulate this balance have been extensively studied at systems and physiological levels, relatively little is known about how the molecular properties of motor circuits influence motor stability versus flexibility. Here, we characterize the region- and cell-type specific expression patterns of neuropeptide systems across the neural circuit that controls the learning and performance of birdsong, a model for skilled behavior. We identify a number of neuropeptide pathways with differential expression between song regions and surrounding areas that are not involved in song production or learning. One of the strongest enriched genes in song regions is corticotropin releasing hormone binding protein (CRHBP), whose product binds corticotropin releasing hormone (CRH), a neuropeptide implicated in neuronal excitability and plasticity. We find that the expression of CRHBP in the song motor pathway decreases upon deafening-induced song destabilization, increases during song acquisition, and increases the more a bird sings. CRH and CRHBP are expressed in distinct interneuronal populations in song motor regions, providing a local neuromodulatory circuit well-positioned to regulate song performance. Consistent with this role, genetic and pharmacological manipulation of the CRH pathway in the song motor pathway resulted in bidirectional modifications of song variability, with elevated CRHBP acting to maintain low variability and elevated CRH acting to increase variability. These data indicate that an interneuronal neuropeptidergic pathway maintains the stability of song, acting as a local mechanism that regulates the balance between motor consistency versus flexibility.

• Synaptic Dysfunction and Compensation After NMDA Receptor Ablation in the Mouse Medial Prefrontal Cortex
  Authors: Dick, R. M.; Cunitz, L. B.; Perez, A. T.; Ahmed, H.; Mitchell, J. S.; Marron Fernandez de Velasco, E.; Grissom, N. M.; Rothwell, P. E.
  Published: 2025-08-17 (new results)
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  The glutamate hypothesis of schizophrenia posits that patients' symptoms arise from abnormal corticolimbic glutamatergic signaling, which is supported by evidence of abnormal expression of N-methyl-D-aspartate receptors (NMDARs) and decreased dendritic spine density in the prefrontal cortex (PFC). Pharmacological blockade of NMDARs in humans and animal models induces psychotomimetic symptoms, cognitive deficits, and decreased neural synchrony, with genetic knockdown of NMDARs providing further evidence of altered spine density and synaptic transmission. However, it is unknown how chronic loss of NMDARs in the PFC during adolescence - a developmental time period associated with significant synaptic pruning and symptom onset in patients - affects spine density and neurotransmission, and whether compensatory mechanisms emerge over time. In this study, we used in vivo genome editing to ablate expression of the Grin1 gene, which encodes the obligate GluN1 subunit of NMDARs, in neurons in the medial PFC of female and male adolescent mice. We assessed synaptic density and function in layer V pyramidal neurons at multiple time points using whole-cell patch-clamp electrophysiology, integrated with confocal imaging of dendritic spine architecture in recorded neurons. NMDAR ablation caused an early decrease in basilar dendritic spine density, followed by a rebound over baseline in spine density and a corresponding increase in AMPAR-mediated synaptic transmission. Inhibitory spontaneous neurotransmission was also increased, suggesting that synaptic compensation maintains an allostatic set point. Our findings demonstrate that NMDAR ablation initially disrupts local PFC networks, followed by recovery via compensatory processes that may be impaired in the disease state.

• Theta-paced stimulation of the thalamic nucleus reuniens en-trains mPFC-HPC oscillations and facilitates the acquisition of extinction memories
  Authors: Tuna, T.; Mourao, F.; Maren, S.
  Published: 2025-08-16 (new results)
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  The nucleus reuniens (RE) is a midline thalamic nucleus interconnecting the medial prefrontal cortex (mPFC) and the hippocampus (HPC), structures known to be involved in aversive memory processes. Recent work indicates that the RE plays a critical role in the acquisition and retrieval of fear extinction memories. Specifically, the RE coordinates theta oscillations between the mPFC and HPC during extinction retrieval. Pharmacological inactivation of the RE impairs both mPFC-HPC theta coherence and the retrieval of extinction memory. Furthermore, theta-paced (8-Hz) optogenetic stimulation of the RE prevents fear renewal after extinction, a common form of fear relapse. However, it remains unclear whether theta-paced RE stimulation can entrain theta oscillations in the mPFC and HPC, and whether such entrainment is sufficient to facilitate the acquisition of extinction memories. To this end, we performed theta-paced optogenetic stimulation of the RE in adult male and female Long-Evans rats during extinction training. Animals underwent auditory fear conditioning, extinction, and an extinction retrieval test, each separated by 24 h. During extinction, 8-Hz stimulation of the RE was delivered concurrently with the presentation of the conditioned stimuli (CS). Theta-paced stimulation of the RE during extinction training significantly decreased freezing behavior compared to the control group. Notably, this reduction in conditioned behavior was also evident during the subsequent stimulation-free retrieval test, suggesting that RE stimulation not only suppresses conditioned fear responses acutely, but also facilitates the acquisition of long-term extinction memories. In a separate set of animals, we observed that theta-paced RE stimulation markedly enhanced both neural activity and entrained oscillations in the mPFC and dHPC at 8-Hz. This work suggests that the RE oscillatory activity is critical for the acquisition of extinction memories through the modulation of hippocampal-prefrontal network dynamics.

• Lead (Pb) exposure alters neural cell fate in the developing human brain
  Authors: Sampson, M. M.; Sonsurkar, S. J.; Nieland, L.; Pan, L.; Kan, R. L.; Azizad, D. J.; Li, X.; Kebede, N.; Lane, A. R.; DSouza, P. E.; Panuwet, P.; Hill, E. J.; Lanjewar, S. N.; Voss, A. N.; Fawwal, D.; Sing, A.; King, A.; Werner, E.; Spangle, J. M.; Barr, D. B.; Bhaduri, A.; Zhang, Y.; Faundez, V.; Sloan, S. A.
  Published: 2025-08-17 (new results)
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  The heavy metal lead (Pb) is a developmental neurotoxicant associated with cognitive and behavioral deficits, but the cellular mechanisms underlying these impairments remain unclear. Here we show that prenatal Pb exposure biases human radial glia fate, prolonging neurogenesis and suppressing astrogenesis. We used hiPSC-derived cortical organoids, primary human fetal tissue, and in vivo xenografts to demonstrate that Pb exposure alters radial glial differentiation. Pb-exposed organoids contain a higher proportion of neurons and fewer astrocytes. We validated this differentiation bias in primary radial glia from human cortices (GW16-20), observing Pb-associated reductions in astrocyte commitment via genetic lineage tracing. This correlated with increased H3K27me3, a repressive histone modification deposited by the histone methyltransferase complex PRC2, suggesting epigenetic reprogramming as a mechanistic link between Pb and neural cell fate commitment. Our findings indicate that prenatal Pb exposure impacts lineage commitment in the developing brain, which may contribute to cognitive and behavioral impairment.

• Population trajectory analysis reveals divergent state-space geometries across three cortical excitatory cell types
  Authors: Yang, Z.
  Published: 2025-08-17 (new results)
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  Understanding how cortical cell types differ in state-space geometry is central to linking circuit composition with population coding. Population neural trajectories provide a compact representation of high-dimensional activity, capturing both spatial configuration and temporal evolution. In the visual cortex, excitatory subtypes differ in laminar location, projection targets, and synaptic integration, yet most trajectory analyses pool mixed populations, obscuring subtype-specific contributions. Here, we compared trajectory geometries across three genetically defined excitatory subtypes-Cux2-CreERT2, Emx1-IRES-Cre, and Slc17a7-IRES2-Cre-in the mouse primary visual cortex, using large-scale two-photon calcium imaging data from the Allen Brain Observatory and five complementary structural metrics. Across all metrics, Cux2 neurons exhibited consistently smaller trajectory scales than the other two types, with medium effect sizes stable across time windows, stimulus orientations, and leave-one-out validation. Emx1 and Slc17a7 populations showed broadly overlapping profiles, with the largest differences emerging in the mid-response window, corresponding to the sensory integration phase of population dynamics. These findings reveal distinct geometric signatures imposed by excitatory subtypes: Cux2 circuits favor localized, stable representations, whereas Emx1 and Slc17a7 circuits support broader, distributed integration. This provides a framework for linking microcircuit composition to population-level dynamics under identical sensory conditions.

• Theta-rhythmic attentional exploration of space
  Authors: Senoussi, M.; Galas, L.; Busch, N. A.; Dugue, L.
  Published: 2025-08-17 (new results)
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  Attention facilitates stimulus processing by selecting specific locations (spatial attention) or features (feature-based attention). It can be sustained on a given location or feature, or re-oriented between locations or between features, enabling attentional exploration. Sustained attention was associated with alpha (8-12Hz) oscillations. More recently, authors suggested that exploratory attention was instead related to theta (4-7Hz). To date, there is no systematic evaluation of attentional exploration across stimulus dimensions (space, features) in relation to theta oscillations. Using attentional cueing and electroencephalography (EEG) in humans, we assessed exploration of stimulus dimension during the (1) precue-to-stimulus (first attentional orienting) and (2) post-stimulus (during stimulus processing) trial periods. In the precue-to-stimulus period, we classified the cued dimension (attending to a location/feature) from EEG topographies to assess the neural dynamics of sustained and exploratory attentional orienting. Temporal generalization matrices showed oscillatory patterns of classification accuracies across time. When attention was sustained on a cued location but explored the feature dimension as the target feature was unknown, only the alpha frequency was observed. When attention was sustained on a cued feature but explored locations, both alpha and theta frequencies were observed. Focusing on post-stimulus theta oscillations revealed increased theta power in invalid trials (attention reorients from the precued distractor location/feature to the target, i.e., exploration) relative to valid trials in both feature-based and spatial attention conditions. Post-stimulus theta oscillations further predicted behavioral performance. Together, our results show that while alpha oscillations are associated with sustained attention regardless of the attended dimension, theta oscillations are specifically related to spatial exploration.

• Parvalbumin interneurons mediate spontaneous hemodynamic fluctuations
  Authors: Rakymzhan, A.; Fukuda, M.; Vazquez, A. L.
  Published: 2025-08-17 (new results)
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  Resting-state hemodynamic fluctuations are closely linked to gamma-band neural activity, yet the cellular drivers of this neurovascular coupling remain unclear. Given their established contribution in generating gamma oscillations, parvalbumin (PV) interneurons are prime candidates for regulating spontaneous cerebral blood flow (CBF) dynamics. Using chemogenetic tools in awake PV-Cre mice, we modulated PV interneuron activity and measured effects on neural network activity, local field potentials (LFP), and hemodynamics. Two-photon (2P) calcium imaging confirmed effective PV modulation, which affected excitatory neuron activity. PV suppression reduced high-gamma power, increased low-frequency LFP activity, and elevated basal CBF. 2P vessel imaging showed increased basal arterial diameter and significantly greater diameter fluctuation power in deeper cortical layers enriched with PV cells, but not in superficial layers. PV suppression also significantly weakened the correlation between gamma LFP power and CBF. Despite increased apparent neuronal synchrony during PV suppression, its relationship to arterial dynamics remained stable, possibly due to compensatory regulation by subsets of PV-positive and PV-negative cells. These findings provide causal evidence that PV interneuron contribute to spontaneous neurovascular dynamics and mediate the link between gamma oscillations and resting-state hemodynamic signals, revealing their significant role in maintaining functional connectivity and vascular regulation during non-task-engaged brain states.

• The inner ear's active process contributes to selective attention to speech in noise
  Authors: Steinebach, J.; Reichenbach, T.
  Published: 2025-08-17 (new results)
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  Humans are remarkably skilled at understanding speech in noisy environments. While segregation of different audio streams is mostly accomplished in the auditory cortex, it remains unclear whether the inner ear, where the sound detection occurs, already contributes to selective attention. In particular, the cochlea possesses an active process enabling it to amplify sound in a frequency-dependent manner. A physiological correlate of the active process are distortion-product otoacoustic emissions (DPOAEs) that can be measured non-invasively from the ear canal. Here we employed speech-DPOAEs that are connected to the spectral structure of voiced speech to show that these emissions are modulated by selective attention to one of two competing voices. We found that speech-DPOAEs evoked by the resolved harmonics of a voice were significantly reduced when that voice was attended as compared to when it was ignored. No such effect was observed for the unresolved harmonics of the target voice when the competing voice's harmonics in that range were unresolved as well, indicating that attentional modulation is specific to those components of voiced speech that are spectrally resolved. Our findings demonstrate for the first time that selective attention to speech in noise is already shaped by the inner ear's active process.

- Cell

• Arrestin-biased allosteric modulator of neurotensin receptor 1 alleviates acute and chronic pain
  Authors: Guo R.; Chen O.; Zhou Y.; Bang S.; Chandra S.; Li Y.; Chen G.; Xie R.; He W.; Xu J.; Zhou R.; Song S.; Person K.; Moore M.; Alwin A.; Spasojevic I.; Jackson M.; Olson S.; Caron M.; Slosky L.; Wetsel W.; Barak L.; Ji R.
  Published: 2025/8 (journal-article)
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• A mechano-resistance mechanism in skin adapts to terrestrial locomotion
  Authors: Di R.; Du Q.; Xie Y.; Lu Y.; Gao W.; Zhang L.; Qi X.; Fan Y.; Li J.; Wang F.; Chen S.; Chen T.
  Published: 2025/8 (journal-article)
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• Small RNAs are modified with N-glycans and displayed on the surface of living cells
  Authors: Flynn R.; Pedram K.; Malaker S.; Batista P.; Smith B.; Johnson A.; George B.; Majzoub K.; Villalta P.; Carette J.; Bertozzi C.
  Published: 2025/8 (journal-article)
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• The genetic history of the Southern Caucasus from the Bronze Age to the Early Middle Ages: 5,000 years of genetic continuity despite high mobility
  Authors: Skourtanioti E.; Jia X.; Tavartkiladze N.; Bitadze L.; Shengelia R.; Tushabramishvili N.; Aslanishvili V.; Gasparyan B.; Kandel A.; Naumann D.; Neumann G.; Bianco R.; Mötsch A.; Prüfer K.; Lamnidis T.; Traverso L.; Ghalichi A.; Ellingvåg S.; Stockhammer P.; Krause J.; Ringbauer H.
  Published: 2025/8 (journal-article)
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• The human proteome with direct physical access to DNA
  Authors: Trendel J.; Trendel S.; Sha S.; Greulich F.; Goll S.; Wudy S.; Kleigrewe K.; Kubicek S.; Uhlenhaut N.; Kuster B.
  Published: 2025/8 (journal-article)
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• Systematic profiling reveals betaine as an exercise mimetic for geroprotection
  Authors: Geng L.; Ping J.; Wu R.; Yan H.; Zhang H.; Zhuang Y.; Ning T.; Wang J.; Liang C.; Zhang J.; Chu Q.; Zhang J.; Wen Y.; Jing Y.; Sun S.; Qiao Q.; Zhao Q.; Ji Q.; Ma S.; Cai Y.; Zheng Y.; Zou Z.; Diao Z.; Li M.; Zhang H.
  Published: 2025/8 (journal-article)
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• In vivo prime editing rescues alternating hemiplegia of childhood in mice
  Authors: Sousa A.; Terrey M.; Sakai H.; Simmons C.; Arystarkhova E.; Morsci N.; Anderson L.; Xie J.; Suri-Payer F.; Laux L.; Roze E.; Forlani S.; Gao G.; Frost S.; Frost N.; Sweadner K.; George A.; Lutz C.; Liu D.
  Published: 2025/8 (journal-article)
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• Bronze Age Yersinia pestis genome from sheep sheds light on hosts and evolution of a prehistoric plague lineage
  Authors: Light-Maka I.; Hermes T.; Bianco R.; Semerau L.; Kosintsev P.; Alekseeva V.; Kim D.; Hanage W.; Herbig A.; Jeong C.; Warinner C.; Key F.
  Published: 2025/8 (journal-article)
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• Design of soluble Notch agonists that drive T cell development and boost immunity
  Authors: Mout R.; Jing R.; Tanaka-Yano M.; Egan E.; Eisenach H.; Kononov M.; Windisch R.; Najia M.; Tompkins A.; Hensch L.; Bingham T.; Gunage R.; Zhao Y.; Edman N.; Li C.; Wang D.; Schlaeger T.; Zon L.; North T.; Lendahl U.; Rowe R.; Baker D.; Blacklow S.; Daley G.
  Published: 2025/8 (journal-article)
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• Microbiota-derived inosine programs protective CD8+ T cell responses against influenza in newborns
  Authors: Stevens J.; Culberson E.; Kinder J.; Ramiriqui A.; Gray J.; Bonfield M.; Shao T.; Al Gharaibeh F.; Peterson L.; Steinmeyer S.; Eshleman E.; Negi S.; Zacharias W.; Pryhuber G.; Paul O.; Sengupta S.; Alenghat T.; Way S.; Deshmukh H.
  Published: 2025/8 (journal-article)
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• Principles of cotranslational mitochondrial protein import
  Authors: Zhu Z.; Mallik S.; Stevens T.; Huang R.; Levy E.; Shan S.
  Published: 2025/8 (journal-article)
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• A complete model of mouse embryogenesis through organogenesis enabled by chemically induced embryo founder cells
  Authors: Li H.; Guan W.; Huang J.; Shen P.; Wu J.; Luo H.; Yang Y.; Ning S.; Chang L.; Zhao H.; Chen C.; Gao Y.; Chen Y.; Yang X.; Costa Y.; Cai C.; Pei D.; Peng G.; Wu G.; Chen J.; Zhang J.; Jing N.; Silva J.
  Published: 2025/8 (journal-article)
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• Engineering crop flower morphology facilitates robotization of cross-pollination and speed breeding
  Authors: Xie Y.; Zhang T.; Yang M.; Lyu H.; Zou Y.; Sun Y.; Xiao J.; Lian W.; Tao J.; Han H.; Xu C.
  Published: 2025/8 (journal-article)
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• Molecular and neural control of social hierarchy by a forebrain-thalamocortical circuit
  Authors: Nelson A.; Kapoor V.; Vaughn E.; Gnanasegaram J.; Rubinstein N.; Talay M.; Murthy V.; Dulac C.
  Published: 2025/8 (journal-article)
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• Co-development of mesoderm and endoderm enables organotypic vascularization in lung and gut organoids
  Authors: Miao Y.; Pek N.; Tan C.; Jiang C.; Yu Z.; Iwasawa K.; Shi M.; Kechele D.; Sundaram N.; Pastrana-Gomez V.; Sinner D.; Liu X.; Lin K.; Na C.; Kishimoto K.; Yang M.; Maharjan S.; Tchieu J.; Whitsett J.; Zhang Y.; McCracken K.; Rottier R.; Kotton D.; Helmrath M.; Wells J.
  Published: 2025/8 (journal-article)
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• Composite transposons with bivalent histone marks function as RNA-dependent enhancers in cell fate regulation
  Authors: Zhou Z.; Zhu S.; Hong Y.; Jin G.; Ma R.; Lin F.; Zhang Y.; Lee H.; Liu N.
  Published: 2025/8 (journal-article)
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• Iterative recombinase technologies for efficient and precise genome engineering across kilobase to megabase scales
  Authors: Sun C.; Li H.; Liu Y.; Li Y.; Gao R.; Shi X.; Fei H.; Liu J.; Liang R.; Gao C.
  Published: 2025/8 (journal-article)
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• VIVIT: Resolving trans-scale volumetric biological architectures via ionic glassy tissue
  Authors: Gao Y.; Xin F.; Wang T.; Shao C.; Hu Y.; Chen Z.; Wang Y.; Xie F.; Li T.; Li S.; Ren L.; Li C.; Yang X.; Yang Z.; Li M.; Tan K.; Bai T.; Wei C.; Peng H.; Li K.; Jia Y.; Yuan K.
  Published: 2025/8 (journal-article)
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• Identification and application of cell-type-specific enhancers for the macaque brain
  Authors: Li L.; Huang Y.; Lu D.; Fu J.; Wu L.; Chen Z.; Liao H.; Zhang J.; Li L.; Gu T.; He F.; Liu H.; Leng X.; Tang J.; Yan J.; Liu C.; Li C.; Huang H.; Wang L.; Liu L.; Li C.; Poo M.; Li H.; Sun Y.; Liu Z.
  Published: 2025/8 (journal-article)
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• Inheritance of acquired adaptive cold tolerance in rice through DNA methylation
  Authors: Song X.; Tang S.; Liu H.; Meng Y.; Luo H.; Wang B.; Hou X.; Yan B.; Yang C.; Guo Z.; Wang L.; Jiang S.; Deng X.; Cao X.
  Published: 2025/8 (journal-article)
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• Single-cell multiregion epigenomic rewiring in Alzheimer’s disease progression and cognitive resilience
  Authors: Liu Z.; Zhang S.; James B.; Galani K.; Mangan R.; Fass S.; Liang C.; Wagle M.; Boix C.; Tanigawa Y.; Yun S.; Sung Y.; Xiong X.; Sun N.; Hou L.; Wohlwend M.; Qiu M.; Han X.; Xiong L.; Preka E.; Huang L.; Li W.; Ho L.; Grayson A.; Mantero J.
  Published: 2025/8 (journal-article)
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• Identification of gut microbial bile acid metabolic enzymes via an AI-assisted pipeline
  Authors: Ding Y.; Luo X.; Guo J.; Xing B.; Lin H.; Ma H.; Wang Y.; Li M.; Ye C.; Yan S.; Lin K.; Zhang J.; Zhuo Y.; Nie Q.; Yang D.; Zhang Z.; Pang Y.; Wang K.; Ma M.; Lai L.; Jiang C.
  Published: 2025/8 (journal-article)
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• Response to: The mechanism for GTP-mediated RNA capping by the SARS-CoV-2 NiRAN domain remains unresolved
  Authors: Huang Y.; Tan L.; Liu Y.; Zhao H.; Wang J.; Ge J.; Ye S.; Liu Z.; Lan W.; Huang B.; Zhang H.; Gao Y.; Yan L.; Rao Z.; Lou Z.
  Published: 2025/8 (journal-article)
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• Imaging high-frequency voltage dynamics in multiple neuron classes of behaving mammals
  Authors: Haziza S.; Chrapkiewicz R.; Zhang Y.; Kruzhilin V.; Li J.; Li J.; Delamare G.; Swanson R.; Buzsáki G.; Kannan M.; Vasan G.; Lin M.; Zeng H.; Daigle T.; Schnitzer M.
  Published: 2025/8 (journal-article)
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• Highly conserved Betacoronavirus sequences are broadly recognized by human T cells
  Authors: Pereira Neto T.; Zmasek C.; Avalos L.; Sidney J.; Trevizani R.; Phillips E.; Mallal S.; Frazier A.; Tan G.; Scheuermann R.; Sette A.; Grifoni A.
  Published: 2025/8 (journal-article)
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• Cross-organ metabolite production and consumption in healthy and atherogenic conditions
  Authors: Bae H.; Jung S.; Le J.; Tamburini I.; Kim J.; Wang E.; Song W.; Choi W.; Jang K.; Kang T.; Lopez M.; Ramirez C.; Mohanty I.; Kelly M.; Kim J.; Kim R.; Park S.; Baek J.; Mendez B.; Petrus P.; de Aguiar Vallim T.; Nicholas D.; Smith Q.; Lee G.; Seldin M.
  Published: 2025/8 (journal-article)
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• Trichophyton concentricum fungal infections and skin microbiomes of Indigenous Peninsular Malaysians
  Authors: Er Y.; Lee S.; Aneke C.; Conlan S.; Muslim A.; Deming C.; Che Y.; Yap N.; Tee M.; Abdull-Majid N.; Shahrizal S.; Leong K.; Han J.; Shen Z.; Than L.; Park M.; Mohd Sayed I.; Seyedmousavi A.; Kong H.; Loke P.; Segre J.; Lim Y.
  Published: 2025/8 (journal-article)
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• Vagal blockade of the brain-liver axis deters cancer-associated cachexia
  Authors: Garrett A.; Darzi N.; Deshmukh A.; Rosenfeld N.; Goldman O.; Adler L.; Bab-Dinitz E.; Singer O.; Hassani Najafabadi A.; Wong C.; Bose S.; Randon P.; Bustamante F.; Larios R.; Brandis A.; Mehlman T.; Smaglo B.; Chang P.; Oliva J.; Haymaker C.; Nagawekar L.; Wu S.; Huang Y.; Shen A.; Vora A.
  Published: 2025/8 (journal-article)
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• The mechanism for GTP-mediated RNA capping by the SARS-CoV-2 NiRAN domain remains unresolved
  Authors: Small G.; Darst S.; Campbell E.
  Published: 2025/8 (journal-article)
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• Arrestins and opioid-independent analgesia
  Authors: Didenko O.; Wood J.
  Published: 2025/8 (journal-article)
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• iPSC-derived CAR-NK cells: Off-the-shelf cellular therapy for systemic sclerosis
  Authors: Daher M.; Rezvani K.
  Published: 2025/8 (journal-article)
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• Infrequent strong connections constrain connectomic predictions of neuronal function
  Authors: Currier T.; Clandinin T.
  Published: 2025/8 (journal-article)
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• Repeat-element RNAs integrate a neuronal growth circuit
  Authors: Zahavi E.; Koppel I.; Kawaguchi R.; Oses-Prieto J.; Briner A.; Monavarfeshani A.; Dalla Costa I.; van Niekerk E.; Lee J.; Matoo S.; Hegarty S.; Donahue R.; Sahoo P.; Ben-Dor S.; Feldmesser E.; Ryvkin J.; Leshkowitz D.; Perry R.; Cheng Y.; Farber E.; Abraham O.; Samra N.; Okladnikov N.; Alber S.; Albus C.
  Published: 2025/8 (journal-article)
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• Bivalent chromatin instructs lineage specification during hematopoiesis
  Authors: Yagi M.; Bonilla G.; Hoetker M.; Tsopoulidis N.; Horng J.; Haggerty C.; Meissner A.; Sadreyev R.; Hock H.; Hochedlinger K.
  Published: 2025/8 (journal-article)
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• Brain control of energy homeostasis: Implications for anti-obesity pharmacotherapy
  Authors: Johansen V.; Petersen J.; Lund J.; Mathiesen C.; Fenselau H.; Clemmensen C.
  Published: 2025/8 (journal-article)
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• AI-generated MLH1 small binder improves prime editing efficiency
  Authors: Park J.; Uhm H.; Kim Y.; Oh Y.; Lee J.; Yang J.; Kim K.; Bae S.
  Published: 2025/8 (journal-article)
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• An iPSC-derived CD19/BCMA CAR-NK therapy in a patient with systemic sclerosis
  Authors: Wang X.; Zhang Y.; Jin Y.; Dai L.; Yue Y.; Hu J.; Liu X.; Pang K.; Ye S.; Chen Y.; Ye W.; Shi X.; Ma X.; Guo L.; Liu Y.; Ta N.; Zhu X.; Lin L.; Wang J.; Yan R.; Wang P.; Song X.; Zhou Y.; Zhou L.; Wang Q.
  Published: 2025/8 (journal-article)
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• NRT1.1B acts as an abscisic acid receptor in integrating compound environmental cues for plants
  Authors: Ma X.; Wang W.; Zhang J.; Jiang Z.; Xu C.; Zhu W.; Shi B.; Yang W.; Su H.; Wang X.; Chen D.; Wang Y.; Wang J.; Wang J.; Liu X.; Wang X.; Huang X.; Xie W.; Cai Y.; Xu K.; Xin P.; Liu L.; Lü P.; Wang Y.; Chu J.
  Published: 2025/8 (journal-article)
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• Identification and application of cell-type-specific enhancers for the macaque brain
  Authors: Li L.; Huang Y.; Lu D.; Fu J.; Wu L.; Chen Z.; Liao H.; Zhang J.; Li L.; Gu T.; He F.; Liu H.; Leng X.; Tang J.; Yan J.; Liu C.; Li C.; Huang H.; Wang L.; Liu L.; Li C.; Poo M.; Li H.; Sun Y.; Liu Z.
  Published: 2025/8 (journal-article)
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- Nature

• New discoveries of Australopithecus and Homo from Ledi-Geraru, Ethiopia
  Authors: Villmoare B.; Delezene L.; Rector A.; DiMaggio E.; Campisano C.; Feary D.; Ali B.; Chupik D.; Deino A.; Garello D.; Hayidara M.; Locke E.; Omar O.; Robinson J.; Scott E.; Smail I.; Geleta Terefe K.; Werdelin L.; Kimbel W.; Arrowsmith J.; Reed K.
  Published: 2025/8 (journal-article)
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• The genomic origin of the unique chaetognath body plan
  Authors: Piovani L.; Gavriouchkina D.; Parey E.; Sarre L.; Peijnenburg K.; Martín-Durán J.; Rokhsar D.; Satoh N.; de Mendoza A.; Goto T.; Marlétaz F.
  Published: 2025/8 (journal-article)
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  AbstractThe emergence of animal phyla, each with their unique body plan, was a rapid event in the history of animal life, yet its genomic underpinnings are still poorly understood1. Here we investigate at the genomic, regulatory and cellular levels, the origin of one of the most distinctive animal phyla, the chaetognaths, whose organismal characteristics have historically complicated their phylogenetic placement2,3. We show that these characteristics are reflected at the cell-type level by the expression of genes that originated in the chaetognath lineage, contributing to adaptation to planktonic life at the sensory and structural levels4. Similarly to other members of gnathiferans (which also include rotifers and several other microscopic phyla)5,6, chaetognaths have undergone accelerated genomic evolution with gene loss and chromosomal fusions7,8. Furthermore, they secondarily duplicated thousands of genes9,10, without evidence for a whole-genome duplication, yielding, for instance, tandemly expanded Hox genes, as well as many phylum-specific genes. We also detected repeat-rich highly methylated neocentromeres and a simplified DNA methylation toolkit that is involved in mobile element repression rather than transcriptional control. Consistent with fossil evidence11,12, our observations suggest that chaetognaths emerged after a phase of morphological simplification through a reinvention of organ systems paralleled by massive genomic reorganization, explaining the uniqueness of their body plan.

• Large riverbed sediment flux sustained for a decade after an earthquake 
  Authors: Li G.; West A.; Jin Z.; Qiu H.; Zhang F.; Wang J.; Hammond D.; Densmore A.; Hilton R.; Dong S.; Atwood A.; Fischer W.; Lamb M.
  Published: 2025/8 (journal-article)
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• Just how bad will climate change get? The only way to know is to fund basic research
  Authors: Palmer T.
  Published: 2025/8 (journal-article)
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• Rubber planting and deforestation
  Authors: Sheil D.; Descals A.; Meijaard E.; Gaveau D.
  Published: 2025/8 (journal-article)
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• Air pollution could be reduced by incentivizing local government officials to control crop burning
  Authors: Dipoppa G.; Gulzar S.
  Published: 2025/8 (journal-article)
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• Many planets might be born with orbits misaligned from the spin of their stars
  Authors: None
  Published: 2025/8 (journal-article)
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• Expanding the cytokine receptor alphabet reprograms T cells into diverse states
  Authors: Zhao Y.; Ogishi M.; Pal A.; Su L.; Tao P.; Jiang H.; Rodriguez G.; Chen X.; Sun Q.; Rysavy L.; Limsuwannarot S.; Waghray D.; Kalbasi A.; Garcia K.
  Published: 2025/8 (journal-article)
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• These tiny flyers levitate on the Sun’s heat alone
  Authors: Tollefson J.
  Published: 2025/8 (journal-article)
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• Calving-driven fjord dynamics resolved by seafloor fibre sensing
  Authors: Gräff D.; Lipovsky B.; Vieli A.; Dachauer A.; Jackson R.; Farinotti D.; Schmale J.; Ampuero J.; Berg E.; Dannowski A.; Kneib-Walter A.; Köpfli M.; Kopp H.; van der Loo E.; Mata Flores D.; Mercerat D.; Moser R.; Sladen A.; Walter F.; Wasser D.; Welty E.; Wetter S.; Williams E.
  Published: 2025/8 (journal-article)
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  AbstractInteractions between melting ice and a warming ocean drive the present-day retreat of tidewater glaciers of Greenland1–3, with consequences for both sea level rise4and the global climate system5. Controlling glacier frontal ablation, these ice–ocean interactions involve chains of small-scale processes that link glacier calving—the detachment of icebergs6—and submarine melt to the broader fjord dynamics7,8. However, understanding these processes remains limited, in large part due to the challenge of making targeted observations in hazardous environments near calving fronts with sufficient temporal and spatial resolution9. Here we show that iceberg calving can act as a submarine melt amplifier through excitation of transient internal waves. Our observations are based on front-proximal submarine fibre sensing of the iceberg calving process chain. In this chain, calving initiates with persistent ice fracturing that coalesces into iceberg detachment, which in turn excites local tsunamis, internal gravity waves and transient currents at the ice front before the icebergs eventually decay into fragments. Our observations show previously unknown pathways in which tidewater glaciers interact with a warming ocean and help close the ice front ablation budget, which current models struggle to do10. These insights provide new process-scale understanding pertinent to retreating tidewater glaciers around the globe.

• Null empathy
  Authors: Chang M.
  Published: 2025/8 (journal-article)
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• Sun-powered flyers could explore the mysterious mesosphere
  Authors: Bundell S.; Petrić Howe N.
  Published: 2025/8 (journal-article)
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• NASP modulates histone turnover to drive PARP inhibitor resistance
  Authors: Moser S.; Khalizieva A.; Roehsner J.; Pottendorfer E.; Kaptein M.; Ricci G.; Bhardwaj V.; Bleijerveld O.; Hoekman L.; van der Heijden I.; di Sanzo S.; Fish A.; Chikunova A.; Haarhuis J.; Oldenkamp R.; Robbez-Masson L.; Sprengers J.; Vis D.; Wessels L.; van de Ven M.; Pettitt S.; Tutt A.; Lord C.; Rowland B.; Völker-Albert M.
  Published: 2025/8 (journal-article)
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• n-Type thermoelectric elastomers
  Authors: Liu K.; Wang J.; Pan X.; Tian S.; Liu Y.; Zhang Z.; Di Y.; Chen J.; Wu C.; Deng X.; Wang D.; Li P.; Pan C.; Qi F.; Liu J.; Hua J.; Pei J.; Di C.; Guo Y.; Liu Y.; Lei T.
  Published: 2025/8 (journal-article)
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• Levitating platform could ride sunlight into the ‘ignorosphere’
  Authors: Bargatin I.
  Published: 2025/8 (journal-article)
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• Spatial correlation in economic analysis of climate change
  Authors: Schötz C.
  Published: 2025/8 (journal-article)
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• Astronomers gave up this comet for dead ― but they were wrong
  Authors: None
  Published: 2025/8 (journal-article)
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• The geologic history of marine dissolved organic carbon from iron oxides
  Authors: Galili N.; Bernasconi S.; Nissan A.; Alcolombri U.; Aquila G.; Di Bella M.; Blattmann T.; Haghipour N.; Italiano F.; Jaggi M.; Kaplan-Ashiri I.; Lee K.; Lechte M.; Magnabosco C.; Porter S.; Rudmin M.; Spencer R.; Stocker R.; Wang Z.; Wohlwend S.; Hemingway J.
  Published: 2025/8 (journal-article)
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  AbstractDissolved organic carbon (DOC) is the largest reduced carbon reservoir in modern oceans1,2. Its dynamics regulate marine communities and atmospheric CO2levels3,4, whereas13C compositions track ecosystem structure and autotrophic metabolism5. However, the geologic history of marine DOC remains largely unconstrained6,7, limiting our ability to mechanistically reconstruct coupled ecological and biogeochemical evolution. Here we develop and validate a direct proxy for past DOC signatures using co-precipitated organic carbon in iron ooids. We apply this to 26 marine iron ooid-containing formations deposited over the past 1,650 million years to generate a data-based reconstruction of marine DOC signals since the Palaeoproterozoic. Our predicted DOC concentrations were near modern levels in the Palaeoproterozoic, then decreased by 90−99% in the Neoproterozoic before sharply rising in the Cambrian. We interpret these dynamics to reflect three distinct states. The occurrence of mostly small, single-celled organisms combined with severely hypoxic deep oceans, followed by larger, more complex organisms and little change in ocean oxygenation and finally continued organism growth and a transition to fully oxygenated oceans8,9. Furthermore, modern DOC is13C-enriched relative to the Proterozoic, possibly because of changing autotrophic carbon-isotope fractionation driven by biological innovation. Our findings reflect connections between the carbon cycle, ocean oxygenation and the evolution of complex life.

• How to thrive as a Latin American researcher abroad
  Authors: de la Cruz Pavas V.
  Published: 2025/8 (journal-article)
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• Accuracy of rubber-related deforestation maps
  Authors: Hoang N.; Potapov P.; Olofsson P.; Kanemoto K.
  Published: 2025/8 (journal-article)
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• Octopus motion in the ocean tracked by a deep-sea 3D camera
  Authors: None
  Published: 2025/8 (journal-article)
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• Y. Wang et al. reply
  Authors: Wang Y.; Hollingsworth P.; Zhai D.; West C.; Green J.; Harrison S.; Chen H.; Hurni K.; Su Y.; Warren-Thomas E.; Xu J.; Ahrends A.
  Published: 2025/8 (journal-article)
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• Publisher Correction: Liquid–liquid interfacial tension stabilized Li-metal batteries
  Authors: Ji H.; Xiang J.; Li Y.; Zheng M.; Yuan L.; Liao Y.; Du L.; Li Z.; Xie Z.; Huang K.; Lin X.; Xie Z.; Shen Y.; Chen M.; Li T.; Feng G.; Sun Y.; Qie L.; Li H.; Zhang F.; Guo R.; Feng X.; Chen W.; Ai X.; Lu J.
  Published: 2025/8 (journal-article)
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• Oestrogen defends against kidney damage caused by iron-dependent cell death
  Authors: Vanden Berghe T.
  Published: 2025/8 (journal-article)
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• Watch rappelling robots dive into a lava tube — for science
  Authors: Castelvecchi D.
  Published: 2025/8 (journal-article)
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• Countrywide natural experiment links built environment to physical activity
  Authors: Althoff T.; Ivanovic B.; King A.; Hicks J.; Delp S.; Leskovec J.
  Published: 2025/8 (journal-article)
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  AbstractWhile physical activity is critical to human health, most people do not meet recommended guidelines1,2. Built environments that are more walkable have the potential to increase activity across the population3–8. However, previous studies on the built environment and physical activity have led to mixed findings, possibly due to methodological limitations such as small cohorts, over-reliance on self-reported measures and cross-sectional designs5,7,9–11. Here we address these limitations by leveraging a large US cohort of smartphone users (N= 2,112,288) to evaluate within-person longitudinal behaviour changes that occurred over 248,266 days of objectively measured physical activity across 7,447 relocations among 1,609 US cities. By analysing the results of this natural experiment, which exposed individuals to differing built environments, we find that increases (decreases) in walkability are associated with significant increases (decreases) in physical activity after relocation. For example, moving from a less walkable (25th percentile) city to a more walkable city (75th percentile) increased walking by 1,100 daily steps, on average. These changes hold across different genders, ages and body mass index values, and are sustained over 3 months. The added activity is predominantly composed of moderate-to-vigorous physical activity, which is linked to an array of associated health benefits1. Evidence against residential self-selection confounding is reported. Our findings provide robust evidence supporting the importance of the built environment in directly improving health-enhancing physical activity and offer potential guidance for public policy activities in this area.

• The perplexing body plan of arrow worms decoded
  Authors: Lewin T.; Luo Y.
  Published: 2025/8 (journal-article)
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• Elementary 3D organization of active and silenced E. coli genome
  Authors: Gavrilov A.; Shamovsky I.; Zhegalova I.; Proshkin S.; Shamovsky Y.; Evko G.; Epshtein V.; Rasouly A.; Blavatnik A.; Lahiri S.; Rothenberg E.; Razin S.; Nudler E.
  Published: 2025/8 (journal-article)
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  AbstractUnravelling how genomes are spatially organized and how their three-dimensional (3D) architecture drives cellular functions remains a major challenge in biology1,2. In bacteria, genomic DNA is compacted into a highly ordered, condensed state called nucleoid3–5. Despite progress in characterizing bacterial 3D genome architecture over recent decades6–8, the fine structure and functional organization of the nucleoid remain elusive due to low-resolution contact maps from methods such as Hi-C9–11. Here we developed an enhanced Micro-C chromosome conformation capture, achieving 10-base pair (bp) resolution. This ultra-high-resolution analysis reveals elemental spatial structures in theEscherichia colinucleoid, including chromosomal hairpins (CHINs) and chromosomal hairpin domains (CHIDs). These structures, organized by histone-like proteins H-NS and StpA, have key roles in repressing horizontally transferred genes. Disruption of H-NS causes drastic reorganization of the 3D genome, decreasing CHINs and CHIDs, whereas removing both H-NS and StpA results in their complete disassembly, increased transcription of horizontally transferred genes and delayed growth. Similar effects are observed with netropsin, which competes with H-NS and StpA for AT-rich DNA binding. Interactions between CHINs further organize the genome into isolated loops, potentially insulating active operons. Our Micro-C analysis reveals that all actively transcribed genes form distinct operon-sized chromosomal interaction domains (OPCIDs) in a transcription-dependent manner. These structures appear as square patterns on Micro-C maps, reflecting continuous contacts throughout transcribed regions. This work unveils the fundamental structural elements of theE. colinucleoid, highlighting their connection to nucleoid-associated proteins and transcription machinery.

• Photophoretic flight of perforated structures in near-space conditions
  Authors: Schafer B.; Kim J.; Sharipov F.; Hwang G.; Vlassak J.; Keith D.
  Published: 2025/8 (journal-article)
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• Is gravity quantum? Experiments could finally probe one of physics’ biggest questions
  Authors: Castelvecchi D.
  Published: 2025/8 (journal-article)
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• Bending the curve of land degradation to achieve global environmental goals
  Authors: Maestre F.; Guirado E.; Armenteras D.; Beck H.; AlShalan M.; Al-Saud N.; Chami R.; Fu B.; Gichenje H.; Huber-Sannwald E.; Speranza C.; Martínez-Valderrama J.; McCabe M.; Orr B.; Tang T.; Metternicht G.; Miess M.; Reynolds J.; Stringer L.; Wada Y.; Duarte C.
  Published: 2025/8 (journal-article)
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• Establishment of chromatin architecture interplays with embryo hypertranscription
  Authors: Yu G.; Xu K.; Xia W.; Zhang K.; Xu Q.; Li L.; Lin Z.; Liu L.; Liu B.; Du Z.; Chen X.; Fan Q.; Lai F.; Wang W.; Wang L.; Kong F.; Wang C.; Dai H.; Wang H.; Xie W.
  Published: 2025/8 (journal-article)
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• Clone copy number diversity is linked to survival in lung cancer
  Authors: Pawlik P.; Grigoriadis K.; Bunkum A.; Coggan H.; Frankell A.; Martinez-Ruiz C.; Karasaki T.; Huebner A.; Rowan A.; Fisher J.; Hackshaw A.; Swanton C.; Zaccaria S.; McGranahan N.
  Published: 2025/8 (journal-article)
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  AbstractBoth single nucleotide variants (SNVs) and somatic copy number alterations (SCNAs) accumulate in cancer cells during tumour development, fuelling clonal evolution. However, accurate estimation of clone-specific copy numbers from bulk DNA-sequencing data is challenging. Here we present allele-specific phylogenetic analysis of copy number alterations (ALPACA), a method to infer SNV and SCNA coevolution by leveraging phylogenetic trees reconstructed from multi-sample bulk tumour sequencing data using SNV frequencies. ALPACA estimates the SCNA evolution of simulated tumours with a higher accuracy than current state-of-the-art methods1–4. ALPACA uncovers loss-of-heterozygosity and amplification events in minor clones that may be missed using standard approaches and reveals the temporal order of somatic alterations. Analysing clone-specific copy numbers in TRACERx421 lung tumours5,6, we find evidence of increased chromosomal instability in metastasis-seeding clones and enrichment for losses affecting tumour suppressor genes and amplification affectingCCND1. Furthermore, we identify increased SCNA rates in both tumours with polyclonal metastatic dissemination and tumours with extrathoracic metastases, and an association between higher clone copy number diversity and reduced disease-free survival in patients with lung cancer.

• Delocalized electrolyte design enables 600 Wh kg−1 lithium metal pouch cells
  Authors: Huang H.; Hu Y.; Hou Y.; Wang X.; Dong Q.; Zhao Z.; Ji M.; Zhang W.; Li J.; Xie J.; Guo H.; Han X.; Ouyang X.; Hu W.
  Published: 2025/8 (journal-article)
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• Multiple oestradiol functions inhibit ferroptosis and acute kidney injury
  Authors: Tonnus W.; Maremonti F.; Gavali S.; Schlecht M.; Gembardt F.; Belavgeni A.; Leinung N.; Flade K.; Bethe N.; Traikov S.; Haag A.; Schilling D.; Penkov S.; Mallais M.; Gaillet C.; Meyer C.; Katebi M.; Ray A.; Gerhardt L.; Brucker A.; Becker J.; Tmava M.; Schlicker L.; Schulze A.; Himmerkus N.
  Published: 2025/8 (journal-article)
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• Human emissions drive recent trends in North Pacific climate variations
  Authors: Klavans J.; DiNezio P.; Clement A.; Deser C.; Shanahan T.; Cane M.
  Published: 2025/8 (journal-article)
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• A humidity measure that accounts for redistribution of water across the landscape
  Authors: None
  Published: 2025/8 (journal-article)
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• Acidic oxygen reduction by single-atom Fe catalysts on curved supports
  Authors: Zhao Y.; Wan J.; Ling C.; Wang Y.; He H.; Yang N.; Wen R.; Zhang Q.; Gu L.; Yang B.; Xiang Z.; Chen C.; Wang J.; Wang X.; Wang Y.; Tao H.; Li X.; Liu B.; Zhang S.; Wang D.
  Published: 2025/8 (journal-article)
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• Impact of catastrophic flood might have been exacerbated by river-management programme
  Authors: Finotello A.
  Published: 2025/8 (journal-article)
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• Daily briefing: Bird flu is ‘everywhere’ on dairy farms
  Authors: Graham F.
  Published: 2025/8 (journal-article)
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• Use AI in the classroom to bring problems to life
  Authors: Xie Z.; Zhang C.
  Published: 2025/8 (journal-article)
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• Europe must safeguard climate data following NASA cuts
  Authors: Pinty B.; Thépaut J.
  Published: 2025/8 (journal-article)
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• How Paris dealt with lightning in the Age of Enlightenment
  Authors: None
  Published: 2025/8 (journal-article)
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• Postdoc depression and anxiety rates are rising, finds survey of 872 researchers
  Authors: Gewin V.
  Published: 2025/8 (journal-article)
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• Trump’s chief science adviser faces a storm of criticism: what's next?
  Authors: Tollefson J.
  Published: 2025/8 (journal-article)
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• ‘A whole body of health-equity research is being disappeared’ — why I resigned from the NIH
  Authors: Pariyadath V.
  Published: 2025/8 (journal-article)
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• Study how screen time affects circadian rhythms
  Authors: Kiran F.; Jin Y.; Yuan Y.; Chen H.
  Published: 2025/8 (journal-article)
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• Organs on chips could make biomedical research more equitable
  Authors: del Valle A.
  Published: 2025/8 (journal-article)
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• Margaret Boden obituary: cognitive scientist who explored how machines might emulate human imagination
  Authors: Bryson J.
  Published: 2025/8 (journal-article)
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• Author Correction: RNA codon expansion via programmable pseudouridine editing and decoding
  Authors: Liu J.; Yan X.; Wu H.; Ji Z.; Shan Y.; Wang X.; Ran Y.; Ma Y.; Li C.; Zhu Y.; Gu R.; Wen H.; Yi C.; Chen P.
  Published: 2025/8 (journal-article)
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• How Indigenous values permeate my chemistry teaching and research
  Authors: Byrne D.
  Published: 2025/8 (journal-article)
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• How does agricultural land become forest? I trek to find out
  Authors: Tacon D.
  Published: 2025/8 (journal-article)
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• Catalytic enantioselective synthesis of alkylidenecyclopropanes
  Authors: Golec J.; Tan D.; Yamazaki K.; Tiekink E.; Christensen K.; Hamlin T.; Dixon D.
  Published: 2025/8 (journal-article)
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• Author Correction: A virtual rodent predicts the structure of neural activity across behaviours
  Authors: Aldarondo D.; Merel J.; Marshall J.; Hasenclever L.; Klibaite U.; Gellis A.; Tassa Y.; Wayne G.; Botvinick M.; Ölveczky B.
  Published: 2025/8 (journal-article)
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• Daily briefing: Political officials could control US federal science grants
  Authors: Graham F.
  Published: 2025/8 (journal-article)
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• Six questions to ask before jumping into a spreadsheet
  Authors: Melchor S.
  Published: 2025/8 (journal-article)
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• A rude awakening
  Authors: Martin P.
  Published: 2025/8 (journal-article)
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• Swift bricks, ancient tattoos and more: Books in brief
  Authors: Robinson A.
  Published: 2025/8 (journal-article)
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• Trump order gives political appointees vast powers over research grants
  Authors: Garisto D.
  Published: 2025/8 (journal-article)
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• Decolonize scientific institutions, don’t just diversify them
  Authors: McAllister T.; Walker L.; Smiles N.; Jennings L.; Moggridge B.; Naepi S.; Kamai B.; Milligan-McClellan K.
  Published: 2025/8 (journal-article)
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• How animal paw pads got their toughness
  Authors: None
  Published: 2025/8 (journal-article)
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• Can creativity in science be learnt? These researchers think so
  Authors: Hedley E.
  Published: 2025/8 (journal-article)
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• Daily briefing: US researchers fight back on key climate report
  Authors: Smith J.
  Published: 2025/8 (journal-article)
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• Monoclonal antibodies revolutionized biomedical science and health care
  Authors: None
  Published: 2025/8 (journal-article)
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• How researcher visa curbs threaten science careers
  Authors: Gewin V.
  Published: 2025/8 (journal-article)
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• ‘A biographer’s dream’: this physicist investigated UFOs and flew over Hiroshima
  Authors: Crease R.
  Published: 2025/8 (journal-article)
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• Outrage over Trump team’s climate report spurs researchers to fight back
  Authors: Tollefson J.
  Published: 2025/8 (journal-article)
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• Globally recognized island is losing its trademark glaciers
  Authors: None
  Published: 2025/8 (journal-article)
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• Daily briefing: Lithium supplements reverse Alzheimer’s symptoms in mice
  Authors: Smith J.
  Published: 2025/8 (journal-article)
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• George E. Smith obituary: co-inventor of the charge coupled device, which ushered in an era of digital images
  Authors: Tulloch S.
  Published: 2025/8 (journal-article)
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• These genes can have the opposite effects depending on which parent they came from
  Authors: Fieldhouse R.
  Published: 2025/8 (journal-article)
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• Alien planet glimpsed in star's 'habitable zone'
  Authors: Ahart J.
  Published: 2025/8 (journal-article)
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• The peer-review crisis: how to fix an overloaded system
  Authors: Adam D.
  Published: 2025/8 (journal-article)
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• NSD2 inhibitors rewire chromatin to treat lung and pancreatic cancers
  Authors: Jeong J.; Hausmann S.; Dong H.; Szczepski K.; Flores N.; Garcia Gonzalez A.; Shi L.; Lu X.; Lempiäinen J.; Jakab M.; Zeng L.; Chasan T.; Bareke E.; Dong R.; Carlson E.; Padilla R.; Husmann D.; Thompson J.; Shipman G.; Zahn E.; Barnes C.; Khan L.; Albertorio-Sáez L.; Brill E.; Kumary V.
  Published: 2025/8 (journal-article)
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• Structural basis of fast N-type inactivation in Kv channels
  Authors: Tan X.; Fernández-Mariño A.; Li Y.; Chang T.; Swartz K.
  Published: 2025/8 (journal-article)
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  AbstractAction potentials are generated by opening of voltage-activated sodium (Nav) and potassium (Kv) channels1, which can rapidly inactivate to shape the nerve impulse and contribute to synaptic facilitation and short-term memory1–4. The mechanism of fast inactivation was proposed to involve an intracellular domain that blocks the internal pore in both Nav5,6and Kv7–9channels; however, recent studies in Nav10,11and Kv12,13channels support a mechanism in which the internal pore closes during inactivation. Here we investigate the mechanism of fast inactivation in the Shaker Kvchannel using cryo-electron microscopy, mass spectrometry and electrophysiology. We resolved structures of a fully inactivated state in which the non-polar end of the N terminus plugs the internal pore in an extended conformation. The N-terminal methionine is deleted, leaving an alanine that is acetylated and interacts with a pore-lining isoleucine residue where RNA editing regulates fast inactivation14. Opening of the internal activation gate is required for fast inactivation because it enables the plug domain to block the pore and repositions gate residues to interact with and stabilize that domain. We also show that external K+destabilizes the inactivated state by altering the conformation of the ion selectivity filter rather than by electrostatic repulsion. These findings establish the mechanism of fast inactivation in Kvchannels, revealing how it is regulated by RNA editing and N-terminal acetylation, and providing a framework for understanding related mechanisms in other voltage-activated channels.

• Publisher Correction: NINJ1 regulates plasma membrane fragility under mechanical strain
  Authors: Zhu Y.; Xiao F.; Wang Y.; Wang Y.; Li J.; Zhong D.; Huang Z.; Yu M.; Wang Z.; Barbara J.; Plunkett C.; Zeng M.; Song Y.; Tan T.; Zhang R.; Xu K.; Wang Z.; Cai C.; Guan X.; Hammack S.; Zhang L.; Shi Z.; Xiang F.; Shao F.; Xu J.
  Published: 2025/8 (journal-article)
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• In situ light-field imaging of octopus locomotion reveals simplified control
  Authors: Katija K.; Huffard C.; Roberts P.; Daniels J.; Erickson J.; Klimov D.; Ruhl H.; Sherman A.
  Published: 2025/8 (journal-article)
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• Excised DNA circles from V(D)J recombination promote relapsed leukaemia
  Authors: Gao Z.; Scott J.; Edwards M.; Casey D.; Wang X.; Gillen A.; Ryan S.; Russell L.; Moorman A.; de Tute R.; Cargo C.; Ford A.; Westhead D.; Boyes J.
  Published: 2025/8 (journal-article)
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  AbstractExtrachromosomal DNA amplification is associated with poor cancer prognoses1. Large numbers of excised signal circles (ESCs) are produced as by-products of antigen receptor rearrangement during V(D)J recombination2,3. However, current dogma states that ESCs are progressively lost through cell division4. Here we show that ESCs replicate and persist through many cell generations and share many properties in common with circular extrachromosomal DNAs. Increased ESC copy numbers at diagnosis of B cell precursor acute lymphoblastic leukaemia were highly correlated with subsequent relapse. By taking advantage of the matching recombination footprint that is formed upon the generation of each ESC, we measured ESC persistence and replication and found increased ESC replication in patients who later relapsed. This increased replication is controlled by cell-intrinsic factors and corresponds to increased expression of DNA replication- and repair-associated genes. Consistent with high ESC levels having a role in disease progression, the number of mutations typical of those caused by the V(D)J recombinase–ESC complex was significantly increased at diagnosis in patients who later relapsed. The number of such mutations in genes associated with relapse increased between diagnosis and relapse, and corresponded to clonal expansion of cells with high ESC copy numbers. These data demonstrate that the by-product of V(D)J recombination, when increased in abundance, potently associates with the V(D)J recombinase to cause adverse disease outcomes.

• Data anomalies and the economic commitment of climate change
  Authors: Bearpark T.; Hogan D.; Hsiang S.
  Published: 2025/8 (journal-article)
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• Daily briefing: Reflections from a survivor of the Hiroshima bombing
  Authors: Smith J.
  Published: 2025/8 (journal-article)
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• Therapeutic genetic restoration through allogeneic brain microglia replacement
  Authors: Mader M.; Scavetti A.; Yoo Y.; Chai A.; Uenaka T.; Wernig M.
  Published: 2025/8 (journal-article)
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• Reply to: Inconclusive proof of ferroelectricity in peptide-VDF ribbons
  Authors: Yang Y.; Sai H.; Egner S.; Qiu R.; Palmer L.; Stupp S.
  Published: 2025/8 (journal-article)
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• RNA N-glycosylation enables immune evasion and homeostatic efferocytosis
  Authors: Graziano V.; Porat J.; Ah Kioon M.; Mejdrová I.; Matz A.; Lebedenko C.; Chai P.; Pluvinage J.; Ricci-Azevedo R.; Harrison A.; Wright S.; Wang X.; Strine M.; Wang P.; Wilson M.; Vanaja S.; Zhou B.; Barrat F.; Carell T.; Flynn R.; Rathinam V.
  Published: 2025/8 (journal-article)
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• Ancient marine reptile was a silent swimmer
  Authors: None
  Published: 2025/8 (journal-article)
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• Microglia–neuron crosstalk via Hex–GM2–MGL2 maintains brain homeostasis
  Authors: Frosch M.; Shimizu T.; Wogram E.; Amann L.; Gruber L.; Groisman A.; Fliegauf M.; Schwabenland M.; Chhatbar C.; Zechel S.; Rosewich H.; Gärtner J.; Quintana F.; Buescher J.; Blank T.; Binder H.; Stadelmann C.; Letzkus J.; Hopf C.; Masuda T.; Knobeloch K.; Prinz M.
  Published: 2025/8 (journal-article)
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• Hominins on Sulawesi during the Early Pleistocene
  Authors: Hakim B.; Wibowo U.; van den Bergh G.; Yurnaldi D.; Joannes-Boyau R.; Duli A.; Suryatman N/A.; Sardi R.; Nurani I.; Puspaningrum M.; Mahmud I.; Haris A.; Anshari K.; Saiful A.; Arman Bungaran P.; Adhityatama S.; Muhammad P.; Akib A.; Somba N.; Fakhri N/A.; Burhan B.; Mas’ud Z.; Moore M.; Perston Y.; Yu W.
  Published: 2025/8 (journal-article)
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• Microglia regulate GABAergic neurogenesis in prenatal human brain through IGF1
  Authors: Yu D.; Jain S.; Wangzhou A.; Zhu B.; Shao W.; Coley-O’Rourke E.; De Florencio S.; Kim J.; Choi J.; Paredes M.; Nowakowski T.; Huang E.; Piao X.
  Published: 2025/8 (journal-article)
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  AbstractGABAergic neurons are essential cellular components of neural circuits. Their abundance and diversity have increased significantly in the human brain, contributing to the expanded cognitive capacity of humans1. However, the developmental mechanism underlying the extended production of GABAergic neurons in the human brain remains elusive. Here we uncovered the microglial regulation of the sustained proliferation of GABAergic progenitors and neuroblasts in the human medial ganglionic eminence (hMGE). We showed that microglia are preferentially distributed in the proliferating zone and identified insulin-like growth factor 1 (IGF1) and its receptor IGR1R as the predicted top ligand–receptor pair underlying microglia–progenitor communication in the prenatal hMGE. Using our newly developed neuroimmune hMGE organoids, which mimic the hMGE cytoarchitecture and developmental trajectory, we demonstrated that microglia-derived IGF1 promotes progenitor proliferation and production of GABAergic neurons. Conversely, IGF1-neutralizing antibodies andIGF1knockout human embryonic stem-cell-induced microglia abolish the induced microglia-mediated progenitor proliferation. Together, these findings revealed a previously unappreciated role of microglia-derived IGF1 in promoting the proliferation of neural progenitors and the development of GABAergic neurons in the human brain.

• Stone tools suggest that hominins arrived on Indonesian island much earlier than thought
  Authors: None
  Published: 2025/8 (journal-article)
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• AI learns from nature to design super-adhesive gels that work underwater
  Authors: Russo L.
  Published: 2025/8 (journal-article)
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• Is your AI benchmark lying to you?
  Authors: Brooks M.
  Published: 2025/8 (journal-article)
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• Data-driven de novo design of super-adhesive hydrogels
  Authors: Liao H.; Hu S.; Yang H.; Wang L.; Tanaka S.; Takigawa I.; Li W.; Fan H.; Gong J.
  Published: 2025/8 (journal-article)
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• Stronger El Niños reduce tropical forest arthropod diversity and function
  Authors: Sharp A.; Boyle M.; Bonebrake T.; Guo Y.; Kitching R.; Stork N.; Zeng X.; Ashton L.
  Published: 2025/8 (journal-article)
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• High-accuracy laser spectroscopy of $${{\bf{H}}}_{{\bf{2}}}^{{\boldsymbol{+}}}$$ and the proton–electron mass ratio
  Authors: Alighanbari S.; Schenkel M.; Korobov V.; Schiller S.
  Published: 2025/8 (journal-article)
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  AbstractThe molecular hydrogen ions (MHI) are three-body systems suitable for advancing our knowledge in several domains: fundamental constants, tests of quantum physics, search for new interparticle forces, tests of the weak equivalence principle1and, once the anti-molecule$$\overline{p}\,\overline{p}\,{e}^{+}$$p¯p¯e+becomes available, new tests of charge–parity–time-reversal invariance and local position invariance1–3. To achieve these goals, high-accuracy laser spectroscopy of several isotopologues, in particular$${{\rm{H}}}_{2}^{+}$$H2+, is required4. Here we present a Doppler-free laser spectroscopy of a$${{\rm{H}}}_{2}^{+}$$H2+rovibrational transition, achieving line resolutions as large as 2.2 × 1013. We accurately determine the transition frequency with 8 × 10−12fractional uncertainty. We also determine the spin–rotation coupling coefficient with 0.1 kHz uncertainty and its value is consistent with the state-of-the-art theory prediction5. The combination of our theoretical and experimental$${{\rm{H}}}_{2}^{+}$$H2+data allows us to deduce a new value for the proton-electron mass ratiomp/me. It is in agreement with the value obtained from mass spectrometry and has 2.3 times lower uncertainty. From combined MHI, H/D and muonic H/D data, we determine the baryon mass ratiomd/mpwith 1.1 × 10−10absolute uncertainty. The value agrees with the directly measured mass ratio6. Finally, we present a match between a theoretical prediction and an experimental result, with a fractional uncertainty of 8.1 × 10−12. Both results indicate a notable confirmation of the predictive power of quantum theory and the absence of beyond-the-standard-model effects at these levels.

• Why did researchers stick a duck to a rock? To show off their super glue
  Authors: Petrić Howe N.
  Published: 2025/8 (journal-article)
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• Sexual harassment is rife at US Antarctic research bases, fresh survey finds
  Authors: Witze A.
  Published: 2025/8 (journal-article)
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• A global humidity index with lateral hydrologic flows
  Authors: Miguez-Macho G.; Fan Y.
  Published: 2025/8 (journal-article)
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• Underwater glue shows its sticking power in rubber duck test
  Authors: Thompson B.; Petrić Howe N.
  Published: 2025/8 (journal-article)
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• Does lithium deficiency contribute to Alzheimer’s disease?
  Authors: Bush A.
  Published: 2025/8 (journal-article)
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• The real problems with America's health
  Authors: Fox D.; Graham F.; Pearson H.
  Published: 2025/8 (journal-article)
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• Inconclusive proof of ferroelectricity in peptide-VDF ribbons
  Authors: Litterst M.; Butkevich A.; Kemerink M.
  Published: 2025/8 (journal-article)
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• OpenAI launches reasoning LLM that you can download and tweak
  Authors: Gibney E.
  Published: 2025/8 (journal-article)
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• Highly efficient deep-blue LED devices made using hybrid copper–iodide compound
  Authors: None
  Published: 2025/8 (journal-article)
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• Kinetic turbulence drives MHD equilibrium change via 3D reconnection
  Authors: Park J.; Yoon Y.; Hwang Y.
  Published: 2025/8 (journal-article)
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• New hope for Alzheimer’s: lithium supplement reverses memory loss in mice
  Authors: Peeples L.
  Published: 2025/8 (journal-article)
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• Novel assembly of a head–trunk interface in the sister group of jawed vertebrates
  Authors: Miyashita T.; Janvier P.; Tietjen K.; Berenguer F.; Schöder S.; Marone F.; Gueriau P.; Coates M.
  Published: 2025/8 (journal-article)
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• UK Royal Society adopts ‘subscribe to open’ publishing model
  Authors: Naddaf M.
  Published: 2025/8 (journal-article)
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• Author Correction: Persistent transcriptional programmes are associated with remote memory
  Authors: Chen M.; Jiang X.; Quake S.; Südhof T.
  Published: 2025/8 (journal-article)
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• Parent-of-origin effects found for gene variants that affect human growth and metabolism
  Authors: None
  Published: 2025/8 (journal-article)
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• Merging of magnetic plasma ‘flux ropes’ is driven by turbulence
  Authors: Agudelo Rueda J.
  Published: 2025/8 (journal-article)
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• EBV induces CNS homing of B cells attracting inflammatory T cells
  Authors: Läderach F.; Piteros I.; Fennell É.; Bremer E.; Last M.; Schmid S.; Rieble L.; Campbell C.; Ludwig-Portugall I.; Bornemann L.; Gruhl A.; Eulitz K.; Gueguen P.; Mietz J.; Müller A.; Pezzino G.; Schmitz J.; Ferlazzo G.; Mautner J.; Münz C.
  Published: 2025/8 (journal-article)
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• A diverse and distinct microbiome inside living trees
  Authors: Arnold W.; Gewirtzman J.; Raymond P.; Duguid M.; Brodersen C.; Brown C.; Norbraten N.; Wood Q.; Bradford M.; Peccia J.
  Published: 2025/8 (journal-article)
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• Lithium deficiency and the onset of Alzheimer’s disease
  Authors: Aron L.; Ngian Z.; Qiu C.; Choi J.; Liang M.; Drake D.; Hamplova S.; Lacey E.; Roche P.; Yuan M.; Hazaveh S.; Lee E.; Bennett D.; Yankner B.
  Published: 2025/8 (journal-article)
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• After you left
  Authors: Saha S.
  Published: 2025/8 (journal-article)
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• Whole-genome sequencing of 490,640 UK Biobank participants
  Authors: N/A N/A.; N/A N/A.; Carss K.; Halldorsson B.; Hou L.; Liu J.; Wheeler E.; Lo Y.; Kundu K.; Huang Z.; Lacey B.; Dhindsa R.; Rajan D.; Randjelovic J.; Marriott N.; Scott C.; Yavuz A.; Johnston I.; Howe T.; Black M.; Stefansson K.; Scott R.; Petrovski S.; Li S.; Cortes A.
  Published: 2025/8 (journal-article)
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  AbstractWhole-genome sequencing provides an unbiased and complete view of the human genome and enables the discovery of genetic variation without the technical limitations of other genotyping technologies. Here we report on whole-genome sequencing of 490,640 UK Biobank participants, building on previous genotyping effort1. This advance deepens our understanding of how genetics associates with disease biology and further enhances the value of this open resource for the study of human biology and health. Coupling this dataset with rich phenotypic data, we surveyed within- and cross-ancestry genomic associations and identified novel genetic and clinical insights. Although most associations with disease traits were primarily observed in individuals of European ancestries, strong or novel signals were also identified in individuals of African and Asian ancestries. With the improved ability to accurately genotype structural variants and exonic variation in both coding and UTR sequences, we strengthened and revealed novel insights relative to whole-exome sequencing2,3analyses. This dataset, representing a large collection of whole-genome sequencing data that is available to the UK Biobank research community, will enable advances of our understanding of the human genome, facilitate the discovery of diagnostics and therapeutics with higher efficacy and improved safety profile, and enable precision medicine strategies with the potential to improve global health.

• Optical control of resonances in temporally symmetry-broken metasurfaces
  Authors: Aigner A.; Possmayer T.; Weber T.; Antonov A.; de S. Menezes L.; Maier S.; Tittl A.
  Published: 2025/8 (journal-article)
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  AbstractTunability in active metasurfaces has mainly relied on shifting the resonance wavelength1,2or increasing material losses3,4to spectrally detune or quench resonant modes, respectively. However, both methods face fundamental limitations, such as a limitedQfactor and near-field enhancement control and the inability to achieve resonance on–off switching by completely coupling and decoupling the mode from the far field. Here we demonstrate temporal symmetry breaking in metasurfaces through ultrafast optical pumping, providing an experimental realization of radiative-loss-driven resonance tuning, allowing resonance creation, annihilation, broadening and sharpening. To enable this temporal control, we introduce restored symmetry-protected bound states in the continuum. Even though their unit cells are geometrically asymmetric, coupling to the radiation continuum remains fully suppressed, which, in this work, is achieved by two equally strong antisymmetric dipoles. By using selective Mie-resonant pumping in parts of these unit cells, we can modify their dipole balance to create or annihilate resonances as well as tune the linewidth, amplitude and near-field enhancement, leading to potential applications in optical and quantum communications, time crystals and photonic circuits.

• High levels of circular DNA made as immune cells develop increases the risk of leukaemia relapse
  Authors: Rodgers K.
  Published: 2025/8 (journal-article)
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• One-third of Sun-like stars are born with misaligned planet-forming disks
  Authors: Biddle L.; Bowler B.; Morgan M.; Tran Q.; Wu Y.
  Published: 2025/8 (journal-article)
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• Nuclear-weapons risks are back — and we need to act like it
  Authors: Panda A.
  Published: 2025/8 (journal-article)
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• The protein craze: scientists talk supplements — and who should take them
  Authors: Lenharo M.
  Published: 2025/8 (journal-article)
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• The science fiction science method
  Authors: Rahwan I.; Shariff A.; Bonnefon J.
  Published: 2025/8 (journal-article)
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• Parent-of-origin effects on complex traits in up to 236,781 individuals
  Authors: Hofmeister R.; Cavinato T.; Karimi R.; van der Graaf A.; Pajuste F.; Kronberg J.; Taba N.; N/A N/A.; Metspalu A.; Esko T.; Nelis M.; Hudjashov G.; Mägi R.; Vaudel M.; Rubinacci S.; Johansson S.; Milani L.; Delaneau O.; Kutalik Z.
  Published: 2025/8 (journal-article)
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  AbstractParent-of-origin effects (POEs) occur when the effect of a genetic variant depends on its parental origin1. Traditionally linked to genomic imprinting, POEs are believed to occur due to parental conflict over resource allocation to offspring, resulting in opposing parental influences2. Despite their importance, POEs remain underexplored in complex traits, owing to the lack of parental genomes. Here we present an approach to infer the parent of origin of alleles without parental genomes, leveraging interchromosomal phasing, mitochondrial and X chromosome data, and sex-specific crossover in siblings. Applied to the UK Biobank, this enabled parent-of-origin inference for up to 109,385 individuals. Genome-wide association study scans for 59 complex traits and over 14,000 protein quantitative trait loci contrasting maternal and paternal effects identified over 30 POEs and confirmed more than 50% of known associations. More than one third of these showed opposite parental influences, especially for traits related to growth (for example, IGF1 and height) and metabolism (for example, type 2 diabetes and triglyceride levels). Replication in up to 85,050 individuals from the Estonian Biobank and 42,346 offspring from the Norwegian Mother, Father and Child Cohort Study (MoBa) validated 87% of testable associations. Overall, our findings highlight the contribution of POEs to complex traits and support the parental conflict hypothesis, providing compelling evidence for this understudied evolutionary phenomenon.

• Why suppressing all wildfires has made today’s megafires worse
  Authors: Sharples J.
  Published: 2025/8 (journal-article)
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• Mystery of billions of sea-star deaths solved at last
  Authors: None
  Published: 2025/8 (journal-article)
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• Tiny motor uses heat to perform molecular magic
  Authors: None
  Published: 2025/8 (journal-article)
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• Plan-B careers can be a force for good in science
  Authors: Marrs K.
  Published: 2025/8 (journal-article)
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• Version control: how I combat the rise of generative AI in the classroom
  Authors: Bezrukov N.
  Published: 2025/8 (journal-article)
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• Don’t train medical AI on patients’ data without their knowledge
  Authors: Banerjee T.; Lin R.; Shi M.
  Published: 2025/8 (journal-article)
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• Overcome threats to renewable energy through skilful statecraft
  Authors: Chandrashekeran S.; Fish A.; Thurbon E.; Sovacool B.
  Published: 2025/8 (journal-article)
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• Daily briefing: This marsupial is biofluorescent — the month’s best science images
  Authors: Smith J.
  Published: 2025/8 (journal-article)
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• Breed giant prawns to withstand disease and climate change
  Authors: Li F.; Gao Q.
  Published: 2025/8 (journal-article)
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• Baboons defend themselves by throwing stones
  Authors: None
  Published: 2025/8 (journal-article)
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• Protect Palestinian archaeological sites during war
  Authors: Alsaud L.
  Published: 2025/8 (journal-article)
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• Does ResearchGate have a growing credibility problem?
  Authors: Singh Chawla D.
  Published: 2025/8 (journal-article)
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• ‘The Sun had fallen to Earth’ — a survivor’s recollection of the Hiroshima bombing
  Authors: Sheftall M.
  Published: 2025/8 (journal-article)
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• Tackle fake citations generated by AI
  Authors: Sharifi A.
  Published: 2025/8 (journal-article)
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• Conserve marine migratory species to protect ecological links between land and sea
  Authors: Lassalle G.; Lambert P.; Darnaude A.; de Almeida P.
  Published: 2025/8 (journal-article)
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• Protection from biological hazards at work arrives at last
  Authors: Kathagen G.
  Published: 2025/8 (journal-article)
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• Scientists can help stop a slide to nuclear war — don’t shut them out again
  Authors: None
  Published: 2025/8 (journal-article)
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• Why I co-developed a research career launchpad for first generation students
  Authors: Byrne D.
  Published: 2025/8 (journal-article)
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• How I’m electrifying transportation in Tanzania
  Authors: Forrester N.
  Published: 2025/8 (journal-article)
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• Real-time in-situ magnetization reprogramming for soft robotics
  Authors: Bao X.; Wang F.; Zhang J.; Li M.; Zhang S.; Ren Z.; Liao J.; Yan Y.; Kang W.; Zhang R.; Liu Z.; Wang T.; Sitti M.
  Published: 2025/8 (journal-article)
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• Direct identification of Ac and No molecules with an atom-at-a-time technique
  Authors: Pore J.; Gates J.; Dixon D.; Garcia F.; Gibson J.; Gooding J.; McCarthy M.; Orford R.; Shafi Z.; Shuh D.; Sprouse S.
  Published: 2025/8 (journal-article)
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• Environmental politics is doomed to fail — unless we tell better stories
  Authors: Macnaghten P.
  Published: 2025/8 (journal-article)
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• What it’s like fighting racism and sexism in shark science
  Authors: Hobson M.
  Published: 2025/8 (journal-article)
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• Glow-in-the-dark marsupial shows off its luminous fur — July’s best science images
  Authors: Kavanagh K.
  Published: 2025/8 (journal-article)
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• Exclusive: retraction-prone editors identified at megajournal PLoS ONE
  Authors: Naddaf M.
  Published: 2025/8 (journal-article)
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• To save lives in heatwaves, focus on how human bodies work
  Authors: Jay O.; Vanos J.; Gagnon D.; Tartarini F.
  Published: 2025/8 (journal-article)
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• We need a new ethics for a world of AI agents
  Authors: Gabriel I.; Keeling G.; Manzini A.; Evans J.
  Published: 2025/8 (journal-article)
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• This company claimed to ‘de-extinct’ dire wolves. Then the fighting started.
  Authors: Callaway E.
  Published: 2025/8 (journal-article)
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• Eating ultra-processed foods could make it harder to lose weight
  Authors: Kavanagh K.
  Published: 2025/8 (journal-article)
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• India to penalize universities with too many retractions
  Authors: Mallapaty S.
  Published: 2025/8 (journal-article)
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• I could not have become an astronomer on my own
  Authors: Wild S.
  Published: 2025/8 (journal-article)
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• ‘Congress has your back’: US senators tell scientists they want to protect NIH budget
  Authors: Kozlov M.
  Published: 2025/8 (journal-article)
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• mRNA vaccines for HIV trigger strong immune response in people
  Authors: Mallapaty S.
  Published: 2025/8 (journal-article)
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- Science

• Revisiting the human sociobiology debate Sociobiology: The New Synthesis Edward O. Wilson Harvard University Press, 1975. 697 pp.
  Authors: Brown G.; Barrett H.; Lala K.
  Published: 2025/8 (journal-article)
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  What have we learned 50 years on?

• Strain-coupled, crystalline polymer-inorganic interfaces for efficient magnetoelectric sensing
  Authors: He B.; He Y.; Wang W.; Sun Y.; Kong S.; Huang J.; Ru Y.; Qin B.; Ren H.; He J.; Zhao T.; Li J.; Lu J.; Zhao L.; Liu M.
  Published: 2025/8 (journal-article)
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  Magnetoelectric sensing holds promise for flexible sensors, offering precise detection of both electric and magnetic fields with minimal power consumption. However, its practical use has been constrained by weak magnetoelectric effects and limited overall performance, particularly under mechanical strain. Herein, we fabricated robust magnetoelectric polymer-inorganic nanocomposites through an interfacial cocrystallization strategy. By leveraging diazonium chemistry on vanadium diselenide (VSe2) monolayers, we created a submolecular-flat interface between ferromagnetic VSe2and ferroelectric poly(vinylidene fluoride) (PVDF) nanocrystals. This highly crystalline interface has few mobile polymer chains and thus limits energy dissipation and enhances interfacial energy transfer. The scalable composite films show exceptional magnetoelectric performance, with a magnetocapacitive coefficient of 23.6%. These films enable ultrafast magnetoelectric detection, approaching a 10-fold increase in speed compared with conventional sensors, and offer opportunities for integrating multifunctional materials such as thermoelectric coolers into wearable devices.

• Roxie Laybourne, the first forensic ornithologist The Feather Detective: Mystery, Mayhem, and the Magnificent Life of Roxie Laybourne Chris Sweeney Avid Reader Press, 2025. 320 pp.
  Authors: Venkatraman V.
  Published: 2025/8 (journal-article)
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  A new biography probes the life of a taxidermist turned avian investigator

• Study used DNA from thousands—without consent
  Authors: Inampudi A.
  Published: 2025/8 (journal-article)
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  iPsych, which investigates the genetics of psychiatric disorders, has sent 140,000 opt-out notices amid backlash

• Brazil’s dangerous environmental licensing bill
  Authors: Weidlich E.
  Published: 2025/8 (journal-article)
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• Imaging collective quantum fluctuations of the structure of a complex molecule
  Authors: Richard B.; Boll R.; Banerjee S.; Schäfer J.; Jurek Z.; Kastirke G.; Fehre K.; Schöffler M.; Anders N.; Baumann T.; Eckart S.; Erk B.; De Fanis A.; Dörner R.; Grundmann S.; Grychtol P.; Hofmann M.; Ilchen M.; Kircher M.; Kubicek K.; Kunitski M.; Li X.; Mazza T.; Meister S.; Melzer N.
  Published: 2025/8 (journal-article)
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  Because of the Heisenberg uncertainty principle, the structure of a molecule fluctuates about its mean geometry, even in the ground state. Observing this fundamental quantum effect experimentally—particularly, revealing the collective nature of the structural quantum fluctuations—remains an unmet challenge for complex molecules. In this work, we achieved this for an 11-atom molecule by inducing its Coulomb explosion with an x-ray free-electron laser. We show that the structural fluctuations manifest themselves in correlated variations of ion momenta obtained through coincident detection of the atomic fragments from individual molecules. Our analysis scheme allows extracting these variations, despite our measurements covering only a fraction of the full 33-dimensional momentum space, thereby establishing a general approach for extracting information on high-dimensional structural dynamics using Coulomb explosion.

• Hardening nature’s toughest teeth
  Authors: Scheffel A.
  Published: 2025/8 (journal-article)
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  A protein that underlies the mineralization of chiton teeth is revealed

• Transferrin receptor–targeted anti-amyloid antibody enhances brain delivery and mitigates ARIA
  Authors: Pizzo M.; Plowey E.; Khoury N.; Kwan W.; Abettan J.; DeVos S.; Discenza C.; Earr T.; Joy D.; Lye-Barthel M.; Roche E.; Chan D.; Dugas J.; Gadkar K.; Hamann S.; Meisner R.; Sebalusky J.; Silva Amaral A.; Becerra I.; Chau R.; Chow J.; Clemens A.; Dennis M.; Duque J.; Fusaro L.
  Published: 2025/8 (journal-article)
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  Amyloid-related imaging abnormalities (ARIA), side effects of anti-amyloid drugs seen in magnetic resonance imaging of the brain, are a major safety concern in patients with Alzheimer’s disease. We developed an antibody transport vehicle (ATV) targeting transferrin receptor (TfR) for brain delivery of anti-amyloid-β protein (anti-Aβ) using asymmetrical Fc mutations (ATVcisLALA) that mitigates TfR-related liabilities and retains effector function when bound to Aβ. Administration of ATVcisLALA:Aβ in mice exhibited broad brain distribution and enhanced parenchymal plaque target engagement. This biodistribution reduced ARIA-like lesions and vascular inflammation. Taken together, ATVcisLALAhas the potential to improve the next generation of Aβ immunotherapy through enhanced biodistribution mediated by transport across the blood-brain barrier.

• Evolution of antiviral host defenses against a backdrop of endogenous retroelements
  Authors: Kassiotis G.; Stoye J.
  Published: 2025/8 (journal-article)
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  Mammalian hosts deploy a multitude of germ line–encoded mechanisms to detect and restrict virus infection. These mechanisms must avoid pathological responses to endogenous retroviruses and other endogenous retrotransposable elements (RTEs)—viruses and viruslike genomic parasites that have invaded the host germ line and are passed down the generations as host genes. Although the location, specificity, and sensitivity of innate pattern recognition receptors and restriction factors are tuned to facilitate discrimination of infecting viruses from those that are part of self, immune cross-reactions do occur. The RTE viral heritage may, therefore, compromise the ability of the host to respond to virus infection without risking pathology. Nevertheless, RTEs have the potential to be co-opted as an alarm amplification system, to be repurposed as antiviral factors, and to contribute to the evolution of antiviral genes.

• Radular teeth matrix protein 1 directs iron oxide deposition in chiton teeth
  Authors: Nemoto M.; Okada K.; Akamine H.; Odagaki Y.; Narahara Y.; Okoshi K.; Obuse K.; Kisailus D.; Moriya H.; Satoh A.
  Published: 2025/8 (journal-article)
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  Nature builds multiscale mineral structures with impressive mechanical properties through spatially and temporally orchestrated organic-mineral assembly. One example of regulated mineralization is found in hypermineralized and ultrahard magnetic teeth of chiton, which grind on rock to feed on algae. At early stages of tooth formation, iron oxide deposition is controlled using a chiton-specific radular teeth matrix protein 1 (RTMP1), which is transported into teeth through microvilli. RTMP1 spatially and temporally guides and enhances mineralization on chitinous fibers within the tooth, providing a hard, tough, and strong architecture that enables the organism to perform repetitive abrasive events to survive.

• Opening the gateway to food-induced anaphylaxis
  Authors: Haque T.; Kaplan M.
  Published: 2025/8 (journal-article)
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  Cysteinyl leukotrienes are important drivers of the anaphylactic response to ingested food antigens

• How a diagnosis altered my path
  Authors: De Vuyst M.
  Published: 2025/8 (journal-article)
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• Single-photon detection enabled by negative differential conductivity in moiré superlattices
  Authors: Nowakowski K.; Agarwal H.; Slizovskiy S.; Smeyers R.; Wang X.; Zheng Z.; Barrier J.; Barcons Ruiz D.; Li G.; Bertini R.; Ceccanti M.; Torre I.; Jorissen B.; Reserbat-Plantey A.; Watanabe K.; Taniguchi T.; Covaci L.; Milošević M.; Fal’ko V.; Jarillo-Herrero P.; Krishna Kumar R.; Koppens F.
  Published: 2025/8 (journal-article)
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  Detecting individual light quanta is essential for quantum information, space exploration, advanced machine vision, and fundamental science. In this work, we introduce a single-photon detection mechanism using highly photosensitive nonequilibrium electron phases in moiré materials. Using tunable bands in bilayer graphene/hexagonal boron nitride superlattices, we engineer negative differential conductance and a sensitive bistable state capable of detecting single photons. Operating in this regime, we demonstrate single-photon counting at mid-infrared (11.3 micrometers) and visible wavelengths (675 nanometers) and temperatures up to 25 kelvin. This detector offers prospects for broadband, high-temperature quantum technologies with complementary metal-oxide semiconductor compatibility and seamless integration into photonic-integrated circuits. Our analysis suggests that the underlying mechanism originates from superlattice-induced negative differential velocity.

• Improving Alzheimer’s disease immunotherapy
  Authors: Xing M.; Song W.
  Published: 2025/8 (journal-article)
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  A modified antibody targeting amyloid-β reduces adverse events and increases efficacy in a mouse model

• Sex differences in tissue-specific immunity and immunology
  Authors: Sharma S.; Gibbons A.; Saphire E.
  Published: 2025/8 (journal-article)
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  Biological sex exerts a substantial influence on the immune system and immune-related diseases. Males are more susceptible to the acute effects of viral disease and certain cancers, whereas females exhibit a more robust immune response that can make them prone to developing autoimmune complications. We reflect on the emerging appreciation of sex differences—governed by genetics, sex hormones, and environmental factors—in tissue immunity and immunology. Understanding these tissue context–dependent sex differences in the immune system is critical to deciphering the exact mechanisms that determine why women and men experience organ-specific infections, autoimmune or inflammatory diseases, and cancers differently. Only by parsing distinction at the tissue level can the development of personalized and precision immunotherapy approaches be conceived and then achieved.

• Convergence and divergence of individual immune responses over the life course
  Authors: Metcalf C.; Graham A.; Yates A.; Cummings D.
  Published: 2025/8 (journal-article)
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  Three ingredients create the strikingly variable immune trajectories observed across human populations: (i) genetic variation, (ii) individual-scale generation of additional genetic diversity solely in lymphocytes, and (iii) collision of these processes with a changing environment through life, triggering plastic responses that can have lasting effects. We explore what generates or reduces immune variation, integrating recent empirical advances with potential overarching evolutionary principles. We posit that the multiple components of the immune system each present trade-offs (such as self-defense–self-harm, and investments in memory–retaining flexibility for future responses) that vary through life, and that variation in how immune components balance these trade-offs increases homeostasis to external and internal threats. Disentangling the mechanisms that shape immune diversity could inform effective strategies to manage microbial interactions and mitigate the burden of immune-mediated chronic diseases.

• Losing protection
  Authors: Enserink M.
  Published: 2025/8 (journal-article)
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  The United States helped beat back malaria in Guinea. Now, the disease is set to soar

• Moiré eyes detect the dim
  Authors: Bandurin D.
  Published: 2025/8 (journal-article)
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  Unusual electronic behavior of a moiré superlattice helps detect a single light particle

• Predicting expression-altering promoter mutations with deep learning
  Authors: Jaganathan K.; Ersaro N.; Novakovsky G.; Wang Y.; James T.; Schwartzentruber J.; Fiziev P.; Kassam I.; Cao F.; Hawe J.; Cavanagh H.; Lim A.; Png G.; McRae J.; Banerjee A.; Kumar A.; Ulirsch J.; Zhang Y.; Aguet F.; Wainschtein P.; Sundaram L.; Salcedo A.; Panagiotopoulou S.; Aghamirzaie D.; Padhi E.
  Published: 2025/8 (journal-article)
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  Only a minority of patients with rare genetic diseases are presently diagnosed by exome sequencing, suggesting that additional unrecognized pathogenic variants may reside in noncoding sequence. In this work, we describe PromoterAI, a deep neural network that accurately identifies noncoding promoter variants that dysregulate gene expression. We show that promoter variants with predicted expression-altering consequences produce outlier expression at both the RNA and protein levels in thousands of individuals and that these variants experience strong negative selection in human populations. We observed that clinically relevant genes in patients with rare diseases are enriched for such variants and validated their functional impact through reporter assays. Our estimates suggest that promoter variation accounts for 6% of the genetic burden associated with rare diseases.

• In Science Journals
  Authors: Jiang D.; Aldenderfer M.; Suleymanov Y.; Ferrarelli L.; Szuromi P.; Lavine M.; Ross S.; Maroso M.; Nusinovich Y.; Osborne I.; Berry B.; Olingy C.
  Published: 2025/8 (journal-article)
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  Highlights from theSciencefamily of journals

• Senate panel rejects Trump’s plan to slash NIH’s budget
  Authors: Kaiser J.
  Published: 2025/8 (journal-article)
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  Bipartisan support for agency challenges proposed reorganization and overhead costs cap

• Three-dimensional nucleation and growth of deformation twins in magnesium
  Authors: Lee S.; Pilipchuk M.; Yildirim C.; Greeley D.; Shi Q.; Berman T.; Creuziger A.; Rust E.; Detlefs C.; Sundararaghavan V.; Allison J.; Bucsek A.
  Published: 2025/8 (journal-article)
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  At two-thirds the weight of aluminum, magnesium alloys have the potential to reduce the fuel consumption of transportation vehicles. These advancements depend on our ability to optimize the desirable versus undesirable effects of deformation twins, which are three-dimensional (3D) microstructural domains that form under mechanical stresses. Previously only characterized through surface or thin-film measurements, we present 3D in situ characterization of deformation twinning inside an embedded grain over mesoscopic fields of view using dark-field x-ray microscopy supported by crystal plasticity finite element analysis. The results revealed the role of triple junctions on twin nucleation and the sequence and irregularity of twin growth and showed that twin-grain junctions, twin-twin junctions, and twin boundaries were the sites of localized dislocation accumulation.

• Intestinal mast cell–derived leukotrienes mediate the anaphylactic response to ingested antigens
  Authors: Bachtel N.; Cullen J.; Liu M.; Erickson S.; Kutyavin V.; El-Naccache D.; Florsheim E.; Lim J.; Sullivan Z.; Imaeda R.; Hudak A.; Zhang C.; Medzhitov R.
  Published: 2025/8 (journal-article)
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  Anaphylaxis is a life-threatening complication of food allergen exposure. Although mechanisms governing anaphylaxis after intravenous injection are defined in mice, these models neglect mucosal exposure that accompanies ingestion. We investigated the role of mast cells within the intestine of mice and found that oral anaphylaxis required immunoglobulin E–Fcε receptor 1 (IgE-FcεR1) signaling. Intestinal mast cells were a heterogeneous population, shaped by epithelial cues. Compared with connective tissue mast cells found throughout the body, intestinal mast cells largely resided in the epithelium, displayed divergent transcriptomes and effector functions, and had a diminished ability to generate histamine, but they enhanced leukotriene synthesis. Mice genetically deficient in cysteinyl leukotriene synthesis, or those treated with the arachidonate 5-lipoxygenase (aLOX5) antagonist zileuton, were protected from oral antigen–induced responses, whereas those elicited by intravenous injection were unaltered.

• The multifunctional immune system
  Authors: Ross S.; Ash C.
  Published: 2025/8 (journal-article)
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• New Products
  Authors: None
  Published: 2025/8 (journal-article)
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  A weekly roundup of information on newly offered instrumentation, apparatus, and laboratory materials of potential interest to researchers.

• Census in crisis—further erasure of Indigenous Peoples?
  Authors: Kukutai T.
  Published: 2025/8 (journal-article)
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  In 2013, demographer David Coleman wrote that the population census in its traditional form washeading toward its twilight. Its impending demise was being driven by digitization, rapid data transfer, and data linkage technologies. Declining census response rates and soaring costs hastened the decline. A decade later, that forecasted twilight is coming to pass. For the world’s estimated476 millionIndigenous Peoples, the census crisis comes at a critical point in their fight for rights and recognition.

• An orthogonal T7 replisome for continuous hypermutation and accelerated evolution in E. coli
  Authors: Diercks C.; Sondermann P.; Rong C.; Gillis T.; Ban Y.; Wang C.; Dik D.; Schultz P.
  Published: 2025/8 (journal-article)
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  Systems that perform continuous hypermutation of designated genes without compromising the integrity of the host genome can substantially accelerate the evolution of new or enhanced protein functions. We describe an orthogonal DNA replication system inEscherichia colibased on the controlled expression of the replisome of bacteriophage T7 (T7-ORACLE). The system replicates circular plasmids that enable high transformation efficiencies and seamless integration into standard molecular biology workflows. Engineering of T7 DNA polymerase yielded variant proteins with mutation rates of 1.7 × 10−5substitutions per base in vivo—100,000-fold above the genomic mutation rate. We demonstrated continuous evolution using the T7 replisome by expanding the substrate scope of TEM-1 β-lactamase and increasing activity 5000-fold against clinically relevant monobactam and cephalosporin antibiotics in less than 1 week.

• Community support for inclusive US education
  Authors: Driessen E.; Lane A.
  Published: 2025/8 (journal-article)
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• In Other Journals
  Authors: Vignieri S.; Ray L.; Kelly P.; Wible B.; Stern P.; Huang J.; Smith J.
  Published: 2025/8 (journal-article)
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  Editors’ selections from the current scientific literature

• Cysteinyl leukotrienes stimulate gut absorption of food allergens to promote anaphylaxis in mice
  Authors: Hoyt L.; Liu E.; Olson E.; Jacobsen D.; Siniscalco E.; Krier-Burris R.; Greenfield K.; McBride C.; Alfajaro M.; Amat J.; Zhao Z.; Xu L.; Philip V.; Verma A.; Fourati S.; Senger D.; Zhang L.; Bunyavanich S.; Glass S.; Coffey R.; Wilen C.; Williams A.; Eisenbarth S.
  Published: 2025/8 (journal-article)
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  Food-specific immunoglobulin E (IgE) triggers life-threatening anaphylaxis; however, for unclear reasons, some people with food-specific IgE are asymptomatic upon allergen consumption. We studied strains of mice with different sensitivities to anaphylaxis when orally challenged with allergen to identify possible causes. In resistant C57BL/6 mice, intestinal goblet cells transported less food allergen than did anaphylaxis-susceptible strains, even before allergic sensitization. In a forward genetic screen, resistance was correlated withdipeptidase 1(Dpep1) variants. DPEP1 is expressed in intestinal epithelium and catabolizes leukotriene D4(LTD4). Blocking DPEP1 with cilastatin, deletingDpep1, or administering LTD4orally enhanced allergen transport in resistant mice. Conversely, pretreatment of susceptible mice with a synthesis inhibitor, zileuton, abrogated allergen absorption and oral anaphylaxis, indicating that this could be an approach to treating food allergy.

• The Columbia deal is a tragic wake-up call
  Authors: Thorp H.
  Published: 2025/8 (journal-article)
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  Last month, Columbia University entered an agreement with the US government to restore federal funding for research in exchange for actions by the university to address complaints by the Trump administration about antisemitism on campus and civil rights violations in admissions and faculty hiring. In reaching the deal, the government wielded science funding—at least $1.3 billion dollars annually—as a powerful lever to influence the university, and signing it was probably unavoidable. Although there is much to criticize in the agreement, it stands as a reminder that accepting federal dollars for research has always come with the possibility that those funds could be clawed back under circumstances deemed a misuse of taxpayer money. Universities are now witnessing this power-of-the-purse at an unparalleled magnitude.

• The membrane skeleton is constitutively remodeled in neurons by calcium signaling
  Authors: Heller E.; Kurup N.; Zhuang X.
  Published: 2025/8 (journal-article)
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  The membrane skeleton in neurons adopts a periodic lattice structure in which actin filaments, capped by adducin and tropomodulin, form ring-shaped structures connected by spectrin tetramers along neurites. This membrane-associated periodic skeleton (MPS) is important for many neuronal functions. Using live-cell super-resolution imaging, we found that the MPS is surprisingly dynamic, undergoing local disassembly and reformation constitutively in axons. MPS remodeling is driven by calcium signaling, leading to actin-ring destabilization through protein kinase C–mediated adducin phosphorylation and to spectrin degradation by calpain. Formin, an actin-nucleating and -polymerizing enzyme, plays a dual role in MPS remodeling and maintenance. MPS remodeling is enhanced by neuronal activity and functionally facilitates endocytosis. Our results highlight the importance of a dynamic membrane skeletal structure in neuronal function.

• Thank ketchup, and interbreeding, for your French fries
  Authors: Stokstad E.
  Published: 2025/8 (journal-article)
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  Hybridization 9 million years ago gave potatoes the genetic knack to develop tubers, a new study finds

• Immune system influence on physiology
  Authors: Nahrendorf M.; Ginhoux F.; Swirski F.
  Published: 2025/8 (journal-article)
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  The immune system’s central function is to maintain homeostasis by guarding the organism against dangerous external and internal stressors. Immunity’s operational toolbox contains diverse processes, such as phagocytosis, antigen recognition, cell killing, and secretion of cytokines and antibodies. Although immune cells interact with each other, they also communicate with cells typically associated with other organ systems, including the nervous, circulatory, metabolic, musculoskeletal, endocrine, and hematopoietic. This abundant cross-talk shows that immunity transcends defense and homeostasis: It is a network that participates in many physiological processes necessary for life. By accessing the circulation and inhabiting every tissue, leukocytes sense, interpret, and regulate biological processes. In this Review, we highlight recent studies that illustrate the often bidirectional and symbiotic relationships through which the immune system regulates physiology.

• Brazil’s “devastation bill” empowers criminals
  Authors: Giles A.; Flores B.
  Published: 2025/8 (journal-article)
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• NextGen Voices: National Assessments in Verse
  Authors: None
  Published: 2025/8 (journal-article)
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• AI-generated text surges in research papers
  Authors: Jacobs P.
  Published: 2025/8 (journal-article)
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  One-fifth of computer science papers may include AI-written sentences

• Quantum technology governance: A standards-first approach
  Authors: Aboy M.; Gasser U.; Cohen I.; Kop M.
  Published: 2025/8 (journal-article)
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  Standards offer a flexible, globally harmonized path to govern early-stage quantum technologies while preserving innovation, security, and international cooperation

• Study reveals industrial-scale publishing fraud
  Authors: O’Grady C.
  Published: 2025/8 (journal-article)
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  Sophisticated global networks are infiltrating journals to publish fake papers

- Nature Reviews Neuroscience

• Synaptic connectomics: status and prospects
  Authors: Bock D.
  Published: 2025/8 (journal-article)
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• CRISPR-TO: a versatile tool for programmable control of the spatial transcriptome
  Authors: Han M.
  Published: 2025/8 (journal-article)
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• A gut instinct for microbial patterns
  Authors: Lewis S.
  Published: 2025/8 (journal-article)
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• The emergence of NeuroAI: bridging neuroscience and artificial intelligence
  Authors: Sadeh S.; Clopath C.
  Published: 2025/8 (journal-article)
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• The vascular contribution to cognitive decline in ageing and dementia
  Authors: Anderle S.; Dixon M.; Quintela-Lopez T.; Sideris-Lampretsas G.; Attwell D.
  Published: 2025/8 (journal-article)
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• A maturing view on interneuron development
  Authors: Yates D.
  Published: 2025/8 (journal-article)
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- Nature Methods

• Co-profiling of in situ RNA-protein interactions and transcriptome in single cells and tissues
  Authors: Cheng Q.; Xie G.; Zhang X.; Wang J.; Ding S.; Wu Y.; Shi M.; Duan F.; Wan Z.; Wei J.; Xiao J.; Wang Y.
  Published: 2025/8 (journal-article)
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• MAPIT-seq reveals both RBP targets and transcriptome-wide gene expression profiles
  Authors: None
  Published: 2025/8 (journal-article)
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• Author Correction: A universal language for finding mass spectrometry data patterns
  Authors: Damiani T.; Jarmusch A.; Aron A.; Petras D.; Phelan V.; Zhao H.; Bittremieux W.; Acharya D.; Ahmed M.; Bauermeister A.; Bertin M.; Boudreau P.; Borges R.; Bowen B.; Brown C.; Chagas F.; Clevenger K.; Correia M.; Crandall W.; Crüsemann M.; Fahy E.; Fiehn O.; Garg N.; Gerwick W.; Gilbert J.
  Published: 2025/8 (journal-article)
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• Unravelling cellular interactions using flow cytometry
  Authors: None
  Published: 2025/8 (journal-article)
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• Ultra-high-scale cytometry-based cellular interaction mapping
  Authors: Vonficht D.; Jopp-Saile L.; Yousefian S.; Flore V.; Simó Vesperinas I.; Teuber R.; Avanesyan B.; Luo Y.; Röthemeier C.; Grünschläger F.; Fernandez-Vaquero M.; Fregona V.; Ordoñez-Rueda D.; Schmalbrock L.; Deininger L.; Yamachui Sitcheu A.; Gu Z.; Funk M.; Mikut R.; Heikenwälder M.; Eggert A.; von Stackelberg A.; Kobold S.; Krönke J.; Keller U.
  Published: 2025/8 (journal-article)
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  AbstractCellular interactions are of fundamental importance, orchestrating organismal development, tissue homeostasis and immunity. Recently, powerful methods that use single-cell genomic technologies to dissect physically interacting cells have been developed. However, these approaches are characterized by low cellular throughput, long processing times and high costs and are typically restricted to predefined cell types. Here we introduce Interact-omics, a cytometry-based framework to accurately map cellular landscapes and cellular interactions across all immune cell types at ultra-high resolution and scale. We demonstrate the utility of our approach to study kinetics, mode of action and personalized response prediction of immunotherapies, and organism-wide shifts in cellular composition and cellular interaction dynamics following infection in vivo. Our scalable framework can be applied a posteriori to existing cytometry datasets or incorporated into newly designed cytometry-based studies to map cellular interactions with a broad range of applications from fundamental biology to applied biomedicine.

• Combating hallucination in digital pathology
  Authors: Tang L.
  Published: 2025/8 (journal-article)
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• Machine learning-trained protein domain insertion for the design of switchable proteins
  Authors: Holzleitner N.; Grünewald J.
  Published: 2025/8 (journal-article)
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• Deep-learning-based gene perturbation effect prediction does not yet outperform simple linear baselines
  Authors: Ahlmann-Eltze C.; Huber W.; Anders S.
  Published: 2025/8 (journal-article)
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  AbstractRecent research in deep-learning-based foundation models promises to learn representations of single-cell data that enable prediction of the effects of genetic perturbations. Here we compared five foundation models and two other deep learning models against deliberately simple baselines for predicting transcriptome changes after single or double perturbations. None outperformed the baselines, which highlights the importance of critical benchmarking in directing and evaluating method development.

• Push-button science
  Authors: None
  Published: 2025/8 (journal-article)
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• Is single-molecule protein sequencing here yet?
  Authors: Marx V.
  Published: 2025/8 (journal-article)
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• The biofouling tubeworm Hydroides elegans
  Authors: Farrell M.; Darin E.; Shikuma N.
  Published: 2025/8 (journal-article)
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• Morphological map of under- and overexpression of genes in human cells
  Authors: Chandrasekaran S.; Alix E.; Arevalo J.; Borowa A.; Byrne P.; Charles W.; Chen Z.; Cimini B.; Deng B.; Doench J.; Ewald J.; Fritchman B.; Fuller C.; Gaetz J.; Goodale A.; Haghighi M.; Han Y.; Hanifehlou Z.; Hennig H.; Hernandez D.; Jacob C.; James T.; Jetka T.; Kalinin A.; Komalo B.
  Published: 2025/8 (journal-article)
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• Spatiotemporal lipidomics in living tissue
  Authors: Singh A.
  Published: 2025/8 (journal-article)
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• Capturing host–microbe interactions
  Authors: Mukhopadhyay M.
  Published: 2025/8 (journal-article)
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• The Platinum Pedigree: a long-read benchmark for genetic variants
  Authors: Kronenberg Z.; Nolan C.; Porubsky D.; Mokveld T.; Rowell W.; Lee S.; Dolzhenko E.; Chang P.; Holt J.; Saunders C.; Olson N.; Steely C.; McGee S.; Guarracino A.; Koundinya N.; Harvey W.; Watkins W.; Munson K.; Hoekzema K.; Chua K.; Chen X.; Fanslow C.; Lambert C.; Dashnow H.; Garrison E.
  Published: 2025/8 (journal-article)
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• Neuropixels for nonhuman primates
  Authors: Vogt N.
  Published: 2025/8 (journal-article)
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• Enhancing CRISPR DNA imaging
  Authors: Tang L.
  Published: 2025/8 (journal-article)
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• Rational engineering of allosteric protein switches by in silico prediction of domain insertion sites
  Authors: Wolf B.; Shehu P.; Brenker L.; von Bachmann A.; Kroell A.; Southern N.; Holderbach S.; Eigenmann J.; Aschenbrenner S.; Mathony J.; Niopek D.
  Published: 2025/8 (journal-article)
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  AbstractDomain insertion engineering is a powerful approach to juxtapose otherwise separate biological functions, resulting in proteins with new-to-nature activities. A prominent example are switchable protein variants, created by receptor domain insertion into effector proteins. Identifying suitable, allosteric sites for domain insertion, however, typically requires extensive screening and optimization. We present ProDomino, a machine learning pipeline to rationalize domain recombination, trained on a semisynthetic protein sequence dataset derived from naturally occurring intradomain insertion events. ProDomino robustly identifies domain insertion sites in proteins of biotechnological relevance, which we experimentally validated inEscherichia coliand human cells. Finally, we used light- and chemically regulated receptor domains as inserts and demonstrate the rapid, model-guided creation of potent, single-component opto- and chemogenetic protein switches. These include novel CRISPR–Cas9 and –Cas12a variants for inducible genome engineering in human cells. Our work enables one-shot domain insertion engineering and substantially accelerates the design of customized allosteric proteins.

• PANCS-Binders: a rapid, high-throughput binder discovery platform
  Authors: Styles M.; Pixley J.; Wei T.; Basile C.; Lu S.; Dickinson B.
  Published: 2025/8 (journal-article)
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- Nature Neuroscience

• Turning back the clock on age-related neurodegeneration
  Authors: None
  Published: 2025/8 (journal-article)
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• Impaired capillary–venous drainage contributes to gliosis and demyelination in mouse white matter during aging
  Authors: Stamenkovic S.; Schmid F.; Gurler G.; Abolmaali F.; Weitermann N.; Takasaki K.; Bonney S.; Sosa M.; Bennett H.; Kim Y.; Waters J.; Shih A.
  Published: 2025/8 (journal-article)
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  AbstractThe progressive loss of cerebral white matter during aging contributes to cognitive decline, but whether reduced blood flow is a cause or a consequence remains debatable. Using deep multi-photon imaging in mice, we examined microvascular networks perfusing myelinated tissues in cortical layer 6 and the corpus callosum. We identified sparse, wide-reaching venules, termed principal cortical venules, which exclusively drain deep tissues and resemble the vasculature at the human cortex and U-fiber interface. Aging led to selective constriction and rarefaction of capillaries in deep branches of principal cortical venules. This resulted in mild hypoperfusion that was associated with microgliosis, astrogliosis and demyelination in deep tissues, but not the upper cortex. Induction of comparable hypoperfusion in adult mice using carotid artery stenosis triggered a similar tissue pathology specific to layer 6 and the corpus callosum. Thus, impaired capillary–venous drainage is a contributor to hypoperfusion and a potential therapeutic target for preserving blood flow to white matter during aging.

• Cross-species analysis of adult hippocampal neurogenesis reveals human-specific features
  Authors: None
  Published: 2025/8 (journal-article)
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• The brain drain puts aging myelin in deep trouble
  Authors: Assali A.; Renier N.
  Published: 2025/8 (journal-article)
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• Embryonic motor neuron programming factors reactivate immature gene expression and suppress ALS pathologies in postnatal motor neurons
  Authors: Lowry E.; Patel T.; Costa J.; Chang E.; Tariq S.; Melikyan H.; Davis I.; Aziz S.; Ntermentzaki G.; Lotti F.; Wichterle H.
  Published: 2025/8 (journal-article)
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• Aberrant splicing exonizes C9orf72 repeat expansion in ALS/FTD
  Authors: Yang S.; Wijegunawardana D.; Sheth U.; Veire A.; Salgado J.; Arab T.; Agrawal M.; Zhou J.; Pereira J.; Gendron T.; Guo J.
  Published: 2025/8 (journal-article)
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• Cross-species analysis of adult hippocampal neurogenesis reveals human-specific gene expression but convergent biological processes
  Authors: Zhou Y.; Su Y.; Yang Q.; Li J.; Hong Y.; Gao T.; Zhong Y.; Ma X.; Jin M.; Liu X.; Yuan N.; Kennedy B.; Wang L.; Yan L.; Viaene A.; Helbig I.; Kessler S.; Kleinman J.; Hyde T.; Nauen D.; Liu C.; Liu Z.; Shen Z.; Li C.; Xu S.
  Published: 2025/8 (journal-article)
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• Differential kinematic coding in sensorimotor striatum across behavioral domains reflects different contributions to movement
  Authors: Hardcastle K.; Marshall J.; Gellis A.; Klibaite U.; Bhatia C.; Wang W.; Chalyshkan S.; Ölveczky B.
  Published: 2025/8 (journal-article)
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• Layer-specific changes in sensory cortex across the lifespan in mice and humans
  Authors: Liu P.; Doehler J.; Henschke J.; Northall A.; Knaf-Serian A.; Loaiza-Carvajal L.; Budinger E.; Schwarzkopf D.; Speck O.; Pakan J.; Kuehn E.
  Published: 2025/8 (journal-article)
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  AbstractThe segregation of processes into cortical layers is a convergent feature in animal evolution. However, how changes in the cortical layer architecture interact with sensory system function and dysfunction remains unclear. Here we conducted functional and structural layer-specific in vivo 7T magnetic resonance imaging of the primary somatosensory cortex in two cohorts of healthy younger and older adults. Input layer IV is enlarged and more myelinated in older adults and is associated with extended sensory input signals. Age-related cortical thinning is driven by deep layers and accompanied by increased myelination, but there is no clear evidence for reduced inhibition. Calcium imaging and histology in younger and older mice revealed increased sensory-evoked neuronal activity accompanied by increased parvalbumin expression as a potential inhibitory balance, with dynamic changes in layer-specific myelination across age groups. Using multimodal imaging, we demonstrate that middle and deep layers show specific sensitivity to aging across species.

• Potentiation of mitochondrial function by mitoDREADD-Gs reverses pharmacological and neurodegenerative cognitive impairment in mice
  Authors: Pagano Zottola A.; Martín-Jiménez R.; Lavanco G.; Hamel-Côté G.; Ramon-Duaso C.; Rodrigues R.; Mariani Y.; Khan M.; Drago F.; Jean S.; Río I.; Jimenez-Blasco D.; Egaña-Huguet J.; Eraso-Pichot A.; Beriain S.; Cannich A.; Vidal-Palencia L.; Infantino R.; Julio-Kalajzić F.; Gisquet D.; Goncalves A.; Al-Younis I.; Baussan Y.; Duvezin-Caubet S.; Devin A.
  Published: 2025/8 (journal-article)
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• A pancreas–hippocampus feedback mechanism regulates circadian changes in depression-related behaviors
  Authors: Liu Y.; Wang Q.; She X.; Li L.; Wang B.; Yang R.; Li Q.; Lu S.; Wang Y.; Shen W.; Fu C.; Li D.; Yi L.; Wang C.; Shi W.; Cheng X.; Cao L.; Mi S.; Yao J.
  Published: 2025/8 (journal-article)
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• Hypoxia ameliorates neurodegeneration and movement disorder in a mouse model of Parkinson’s disease
  Authors: Marutani E.; Miranda M.; Durham T.; Kim S.; Russell D.; Wiesenthal P.; Lichtenegger P.; Menard M.; Brzozowski C.; Li H.; Ruvkun G.; Meisel J.; Volpicelli-Daley L.; Mootha V.; Ichinose F.
  Published: 2025/8 (journal-article)
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  AbstractParkinson’s disease (PD) is characterized by inclusions of α-synuclein (α-syn) and mitochondrial dysfunction in dopaminergic (DA) neurons of the substantia nigra pars compacta (SNpc). Patients with PD anecdotally experience symptom improvement at high altitude; chronic hypoxia prevents the development of Leigh-like brain disease in mice with mitochondrial complex I deficiency. Here we report that intrastriatal injection of α-syn preformed fibrils (PFFs) in mice resulted in neurodegeneration and movement disorder, which were prevented by continuous exposure to 11% oxygen. Specifically, PFF-induced α-syn aggregation resulted in brain tissue hyperoxia, lipid peroxidation and DA neurodegeneration in the SNpc of mice breathing 21% oxygen, but not in those breathing 11% oxygen. This neuroprotective effect of hypoxia was also observed inCaenorhabditis elegans. Moreover, initiating hypoxia 6 weeks after PFF injection reversed motor dysfunction and halted further DA neurodegeneration. These results suggest that hypoxia may have neuroprotective effects downstream of α-syn aggregation in PD, even after symptom onset and neuropathological changes.

• Serotonergic modulation of the BNST–CeA pathway reveals sex differences in fear learning
  Authors: Ravenelle R.; Lee J.; Fernandes-Henriques C.; Liu J.; Friedman A.; Likhtik E.; Burghardt N.
  Published: 2025/8 (journal-article)
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• The psychoplastogen tabernanthalog induces neuroplasticity without proximate immediate early gene activation
  Authors: Aarrestad I.; Cameron L.; Fenton E.; Casey A.; Rijsketic D.; Patel S.; Sambyal R.; Johnson S.; Ly C.; Viswanathan J.; Barragan E.; Lozano S.; Seban N.; Hu H.; Powell N.; Chytil M.; Meyer R.; Rose D.; Hempel C.; Olson E.; Hansen H.; Madsen C.; Knudsen G.; Redd C.; Wheeler D.
  Published: 2025/8 (journal-article)
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• Alzheimer’s disease transcriptional landscape in ex vivo human microglia
  Authors: Kosoy R.; Fullard J.; Bendl J.; Kleopoulos S.; Shao Z.; Argyriou S.; Mathur D.; Psychogyiou K.; Malakates P.; Vicari J.; Ma Y.; Humphrey J.; Brophy E.; Raj T.; Katsel P.; Voloudakis G.; Lee D.; Bennett D.; Haroutunian V.; Hoffman G.; Roussos P.
  Published: 2025/8 (journal-article)
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• Big data for classifying ASD
  Authors: Wiseman S.
  Published: 2025/8 (journal-article)
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• Swapping microglia to treat ALSP
  Authors: Wright R.
  Published: 2025/8 (journal-article)
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• Neurons feed tumors
  Authors: Zelenka L.
  Published: 2025/8 (journal-article)
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- Behavioral and Brain Sciences

- Nature Cell Biology

• A multichaperone condensate enhances protein folding in the endoplasmic reticulum
  Authors: Leder A.; Mas G.; Szentgyörgyi V.; Jakob R.; Maier T.; Spang A.; Hiller S.
  Published: 2025/8 (journal-article)
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  AbstractProtein folding in the endoplasmic reticulum (ER) relies on a network of molecular chaperones that facilitates the folding and maturation of client proteins. How the ER chaperones organize in a supramolecular manner to exert their cooperativity has, however, remained unclear. Here we report the discovery of a multichaperone condensate in the ER lumen, which is formed around the chaperone PDIA6 during protein folding homeostasis. The condensates form in a Ca2+-dependent manner and we resolve the underlying mechanism at the atomic and cellular levels. The PDIA6 condensates recruit further chaperones—Hsp70 BiP, J-domain protein ERdj3, disulfide isomerase PDIA1 and Hsp90 Grp94—which constitute some of the essential components of the early folding machinery. The chaperone condensates enhance folding of proteins, such as proinsulin, and prevent protein misfolding in the ER lumen. The PDIA6-scaffolded chaperone condensates hence provide the functional basis for spatial and temporal coordination of the dynamic ER chaperone network.

• Author Correction: SHP-1 inhibition targets leukaemia stem cells to restore immunosurveillance and enhance chemosensitivity by metabolic reprogramming
  Authors: Xu X.; Yu Y.; Zhang W.; Ma W.; He C.; Qiu G.; Wang X.; Liu Q.; Zhao M.; Xie J.; Tao F.; Perry J.; Liu Q.; Rao S.; Kang X.; Zhao M.; Jiang L.
  Published: 2025/8 (journal-article)
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• The intrinsically disordered regions of organellophagy receptors are interchangeable and control organelle fragmentation, ER-phagy and mitophagy flux
  Authors: Rudinskiy M.; Galli C.; Raimondi A.; Molinari M.
  Published: 2025/8 (journal-article)
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  AbstractOrganellophagy receptors control the generation and delivery of portions of their homing organelle to acidic degradative compartments to recycle nutrients, remove toxic or aged macromolecules and remodel the organelle upon physiologic or pathologic cues. How they operate is not understood. Here we show that organellophagy receptors are composed of a membrane-tethering module that controls organellar and suborganellar distribution and by a cytoplasmic intrinsically disordered region (IDR) with net cumulative negative charge that controls organelle fragmentation and displays an LC3-interacting region (LIR). The LIR is required for lysosomal delivery but is dispensable for organelle fragmentation. Endoplasmic reticulum (ER)-phagy receptors’ IDRs trigger DRP1-assisted mitochondrial fragmentation and mitophagy when transplanted at the outer mitochondrial membrane. Mitophagy receptors’ IDRs trigger ER fragmentation and ER-phagy when transplanted at the ER membrane. This offers an interesting example of function conservation on sequence divergency. Our results imply the possibility to control the integrity and activity of intracellular organelles by surface expression of organelle-targeted chimeras composed of an organelle-targeting module and an IDR module with net cumulative negative charge that, if it contains a LIR, eventually tags the organelle portions for lysosomal clearance.

• Author Correction: Endoplasmic reticulum–mitochondria contacts are prime hotspots of phospholipid peroxidation driving ferroptosis
  Authors: Sassano M.; Tyurina Y.; Diokmetzidou A.; Vervoort E.; Tyurin V.; More S.; La Rovere R.; Giordano F.; Bultynck G.; Pavie B.; Swinnen J.; Bayir H.; Kagan V.; Scorrano L.; Agostinis P.
  Published: 2025/8 (journal-article)
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• The molecular basis of human transcription-coupled DNA repair
  Authors: van der Meer P.; Luijsterburg M.
  Published: 2025/8 (journal-article)
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• Noncatalytic telomerase function in inflammation
  Authors: Ye J.; Gilson E.
  Published: 2025/8 (journal-article)
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• A pH-dependent condensate switch
  Authors: Gross P.
  Published: 2025/8 (journal-article)
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• Diet-derived galactose reprograms hepatocytes to prevent T cell exhaustion and elicit antitumour immunity
  Authors: Du X.; Li W.; Li G.; Guo C.; Tang X.; Bao R.; Li R.; Huang H.; Xu S.; Yu X.; Han Q.; Wan J.; Li S.; Sun J.; Zhao R.; Ye Y.; Gao Q.; Ni Z.; Cui X.; Zou Q.
  Published: 2025/8 (journal-article)
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• A programmed decline in ribosome levels governs human early neurodevelopment
  Authors: Ni C.; Wei Y.; Vona B.; Park D.; Wei Y.; Schmitz D.; Ding Y.; Sakurai M.; Ballard E.; Li L.; Liu Y.; Kumar A.; Xing C.; Qin S.; Kim S.; Foglizzo M.; Zhao J.; Kim H.; Ekmekci C.; Karimiani E.; Imannezhad S.; Eghbal F.; Badv R.; Schwaibold E.; Dehghani M.
  Published: 2025/8 (journal-article)
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  AbstractMany neurodevelopmental defects are linked to genes involved in housekeeping functions, such as those encoding ribosome biogenesis factors. How reductions in ribosome biogenesis can result in tissue- and developmental-specific defects remains unclear. Here we describe variants in the ribosome biogenesis factorAIRIM/C1orf109that are primarily associated with neurodevelopmental disorders. Using human cerebral organoids in combination with proteomic, single-cell RNA sequencing and single-organoid translation analyses, we identify a previously unappreciated drop in protein production during early brain development. We find that ribosome levels decrease during neuroepithelial differentiation, making differentiating cells particularly vulnerable to perturbations in ribosome biogenesis during this time. Reduced ribosome availability more profoundly impacts the translation of specific transcripts, disrupting both survival and cell fate commitment of transitioning neuroepithelia. Enhancing mTOR activity suppresses the growth and developmental defects associated withAIRIM/C1orf109variants. This work provides evidence for the functional importance of regulated changes in global protein synthesis capacity during cellular differentiation.

• Metabolic regulation of RIPK1
  Authors: Wang Z.
  Published: 2025/8 (journal-article)
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• Evolutionarily conserved role of telomerase reverse transcriptase in programming the microenvironment via regulation of the cGAS–STING pathway
  Authors: Akincilar S.; Fidan K.; Kumar N.; Ng Q.; Majee P.; Wu L.; Han D.; Chan C.; Chua J.; Idzham K.; Oji A.; Lee W.; Oehlers S.; Ikawa M.; Tergaonkar V.
  Published: 2025/8 (journal-article)
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• A SETD2–CDK1–lamin axis maintains nuclear morphology and genome stability
  Authors: Khan A.; Zhang C.; Nguyen P.; Metts J.; Collins L.; Jain K.; Mills C.; Vlach L.; Li K.; Brademeyer A.; Bowman B.; Major M.; Aubé J.; Herring L.; Rathmell W.; Mason F.; Davis I.; Zhang Q.; Strahl B.
  Published: 2025/8 (journal-article)
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• The liver metabolizes dietary galactose to fuel antitumour T cell immunity
  Authors: None
  Published: 2025/8 (journal-article)
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• Ribogenesis shaping the brain
  Authors: Tran T.; Osterweil E.
  Published: 2025/8 (journal-article)
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• Vimentin intermediate filaments as structural and mechanical coordinators of mesenchymal cells
  Authors: Guo M.; Wong I.; Moore A.; Medalia O.; Lippincott-Schwartz J.; Weitz D.; Goldman R.
  Published: 2025/8 (journal-article)
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• Responses to stiffening
  Authors: David D.
  Published: 2025/8 (journal-article)
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- Trends in Neurosciences

• Life without microglia
  Authors: Hume D.
  Published: 2025/8 (journal-article)
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• Integrating and interpreting brain maps
  Authors: Hansen J.; Misic B.
  Published: 2025/8 (journal-article)
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• Copine-6 as a regulator of TRPM3 membrane trafficking and noxious heat sensation
  Authors: Zhang C.; Han Q.
  Published: 2025/8 (journal-article)
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• Induction of plasticity and metaplasticity using noninvasive brain stimulation
  Authors: Bhattacharya A.; Darmani G.; Udupa K.; Nankoo J.; Ding M.; Chen R.
  Published: 2025/8 (journal-article)
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• Hypothalamic prolactin signaling protects against overheating in pregnancy
  Authors: Cortes L.; Correa S.
  Published: 2025/8 (journal-article)
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• The role of efferocytosis in ischemic stroke and insights from retinopathy
  Authors: Morris C.; Sadek M.; Modi P.; Abdelnaem S.; Rusch N.; Shosha E.; Fouda A.
  Published: 2025/8 (journal-article)
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• Genetic architecture of FTLD-TDP pathological subtypes
  Authors: Dols-Icardo O.; Reus L.; Ramirez A.
  Published: 2025/8 (journal-article)
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• Subscription and Copyright Information
  Authors: None
  Published: 2025/8 (journal-article)
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• Personalizing transcranial electrical stimulation
  Authors: Van Hoornweder S.; Stagg C.; Wischnewski M.
  Published: 2025/8 (journal-article)
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• The production and functions of caudal ganglionic eminence-derived inhibitory neurons
  Authors: Horton E.; Paredes M.
  Published: 2025/8 (journal-article)
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• Capturing α-synuclein aggregation interactors using UltraID-LIPA
  Authors: Reddy K.; Dieriks B.
  Published: 2025/8 (journal-article)
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• Untangling the multifaceted VTA responses to stress
  Authors: Skupio U.; Harris A.; Polter A.
  Published: 2025/8 (journal-article)
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• Advisory Board and Contents
  Authors: None
  Published: 2025/8 (journal-article)
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• What would it take to prove that a chronic infection is a causal agent in Alzheimer’s disease?
  Authors: Brutkiewicz R.; Cao W.; Morgan D.; Reis R.; Suryadevara V.; Willette A.; Willette S.; Wyatt-Johnson S.; Duggan M.
  Published: 2025/8 (journal-article)
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- Nature Communications

• ROSIE: AI generation of multiplex immunofluorescence staining from histopathology images
  Authors: Wu E.; Bieniosek M.; Wu Z.; Thakkar N.; Charville G.; Makky A.; Schürch C.; Huyghe J.; Peters U.; Li C.; Li L.; Giba H.; Behera V.; Raman A.; Trevino A.; Mayer A.; Zou J.
  Published: 2025/8 (journal-article)
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• Cryo-EM identifies F-ENA of Bacillus thuringiensis as a widespread family of endospore appendages across Firmicutes
  Authors: Sleutel M.; Sogues A.; Van Gerven N.; Jonsmoen U.; Van Molle I.; Fislage M.; Theunissen L.; Bellis N.; Baquero D.; Egelman E.; Krupovic M.; Wang F.; Aspholm M.; Remaut H.
  Published: 2025/8 (journal-article)
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• Effect of a single low-dose esketamine administration during surgical abortion on postoperative sleep disturbance: a randomized controlled trial
  Authors: Song Z.; Miao M.; Huang F.; Hu L.; Yang X.; Cui W.; Yu Y.; Wang G.; Wang C.; Zhang L.
  Published: 2025/8 (journal-article)
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• Catalyst-free partial oxidation of methane under ambient conditions boosted by mechanical stirring-enhanced ultrasonic cavitation
  Authors: Pan Y.; Li R.; Zhang L.; Liu J.; Wang W.; Zhang G.
  Published: 2025/8 (journal-article)
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• Anchored atomic Ru-O4 architecture enables ultra-effective Fe(VI) activation via avoiding Fe(VI) self-decay for water purification
  Authors: Chen Y.; Ge X.; Li J.; Zhang Z.; Li Z.
  Published: 2025/8 (journal-article)
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• Photochemical permutation of meta-substituted phenols
  Authors: Alonso M.; Lonardi G.; Arpa E.; Roure B.; Ruffoni A.; Leonori D.
  Published: 2025/8 (journal-article)
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  AbstractPhenols and their derivatives are highly relevant motifs in pharmaceuticals, natural products, and other functional materials. Conventional strategies for phenol synthesis rely on classical aromatic functionalization, which is often dictated by electronic and steric factors. Herein, we report an alternative approach for phenol synthesis where irradiation in the presence of Lewis or Brønsted acids enables the selective migration of alkyl and aryl groups frommetato either theorthoorparapositions. This method exploits the intrinsic photochemical properties of phenolic arenium ions and their rearrangement via 4π electrocyclization and following “1,2-methylene shift”. By leveraging selective photoexcitation of these species, we can achieve precise control over the directionality of the permutation process. Specifically, short-wavelength irradiation (λ = 310 nm) promotesmeta→paramigration, while longer-wavelength irradiation (λ = 390 nm)meta→ortho. This approach offers a late-stage method to use readily available phenols as templates for the preparation of other isomers without de novo synthesis. The applicability of the method has been demonstrated on the isomerization of poly-substituted derivatives including some bioactive species.

• The structure of the mammalian bornavirus polymerase complex
  Authors: Carrique L.; Günl F.; Deng A.; Grimes J.; Keown J.
  Published: 2025/8 (journal-article)
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  AbstractBorna disease virus 1 (BoDV-1) is a non-segmented RNA virus with one of the smallest known RNA virus genomes. BoDV-1 replicates in the nucleus of infected cells using a virally encoded polymerase complex composed of the large protein and phosphoprotein. Here, we present the BoDV-1 polymerase complex at resolutions up to 2.8 Å, describing the fully ordered large polymerase protein bound to tetrameric phosphoprotein. The complex is maintained through the ordered C-terminal region of one copy of the phosphoprotein. Analysis of the model reveals a conserved methyltransferase domain, though key S-adenosyl methionine binding residues are missing. While no RNA is observed in our models, analysis of a sample under reaction conditions induces an opening and closing of the template entry and exit channels, respectively. Higher-order polymerase assemblies suggest oligomerisation as a conserved feature of negative strand RNA virus polymerases. We provide a molecular framework to investigate bornavirus replication and transcription.

• Directly synthesized cobalt oxyhydroxide as an oxygen evolution catalyst in proton exchange membrane water electrolyzers
  Authors: Huang J.; Zhang Z.; Spezzati C.; Clark A.; Hales N.; Genz N.; Daffé N.; Skoupy R.; Gubler L.; Castelli I.; Schmidt T.; Fabbri E.
  Published: 2025/8 (journal-article)
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  AbstractThe limited choice of oxygen evolution reaction catalysts for proton exchange membrane water electrolyzers hinders their large-scale commercialization. Cobalt-based catalysts are promising candidates and usually undergo surface reconstruction into CoOOH-like structures. However, the directly synthesized CoOOH has not yet been investigated in acidic environments. Here, we show that the CoOOH is active across the whole pH range, while its redox features are pH dependent. Operando hard X-ray absorption spectroscopy characterizations show a pH-induced change in Co oxidation onset, but no change in the coverage of redox-active Co species before the oxygen evolution reaction. The pH-dependent catalytic performance is connected to the interfacial Co oxidative transformations under electrocatalytic conditions. By combining the kinetic isotope effect and the apparent activation energy with theoretical verification, we offer the mechanistic discussion of the possible reaction pathway for CoOOH. In addition, CoOOH demonstrates a stable cell potential of 100 mA cm−2for 400 h in a proton exchange membrane water electrolyzer. These results shed light on both the fundamental electrochemical properties of CoOOH and its potential for practical device applications.

• Isoreticular moiré metal-organic frameworks with quasiperiodicity
  Authors: Kim J.; Lee J.; Cho C.; Nam J.; Ji B.; Cho H.; Shin H.; Sivanesan D.; Park S.; Kim J.; Choe W.
  Published: 2025/8 (journal-article)
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• Single extracellular vesicle imaging via rolling circle amplification–expansion microscopy
  Authors: Wu J.; Dou Q.; Mao M.; Wan X.; Wu M.; Hu T.; Zhang Y.
  Published: 2025/8 (journal-article)
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• CYP1B1-AS1 regulates CYP1B1 to promote Coxiella burnetii pathogenesis by inhibiting ROS and host cell death
  Authors: Arunima A.; Niyakan S.; Butler S.; Clark S.; Pinson A.; Kwak D.; Case E.; Qian X.; de Figueiredo P.; van Schaik E.; Samuel J.
  Published: 2025/8 (journal-article)
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• Smart phosphor with neuromorphic behaviors enabling full-photoluminescent Write and Read for all-optical physical reservoir computing
  Authors: Zhao Y.; Li M.; Wong M.; Han X.; Guo F.; Liu Y.; Lao X.; Dang Z.; Pang S.; Wu Z.; Ye S.; Hao J.
  Published: 2025/8 (journal-article)
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• Multivalent interactions with CCR4–NOT and PABPC1 determine mRNA repression efficiency by tristetraprolin
  Authors: Pekovic F.; Lai W.; Corbo J.; Hicks S.; Luke K.; Blackshear P.; Valkov E.
  Published: 2025/8 (journal-article)
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  AbstractTristetraprolin family of proteins regulate mRNA stability by binding to specific AU-rich elements in transcripts. This binding promotes the shortening of the mRNA poly(A) tail, or deadenylation, initiating mRNA degradation. The CCR4–NOT complex plays a central role in deadenylation, while the cytoplasmic poly(A)-binding protein PABPC1 typically protects mRNAs from decay. Here, we investigate how tristetraprolin interacts with CCR4–NOT and PABPC1 to control mRNA stability. Using purified proteins and in vitro assays, we find that tristetraprolin engages CCR4–NOT through multiple interaction sites and promotes its activity, emphasizing the importance of multivalent binding for efficient deadenylation. Phosphorylation of tristetraprolin does not affect its interaction with CCR4–NOT or its deadenylation activity, but is essential for tristetraprolin’s binding to PABPC1. We propose that tristetraprolin promotes the processive deadenylation activity of CCR4–NOT on mRNAs containing AU-rich elements, with phosphorylation-dependent interactions with PABPC1 potentially enhancing deadenylation and promoting regulated mRNA decay.

• Microtubule mechanotransduction refines cytomegalovirus interactions with and remodeling of host chromatin
  Authors: Rosencrance C.; Walsh D.
  Published: 2025/8 (journal-article)
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• The topological properties of the protein universe
  Authors: Madsen C.; Barbensi A.; Zhang S.; Ham L.; David A.; Pires D.; Stumpf M.
  Published: 2025/8 (journal-article)
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• Controllable gliders in a nanomagnetic metamaterial
  Authors: Penty A.; Jensen J.; Breivik I.; Strømberg A.; Folven E.; Tufte G.
  Published: 2025/8 (journal-article)
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  AbstractArtificial Spin Ice (ASI) are promising metamaterials for neuromorphic computing, composed of interacting nanomagnets arranged in the plane. Every computing device requires the ability to transform, transmit and store information. While ASI excel at data transformation, their transmission and storage capabilities have been lacking. Here, we take inspiration from Cellular Automata, where information transmission and storage can be realised by the glider, a simple moving structure. Employing an evolutionary algorithm, we discover the snake, a glider in pinwheel ASI. The snake is controlled by a global field protocol, providing precise manipulation of a magnetic texture on the order of 100 nm. We present the snake, both in simulation and experimentally, investigate the mechanism behind its movement and its robustness to disorder. Finally, we demonstrate how the snake can be exploited for computation and memory. The snake enables the integration of information transmission, storage and transformation into one magnetic substrate, unlocking the potential for ultra-low power computing devices.

• Structural insights into SSNA1 self-assembly and its microtubule binding for centriole maintenance
  Authors: Agostini L.; Pfister J.; Basnet N.; Ding J.; Zhang R.; Biertümpfel C.; O’Connell K.; Mizuno N.
  Published: 2025/8 (journal-article)
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  AbstractSSNA1 is a fibrillar protein involved in dynamic microtubule remodeling, including nucleation, co-polymerization, and microtubule branching. The underlying molecular mechanism has remained unclear due to a lack of structural information. Here, we determine the cryo-EM structure ofC.elegansSSNA-1 at 4.55-Å resolution and evaluate its role in embryonic development. We find that SSNA-1 forms an anti-parallel coiled-coil, with self-assembly facilitated by an overhang of 16 C-terminal residues that form a triple-stranded helical junction. The microtubule-binding region is within the triple-stranded junction, suggesting that self-assembly of SSNA-1 creates hubs for effective microtubule interaction. Genetical analysis elucidates that SSNA-1 deletion significantly reduces embryonic viability, and causes multipolar spindles during cell division. Interestingly, impairing SSNA-1 self-assembly has a comparable effect on embryonic viability as the knockout strain. Our study provides molecular insights into SSNA-1’s self-assembly and its role in microtubule binding and cell division regulation through centriole stability.

• A dream EEG and mentation database
  Authors: Wong W.; Herzog R.; Andrade K.; Andrillon T.; de Araujo D.; Arnulf I.; Ataei S.; Avvenuti G.; Baird B.; Bellesi M.; Bergamo D.; Bernardi G.; Blagrove M.; Decat N.; Demirel Ç.; Dresler M.; Eichenlaub J.; Elce V.; Gais S.; De Gennaro L.; Gott J.; Hiramatsu C.; Juel B.; Konkoly K.; Kumral D.
  Published: 2025/8 (journal-article)
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  AbstractMagneto/electroencephalography (M/EEG) studies of dreaming are an essential paradigm in the investigation of neurocognitive processes of human consciousness during sleep, but they are limited by the number of observations that can be collected per study. Dream research also involves substantial methodological and conceptual variability, which poses problems for the integration of results. To address these issues, here we present the DREAM database—an expanding collection of standardized datasets on human sleep M/EEG combined with dream report data—with an initial release comprising 20 datasets, 505 participants, and 2643 awakenings. Each awakening consists, at minimum, of sleep M/EEG ( ≥ 20 s, ≥100 Hz, ≥2 electrodes) up to the time of waking and a standardized dream report classification of the subject’s experience during sleep. We observed that reports of conscious experiences can be predicted with objective features extracted from EEG recordings in both Rapid Eye Movement (REM) and non-REM (NREM) sleep. We also provide several examples of analyses, showcasing the database’s high potential in paving the way for new research questions at a scale beyond the capacity of any single research group.

• Domestic wastewater is an overlooked source and quantity in global river dissolved carbon
  Authors: Cao X.; Chen S.; Liu Y.; Long G.; Xu Y.
  Published: 2025/8 (journal-article)
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• Cellulose hydrogel with in-situ confined nanopores for boosting moist-electric conversion
  Authors: Lin X.; Tao S.; Mo J.; Wang X.; Shao Y.; Hu Y.; Qiu C.; Shen K.; Dang C.; Qi H.
  Published: 2025/8 (journal-article)
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• Strengthening vaccine capacity building on the African continent
  Authors: None
  Published: 2025/8 (journal-article)
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• Effects of unconditional cash transfers on family processes and wellbeing among mothers with low incomes
  Authors: Magnuson K.; Duncan G.; Yoshikawa H.; Yoo P.; Han S.; Gennetian L.; Halpern-Meekin S.; Fox N.; Noble K.
  Published: 2025/8 (journal-article)
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  AbstractThis study examines causal impacts of unconditional cash transfers on economic hardship and key family processes that may affect children’s development. The study randomized 1000 mothers of newborns, with prior-year household income below the federal poverty threshold, to receive unconditional cash transfers of $333 or $20 per month (Clinical Trial Registry number NCT03593356). Data collected approximately 12, 24 and 36 months after the child’s birth show a moderate increase in household income and reductions in poverty; no statistically significant improvements in subjective economic hardship reports or quality of play with infants; and small, mostly statistically non-significant, increases in parental psychological distress and declines in mothers’ relationship quality. However, mothers receiving the higher amount reported more frequently engaging in enriching child activities than mothers receiving the lower amount. Cash support may provide other benefits for families and children, but moderate support levels do not appear to address self-reported economic hardship or standard survey measures of maternal well-being. However, these results do not rule out the possibility of very small effects.

• Emergent topological polarization textures in relaxor ferroelectrics
  Authors: Eremenko M.; Krayzman V.; Gorfman S.; Bosak A.; Playford H.; Chater P.; Ravel B.; Laws W.; Ye F.; Minelli A.; Wang B.; Ye Z.; Tucker M.; Levin I.
  Published: 2025/8 (journal-article)
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  AbstractRelaxor ferroelectrics underpin high-performance actuators and sensors, yet the nature of polar heterogeneities driving their broadband dielectric response remains debated. Using a unified, multimodal structural refinement framework— simultaneously fitting complementary X-ray and neutron total scattering, X-ray absorption spectra, and diffuse scattering—we reconstruct 3D mesoscale polarization maps in the classic relaxor system PbMg1/3Nb2/3O3–PbTiO3. We uncover self-organized swirling polarization textures with half-skyrmion (meron) vortices, challenging models of independent polar nanoregions. These textures, characterized by smooth changes in the polarization direction, originate from overlapping volumes in which the projections of locally correlated polarization vectors onto each volume’s long axis share the same sign. Vortex cores correlate strongly with local charge and strain gradients imposed by compositional heterogeneities. In this work, our results suggest that chemical disorder, acting via depolarizing and strain fields, stabilizes topological vortex textures of the polarization field, offering a route for engineering new dielectric and ferroelectric functionalities.

• Dopamine signaling drives skin invasion by human-infective nematodes
  Authors: Patel R.; Bartolo G.; Castelletto M.; Garcia Romero A.; Bryant A.; Agak G.; Hallem E.
  Published: 2025/8 (journal-article)
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  AbstractSkin-penetrating nematodes are one of the most prevalent causes of disease worldwide. The World Health Organization has targeted these parasites for elimination by 2030, but the lack of preventative measures is a major obstacle to this goal. Infective larvae enter hosts through skin and blocking skin penetration could prevent infection. However, in order to prevent worm ingress via the skin, an understanding of the behavioral and neural mechanisms that drive skin penetration is required. Here, we describe the skin-penetration behavior of the human-infective threadwormStrongyloides stercoralis. We show thatS. stercoralisengages in repeated cycles of pushing, puncturing, and crawling on the skin surface before penetrating. Pharmacological inhibition of dopamine signaling inhibits these behaviors inS. stercoralisand the human hookwormAncylostoma ceylanicum, suggesting a critical role for dopamine signaling in driving skin penetration across distantly related nematodes. CRISPR-mediated disruption of dopamine biosynthesis and chemogenetic silencing of dopaminergic neurons also inhibit skin penetration. Finally, inactivation of the TRPN channel TRP-4, which is expressed in the dopaminergic neurons, blocks skin penetration. Our results suggest that drugs targeting TRP-4 and other nematode-specific components of the dopaminergic pathway could be developed into topical prophylactics that block skin penetration, thereby preventing infections.

• The anterior-posterior gradient of the fusiform gyrus modulates the transition between mnemonic and perceptual features during reminiscences
  Authors: Yuan M.; Li Y.; Wang J.; Cai Y.; Yang W.; Wang M.; Zhang B.; Sun H.; Luan G.; Northoff G.; Wang L.
  Published: 2025/8 (journal-article)
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• Translational fidelity and longevity are genetically linked
  Authors: Zheng B.; Zhang W.; Yu G.; Shi W.; Deng S.; Zhang X.; Chen J.; Zhou Z.; Shan Y.; Wu W.; Long E.; Chen X.; Yang J.
  Published: 2025/8 (journal-article)
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  AbstractAging is a series of adverse changes over time that increases mortality risk. Several hypotheses have been proposed to explain aging, including Leslie Orgel’s Error-Catastrophe Theory, which asserts that translation errors erode the translational machinery, become self-amplifying, and eventually lead to death. Evidence for the theory is scarce, especially regarding intra-specific fidelity-longevity correlations. Here, we demonstrate that the correlation can be hidden by the constrained evolution of translational fidelity, but remains detectable in long-lived samples. Measuring the lifespan and translational fidelity of a panel of BY × RM yeast recombinant haploid progenies, we validate the fidelity-longevity correlation. QTL analyses reveal that both fidelity and longevity are most strongly associated with a locus encoding vacuolar protein sorting-associated protein 70(VPS70). ReplacingVPS70in BY by its RM allele reduces translation error by ~8.0% and extends lifespan by ~8.9% through a vacuole-dependent mechanism. Our results support the impact of translational fidelity on intra-specific longevity variation.

• Photoredox catalytic asymmetric dearomative [3 + 2] cycloaddition of isoquinolines with enones
  Authors: Huo J.; Yang S.; Kong M.; Xi M.; Qiao B.; Jiang Z.
  Published: 2025/8 (journal-article)
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• Giant intrinsic electrocaloric effect in ferroelectrics by local structural engineering
  Authors: Wu B.; Tao H.; Chen K.; Xing Z.; Wu Y.; Thong H.; Zhao L.; Zhao C.; Xu Z.; Liu Y.; Yao F.; Zhou T.; Ma J.; Wei Y.; Wang K.; Zhang S.
  Published: 2025/8 (journal-article)
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• Tonic dopamine and biases in value learning linked through a biologically inspired reinforcement learning model
  Authors: Romero Pinto S.; Uchida N.
  Published: 2025/8 (journal-article)
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• Highly efficient photonic convolver via lossless mode-division fan-in
  Authors: Sun S.; Zhang S.; Wu B.; Jiang S.; Zhao B.; Zhou H.; Dong J.; Zhang X.
  Published: 2025/8 (journal-article)
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• Author Correction: Absorbable hemostatic hydrogels comprising composites of sacrificial templates and honeycomb-like nanofibrous mats of chitosan
  Authors: Leonhardt E.; Kang N.; Hamad M.; Wooley K.; Elsabahy M.
  Published: 2025/8 (journal-article)
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• In-situ thermo-mechano-chemical transformation and consolidation of Sm-Co powders via a single-step route for bulk magnet fabrication
  Authors: Malakar A.; Martin A.; Ishrak F.; Schenck C.; Yu A.; Pole M.; Darsell J.; Wang T.; Helsing J.; Thornton J.; Lastovich M.; Kovarik L.; Grant G.; Tracy J.; Thuo M.; Efe M.; Gwalani B.
  Published: 2025/8 (journal-article)
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• Large language model powered knowledge graph construction for mental health exploration
  Authors: Gao S.; Yu K.; Yang Y.; Yu S.; Shi C.; Wang X.; Tang N.; Zhu H.
  Published: 2025/8 (journal-article)
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• Range-wide climate risk and adaptive potential in a cold-water fish species
  Authors: Meek M.; Mamoozadeh N.; Glaubitz J.; Hare M.; Kraft C.
  Published: 2025/8 (journal-article)
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• Modeling the genomic architecture of adiposity and anthropometrics across the lifespan
  Authors: Arehart C.; Lin M.; Gibson R.; N/A N/A.; Anderson H.; Aquilante C.; Arbogast K.; Arehart C.; Brooks I.; Brunetti T.; Brutus-Lestin J.; Burke E.; Casteel E.; Cole J.; Coughlin C.; Crooks K.; Crawford J.; Culver E.; Edelmann M.; Fisher M.; Franklin A.; Frye T.; George H.; Gignoux C.; Gilliland E.
  Published: 2025/8 (journal-article)
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• A non-metal-to-metal I+−Ag+ coordination bond
  Authors: Puttreddy R.; Limberg N.; Müller C.; Riedel S.; Frontera A.; Lundell J.; Rissanen K.
  Published: 2025/8 (journal-article)
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• Arctic zircon U-Pb ages reveal multiphase glaciations in East Siberia during the late Quaternary
  Authors: Feng H.; Yao Z.; Shi X.; Zhang Z.; Lu H.; Zhang H.; Liu Y.; Shan X.; Dong J.; Dong L.; Yang G.; Hu L.; Vasilenko Y.; Astakhov A.; Bosin A.
  Published: 2025/8 (journal-article)
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  AbstractTracing ice-rafted debris (IRD) in Arctic Ocean sediments is crucial for understanding the evolution of Northern Hemisphere ice cover. However, uncertainties in identifying the provenance of IRD across circum-Arctic shelves have complicated reconstructions of the East Siberian Ice Sheet (ESIS). Here, we present a provenance study using 10,111 detrital zircon U-Pb ages from circum-Arctic shelf sediments and central Arctic IRD. Our results reveal that a prominent ~90–110 Ma zircon peak serves as a distinctive fingerprint for East Siberian-sourced sediments. Central Arctic IRD from at least four glacial periods contains this signature, indicating repeated ESIS glaciation, likely within the past three glacial cycles. This multiphase glaciation of East Siberia exerted significant, though poorly understood, influences on both polar and global climates during the late Quaternary. Our findings provide valuable insights into the history of Northern Hemisphere glaciation and offer an effective approach for reconstructing ice sheet evolution.

• Ferri- and ferro-electric switching in spontaneously chiral polar liquid crystals
  Authors: Hobbs J.; Gibb C.; Mandle R.
  Published: 2025/8 (journal-article)
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  AbstractThe recent discovery of spontaneous chiral symmetry breaking has demonstrated the possibility of discovering the exotic textures of ferromagnetic systems in liquid crystalline fluid ferro-electrics. We show that the polar smectic mesophase exhibited by the first molecule discovered to exhibit a spontaneously chiral ferroelectric nematic phase is also helical has a strongly varied textural morphology depending in its thermal history and phase ordering. Electro-optic studies demonstrate that the two spontaneously chiral phases exhibit field-induced phase transitions. For the nematic variant, this process is threshold-less and has no hysteresis, while for the smectic it has a clear threshold and shows hysteresis meaning this phase exhibits pseudo-ferrielectric switching, the first of its kind for ferroelectric nematic like phases. We show that helix formation can be both 1st and 2nd order, but when it is 1st it is accompanied by pre-transitional helix formation extending from the phase boundary into the preceding ferroelectric nematic phase.

• An organometallic approach to the synthesis of heteropolycyclic compounds from benzenes
  Authors: Siano P.; Diment L.; Siela D.; Ericson M.; McGraw M.; Livaudais B.; Dickie D.; Harman W.
  Published: 2025/8 (journal-article)
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  AbstractThe emerging field of dearomatization capitalizes on the synthetic potential of aromatic molecules. By using a transition metal to bind to two carbons of a benzene ring, the remaining four carbons are left available for the attachment of various chemical fragments. If these fragments are connected, this process could be a blueprint for synthesizing polycyclic architectures. The objective of this study is to develop a modular approach for creating classes of saturated polycyclic compounds that are currently underrepresented in the landscape of druggable chemical space. Herein, the phenyl group of methylphenylsulfone is coordinated to the tungsten complex {WTp(NO)(PMe3)}, largely interrupting its aromatic stabilization because of strong metal-to-ligand backbonding. Through the combination of ester enolate and amine addition reactions to the arene carbons, a wide array of chemically diverse polyheterocyclic systems is prepared. The tungsten stereogenic center influences the configurations of 3-5 stereocenters derived from the phenyl carbons.

• FedECA: federated external control arms for causal inference with time-to-event data in distributed settings
  Authors: Ogier du Terrail J.; Klopfenstein Q.; Li H.; Mayer I.; Loiseau N.; Hallal M.; Debouver M.; Camalon T.; Fouqueray T.; Arellano Castro J.; Yanes Z.; Dahan L.; Taïeb J.; Laurent-Puig P.; Bachet J.; Zhao S.; Nicolle R.; Cros J.; Gonzalez D.; Carreras-Torres R.; Garcia Velasco A.; Abdilleh K.; Doss S.; Balazard F.; Andreux M.
  Published: 2025/8 (journal-article)
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• Fbxo42 promotes the degradation of Ataxin-2 granules to trigger terminal Xbp1 signaling
  Authors: Santos C.; Schweizer N.; Cairrão F.; Ramirez J.; Osinalde N.; Yang M.; Gaspar C.; Rasheva V.; Trigo M.; Hensel Z.; Adrain C.; Cordeiro T.; Voigt F.; Gameiro P.; Mayor U.; Domingos P.
  Published: 2025/8 (journal-article)
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• Reticulate allopolyploidy and subsequent dysploidy drive evolution and diversification in the cotton family
  Authors: Zhang R.; Zhao H.; Conover J.; Shang H.; Liu D.; Zhou M.; Liu X.; Jia K.; Shao S.; Li M.; Jin C.; Liu Y.; Shen X.; Li D.; Lysak M.; Wendel J.; Ge X.; Ma Y.
  Published: 2025/8 (journal-article)
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  AbstractPolyploidy and subsequent post-polyploid diploidization (PPD) are key drivers of plant genome evolution, yet their contributions to evolutionary success remain debated. Here, we analyze the Malvaceae family as an exemplary system for elucidating the evolutionary role of polyploidy and PPD in angiosperms, leveraging 11 high-quality chromosome-scale genomes from all nine subfamilies, including newly sequenced, near telomere-to-telomere assemblies from four of these subfamilies. Our findings reveal a complex reticulate paleoallopolyploidy history early in the diversification of the Malvadendrina clade, characterized by multiple rounds of species radiation punctuated by ancient allotetraploidization (Mal-β) and allodecaploidization (Mal-α) events around the Cretaceous–Paleogene (K–Pg) boundary. We further reconstruct the evolutionary dynamics of PPD and find a strong correlation between dysploidy rate and taxonomic richness of the paleopolyploid subfamilies (R2≥ 0.90,P< 1e-4), supporting the “polyploidy for survival and PPD for success” hypothesis. Overall, our study provides a comprehensive reconstruction of the evolutionary history of the Malvaceae and underscores the crucial role of polyploidy–dysploidy waves in shaping plant biodiversity.

• REST/NRSF Preserves muscle stem cell identity by repressing alternate cell fate
  Authors: Sahinyan K.; Blackburn D.; Simon M.; Lazure F.; Kwan T.; Wilson D.; Vahidyeganeh M.; Alsadi N.; von Maltzahn J.; Yamada Y.; Jahani-Asl A.; Bourque G.; Rudnicki M.; Soleimani V.
  Published: 2025/8 (journal-article)
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• Structural basis for membrane microdomain formation by a human Stomatin complex
  Authors: Stoner J.; Li S.; Fu Z.
  Published: 2025/8 (journal-article)
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  AbstractBiological membranes are not just passive barriers—they actively sense and respond to mechanical forces, in part through specialized proteins embedded within them. Among these are Stomatin-family proteins, which are known to influence membrane stiffness and regulate ion channels, yet how they achieve these functions at the molecular level has remained elusive. Here, we report the 2.2 Å cryo-electron microscopy structure of the human Stomatin complex in a native membrane environment. We find that Stomatin assembles into a 16-subunit ring-shaped homo-oligomer, forming a ~12 nm-wide cage that defines a mechanically distinct, curvature-resistant membrane microdomain. While the majority of the complex exhibits C16 symmetry, the C-terminal domains adopt two alternating conformations, producing a symmetry-broken hydrophobic β-barrel pore with local C8 symmetry. The membrane beneath the complex remains flat despite surrounding curvature, indicating localized membrane stiffening. The structure reveals a conserved network of inter-subunit salt bridges that stabilize the assembly. These findings provide a molecular framework for how Stomatin oligomers shape membrane architecture and mechanics, offering insight into their roles in mechanotransduction and diseases such as nephrotic syndrome.

• Quantum tomography of a third-order exceptional point in a dissipative trapped ion
  Authors: Chen Y.; Li K.; Zhang L.; Wu Y.; Ma J.; Yang H.; Zhang C.; Qi B.; Zhou Z.; Hou P.; Xu Y.; Duan L.
  Published: 2025/8 (journal-article)
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• Conductivity hysteresis in MXene driven by structural dynamics of nanoconfined water
  Authors: Zhang T.; Mazzio K.; Wang R.; Lounasvuori M.; Al-Temimy A.; Amargianou F.; Mawass M.; Kronast F.; Többens D.; Lips K.; Petit T.; Gogotsi Y.
  Published: 2025/8 (journal-article)
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• Selective conversion of CO2 to C2H6 in pure water photocatalyzed by fluorobenzene-linked perylene diimide
  Authors: Xiao Y.; Ding G.; Tao J.; Wang Z.; Chen Z.; Chen L.; Shuai L.; Liao G.
  Published: 2025/8 (journal-article)
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• Dual-targeted siRubicon delivery strategy triggers hepatocellular lipophagy for mitigating liver steatosis
  Authors: Lan T.; Li Q.; Yu M.; Duan X.; Ming T.; Li S.; Wang C.; Zhu Y.; Shen Z.; Kong D.; Liu Y.
  Published: 2025/8 (journal-article)
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• The long non-coding RNA RSDR protects against acute kidney injury in mice by interacting with hnRNPK to regulate DHODH-mediated ferroptosis
  Authors: Li B.; Lin F.; Song B.; Han S.; Ye Z.; Sun Y.; Wang P.; Xia Y.; Yu W.; Zhou X.; Cheng F.
  Published: 2025/8 (journal-article)
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• Programmable synthetic magnetism and chiral edge states in nano-optomechanical quantum Hall networks
  Authors: Slim J.; del Pino J.; Verhagen E.
  Published: 2025/8 (journal-article)
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• Estimated transmission dynamics of SARS-CoV-2 variants from wastewater are unbiased and robust to differential shedding
  Authors: Dreifuss D.; Huisman J.; Rusch J.; Caduff L.; Ganesanandamoorthy P.; Devaux A.; Gan C.; Stadler T.; Kohn T.; Ort C.; Beerenwinkel N.; Julian T.
  Published: 2025/8 (journal-article)
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  AbstractThe COVID-19 pandemic has accelerated the development and adoption of wastewater-based epidemiology. Wastewater samples can provide genomic information for detecting and assessing the spread of SARS-CoV-2 variants in communities and for estimating important epidemiological parameters such as the selection advantage of a viral variant. However, despite demonstrated successes, epidemiological data derived from wastewater suffers from potential biases. Of particular concern are shedding profiles, which can affect the relationship between true viral incidence and viral loads in wastewater. Changes in shedding between variants may decouple the established relationship between wastewater loads and clinical test data. Using mathematical modeling, simulations, and Swiss surveillance data, we demonstrate that estimates of the selection advantage of a variant are not biased by shedding profiles. We show that they are robust to differences in shedding between variants under a wide range of assumptions, and identify specific conditions under which this robustness may break down. Additionally, we demonstrate that differences in shedding only briefly affect estimates of the effective reproduction number. Thus, estimates of selective advantage and reproduction numbers derived from wastewater maintain their advantages over traditional clinical data, even when there are differences in shedding among variants.

• YAP charge patterning mediates signal integration through transcriptional co-condensates
  Authors: Meyer K.; Yserentant K.; Cheloor-Kovilakam R.; Ruff K.; Chung C.; Shu X.; Huang B.; Weiner O.
  Published: 2025/8 (journal-article)
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  AbstractTranscription factor dynamics are used to selectively engage gene regulatory programs. Biomolecular condensates have emerged as an attractive signaling module in this process, but the underlying mechanisms are not well-understood. Here, we probe the molecular basis of YAP signal integration through transcriptional condensates. Leveraging light-sheet single-molecule imaging and synthetic condensates, we demonstrate charge-mediated co-condensation of the transcriptional regulators YAP and Mediator into transcriptionally active condensates in stem cells. Intrinsically disordered region sequence analysis and YAP protein engineering demonstrate that the signaling specificity of YAP is established, in part, through complementary electrostatic interactions between negatively charged blocks within YAP and positively charged blocks within Mediator. YAP/Mediator co-condensation is counteracted by negative feedback from transcription, driving an adaptive transcriptional response that is well-suited for decoding dynamic inputs. Our work reveals a molecular framework for YAP condensate formation and sheds light on the function of YAP condensates for emergent gene regulatory behavior.

• Boosting carrier mobility in MgAgSb via in-situ InSb nanoprecipitates for high-efficiency segmented thermoelectric module
  Authors: Xie L.; Tong H.; Peng G.; Wu H.; Shi W.; Yu K.; Hu J.; Jiao L.; Dong X.; Guo F.; Cai W.; Zhang Y.; Wu H.; Liu Z.; Sui J.
  Published: 2025/8 (journal-article)
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• Keto-enol tautomerism as dynamic electron/hole traps promote charge carrier separation for hydrogen peroxide photosynthesis
  Authors: Ma F.; Gao T.; Sun X.; Han C.; Wang Y.; Jiang A.; Zhou Y.; Liang G.; Wang H.; Wang L.; Jia B.; Huang Y.; Huang H.; Kong X.; Li H.; Huang N.; Ma T.; Ye L.
  Published: 2025/8 (journal-article)
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• Digital-analog hybrid matrix multiplication processor for optical neural networks
  Authors: Meng X.; Kong D.; Kim K.; Li Q.; Dong P.; Cox I.; Lioma C.; Hu H.
  Published: 2025/8 (journal-article)
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• A citrullinated histone H3 monoclonal antibody for immune modulation in sepsis
  Authors: Ouyang W.; Chen Y.; Tan T.; Song Y.; Dong T.; Yu X.; Lee K.; Zhou X.; Tetz Z.; Go S.; Zeng X.; Shao L.; Quan C.; Zhao T.; Tian Y.; Kurabayashi K.; Jin H.; Ma J.; Qin J.; Williams B.; Li Q.; Zhu G.; Alam H.; Stringer K.; Li Y.
  Published: 2025/8 (journal-article)
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• Spatiotemporal patterns of methane fluxes across alpine permafrost region on the Tibetan Plateau
  Authors: Huang L.; Qin S.; Kou D.; Ciais P.; Xu X.; Peñuelas J.; Xi Y.; Yang G.; Song Y.; Yao S.; Chang J.; Yang Y.
  Published: 2025/8 (journal-article)
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• The impact of temporal hydrogen regulation on hydrogen exporters and their domestic energy transition
  Authors: Schumm L.; Abdel-Khalek H.; Brown T.; Ueckerdt F.; Sterner M.; Parzen M.; Fioriti D.
  Published: 2025/8 (journal-article)
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  AbstractAs global demand for green hydrogen rises, potential hydrogen exporters move into the spotlight. While exports can bring countries revenue, large-scale on-grid hydrogen electrolysis for export can profoundly impact domestic energy prices and energy-related emissions. Our investigation explores the interplay of hydrogen exports, domestic energy transition and temporal hydrogen regulation, employing a sector-coupled energy model in Morocco. We find substantial co-benefits of domestic carbon dioxide mitigation and hydrogen exports, whereby exports can reduce market-based costs for domestic electricity consumers while mitigation reduces costs for hydrogen exporters. However, increasing hydrogen exports in a fossil-dominated system can substantially raise market-based costs for domestic electricity consumers, but surprisingly, temporal matching of hydrogen production can lower these costs by up to 31% with minimal impact on exporters. Here, we show that this policy instrument can steer the welfare (re-)distribution between hydrogen exporting firms, hydrogen importers, and domestic electricity consumers and hereby increases acceptance among actors.

• Improving reproducibility of differentially expressed genes in single-cell transcriptomic studies of neurodegenerative diseases through meta-analysis
  Authors: Nakatsuka N.; Adler D.; Jiang L.; Hartman A.; Cheng E.; Klann E.; Satija R.
  Published: 2025/8 (journal-article)
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• A general esterolysis strategy for upcycling waste polyesters into high-value esters
  Authors: Zhang M.; Yu Y.; Han B.; Mei Q.
  Published: 2025/8 (journal-article)
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  AbstractThe upcycling of waste polyesters into high-value chemicals offers a sustainable and economically viable solution to the global plastic waste crisis. Herein, we report a general esterolysis strategy for the efficient depolymerization of polyesters to produce high-value ester products, utilizing a broad range of esters, including carboxylates, carbonates, and C/Si/Ti/P-based esters. Using the 1-ethyl-3-methylimidazolium acetate as a highly effective catalyst, polyethylene terephthalate is selectively converted into dimethyl terephthalate and ethylene carbonate with remarkable yields of 99% and 90%, respectively. Mechanistic studies reveal that methanol, generated in situ via the 1-ethyl-3-methylimidazolium acetate-catalyzed hydrolysis of dimethyl carbonate, drives the cleavage of C–O ester bonds in polyethylene terephthalate. This strategy demonstrates broad applicability, achieving high conversion efficiencies across various mixed and colored commercial waste polyesters. The energy efficiency and versatility of this approach establish a transformative route to diverse high-value esters, advancing the development of circular plastic economies and sustainable chemistry.

• Addendum: Unified framework for open quantum dynamics with memory
  Authors: Peng R.; Ivander F.; Lindoy L.; Lee J.
  Published: 2025/8 (journal-article)
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  AbstractThis Addendum presents a detailed analysis of the discretization error in time-integration and time-derivative that appear in the Nakajima-Zwanzig equation. This was brought to our attention by Makri et al. [arXiv:2410.08239]. Our analysis in the Addendum shows that the relationship derived in our earlier work [Nat. Commun. 15, 8087 (2024)] is valid within the choice of discretization and is not contaminated by the discretization error.

• Building a Synthetic Cell Together
  Authors: Giaveri S.; Abil Z.; Kohyama S.; Fu M.; Levrier A.; Adamala K.; Chinantuya W.; Dekker C.; Deng N.; Fredens J.; Hagino K.; Jahnke K.; Li X.; Lindner A.; Liu C.; Majumder S.; Noireaux V.; Schwille P.; Westensee I.
  Published: 2025/8 (journal-article)
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• Viral proteins suppress rice defenses by boosting OsTSN1 RNA decay via phase separation and multimerization
  Authors: Zeng M.; Fu S.; Xu Y.; Li L.; Wang D.; Gao S.; Zheng L.; Zhang Y.; Zhang C.; Fei S.; Ye X.; Chen L.; Wang Y.; Zhang T.; Zhou X.; Wu J.
  Published: 2025/8 (journal-article)
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• Self-assembled metal clustersomes and chirality transfer to colloidal photonic crystals
  Authors: Wang Y.; Zheng K.; Yu Y.; Xie Z.; Xing P.; Zang S.
  Published: 2025/8 (journal-article)
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• A hollow-tube-like hydrospongel for multimodal therapy of advanced colorectal cancer
  Authors: Wu T.; Li T.; Zhang C.; Tian Y.; Li H.; He Y.; Yan X.; Gong T.; Zhao J.; Wang Z.
  Published: 2025/8 (journal-article)
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  AbstractPreserving anal function in advanced-stage colorectal cancer (CRC) treatment remains a significant challenge. Here we introduce a hollow-tube-like hydrospongel (HTHSG) as an advanced neoadjuvant therapy. Constructed from cellulose nanofibers crosslinked with Fe3O4@PDA (polydopamine) nanoparticles, the HTHSG combines quick swelling (~10 seconds) with high fracture strength (>250 kPa) for enhanced mechanical stability. The hydrospongel enables precise, localized delivery of the chemotherapeutic agent 5-FU directly to the tumor site. Beyond conventional chemotherapy, HTHSG employs electromagnetic induction to achieve targeted thermal ablation and chemodynamic therapy, minimizing collateral damage to healthy tissues. Comparative studies in orthotopic, cell-derived, and patient-derived xenograft models demonstrate the superior tumor-reduction efficacy of HTHSG over traditional neoadjuvant therapies. Feasibility studies in a beagle model and human-sized dummy model further validate the HTHSG’s potential for clinical application, showing preserved anal function and biocompatibility. These findings establish HTHSG as a promising pre-surgical treatment option for advanced-stage CRC, offering improved therapeutic outcomes and quality of life for patients.

• Adaptive spatial-temporal information processing based on in-memory attention-inspired devices
  Authors: Pan J.; Wu F.; Qian K.; Jiang K.; Liu Y.; Wang Z.; Guo P.; Yin J.; Yang D.; Tian H.; Yang Y.; Ren T.
  Published: 2025/8 (journal-article)
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  AbstractSpatial-temporal information perception is widely used for motion processing in dynamic scenes, but present technology requires relatively huge hardware resource consumption. The attention mechanism helps the human brain extract required information from tremendous data at a low cost. Here, we propose an attention-inspired artificial intelligence architecture based on hetero-dimensional modulations between zero-dimensional contact and two-dimensional electrostatic interfaces. An adaptive spatial-temporal information processing primitive is successfully implemented based on in-memory analog computing. Experiments of attention adjustments responding to different situations validate the adaptation capability to environmental changes. A demonstration of 5×5-unit data stream processing is conducted, and intensities of spatial and temporal information are varied with attention distribution from 0% to 100%. The attention-inspired device is applied to autonomous driving edge intelligence scenarios, showing high adaptability to traffic scene variations. The proposed architecture exhibits a tens-fold latency reduction, hundreds-fold area improvement, and thousands-fold energy saving compared to the conventional transistor-based circuit.

• Rational design and synthesis of narrow-band emitting Eu(II)-based hybrid halides via alkyl thermal cleavage
  Authors: Li L.; Jin J.; Han K.; Wang Y.; Xia Z.
  Published: 2025/8 (journal-article)
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• Diminished immune cell adhesion in hypoimmune ICAM-1 knockout human pluripotent stem cells
  Authors: Saha S.; Haynes W.; Seo J.; Del Rio N.; Young E.; Zhang J.; Holm A.; Pimentel M.; Flannagan L.; Huang L.; Blashka W.; Murphy L.; Scholz M.; Henrichs A.; Suresh Babu J.; Steill J.; Kratz J.; Stewart R.; Kamp T.; Brown M.
  Published: 2025/8 (journal-article)
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• Targeted gene editing and near-universal cDNA insertion of CYBA and CYBB as a treatment for chronic granulomatous disease
  Authors: Wolff J.; Skov T.; Haslund D.; Dorset S.; Revenfeld A.; Aussel C.; Jørgensen S.; Holm M.; Thomsen M.; Ammann S.; Cathomen T.; Mogensen T.; Møller B.; Bak R.; Mikkelsen J.
  Published: 2025/8 (journal-article)
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  AbstractChronic granulomatous disease (CGD) is a severe inborn error of immunity caused by NADPH oxidase defects. Here, we develop CRISPR/Cas9-based gene editing strategies for correction of variants in theCYBAandCYBBgenes causing CGD. For X-linked CGD, we also develop a near-universal gene editing strategy by targeted integration of a truncatedCYBBcDNA in CD34+hematopoietic stem and progenitor cells (HSPCs). Throughout, off-target editing and chromosomal translocations are evident, which negatively impact the ability of gene-edited HSPCs to engraft in immunodeficient mice. However, by employing a high-fidelity Cas9 to minimize off-target editing, we demonstrate restoration of the multilineage engraftment potential of gene-edited HSPCs. Moreover, to further improve safety, we develop a D10A Cas9n editing approach with no detectable off-target activity or chromosomal translocations. Collectively, through risk assessments of different gene editing approaches, we present a D10A Cas9n-based strategy with improved safety, offering a potentially curative treatment for CGD patients.

• Hierarchical luminescence center coupling enables time-dependent phosphorescence color from self-protective carbonized polymer dots
  Authors: Shi M.; Gao Q.; Chen M.; Lv Z.; Rao J.; Chen G.; Lü B.; Qi W.; Ren J.; Peng F.
  Published: 2025/8 (journal-article)
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• On-chip integration of achromatic metalens arrays
  Authors: Zhang Y.; Jiang X.; Qu G.; Han J.; Li C.; Bo B.; Ruan Q.; Liu Z.; Song Q.; Xiao S.
  Published: 2025/8 (journal-article)
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• High-throughput micro-scale bandgap mapping for perovskite-inspired materials with complex composition space
  Authors: Sheng F.; Ji K.; Dai L.; Siemenn A.; Aissi E.; Kavak H.; Das B.; Liu T.; Sun S.; Buonassisi T.
  Published: 2025/8 (journal-article)
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  AbstractTo realize the full promise of high-throughput experimental workflows, the rate of sample synthesis must be matched by that of characterization. Of growing interest are contactless optical techniques that can rapidly measure material homogeneity and properties. Here, we present a hyperspectral imaging method to measure local optical bandgap distributions within samples, utilizing spatially-resolved reflectance spectra coupled with automated data analysis. We collect approximately one million optical bandgap data across the compositional space of Cs3(BixSb1-x)2(BryI1-y)9perovskite-inspired materials. Our results show non-monotonic bandgap variations (i.e., bandgap bowing) along six composition gradient sequences, in addition to identifying samples with multiple bandgaps in statistics. High-throughput transient absorption spectroscopy reveals that within these compositions, the depletion of the ground state carriers to excited states occurred at discrete energy levels with independent carrier dynamics, consistent with the bandgap observation and indicative of phase separation. This work demonstrates the potential for rapid optical measurements to assess material quality and homogeneity in a high-throughput experimental setting, supporting screening and recipe optimization of optoelectronic material candidates with desired carrier dynamics and optical properties.

• Time cell sequences during delay intervals are not dependent on brain state and do not support hippocampus-dependent working memory
  Authors: Yuan L.; Figueroa J.; Khan A.; Narayan G.; Leutgeb J.; Leutgeb S.
  Published: 2025/8 (journal-article)
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  AbstractWorking memory (WM) is essential for performing cognitive tasks, and sequentially active hippocampal cells over many seconds (‘time cells’) have been observed during WM retention. Time cells predominantly occur when neural activity oscillates at theta frequency. To examine whether time cells during WM maintenance depend on ongoing theta oscillations, we controlled the persistence of theta during 10 s and 30 s delay intervals by either having rats run or rest, which resulted in conditions with and without persistent theta oscillations. In either condition, reliable time cells were limited to only the first few seconds of the delay interval while a second population of constitutively active cells emerged during the remainder of the delay period, neither of which were memory-related. Our results show that hippocampal sequential activity patterns are short-lasting and uninformative for WM, and that WM retention over more than ~5 s needs to include mechanisms other than hippocampal time cells.

• Epigenetic control of topoisomerase 1 activity presents a cancer vulnerability
  Authors: Lee T.; Qiao C.; Kuzin V.; Shi Y.; Farkas M.; Zhao Z.; Ramanarayanan V.; Wu T.; Guan T.; Zhou X.; Corujo D.; Buschbeck M.; Baranello L.; Oberdoerffer P.
  Published: 2025/8 (journal-article)
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  AbstractDNA transactions introduce torsional constraints that pose an inherent risk to genome integrity. While topoisomerase 1 (TOP1) activity is essential for DNA supercoil removal, the aberrant stabilization of TOP1:DNA cleavage complexes (TOP1ccs) can result in cytotoxic DNA lesions. What protects genomic hot spots of topological stress from excessive TOP1cc accumulation remains unknown. Here, we identify chromatin context as an essential means to coordinate TOP1cc resolution. Through its ability to bind poly(ADP-ribose) (PAR), the histone variant macroH2A1.1 facilitates TOP1cc repair factor recruitment and lesion turnover, thereby preventing DNA damage in response to transcription-associated topological stress. The alternatively spliced macroH2A1.2 isoform is unable to bind PAR or protect from TOP1ccs. Impaired macroH2A1.1 splicing, a frequent cancer feature, was predictive of increased sensitivity to TOP1 poisons in a pharmaco-genomic screen in breast cancer cells, and macroH2A1.1 inactivation mirrored this effect. We propose macroH2A1 alternative splicing as an epigenetic modulator of TOP1-associated genome maintenance and a potential cancer vulnerability.

• 25 nm-Feature, 104-aspect-ratio, 10 mm2-area single-pulsed laser nanolithography
  Authors: Chen Z.; Zhong L.; Sun X.; Fu Y.; He H.; Ji H.; Wang Y.; Liu X.; Xu B.; Wu Z.; Zou C.; Ma Z.; Zhang J.; Dong G.; Barillaro G.; Qiu C.; Qiu J.; Qiu J.
  Published: 2025/8 (journal-article)
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• Structure guided functional analysis of the S. cerevisiae Mre11 complex
  Authors: Hohl M.; Yu Y.; Kuryavyi V.; Patel D.; Petrini J.
  Published: 2025/8 (journal-article)
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• COUP-TFII-mediated reprogramming of the vascular endothelium counteracts tumor immune evasion
  Authors: Zhu Y.; Brulois K.; Dinh T.; Pan J.; Butcher E.
  Published: 2025/8 (journal-article)
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  AbstractT cell scarcity in tumor tissues poses a critical challenge to cancer immunotherapy. Here we manipulate the tumor vasculature, an essential regulator of immune cell trafficking, to reinvigorate anti-tumor T cell responses in “cold” tumors. We show that ectopic pan-endothelial expression of COUP-TFII, a master transcription factor for venous development, induces molecular programs of post-capillary venules in tumor endothelium. Venular reprogramming selectively promotes T cell recruitment into tumors, inhibits tumor growth in mouse models of breast and pancreatic cancers, and sensitizes tumors to immune checkpoint blockade and adoptive T cell transfer therapies. Mechanistic studies show that enhanced recruitment of anti-tumor T cells and tumor inhibition are mediated by COUP-TFII-induced vascular adhesion receptors. Our study supports a pivotal role of vascular endothelial cells in governing tumor immune evasion, and proposes venular reprogramming as a therapeutic strategy to bolster anti-tumor immunity and immunotherapy.

• Dengue virus susceptibility in Aedes aegypti linked to natural cytochrome P450 promoter variants
  Authors: Merkling S.; Couderc E.; Crist A.; Dabo S.; Daron J.; Jupatanakul N.; Burckbuchler M.; Vial T.; Sismeiro O.; Legendre R.; Pain A.; Varet H.; Jiolle D.; Ayala D.; Paupy C.; Marois E.; Lambrechts L.
  Published: 2025/8 (journal-article)
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  AbstractThe mosquitoAedes aegyptiis the primary vector for dengue virus (DENV), which infects millions of people annually. Variability in DENV susceptibility among wildAe. aegyptipopulations is governed by genetic factors, but specific causal variants are unknown. Here, we identify a cytochrome P450-encoding gene (CYP4G15) whose genetic variants drive differences in DENV susceptibility in a naturalAe. aegyptipopulation.CYP4G15is transiently upregulated in DENV-resistant midguts, while knockdown increases susceptibility, and transgenic overexpression enhances resistance. A naturally occurring 18-base-pair promoter deletion reducesCYP4G15expression and confers higher DENV susceptibility. The unexpected role of a cytochrome P450 in DENV susceptibility challenges the long-standing focus on canonical immune pathways and opens new avenues for understanding antiviral defense and DENV transmission in mosquitoes.

• Skillful subseasonal soil moisture drought forecasts with deep learning-dynamic models
  Authors: Lesinger K.; Tian D.
  Published: 2025/8 (journal-article)
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• Recent community warming of moths in Finland is driven by extinction in the north and colonisation in the south
  Authors: Ellis E.; Antão L.; Davrinche A.; Mäkinen J.; Rees M.; Conenna I.; Huikkonen I.; Leinonen R.; Pöyry J.; Suuronen A.; Laine A.; Saastamoinen M.; Vanhatalo J.; Roslin T.
  Published: 2025/8 (journal-article)
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  AbstractAs the climate warms, species are shifting their ranges to match their climatic niches, leading to the warming of ecological communities (thermophilisation). We currently have little understanding of the population-level processes driving this community-level warming, particularly at rapidly warming high latitudes. Using 30 years of high-resolution moth monitoring data across a 1200 km latitudinal gradient in Finland, we find that higher latitude communities are experiencing more rapid thermophilisation. We attribute this spatial variation to colonisation-extinction dynamics, both for the full community and for thermal affinity groups. Our findings reveal that latitudinal variation in the pathways underpinning thermophilisation is the net outcome of opposite forces: in the north, community warming is driven by the extinction of cold-affiliated species, while in the south it is driven by high colonisation rates of warm-affiliated species. Thus, we show how species’ thermal affinities influence community reorganisation and highlight the elevated extinction risk among cold-affiliated species.

• Nitrogen and CO2 enrichment interact to decrease biodiversity impact on complementarity and selection effects
  Authors: Huang M.; Reich P.; Wang S.; Feng Y.; Hong P.; Barry K.; He M.; Lyu S.; Zhou S.; Mohanbabu N.; Isbell F.; Hautier Y.
  Published: 2025/8 (journal-article)
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  AbstractGlobal environmental change is causing a decline in biodiversity with profound implications for ecosystem functioning and stability. It remains unclear how global change factors interact to influence the effects of biodiversity on ecosystem functioning and stability. Here, using data from a 24-year experiment, we investigate the impacts of nitrogen (N) addition, enriched CO2(eCO2), and their interactions on the biodiversity-ecosystem functioning relationship (complementarity effects and selection effects), the biodiversity-ecosystem stability relationship (species asynchrony and species stability), and their connections. We show that biodiversity remains positively related to both ecosystem productivity (functioning) and its stability under N addition and eCO2. However, the combination of N addition and eCO2diminishes the effects of biodiversity on complementarity and selection effects. In contrast, N addition and eCO2do not alter the relationship between biodiversity and either species asynchrony or species stability. Under ambient conditions, both complementarity and selection effects are negatively related to species asynchrony, but neither are related to species stability; these links persist under N addition and eCO2. Our study offers insights into the underlying processes that sustain functioning and stability of biodiverse ecosystems in the face of global change.

• Catalyst-free Ullmann coupling in aqueous microdroplets
  Authors: Jia M.; Zhou Y.; Yang J.; Liu Q.; Cai Z.
  Published: 2025/8 (journal-article)
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• Sustainable DNA-polysaccharide hydrogels as recyclable bioplastics
  Authors: Ke Y.; Lan K.; Wong J.; Lu H.; Gao S.; Ryu K.; Chen F.; Loh W.; Dong Z.; Lim J.; Dong Z.; Chen X.; Willner I.; Hu Y.
  Published: 2025/8 (journal-article)
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  AbstractTraditional petrochemical-derived plastics are challenging to recycle and degrade, and the existing (re)process methods are organic solvent-based and/or energy-intensive, resulting in significant environmental contamination and greenhouse gas emissions. This study presents a sustainable bioplastic material characterized by multi-closed-loop recyclability and water (re)processability. The bioplastics are derived from abundant polysaccharide sources of dextran, alginic acid, carboxymethyl cellulose, and DNA of plant and living organism waste. The process involves chemical oxidation of polysaccharides to produce aldehyde-functionalized derivatives, which subsequently form reversible imine covalent bonds with amine groups in DNA. This reaction yields water-processable polysaccharide/DNA crosslinked hydrogels, serving as raw materials for producing sustainable bioplastics. The bioplastic products exhibit (bio)degradability and recyclability, enabling aqueous recovery of the hydrogel constituents through plastic hydrolysis and the natural biodegradability of DNA and polysaccharides. These products demonstrate excellent resistance to organic solvents, self-healing, scalability, and effective processing down to nanometer scales, underscoring their potential for broad and versatile applications. The work provides potential pathways for advancing sustainable and environmentally friendly bioplastic materials.

• Unraveling the dynamics of conductive filaments in MoS2-based memristors by operando transmission electron microscopy
  Authors: Ran K.; Jo J.; Cruces S.; Wang Z.; Dunin-Borkowski R.; Mayer J.; Lemme M.
  Published: 2025/8 (journal-article)
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  AbstractAdvancedoperandotransmission electron microscopy (TEM) techniques enable the observation of nanoscale phenomena in electronic devices during operation. Here, we investigated lateral memristive devices composed of two dimensional layered MoS2with Pd and Ag electrodes. Under external bias voltage, we visualized the formation and migration of Ag conductive filaments (CFs) between the two electrodes, and their complete dissolution upon reversing the biasing polarity. The CFs exhibited a wide range of sizes, from several Ångströms to tens of nanometers, and followed diverse pathways: along the MoS2surfaces, within the van der Waals gap between MoS2layers, and through the spacing between MoS2bundles. Our method enables correlation between current-voltage responses and real-time TEM imaging, offering insights into failed and anomalous switching behaviors, and clarifying the cycle-to-cycle variabilities. Our findings provide solid evidence for the electrochemical metallization mechanism, elucidate the formation dynamics of CFs, and reveal key parameters influencing the switching performance.

• Screening and dissecting electroorganic synthesis by mass spectrometry decoupling of electrode and homogeneous processes
  Authors: Zhang X.; Zhang Y.; Li M.; Yan Q.; Lu W.; Zhu J.; Cheng X.; Min Q.
  Published: 2025/8 (journal-article)
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• Irreversible furin cleavage site exposure renders immature tick-borne flaviviruses fully infectious
  Authors: Holoubek J.; Salát J.; Matkovic M.; Bednář P.; Novotný P.; Hradilek M.; Majerová T.; Rosendal E.; Eyer L.; Fořtová A.; Beránková M.; Bell-Sakyi L.; Överby A.; Cavalli A.; Bonomi M.; Rey F.; Růžek D.
  Published: 2025/8 (journal-article)
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  AbstractFlavivirus assembly is driven by the envelope glycoproteins pre-membrane (prM) and envelope (E) in the neutral pH environment of the endoplasmic reticulum. Newly budded, spiky particles are exported through the Golgi apparatus, where mildly acidic pH induces a major surface rearrangement. The glycoproteins reorganize into (prM/E)\₂ complexes at the surface of smooth particles, with prM trapped at the E dimer interface, thereby exposing a furin cleavage site (FCS) for proteolytic maturation into infectious virions. Here, we show that in the absence of furin, immature tick-borne flavivirus particles—tick-borne encephalitis virus, Langat virus, and Louping ill virus—remain fully infectious and pathogenic in female BALB/c mice, in contrast to mosquito-borne flaviviruses such as Usutu, West Nile, and Zika viruses. We further show that the FCS in tick-borne viruses remains exposed at neutral pH, allowing furin at the surface of target cells to activate viral fusogenicity, while mosquito-borne counterparts require acidic re-exposure. Mutations increasing the dynamic behavior of the E dimer mimic the mosquito-borne phenotype, with retracted FCS at neutral pH and loss of infectivity. Our multidisciplinary approach—combining virological assays, targeted mutagenesis, structural modeling, and molecular dynamics simulations—highlights the role of E dimer dynamics in regulating flavivirus maturation and infectivity.

• Understanding rate-dependent textured growth in zinc electrodeposition via high-throughput in situ x-ray diffraction
  Authors: Ma Y.; Pepas J.; Zhang G.; Liu Z.; Su Y.; Bai J.; Zhong H.; Li T.; Xu W.; Kang M.; Carsley J.; Kacher J.; Chen H.
  Published: 2025/8 (journal-article)
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• Fluctuating local polarization: a generic fingerprint for enhanced piezoelectricity in Pb-based and Pb-free perovskite ferroelectrics
  Authors: Yao Y.; Liu H.; Hu Y.; Datta K.; Wu J.; Zhang Y.; Tucker M.; Liu S.; Neuefeind J.; Zhang S.; Chen J.
  Published: 2025/8 (journal-article)
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• Complementary cytoskeletal feedback loops control signal transduction excitability and cell polarity
  Authors: Kuhn J.; Banerjee P.; Haye A.; Robinson D.; Iglesias P.; Devreotes P.
  Published: 2025/8 (journal-article)
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• A retrospective analysis of combination therapy with GLP-1 receptor agonists and SGLT2 inhibitors versus SGLT2 inhibitor monotherapy in patients with MASLD
  Authors: Wu J.; Hsu W.; Kuo C.; Tsai Y.; Liu T.; Huang P.; Chuang M.; Hung K.; Yu T.; Lai C.
  Published: 2025/8 (journal-article)
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• DNA polymerase actively and sequentially displaces single-stranded DNA-binding proteins
  Authors: Xu L.; Jin S.; Urem M.; Lee S.; Lamers M.; Chen X.; Wolynes P.; Wuite G.
  Published: 2025/8 (journal-article)
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• Overcoming activity/stability tradeoffs in CO oxidation catalysis by Pt/CeO2
  Authors: Bohigues B.; Rojas-Buzo S.; Salusso D.; Xia Y.; Corma A.; Bordiga S.; Boronat M.; Willhammar T.; Moliner M.; Serna P.
  Published: 2025/8 (journal-article)
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• Discovery of multi-target anti-gout agents from Eurycoma longifolia Jack through phenotypic screening and structural optimization
  Authors: Zhang Z.; Shi X.; Wu T.; He Z.; Liang R.; Ye W.; Wu Z.; Liao H.; Zheng F.; Yang Q.; Zhao Z.; Chen Y.; Gao Z.; Wang S.; Wang M.; Wang Z.; Qi D.; Yang M.; Xu S.; Wang Y.; Zhao T.; Egea J.; Liu X.; Pang J.; Yi F.
  Published: 2025/8 (journal-article)
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• Genetic architecture of bone marrow fat fraction implies its involvement in osteoporosis risk
  Authors: Wu Z.; Yang Y.; Ning C.; Li J.; Cai Y.; Li Y.; Cao Z.; Tian S.; Peng J.; Ma Q.; He C.; Xia S.; Chen J.; Miao X.; Li Z.; Zhu Y.; Chu Q.; Tian J.
  Published: 2025/8 (journal-article)
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• Synthesis and properties of mirror-like large-grain graphite films
  Authors: Zhang L.; Wang M.; Jeon D.; Meng Y.; Lee S.; Choe M.; Li Y.; Wang M.; Lu S.; Lee Z.; Seong W.; Ruoff R.
  Published: 2025/8 (journal-article)
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• Conversion of methane to C2 liquid oxygenates by Ru atom arrays
  Authors: Bu F.; Xue Y.; Sun M.; Huang B.; Yan J.; Qi L.; Zhao S.; Li Y.
  Published: 2025/8 (journal-article)
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• Trans-synaptic molecular context of NMDA receptor nanodomains
  Authors: Anderson M.; Dharmasri P.; Damenti M.; Metzbower S.; Laghaei R.; Blanpied T.; Levy A.
  Published: 2025/8 (journal-article)
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• A clonally expanded nodal T-cell population diagnosed as T-cell lymphoma after CAR-T therapy
  Authors: Maurer K.; Weir J.; Nagler A.; Haradhvala N.; Bharadwaj H.; Shapiro J.; Alakwe S.; Kumar V.; Waller B.; McDonough M.; Dela Cruz J.; Luna L.; Lin E.; Gong L.; Gong Q.; Borji M.; Michaels P.; Laubach J.; Pinkus G.; Getz G.; Wu C.; Chen F.; Jacobson C.
  Published: 2025/8 (journal-article)
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  AbstractReports of secondary malignancies after chimeric antigen receptor (CAR)-T and possible CAR-T derived malignant transformation necessitate caution. Here we describe a patient with diffuse large B-cell lymphoma who developed new lymphadenopathy 2.5 years after CAR-T in the context of COVID-19 infection with histopathologic features consistent with T-cell lymphoma (TCL). Deep molecular interrogation with genomic sequencing and single-cell spatial transcriptomics reveals a highly proliferative clonal T-cell population co-expressing CD4 and CD8 with biallelic TCR rearrangement and no evidence of the CAR construct. The expanded clonotype displayed T follicular helper (TFH) cell transcriptomic programs and occupies immune-excluded spatial niches within the lymph node, supportive of TFH-like neoplastic T cell behavior. Remarkably, the lymphadenopathy spontaneously resolved on interval imaging. Our data underscore the need for better understanding of post-CAR-T clonal T-cell lymphoproliferative disorders to avoid unnecessary treatment and higher specificity in diagnostic methods for TCL.

• Reconciling flexibility and efficiency: medial entorhinal cortex represents a compositional cognitive map
  Authors: Piray P.; Daw N.
  Published: 2025/8 (journal-article)
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• Normal meiosis in the fungus Sclerotinia sclerotiorum despite the irregular distribution of haploid chromosomes between two nuclei
  Authors: Tian L.; Xu Y.; Li J.; Tan J.; Zhang Y.; Li X.
  Published: 2025/8 (journal-article)
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• Mapping the coupling between tract reachability and cortical geometry of the human brain
  Authors: Li D.; Zalesky A.; Wang Y.; Wang H.; Ma L.; Cheng L.; Banaschewski T.; Barker G.; Bokde A.; Brühl R.; Desrivières S.; Flor H.; Garavan H.; Gowland P.; Grigis A.; Heinz A.; Lemaître H.; Martinot J.; Martinot M.; Artiges E.; Nees F.; Orfanos D.; Poustka L.; Smolka M.; Vaidya N.
  Published: 2025/8 (journal-article)
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• Comparative genomic analyses reveal different genetic basis of two types of fruit in Maloideae
  Authors: Wang Y.; Hu H.; Jin J.; Yuan H.; Zhang J.; Wang Y.; Wang M.; Yin S.; Zhao J.; Lin S.; Liang Y.; Wang J.; Wei S.; Liu W.; Li B.; Ji Y.; Wang A.
  Published: 2025/8 (journal-article)
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• Lipid interactions and gating hysteresis suggest a physiological role for mechanosensitive channel YnaI
  Authors: Will N.; Hiotis G.; Nakayama Y.; Angiulli G.; Zhou Z.; Cox C.; Martinac B.; Walz T.
  Published: 2025/8 (journal-article)
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• Highly selective synthesis of interlocked carbazole-based cages and their applications in photothermal seawater desalination
  Authors: Lu M.; Yang J.; Xu Y.; Chai Y.; Wan X.; Zhao Y.; Aznarez F.; Tian D.; Dang L.; Ma L.
  Published: 2025/8 (journal-article)
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• A blueprint for biomolecular condensation driven by bacterial microcompartment encapsulation peptides
  Authors: Trettel D.; López C.; Rodriguez E.; Marrone B.; Gonzalez-Esquer C.
  Published: 2025/8 (journal-article)
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  AbstractBacterial microcompartments are protein organelles with diverse metabolic capabilities. Their functional diversity is determined by an enzymatic core that is sequestered within a structurally conserved protein shell architecture. Segregation of protein cargo into the bacterial microcompartment is enabled by encapsulation peptides, which are short helical domains fused to core proteins through a disordered linker. Here, we investigate how encapsulation peptides drive multicomponent cargo assembly into biomolecular condensates. In vitro experiments supported by molecular dynamics simulations demonstrate the importance of both conserved hydrophobic packing and electrostatic interactions in stabilizing trimeric encapsulation peptide bundles. Topological rearrangements of encapsulation peptide domains can drive programmable liquid- or gel-like partitioning in vitro and in vivo. This partitioning is found to be encapsulation peptide-specific, modular, and can co-assemble at least three fluorescent reporters. In summary, we describe the molecular features necessary to drive biomolecular condensation using a widespread peptide tag. This work can serve as a blueprint for implementing encapsulation peptide biotechnology across diverse applications.

• Conservation of dark CPD photolyase function in blind cavefish
  Authors: Li H.; Scheitle C.; Di Mauro G.; Fuselli S.; Fritsch-Decker S.; Todo T.; Weiss C.; Vallone D.; Lamparter T.; Bertolucci C.; Foulkes N.
  Published: 2025/8 (journal-article)
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  AbstractDNA damage is generated by various environmental stressors and so DNA repair systems must inevitably adapt to changing environments. Photolyases represent a highly conserved class of enzymes which repair UV-induced covalent crosslinks between adjacent pyrimidine bases (CPD and 6-4 photoproducts) via photoreactivation. In the blind cavefishPhreatichthys andruzziiwhich has evolved for millions of years completely isolated from UV radiation and visible light, we have documented multiple polymorphisms and loss of function mutations affecting both the 6-4phr and DASHphr photolyase genes while strangely, the CPDphr gene remains highly conserved. Using loss and gain of photolyase function medaka and mammalian cell lines, we reveal a novel function for CPDphr. Specifically, it enables the light-independent repair of CPD as well as 8-OHdG, an oxidatively modified form of guanosine which are both generated under oxidative stress in the absence of UV radiation. Thereby we document selective conservation of light-independent photolyase function in blind cavefish, enabling the repair of DNA damage encountered in an extreme subterranean environment.

• Milli-Tesla quantization enabled by tuneable Coulomb screening in large-angle twisted graphene
  Authors: Babich I.; Reznikov I.; Begichev I.; Kazantsev A.; Slizovskiy S.; Baranov D.; Šiškins M.; Zhan Z.; Pantaleon P.; Trushin M.; Zhao J.; Grebenchuk S.; Novoselov K.; Watanabe K.; Taniguchi T.; Fal’ko V.; Principi A.; Berdyugin A.
  Published: 2025/8 (journal-article)
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• Molecular basis of human taurine transporter uptake and inhibition
  Authors: Du B.; Cheng L.; Xie J.; Chen L.; Yan K.
  Published: 2025/8 (journal-article)
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• Ultra-long-range optical pulling with an optical nanofibre
  Authors: Zhang J.; Liu K.; Wang P.; Tong L.; Guo X.
  Published: 2025/8 (journal-article)
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• Semitransparent organic photovoltaics with wide geographical adaptability as sustainable smart windows
  Authors: Yu J.; Pu J.; Xie D.; Ai Z.; Lang Y.; Cao M.; Duan C.; Lu L.; Li G.
  Published: 2025/8 (journal-article)
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• Increasing certainty in systems biology models using Bayesian multimodel inference
  Authors: Linden-Santangeli N.; Zhang J.; Kramer B.; Rangamani P.
  Published: 2025/8 (journal-article)
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  AbstractMathematical models are indispensable for studying the architecture and behavior of intracellular signaling networks. It is common to develop models using phenomenological approximations due to the difficulty of fully observing the intermediate steps in intracellular signaling pathways. Thus, multiple models can be built to represent the same pathway. This opens up challenges for model selection and decreases certainty in predictions. Here, we investigate Bayesian multimodel inference (MMI) as an approach to increase certainty in systems biology predictions, which becomes relevant when one wants to leverage a set of potentially incomplete models. Using existing models of the extracellular-regulated kinase (ERK) pathway, we show that MMI successfully combines models and yields predictors robust to model set changes and data uncertainties. We then use MMI to identify possible mechanisms of experimentally measured subcellular location-specific ERK activity. This work highlights MMI as a disciplined approach to increasing the certainty of intracellular signaling activity predictions.

• Gamma-band synchronization between neurons in the visual cortex is causal for effective information processing and behavior
  Authors: Drebitz E.; Rausch L.; Kreiter A.
  Published: 2025/8 (journal-article)
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  AbstractSuccessful behavior relies on the brain’s ability to process selectively attended information while suppressing irrelevant information. Visual neurons show such functional flexibility by selectively responding to subsets of inputs representing attended objects while ignoring those conveying information about irrelevant objects. Several neuronal mechanisms have been proposed to explain this attention-dependent processing, yet none has been proven as a causal mechanism. One requires precise synchronization between spikes carrying relevant information and the gamma-oscillatory activity in receiving neurons. To investigate its causal relevance, we electrically evoked single volleys of spikes in area V2 of two male macaque monkeys performing a selective-attention task and recorded neuronal activity in downstream area V4. Strongly depending on the γ-phase, when these additional spikes arrived in V4, they impaired monkeys’ performance and evoked a spiking response. This establishes the causal relevance of subtle changes in spike timing, specifically by phase synchronization, for neuronal mechanisms serving cognitive processes.

• Atomic-scale visualization of strain-tailored noncollinear spin textures in an antiferromagnetic ultrathin film
  Authors: Chen C.; Drevelow T.; Lin Y.; Chen Y.; Cheng T.; Lin Y.; Heinze S.; Hsu P.
  Published: 2025/8 (journal-article)
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• In vivo antimicrobial activity of engineered mesoporous silica nanoparticles targeting intracellular mycobacteria
  Authors: Aguilera-Correa J.; Tasrini Y.; Gisbert-Garzarán M.; Boulay A.; Carvalho T.; Blanchet F.; Vallet-Regí M.; Kremer L.
  Published: 2025/8 (journal-article)
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  AbstractTreatments ofMycobacterium marinum, a common non-tuberculous mycobacterium associated with cutaneous infections are very challenging, emphasizing the development of new therapeutic approaches. Here we report the functionalization of mesoporous silica nanoparticles (MSN) with a series of triphenylphosphonium (TPP) substituents, which endowed them with affinity towards the surface ofM. marinumin vitro, as well as within infected THP-1 cells. The presence of these nanoparticles at the bacterial surface prevents their uptake by human macrophages and dendritic cells. When loaded with doxycycline, the nanosystem exerts a potent anti-bacterial effect in planktonic cultures, biofilms, and inM. marinum-infected macrophages. Strikingly, in theM. marinum/zebrafish infection model, the doxycycline-loaded nanoparticles are associated with a pronounced decrease in the bacterial burden and a high embryo survival rate. These results disclose the proposed MSN nanosystems as a promising alternative for the treatment ofM. marinuminfection and, presumably, against a broader range of mycobacterial infections.

• Mechanically robust eutectogels enabled by precisely engineered crystalline domains
  Authors: Jiang Y.; Tang N.; Wang X.; Pei D.; Zhang H.; Li M.; Hu J.
  Published: 2025/8 (journal-article)
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• Mid-Holocene extreme precipitation in the Tibesti, Central Sahara
  Authors: Hoelzmann P.; Claussen M.; Dallmeyer A.; Darius F.; Dinies M.; Reinhardt-Imjela C.; Jungandreas L.; Schröder B.; Kröpelin S.
  Published: 2025/8 (journal-article)
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  AbstractDuring the early and mid Holocene deep lakes existed in the Tibesti volcanic complex, the highest mountain in the Sahara, but it is still unclear why they formed. Here, we combine sedimentary data analyses, high-resolution climate modelling and water balance modelling to provide a quantitative and differentiated estimate of the mid-Holocene water balance of the Trou au Natron (Doon Orei) and Era Kohor crater lakes and to discuss the underlying atmospheric circulation. During the mid-Holocene, the Tibesti received at least an order of magnitude more precipitation than the surrounding plains due to strong orographic uplift of moist air masses, which were surprisingly brought in by north-easterly winds from the Mediterranean, not by the stronger West African monsoon from the south. This may explain differences in the water levels between the Trou au Natron in the north-western part of the Tibesti and the Era Kohor in the south-eastern, leeward part. Our analysis demonstrates the importance of orographic precipitation for evaluating the hydroclimate of the central part of the Sahara – a factor grossly underestimated in the global climate models commonly used for palaeo and future climate simulations.

• Computationally unmasking each fatty acyl C=C position in complex lipids by routine LC-MS/MS lipidomics
  Authors: Lamp L.; Murawska G.; Argus J.; Armando A.; Talmazan R.; Pühringer M.; Rampler E.; Quehenberger O.; Dennis E.; Hartler J.
  Published: 2025/8 (journal-article)
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  AbstractIdentifying carbon-carbon double bond (C=C) positions in complex lipids is essential for elucidating physiological and pathological processes. Currently, this is impossible in high-throughput analyses of native lipids without specialized instrumentation that compromises ion yields. Here, we demonstrate automated, chain-specific identification of C=C positions in complex lipids based on the retention time derived from routine reverse-phase chromatography tandem mass spectrometry (RPLC-MS/MS). We introduce LC=CL, a computational solution that utilizes a comprehensive database capturing the elution profile of more than 2400 complex lipid species identified in RAW264.7 macrophages, including 1145 newly reported compounds. Using machine learning, LC=CL provides precise and automated C=C position assignments, adaptable to any suitable chromatographic condition. To illustrate the power of LC=CL, we re-evaluated previously published data and discovered new C=C position-dependent specificity of cytosolic phospholipase A2(cPLA2). Accordingly, C=C position information is now readily accessible for large-scale high-throughput studies with any MS/MS instrumentation and ion activation method.

• Interface-controlled uniaxial in-plane ferroelectricity in Hf0.5Zr0.5O2(100) epitaxial thin films
  Authors: Liu K.; Jin F.; Zhu T.; Fang J.; Zhang X.; Peng E.; Liu K.; Lv Q.; Dai K.; Tao Y.; Lu J.; Huang H.; Li J.; Dong S.; Shen S.; Yin Y.; Huang H.; Luo Z.; Ma C.; Liu S.; Wang L.; Wu W.
  Published: 2025/8 (journal-article)
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• AI-assisted cervical cytology precancerous screening for high-risk population in resource-limited regions using a compact microscope
  Authors: Bai J.; Li N.; Ye H.; Li X.; Chen L.; Hu J.; Pang B.; Chen X.; Rao G.; Hu Q.; Liu S.; Sun S.; Li C.; Lv X.; Zeng S.; Cai J.; Cheng S.; Liu X.
  Published: 2025/8 (journal-article)
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• In situ molecular weaving of ionic polymers into metal-organic frameworks for radioactive anion capture
  Authors: Li X.; Lin X.; Feng Z.; Chen F.; Huang Q.; Zheng L.; Wu H.; Yuan J.; Liao Y.; Zhang W.
  Published: 2025/8 (journal-article)
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  AbstractEncapsulation of polymer chains into nanochannels of metal-organic frameworks (MOFs) to construct polymer-MOF hybrid materials can retain the desired properties of two disparate materials. However, the facile fabrication of such hybrids remains challenging, given the difficulty in unraveling entanglement of polymer chains and constraining them into ordered conformations. Herein, we introduce an in situ molecular weaving strategy to construct ionic polymer-MOF hybrid materials, employing shear forces and coordination interactions to untangle cationic polymer chains and guide their realignment within MOF nanochannels during framework formation. Notably, this realignment promotes uniform polymer distribution and exposes more anion-exchange sites. The resulting hybrids capture ReO4¯(a nonradioactive surrogate of99TcO4¯) with a capacity of 438 mg g-1and reach adsorption equilibrium within 20 min. Characterization and theoretical calculations reveal that the hydrophobic pores in the hybrid materials confer strong affinity toward less hydrated99TcO4¯anions, thereby enhancing their selectivity over competing anions.

• Mechanisms and interventions promoting healthy frontostriatal dynamics in obsessive-compulsive disorder
  Authors: Naze S.; Hearne L.; Sanz-Leon P.; Robinson C.; Hall C.; Sonkusare S.; Burgher B.; Zalesky A.; Roberts J.; Cocchi L.
  Published: 2025/8 (journal-article)
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  AbstractChanges in the frontostriatal system activity support individuals’ perseverance in distressful thoughts and rigid, repetitive behaviours that define obsessive-compulsive disorder (OCD). Converging evidence from preclinical and clinical work suggests that OCD maps onto a functional imbalance in the ventral and dorsal frontostriatal circuits. However, the neural mechanisms supporting these dysregulations remain elusive, their association with symptom severity is unclear, and therapeutic interventions are limited. To address these gaps, we combined neuroimaging and behavioural data from individuals with OCD and controls with computational modelling. We found that bidirectionally decreasing spontaneous neural coupling in the ventromedial circuit while concurrently increasing dorsolateral cortico-striatal coupling delivered the highest functional improvements in OCD. The analysis of longitudinal changes in obsessions and compulsions with respect to modelled neural interventions supported our predictions. By highlighting behaviourally meaningful neural mechanisms hidden from traditional neuroimaging analysis, this study advances knowledge on the neural basis of OCD and provides new therapeutic targets for obsessions and compulsions.

• Observation of dendrite formation at Li metal-electrolyte interface by a machine-learning enhanced constant potential framework
  Authors: Hu T.; Huang H.; Zhou G.; Wang X.; Zhu J.; Cheng Z.; Fu F.; Wang X.; Dai F.; Yu K.; Xu S.
  Published: 2025/8 (journal-article)
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• Surface chemistry-mediated porewater fluctuations boost CO2 docking in calcium silicate hydrates
  Authors: Li G.; Tao Y.; Gao Y.; Pellenq R.; Shen P.; Qian X.; Poon C.
  Published: 2025/8 (journal-article)
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• European and African ancestry-specific plasma protein-QTL and metabolite-QTL analyses identify ancestry-specific T2D effector proteins and metabolites
  Authors: Yang C.; Gorijala P.; Timsina J.; Wang L.; Liu M.; Wang C.; Brock W.; Wang Y.; Urano F.; Sung Y.; Cruchaga C.
  Published: 2025/8 (journal-article)
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• AI-driven fusion of multimodal data for Alzheimer’s disease biomarker assessment
  Authors: Jasodanand V.; Kowshik S.; Puducheri S.; Romano M.; Xu L.; Au R.; Kolachalama V.
  Published: 2025/8 (journal-article)
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• Tailoring the energy landscape of a bloch point domain wall with curvature
  Authors: Ruiz-Gómez S.; Abert C.; Morales-Fernández P.; Fernández-González C.; Koraltan S.; Danesi L.; Suess D.; Varela M.; Sánchez-Santolino G.; Bagués N.; Foerster M.; Niño M.; Mandziak A.; Wilgocka-Ślęzak D.; Nita P.; Koenig M.; Seifert S.; Hierro-Rodriguez A.; Fernández-Pacheco A.; Donnelly C.
  Published: 2025/8 (journal-article)
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  AbstractTopological defects, or singularities, play a key role in the statics and dynamics of complex systems. In magnetism, Bloch point singularities represent point defects that mediate the nucleation of textures such as skyrmions and hopfions. While these textures are typically stabilised in chiral magnets, the influence of chirality and symmetry breaking on Bloch point singularities remains relatively unexplored. Here, we harness advanced three-dimensional nanofabrication to explore the influence of symmetry breaking on Bloch point textures by introducing controlled nano-curvature in a ferromagnetic nanowire. Combining X-ray magnetic microscopy with the application of in situ magnetic fields, we demonstrate that Bloch point singularity-containing domain walls are stabilised in straight regions of the sample, and determine that curvature can be used to tune the energy landscape of the Bloch points. Not only are we able to pattern pinning points but, by controlling the gradient of curvature, we define asymmetric potential wells to realise a robust Bloch point texture shift-register with non-reciprocal behaviour. These insights into the influence of symmetry on singularities offer a route to the controlled nucleation and propagation of topological textures, providing opportunities for logic and computing devices.

• Giant extrachromosomal element “Inocle” potentially expands the adaptive capacity of the human oral microbiome
  Authors: Kiguchi Y.; Hamamoto N.; Kashima Y.; Runtuwene L.; Ishizaka A.; Kuze Y.; Enokida T.; Tanaka N.; Tahara M.; Kageyama S.; Fujisawa T.; Yamashita R.; Kanai A.; Tuda J.; Mizutani T.; Suzuki Y.
  Published: 2025/8 (journal-article)
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• Unique metabolic regulation of micromeres contributes to gastrulation in the sea urchin embryo
  Authors: Isaac S.; Dubosky D.; Waldron A.; Emura N.; Furze A.; Rao K.; Mori M.; Ragavendran A.; Makinoshima H.; Yajima M.
  Published: 2025/8 (journal-article)
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• Future heat-related mortality in Europe driven by compound day-night heatwaves and demographic shifts
  Authors: Wu X.; Wang J.; Ge Y.; Lai S.; Zhang D.; Ren Z.; Wang J.
  Published: 2025/8 (journal-article)
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• Cross-membrane cooperation among bacteria can facilitate intracellular pathogenesis
  Authors: Schator D.; G. Kumar N.; Chong S.; Jung T.; Jedel E.; Smith B.; Evans D.; Fleiszig S.
  Published: 2025/8 (journal-article)
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  AbstractPseudomonas aeruginosais a Gram-negative opportunistic pathogen able to cause life- and sight-threatening infections. Once considered an extracellular pathogen, numerous studies have shown it can survive intracellularly. Previously, we showed thatP. aeruginosainside cells can diversify into distinct subpopulations in vacuoles and the cytoplasm. Here, we report that the transition from vacuoles to cytoplasm requires collaboration with the extracellular subpopulation, through Ca2+influx enabled by their type III secretion system (T3SS) translocon pore proteins. Moreover, we show that collaboration amongP. aeruginosasubpopulations can contribute to disseminating intracellular bacteria in vivo in a mouse infection model. This study lays the groundwork for future investigations into how cooperation between extracellular and intracellular bacteria within the host contributes to disease progression and persistence.

• Computational field-resolved coherent chemical imaging
  Authors: Zhao S.; Chibani L.; Chandler E.; Liu F.; Hu J.; Valzania L.; Kamilov U.; B. de Aguiar H.
  Published: 2025/8 (journal-article)
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• From fish to fiber: 3D-nanoprinted optical neuromast for multi-integrated underwater detection
  Authors: Li L.; Fan X.; Chen G.; Liu Y.; Zhang F.; Chen Z.; Zhang Z.; Xu W.; Zhang S.; Liu Y.; Li Z.; Gao H.; Yan Z.; Xiong W.; Sun Q.
  Published: 2025/8 (journal-article)
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• Powder diffraction crystal structure determination using generative models
  Authors: Li Q.; Jiao R.; Wu L.; Zhu T.; Huang W.; Jin S.; Liu Y.; Weng H.; Chen X.
  Published: 2025/8 (journal-article)
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• A fundamental mass transport model based on molecular insights for pervaporation desalination
  Authors: Li S.; Mao H.; Feng Y.; Xu L.; Qi H.; Zhao Z.
  Published: 2025/8 (journal-article)
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• Slope inspection under dense vegetation using LiDAR-based quadrotors
  Authors: Liu W.; Ren Y.; Guo R.; Kong V.; Hung A.; Zhu F.; Cai Y.; Wu H.; Zou Y.; Zhang F.
  Published: 2025/8 (journal-article)
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• A continuously oxygenated macroencapsulation system enables high-density packing and delivery of insulin-secreting cells
  Authors: Pham T.; Tran P.; Tempelman L.; Stone S.; Piccirillo C.; Li A.; Flanders J.; Ma M.
  Published: 2025/8 (journal-article)
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• Mechanistic insights into the versatile stoichiometry and biased signaling of the apelin receptor-arrestin complex
  Authors: Yue Y.; Xu C.; Wu L.; Na M.; Xu K.; Chen X.; Song Y.; Weng S.; Xu L.; Li F.; Lin X.; Wang A.; Liu J.; Xu F.
  Published: 2025/8 (journal-article)
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• CRISPR screening reveals that RNA helicase DDX41 triggers ribosome biogenesis and cancer progression through R-loop-mediated RPL/RPS transcription
  Authors: Li H.; He Y.; Jiang J.; Liu Z.; Liu Y.; Shi Q.; Ding J.; Li H.; Sun W.; Hu X.; Chen Z.; He X.
  Published: 2025/8 (journal-article)
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• Correcting market failure for no-regret electric road investments under uncertainty
  Authors: Rogstadius J.; Alfredsson H.; Sällberg H.; Faxén K.
  Published: 2025/8 (journal-article)
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  AbstractSeveral electric road system technologies that enable in-motion charging of electric vehicles are nearing market readiness. However, substantial contribution to decarbonization requires rapid deployment on an international scale. Investment is discouraged by prior research that has identified that declining battery costs may eventually leave the infrastructure a stranded asset. We explore under what circumstances electric roads offer effective and low-risk decarbonization of European heavy-duty road freight. Transport system dynamics are explored and quantified, through pairwise comparison of scenarios with and without electric road incorporation, using a purpose-built agent-based simulation (MOSTACHI). Prior stranded asset risks are confirmed, but we show that policy that encourages high electric road utilization can correct for market failures and make the infrastructure a no-regret investment in much of Europe – never yielding worse outcomes than not investing. Electric roads are shown to be an effective risk mitigation strategy, achieving market-driven phase-out of fossil fuels before 2050, also in pessimistic scenarios where static charging alone would be insufficient. Electric roads reduce levelized system cost by 0–17%, greenhouse gas emissions by 7–63% (2030 to 2050, cumulative) and battery mineral demand by 20–40%. Benefits are maximized with early and predictable deployment.

• An RNA modification prevents extended codon-anticodon interactions from facilitating +1 frameshifting
  Authors: Kimbrough E.; Nguyen H.; Li H.; Mattingly J.; Bailey N.; Ning W.; Gamper H.; Hou Y.; Gonzalez R.; Dunham C.
  Published: 2025/8 (journal-article)
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• SLAMseq reveals potential transfer of RNA from liver to kidney in the mouse
  Authors: Hunter R.; Sun J.; Palmer T.; Czopek A.; Nespoux J.; Bailey M.; Dhaun N.; Buck A.; Dear J.
  Published: 2025/8 (journal-article)
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  AbstractExtracellular RNA (exRNA) mediates intercellular communication in lower animals; whether it serves a signalling function in mammals is uncertain. Reductionist experiments, in which a single RNA is over-expressed or tagged, have shown RNA transfer between tissues but may not be relevant to normal physiology. Here, we seek to determine the scale of RNA transfer between liver and kidney using metabolic RNA labelling in mice. We use 4-thiouracil to label RNA in hepatocytes and then detect labelled RNA in the kidney using SLAMseq: SH-Linked Alkylation for Metabolic RNA sequencing. We show that in the kidney, 5% of mRNA transcripts are labelled in health, increasing to 34% after acute hepatocellular injury. In the kidney, we do not detect labelled small RNA, but do find higher levels of the liver-enriched miRNA, miR-122 after liver injury. Our results show potential transfer of RNA from liver to kidney: a phenomenon that is augmented by liver injury. There were important limitations: we could not confidently identify transferred RNA transcripts at the single-gene level and we did not assess the physiological consequences of any RNA transfer.

• Author Correction: Plants interfere with non-self recognition of a phytopathogenic fungus via proline accumulation to facilitate mycovirus transmission
  Authors: Hai D.; Li J.; Jiang D.; Cheng J.; Fu Y.; Xiao X.; Yin H.; Lin Y.; Chen T.; Li B.; Yu X.; Cai Q.; Chen W.; Kotta-Loizou I.; Xie J.
  Published: 2025/8 (journal-article)
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• Decoupling polarization and coercive field in AlScN/AlN/AlScN stack for enhanced performance in ferroelectric thin-film transistors
  Authors: Kim K.; Ryoo S.; Yeom M.; Lee S.; Choi W.; Kim Y.; Choi J.; Xin T.; Cheng Y.; Hwang C.
  Published: 2025/8 (journal-article)
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• Philippine archipelago and South China Sea monsoon plus ocean cooling buffer Northwestern Pacific super typhoons
  Authors: Ma T.; Yu W.; Speich S.; Zhao H.; Xin R.; Luo H.; Wu L.
  Published: 2025/8 (journal-article)
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• Ultrasoft and fast self-healing poly(ionic liquid) electrode for dielectric elastomer actuators
  Authors: Wang H.; Gupta A.; Lu Q.; Wu W.; Wang X.; Huang X.; Hu X.; Lee P.
  Published: 2025/8 (journal-article)
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• Theta-phase locking of single neurons during human spatial memory
  Authors: Guth T.; Brandt A.; Reinacher P.; Schulze-Bonhage A.; Jacobs J.; Kunz L.
  Published: 2025/8 (journal-article)
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  AbstractMemory processes may rely on complex interactions between single-neuron activity and local field potentials. To better understand such spike–field relationships in humans, we examined human theta-phase locking—neuronal firing at similar theta phases over time—using single-neuron recordings in epilepsy patients performing a spatial memory task. Applying frequency-adaptive theta-phase estimation in a broad 1–10 Hz frequency range, we found that theta-phase locking was widespread in the human medial temporal lobe during memory encoding and retrieval. Time-resolved spectral parameterization and cycle-by-cycle analysis demonstrated stronger theta-phase locking during steep aperiodic slopes and prominent theta oscillations. Phase-locking strength was similar across successful and unsuccessful memory trials, with most neurons spiking at similar theta phases during encoding and retrieval. Some neurons shifted their preferred phase, supporting theories that encoding and retrieval are separated within the theta cycle. These results show how local field potential properties and memory states influence human theta-phase locking.

• Space-confined synthesis of sinter-resistant high-entropy nanoparticle library
  Authors: Chen S.; Li X.; Qu Z.; Li X.; Gao Y.; Liu P.; Dong Z.; Yu P.; Sun Q.; Dou S.; Liu Z.; Sun J.
  Published: 2025/8 (journal-article)
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  AbstractThe tailorable confinement of high-entropy nanoparticles (HE-NPs) within molecular sieves (HE-NPs@MSs), synergizing merits of cocktail effects and geometric polymorphs, holds potential for advancing heterogeneous catalysis. However, effective and universal synthesis affording size homogeneity and production scalability remains elusive. In this contribution, we present a versatile strategy for encapsulating ultrafine HE-NPs within diverse mesoporous/microporous MSs to enable the rational construction of HE-NPs@MS library. By utilizing the approach of quenching space-confined liquid metal droplets, the resulting HE-NPs@MSs comprise anti-sintered HE-NPs (1 to 5 nm in diameter) with narrow size distributions. As a proof-of-concept demonstration, a HE-NPs@MS prototype catalyst containing trace amounts of Pt is employed in the propane dehydrogenation reaction, achieving a propylene formation rate of up to 44.2 mol gPt⁻¹ h⁻¹, which is 31.6 times greater than that of the monometallic Pt@MS counterpart. Our strategy facilitates high-throughput synthesis and large-scale production, opening tantalizing opportunities in the utilization of high-entropy nanomaterials for various applications.

• Revisiting the role of oxidation in stable and high-performance lead-free perovskite-IGZO junction field-effect transistors
  Authors: Kim S.; Kim S.; Hwang H.; Kim J.; Kim J.; Kwak I.; Kang B.; Lee S.; Jo S.; Ryu D.; Kim H.; Myoung J.; Kang M.; Oh S.; Cho J.
  Published: 2025/8 (journal-article)
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  AbstractMitigating the oxidation susceptibility of Sn remains a critical issue for improving the environmental stability of lead-free perovskites. Herein, we show that the oxidized surface layer of Sn-based perovskites can be utilized to improve transistor performance, rather than being entirely suppressed. We report perovskite-IGZO junction field-effect transistors that use this oxidized layer to suppress gate current to below 10−10A, enabling enhancement-mode operation. We refer to these as barriered junction field-effect transistors. The combination of the gate leakage suppression and high polarizability of the perovskite layer results in a field-effect mobility of 29.4 cm2V−1s−1, subthreshold swing of 67.1 mV dec−1, and on/off current ratio exceeding 105under ≤1 V operation. These devices maintain stable operation in ambient conditions. Furthermore, we demonstrate their applicability by constructing logic gates such as NOT, NOR and NAND. These findings highlight the potential of exploiting Sn-based perovskite oxidation to advance electronic devices.

• Structural insights into Type II-D Cas9 and its robust cleavage activity
  Authors: Wang K.; Wang J.; Yang X.; Sun W.; Sheng G.; Wang Y.
  Published: 2025/8 (journal-article)
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• Adipocyte RNA-binding protein CELF1 promotes beiging of white fat through stabilizing Dio2 mRNA
  Authors: Zeng T.; Xiao L.; Li J.; Wu H.; Guo X.; Zhu F.; Yu X.; Cui Y.; Zhao X.; Wang Y.; Zhang T.; He W.; Zeng H.; Li X.
  Published: 2025/8 (journal-article)
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• Addendum: Global mean nitrogen recovery efficiency in croplands can be enhanced by optimal nutrient, crop and soil management practices
  Authors: You L.; Ros G.; Chen Y.; de Vries W.
  Published: 2025/8 (journal-article)
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• Self-splicing RNA circularization facilitated by intact group I and II introns
  Authors: Shen Y.; Li B.; Dong L.; Tang W.; Ren J.; Chen F.; Zheng W.; Yu Y.; Gao L.; Wei W.
  Published: 2025/8 (journal-article)
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• Gastrointestinal neuroprosthesis for motility and metabolic neuromodulation
  Authors: Srinivasan S.; Antonini M.; Alshareef A.; Sahasrabudhe A.; Jenkins J.; Ishida K.; Kuosmanen J.; Hayward A.; Min S.; Langer R.; Anikeeva P.; Traverso G.
  Published: 2025/8 (journal-article)
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• F-actin disassembly by the oxidoreductase MICAL1 promotes mechano-dependent VWF-GPIbα interaction in platelets
  Authors: Solarz J.; Soukaseum C.; Frémont S.; Eymieux S.; Nabli C.; Repérant C.; Rossi E.; Bordet J.; Denis C.; Mangin P.; Boulaftali Y.; Pasterkamp R.; Raslova H.; Baruch D.; Adam F.; Echard A.; Kauskot A.
  Published: 2025/8 (journal-article)
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  AbstractMechano-dependent interactions are key to thrombus formation and hemostasis, enabling stable platelet adhesion to injured vessels. The interaction between von Willebrand factor (VWF) and the platelet receptor GPIb-IX-V is central to this process. While GPIbα connects to the actin cytoskeleton, whether actin dynamics are important for GPIbα function under hemodynamic, high shear conditions remains largely unknown. Here, we show that actin disassembly is critical for proper VWF-GPIbα binding under shear. Mechanistically, we identify the oxidoreductase MICAL1 as a shear-activated regulator that promotes local F-actin disassembly around the GPIb-IX-V complex. This enables its translocation to lipid rafts and reinforces VWF binding. MICAL1-deficient platelets display impaired adhesion, increased deformability under shear, and defective thrombus formation in vivo. Thus, MICAL1 drives shear-dependent actin remodeling that supports GPIb-IX-V mechanotransduction and platelet function. These findings uncover a role for actin oxidation in platelet adhesion, providing a connection between cytoskeletal redox control and platelet function during thrombus formation.

• Enhanced stability and efficiency in perovskite solar cells via mixed-metal chalcohalide-alloyed formamidinium lead iodide
  Authors: Nie R.; Dai Y.; Wang R.; Li L.; Park B.; Chu W.; Wang C.; Li Z.; Chen S.; Qiao R.; Yin L.; Seok S.
  Published: 2025/8 (journal-article)
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• Fully printable integrated multifunctional sensor arrays for intelligent lithium-ion batteries
  Authors: Sun N.; Rong Q.; Wu J.; Huang L.; Passerini S.; Li H.; Wang H.; Chen J.; Huang Y.; Liu Z.; Hu L.; Xu K.; Lin Y.; He X.
  Published: 2025/8 (journal-article)
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• 2D ferroelectric narrow-bandgap semiconductor Wurtzite’ type α-In2Se3 and its silicon-compatible growth
  Authors: Jiang Y.; Ning X.; Liu R.; Song K.; Ali S.; Deng H.; Li Y.; Huang B.; Qiu J.; Zhu X.; Fan Z.; Li Q.; Qin C.; Xue F.; Yang T.; Li B.; Liu G.; Hu W.; Li L.; Zhang Z.
  Published: 2025/8 (journal-article)
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  Abstract2D van der Waals ferroelectrics, particularlyα-In2Se3, have emerged as an attractive building block for next-generation information storage technologies due to their moderate band gap and robust ferroelectricity stabilized by dipole locking.α-In2Se3can adopt either the distorted zincblende or wurtzite structures; however, the wurtzite phase has yet to be experimentally validated, and its large-scale synthesis poses significant challenges. Here, we report an in-situ transport growth of centimeter-scale wurtzite typeα-In2Se3films directly on SiO2substrates using a process combining pulsed laser deposition and chemical vapor deposition. We demonstrate that it is a narrow bandgap ferroelectric semiconductor, featuring a Curie temperature exceeding 620 K, a tunable bandgap (0.8–1.6 eV) modulated by charged domain walls, and a large optical absorption coefficient of 1.3 × 106/cm. Moreover, light absorption promotes the dynamic conductance range, linearity, and symmetry of the synapse devices, leading to a high recognition accuracy of 92.3% in a supervised pattern classification task for neuromorphic computing. Our findings demonstrate a ferroelectric polymorphism of In2Se3, highlighting its potential in ferroelectric synapses for neuromorphic computing.

• UHRF2 mediates resistance to DNA methylation reprogramming in primordial germ cells
  Authors: Bender A.; Morel M.; Dumas M.; Klopfenstein M.; Osmani N.; Greenberg M.; Bourc’his D.; Ghyselinck N.; Weber M.
  Published: 2025/8 (journal-article)
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  AbstractIn mammals, primordial germ cells (PGCs) undergo global erasure of DNA methylation with delayed demethylation of germline genes and selective retention of DNA methylation at evolutionarily young retrotransposons. However, the molecular mechanisms of persistent DNA methylation in PGCs remain unclear. Here we report that resistance to DNA methylation reprogramming in PGCs requires UHRF2, the paralog of the DNMT1 cofactor UHRF1. PGCs fromUhrf2knock-out mice show loss of retrotransposon DNA methylation, while DNA methylation is unaffected in somatic cells. This is not associated with changes in the expression of retrotransposons in E13.5 PGCs, indicating that other mechanisms compensate for retrotransposon control at this stage. Furthermore,Uhrf2-deficient PGCs show precocious demethylation of germline genes and overexpress meiotic genes in females. Subsequently,Uhrf2-deficient mice show impaired oocyte development and female-specific reduced fertility, as well as incomplete remethylation of retrotransposons during spermatogenesis. These findings reveal a crucial function for the UHRF1 paralog UHRF2 in controlling DNA methylation in the germline.

• A covalent organic framework membrane with highly selective and permeable artificial sodium channels via ion recognition
  Authors: Wang J.; Zhang J.; Jin P.; Wen H.; Dai Z.; Tan H.; Yuan S.; Yang J.; Elimelech M.
  Published: 2025/8 (journal-article)
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• Ligand supplementation restores the cancer therapy efficacy of the antirheumatic drug auranofin from serum inactivation
  Authors: Wang Y.; Cao B.; Wang Q.; Zhong S.; Fang X.; Wang J.; Chan A.; Xiong X.; Zou T.
  Published: 2025/8 (journal-article)
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• Nanoconfinement promotes CO2 electroreduction to methanol on a molecular catalyst
  Authors: Shi G.; Zhang W.; Kang Y.; Zhao J.; Lu T.; Yang C.; Chang M.; Shen Y.; Gao X.; Wu J.; Li Y.; Cao K.; Zhang L.
  Published: 2025/8 (journal-article)
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• Wood decay under anoxia by the brown-rot fungus Fomitopsis pinicola
  Authors: Röllig R.; Lebreton A.; Grenga L.; Cresswell R.; Lett S.; Tryfona T.; Navarro D.; Lambert J.; Grisel S.; Gimbert I.; Martens H.; Miotello G.; Yu X.; Drula E.; Rosso M.; Tarrago L.; Henrissat B.; Johansen K.; Dupree R.; Armengaud J.; Dupree P.; Berrin J.
  Published: 2025/8 (journal-article)
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• Lipid-mediated hydrophobic gating in the BK potassium channel
  Authors: Coronel L.; Di Muccio G.; Rothberg B.; Giacomello A.; Carnevale V.
  Published: 2025/8 (journal-article)
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  AbstractStructures of the large-conductance, calcium-activated potassium (BK) channel in the Ca2+−bound and Ca2+−free states have suggested that K+conduction is not gated via a steric closure of the pore-lining helices of the channel, in contrast to the gating mechanism of other 6TM channels. This has raised the question of how gating might occur in the absence of apparent steric hindrance by protein residues. To answer this question, we perform molecular simulations and free-energy calculations to develop a microscopic picture of the gating mechanism. Our results highlight an unexpected role for annular lipids, which appear to be an integral part of the gating machinery. In the Ca2+−free (“closed”) pore, methyl groups from lipid alkyl chains can enter the pore through fenestrations between the pore-lining helices. This dynamic occupancy directly contributes to dewetting of the inner-pore cavity, thus hindering ion conduction. In contrast, Ca2+binding leads to occlusion of the fenestrations, thus preventing the lipids from entering the pore cavity and permitting pore hydration and ion conduction. This apparent lipid-mediated hydrophobic gating may also explain functional observations that include state-dependent pore accessibility of hydrophobic channel blockers.

• Non-coding genetic elements of lung cancer identified using whole genome sequencing in 13,722 Chinese
  Authors: Zhou D.; Wu M.; Tan Q.; Sun L.; Tu Y.; Zheng W.; Zhu Y.; Yang M.; Hu K.; Hu F.; Xu X.; Zhou H.; Luo T.; Yang F.; Li F.; Jin X.; Tu H.; Li W.; Wu K.; Wu X.
  Published: 2025/8 (journal-article)
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• Lattice stabilization and strain homogenization in Sn-Pb bottom subcells enable stable all-perovskite tandems solar cells
  Authors: Bai Y.; Meng Y.; Yang M.; Tian R.; Wang J.; Jiao B.; Pan H.; Gao J.; Wang Y.; Sun K.; Zhou S.; Lu X.; Song Z.; Liu C.; Ge Z.
  Published: 2025/8 (journal-article)
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• Changes in susceptibility of Plasmodium falciparum to antimalarial drugs in Uganda over time: 2019–2024
  Authors: Okitwi M.; Orena S.; Tumwebaze P.; Katairo T.; Taremwa Y.; Byaruhanga O.; Tukwasibwe S.; Nsobya S.; Legac J.; Bailey J.; Cooper R.; Conrad M.; Rosenthal P.
  Published: 2025/8 (journal-article)
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  AbstractThe treatment and control of malaria in Africa is challenged by drug resistance. We characterized ex vivo susceptibilities to nine drugs of isolates collected from individuals presenting with uncomplicated falciparum malaria in eastern (2019-2024) and northern (2021-2024) Uganda and performed deep sequencing, with analysis of 80Plasmodium falciparumgenes, to evaluate associations between susceptibilities and potential resistance markers for samples studied since 2016. For 1114 evaluated isolates, median half-maximal inhibitory concentrations (IC50s) were low-nanomolar for chloroquine, monodesethylamodiaquine, piperaquine, pyronaridine, lumefantrine, mefloquine, and DHA, but higher for quinine and pyrimethamine. Over time, susceptibilities improved for chloroquine, decreased for lumefantrine, mefloquine, and DHA, and were unchanged for other drugs. Changes in prevalences of known markers of altered drug susceptibility followed the same patterns. Genotypes associated with drug susceptibility were those previously identified for aminoquinolines and pyrimethamine. For lumefantrine, susceptibility was decreased with wild-type PfCRT K76T or PfMDR1 N86Y, mutant PfK13 C469Y or A675V, mutant PfCARL D611N, and other polymorphisms. For DHA, susceptibility was decreased with the PfK13 C469Y or A675V and PfMDR1 Y500N mutations. Decreasing activities of lumefantrine and DHA suggest potential loss of efficacies of leading regimens, although the clinical consequences of these changes are, to date, uncertain.

• Assembled peptoid crystalline nanomaterials as carbonic anhydrase mimics for promoted hydration and sequestration of CO2
  Authors: Chakma P.; Chen Y.; Harris B.; Elhady Y.; Zheng R.; Bowden M.; Shutthanandan V.; Bard A.; Trinh T.; Zheng X.; Mundy C.; Baer M.; Chen C.
  Published: 2025/8 (journal-article)
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• Opposing regulation of the K63-linked polyubiquitination of RIPK3 by SMURF1 and USP5 in necroptosis
  Authors: Hwang C.; Lee M.; Kim J.; Nam Y.; Hwang G.; Ryu H.; Seo J.; Lee E.; Ko H.; Song J.
  Published: 2025/8 (journal-article)
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• Worldwide genetic diversity of Plasmodium vivax Pv47 is consistent with natural selection by anopheline mosquitoes
  Authors: Molina-Cruz A.; Gonzalez-Ceron L.; Dwivedi A.; Torres T.; Raytselis N.; Young M.; Kamath N.; McNinch C.; Su X.; Ford A.; Ferreira M.; Arévalo-Herrera M.; Herrera S.; Lo E.; Silva J.; Barillas-Mury C.
  Published: 2025/8 (journal-article)
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  AbstractPv47 is thePlasmodium vivaxortholog of Pfs47, a protein that allows thePlasmodium falciparummalaria parasite to evade mosquito immunity and adapt to diverse vectors. We analyzed global genetic diversity ofPv47and compared it withPfs47, finding that most commonPv47polymorphisms are non-synonymous and cluster in regions similar to those inPfs47.Pv47domain 2 presents an excess of non-synonymous substitutions, suggesting positive selection. The greatest haplotype diversity is found inPv47from East/Southeast Asia and Oceania. Like Pfs47,Pv47also exhibits a marked geographic population structure worldwide. Notably, a Pv47 polymorphism (K27E) is associated to differences in infectivity toAnopheles (Nyssorhynchus) albimanusandAnopheles pseudopunctipennis, two phylogenetically distant vectors in Mexico. The striking similarities in genetic diversity, population structure, and signatures of natural selection betweenPv47andPfs47suggest that adaptation to differentAnophelinemosquito species drives Pv47 diversity by selecting compatible Pv47 haplotypes.

• DeepISLES: a clinically validated ischemic stroke segmentation model from the ISLES'22 challenge
  Authors: de la Rosa E.; Reyes M.; Liew S.; Hutton A.; Wiest R.; Kaesmacher J.; Hanning U.; Hakim A.; Zubal R.; Valenzuela W.; Robben D.; Sima D.; Anania V.; Brys A.; Meakin J.; Mickan A.; Broocks G.; Heitkamp C.; Gao S.; Liang K.; Zhang Z.; Rahman Siddiquee M.; Myronenko A.; Ashtari P.; Van Huffel S.
  Published: 2025/8 (journal-article)
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  AbstractDiffusion-weighted MRI is critical for diagnosing and managing ischemic stroke, but variability in images and disease presentation limits the generalizability of AI algorithms. We presentDeepISLES, a robust ensemble algorithm developed from top submissions to the 2022 Ischemic Stroke Lesion Segmentation challenge we organized. By combining the strengths of best-performing methods from leading research groups,DeepISLESachieves superior accuracy in detecting and segmenting ischemic lesions, generalizing well across diverse axes. Validation on a large external dataset (N= 1685) confirms its robustness, outperforming previous state-of-the-art models by 7.4% in Dice score and 12.6% in F1 score. It also excels at extracting clinical biomarkers and correlates strongly with clinical stroke scores, closely matching expert performance. Neuroradiologists preferDeepISLES’ segmentations over manual annotations in a Turing-like test. Our work demonstratesDeepISLES’clinical relevance and highlights the value of biomedical challenges in developing real-world, generalizable AI tools.DeepISLESis freely available athttps://github.com/ezequieldlrosa/DeepIsles.

• Molecularly resolved mapping of heterogeneous ice nucleation and crystallization pathways using in-situ cryo-TEM
  Authors: Wang Z.; Yuan Z.; Cheng M.; Huang X.; Liu K.; Wang Y.; Sun H.; Liao L.; Xu Z.; Chen J.; Wang W.; Liu L.; Bai X.; Xu L.; Wang E.; Wang L.
  Published: 2025/8 (journal-article)
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• Cell free RNA detection of pancreatic cancer in pre diagnostic high risk and symptomatic patients
  Authors: Moore T.; Spiliotopoulos E.; Callahan R.; Kirschbaum C.; Bailey C.; Kim H.; Roskams-Hieter B.; Goncalves F.; Keith D.; Grossberg A.; Spellman P.; Mills G.; Sears R.; Morgan T.; Ngo T.
  Published: 2025/8 (journal-article)
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• Lattice-matched antiperovskite-perovskite system toward all-solid-state batteries
  Authors: Ito D.; Kuwata N.; Takemoto S.; Kamiguchi K.; Hasegawa G.; Takada K.
  Published: 2025/8 (journal-article)
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• Single-molecule tweezers decode hidden dimerization patterns of membrane proteins within lipid bilayers
  Authors: Sadongo V.; Kim E.; Kim S.; Wijesinghe W.; Lee T.; Choi J.; Min D.
  Published: 2025/8 (journal-article)
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• Mitochondrial damage triggers the concerted degradation of negative regulators of neuronal autophagy
  Authors: Basak B.; Holzbaur E.
  Published: 2025/8 (journal-article)
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  AbstractMutations that disrupt the clearance of damaged mitochondria via mitophagy are causative for neurological disorders including Parkinson’s. Here, we identify a Mitophagic Stress Response (MitoSR) activated by mitochondrial damage in neurons and operating in parallel to canonical Pink1/Parkin-dependent mitophagy. Increasing levels of mitochondrial stress trigger a graded response that induces the concerted degradation of negative regulators of autophagy including Myotubularin-related phosphatase (MTMR)5, MTMR2 and Rubicon via the ubiquitin-proteasome pathway and selective proteolysis. MTMR5/MTMR2 inhibit autophagosome biogenesis; consistent with this, mitochondrial engulfment by autophagosomes is enhanced upon MTMR2 depletion. Rubicon inhibits lysosomal function, blocking later steps of neuronal autophagy; Rubicon depletion relieves this inhibition. Targeted depletion of both MTMR2 and Rubicon is sufficient to enhance mitophagy, promoting autophagosome biogenesis and facilitating mitophagosome-lysosome fusion. Together, these findings suggest that therapeutic activation of MitoSR to induce the selective degradation of negative regulators of autophagy may enhance mitochondrial quality control in stressed neurons.

• High-dimensional one-shot optical field compressive sensing of structured light
  Authors: Hu Y.; Men T.; Yan M.; Tang W.; Tang H.; Fan K.; Li Z.
  Published: 2025/8 (journal-article)
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• Guanidine aptamers are present in vertebrate RNAs associated with calcium signaling and neuromuscular function
  Authors: Kavita K.; Narunsky A.; Mohsen J.; Mahadeshwar I.; Mohsen M.; Chang Y.; Breaker R.
  Published: 2025/8 (journal-article)
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  AbstractGuanidine is a protein denaturant that is a widely used constituent in explosives, plastics, and resins. Its effects on muscle contraction were initially reported in 1876, which eventually led to the use of guanidine as a treatment for certain ataxia symptoms such as those caused by Lambert-Eaton disease. However, its mechanisms of therapeutic action remained unknown. Guanidine was recently found to be a widespread natural metabolite through the discovery of four bacterial riboswitch classes that selectively recognize this compound. Here, we report the discovery and biochemical validation of vertebrate members of guanidine-I and -II riboswitch aptamer classes that are associated with numerous genes relevant to neuromuscular function, mostly involved in Ca2+transport or signaling. These findings suggest that guanidine is a widely used signaling molecule that serves as an additional layer of regulation of genes relevant to neuromuscular disorders.

• A multivalent mRNA vaccine elicits robust immune responses and confers protection in a murine model of monkeypox virus infection
  Authors: Li Y.; Cheng L.; Jiang L.; Li Z.; Rao J.; Wu T.; Zhang F.; Xie B.; He Y.; Wang L.; Zhang Z.; Chen S.
  Published: 2025/8 (journal-article)
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• Vaccination with Acinetobacter baumannii adhesin Abp2D provides protection against catheter-associated urinary tract infection
  Authors: Timm M.; Tamadonfar K.; Nye T.; Villicaña J.; Pinkner J.; Dodson K.; Ellebedy A.; Hultgren S.
  Published: 2025/8 (journal-article)
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• Heat transfer in metallic nanometre-sized gaps
  Authors: López-Nebreda R.; Mateos-Lopez O.; Martinez P.; García-Esteban J.; Ibabe Á.; Roca-Giménez N.; Segovia P.; Michel E.; Lee E.; Vilhena J.; Cuevas J.; Agraït N.
  Published: 2025/8 (journal-article)
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• The South American MicroBiome Archive (saMBA): enriching the microbiome field by studying neglected populations
  Authors: Valderrama B.; Calderón-Romero P.; Bastiaanssen T.; Lavelle A.; Clarke G.; Cryan J.
  Published: 2025/8 (journal-article)
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  AbstractThe human gut microbiome is associated with numerous health outcomes, often in a region-specific manner. Unfortunately, global microbiome research remains profoundly imbalanced: over 70% of sequenced human microbiomes originate from Europe and North America, which together represent only 15% of the world’s population. To address this disparity, we developed saMBA—the largest archive of gut microbiomes from South America, one of the world’s most microbiome-diverse regions but also among the least studied. The archive comprises 33 studies, ~73% of which had not been included in any previous compendium. A total of 3382 samples were reanalysed, of which 2913 were successfully included after applying quality filters. By leveraging this resource, we reveal both high within-population diversity and between-population uniqueness in the continent, expanding our current understanding of the gut microbiome to be more globally representative. Additionally, saMBA reveals that much of the region’s gut microbiome diversity remains undercharacterised, and provides guidance for future sampling efforts to more accurately capture regional biodiversity. The framework used to build saMBA is compatible with existing global resources and is openly available, thus promoting the inclusion of other underrepresented populations to accelerate microbiome research globally.

• Nucleophilic addition promoted ring rearrangement-aromatization in aza-/thio-sesquiterpenoid biosynthesis
  Authors: Xu H.; Zhang X.; Zhang Y.; Liu G.; Chen Y.; Hou X.; Liu X.; Zhang K.; Ma C.; Feng R.; Shen J.; Pfeifer B.; Che Q.; Zhu T.; Zhang G.
  Published: 2025/8 (journal-article)
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• Design of Ig-like binders targeting α-synuclein fibril for mitigating its pathological activities
  Authors: Zeng S.; Xiong X.; Long H.; Xu Q.; Yu Y.; Sun B.; Liu C.; Wang Z.; Xu W.; Zhang S.; Li D.
  Published: 2025/8 (journal-article)
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• Effect of intrapartum azithromycin on early childhood gut mycobiota development: post hoc analysis of a double-blind randomized trial
  Authors: Sanyang B.; Dabrowska M.; Amenyogbe N.; Camara B.; Beloum N.; Jammeh M.; Bojang D.; Goodall J.; Mohammed N.; Sesay A.; Roca A.; de Silva T.
  Published: 2025/8 (journal-article)
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  AbstractIntrapartum azithromycin prophylaxis reduced maternal infections but showed no effect on neonatal sepsis and mortality. Although antibiotic exposure may indirectly alter the mycobiota (community of fungi that live in a given environment), there is no data available on how intrapartum azithromycin impacts gut mycobiota development. We hereby assess the impact of intrapartum azithromycin on gut mycobiota development from birth to the age of three years, byITS2gene profiling of rectal samples from 102 healthy Gambian infants selected from a double-blind randomized placebo-controlled clinical trial (PregnAnZI-2 – ClinicalTrials.org NCT03199547). In the trial, women received 2 g oral azithromycin or placebo (1:1) during labour with the intension of assessing effect on neonatal sepsis or mortality. Secondary objectives included effects on bacterial carriage and resistance, puerperal infections, and infant growth. Our analysis show that season and parity were key factors that influenced gut mycobiota development. Intrapartum azithromycin increased the abundance ofCandida orthopsilosisbut only in the wet season and did not show different effects by sex of the child. These data suggest that season and parity can be key factors influencing gut mycobiota development and may inform strategies for a wider implementation of intrapartum azithromycin intervention.

• Highly customizable, ultrawide-temperature free-form flexible sensing electronic systems based on medium-entropy alloy paintings
  Authors: Li W.; Li Y.; Xu M.; Zhou Y.; Miao R.; Wang K.; Cao Y.; Song Y.; Dang S.; Zheng L.; Wang X.; Huang W.
  Published: 2025/8 (journal-article)
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• Evidence triangulator: using large language models to extract and synthesize causal evidence across study designs
  Authors: Shi X.; Zhao W.; Chen T.; Yang C.; Du J.
  Published: 2025/8 (journal-article)
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• Mitigating emissions and costs through demand-side solutions in Chinese residential buildings
  Authors: You K.; Li Y.; Cai W.; Zhang L.; Liu Z.; Feng W.; Wei Y.
  Published: 2025/8 (journal-article)
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• Glial reactivity and cognitive decline follow chronic heterochromatin loss in neurons
  Authors: Newman A.; Sharif J.; Bessa P.; Zaqout S.; Brown J.; Richter D.; Dannenberg R.; Nakayama M.; Mueller S.; Schaub T.; Manickaraj S.; Boehm-Sturm P.; Ohara O.; Koseki H.; Singh P.; Tarabykin V.
  Published: 2025/8 (journal-article)
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  AbstractIn aging cells and animal models of premature aging, heterochromatin loss coincides with transcriptional disruption including the activation of normally silenced endogenous retroviruses (ERVs). Here we show that loss of heterochromatin maintenance and de-repression of ERVs result in a chronic inflammatory environment characterized by neurodegeneration and cognitive decline in mice. We identify distinct roles for HP1 proteins to ERV silencing where HP1γ is necessary and sufficient for H4K20me3 deposition and HP1β deficiency causes aberrant DNA methylation. Combined loss of HP1β and HP1γ results in loss of DNA methylation at ERVK elements. Progressive ERV de-repression in HP1β/γ DKO mice is followed by stimulation of the integrated stress response, an increase of Complement 3+ reactive astrocytes and phagocytic microglia. This chronic inflammatory state coincides with age-dependent reductions in dendrite complexity and cognition. Our results demonstrate the importance of preventing loss of epigenetic maintenance that is necessary for protection of postmitotic neuronal genomes.

• Early Locus Coeruleus noradrenergic axon loss drives olfactory dysfunction in Alzheimer’s disease
  Authors: Meyer C.; Niedermeier T.; Feyen P.; Strübing F.; Rauchmann B.; Karali K.; Gentz J.; Tillmann Y.; Landgraf N.; Rumpf S.; Ochs K.; Wind-Mark K.; Biechele G.; Wagner J.; Guersel S.; Kurz C.; Schweiger M.; Prtvar D.; Shi Y.; Banati R.; Liu G.; Middleton R.; Mitteregger-Kretzschmar G.; Perneczky R.; Koeglsperger T.
  Published: 2025/8 (journal-article)
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  AbstractAlzheimer’s disease (AD) often begins with non-cognitive symptoms such as olfactory deficits, which can predict later cognitive decline, though the mechanisms remain unclear. Pathologically, the brainstem locus coeruleus (LC), the main source of the neurotransmitter noradrenalin (NA) modulating olfactory information processing is affected early. Here we show early and distinct loss of noradrenergic input to the olfactory bulb (OB) coinciding with impaired olfaction in an AD mouse model, before appearance of amyloid plaques. Mechanistically, OB microglia recognize and phagocytose LC axons. Reducing phagocytosis genetically preserves LC axons and olfaction. Prodromal AD patients display elevated TSPO-PET signals in the OB, similarly toAppNL-G-Fmice. We further confirm early LC axon degeneration in post-mortem OBs in patients with early AD. Our findings reveal a mechanism linking early LC damage to hyposmia in AD, suggesting olfactory testing and neurocircuit imaging for early diagnosis and enable timely therapeutic intervention for Alzheimer’s disease.

• Regional heterogeneity of the blood-brain barrier
  Authors: Blanchette M.; Bajc K.; Gastfriend B.; Profaci C.; Ruderisch N.; Dorrier C.; Zhong G.; Cuevas-Diaz Duran R.; Harvey S.; Garcia-Pak I.; Pintarić L.; Leclerc M.; Reveret L.; Émond V.; Wang A.; Pant D.; Tsai L.; Calon F.; Isoherranen N.; Palecek S.; Shusta E.; Wu J.; Daneman R.
  Published: 2025/8 (journal-article)
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  AbstractThe blood-brain barrier (BBB), formed by specialized endothelial cells (ECs), regulates the extracellular composition of the central nervous system (CNS). Little is known about whether there are regional specializations of the BBB that may control the function of specific neural circuits. We use single cell RNA-seq to characterize ECs from nine CNS regions in male mice: cortex, hippocampus, cerebellum, spinal cord, striatum, thalamus, hypothalamus, midbrain, and medulla/pons. Although there is a core BBB transcriptional profile, there are significant regional specializations. Stra6, a retinoid transporter, is highly enriched in the BBB of the nucleus accumbens shell (ShNAc) and ventral cochlear nucleus, and is controlled by dietary vitamin A, through endothelial RARƔ. EC Stra6 regulates the deposition of retinoids specifically in the ShNAc and cochlear nucleus, and is required for the function of the ShNAc, in a retinoid-dependent manner. Thus regional specializations of the BBB can regulate the function of local brain regions.

• Development of conformation-selective antibodies targeting human SLC15A4
  Authors: Zhu Y.; Zhang X.; Zhang Q.; Sun P.; Liu K.; Nie X.; Ma J.; Zhang L.; Gao Y.; Wang Y.; Liu S.; Gao A.; Zhang L.; Gao P.
  Published: 2025/8 (journal-article)
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• Lipid-mediated gating of a miniature mechanosensitive MscS channel from Trypanosoma cruzi
  Authors: Zhang J.; Bhatt A.; Maksaev G.; Luo Y.; Yuan P.
  Published: 2025/8 (journal-article)
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  AbstractThe mechanosensitive channel of small conductance (MscS) fromE. coli(EcMscS) has served as the prevailing model system for understanding mechanotransduction in ion channels.Trypanosoma cruzi, the protozoan parasite causing Chagas disease, encodes a miniature MscS ortholog (TcMscS) critical for parasite development and infectivity.TcMscS contains a minimal portion of the canonicalEcMscS fold yet maintains mechanosensitive channel activity, thus presenting a unique model system to assess the essential molecular determinants underlying mechanotransduction. Using cryo-electron microscopy and molecular dynamics simulations, we show thatTcMscS contains two short membrane-embedded helices that would not fully cross an intact lipid bilayer. Consequently, drastic membrane deformation is induced at the protein-lipid interface, resulting in a funnel-shaped bilayer surrounding the channel. Resident lipids within the central pore lumen block ion permeation pathway, and their departure driven by lateral membrane tension is required for ion conduction. Together with electrophysiology and mutagenesis studies, our results support a direct lipid-mediated mechanical gating transition. Moreover, these findings provide a foundation for the development of alternative treatment of Chagas disease by inhibition of theTcMscS channel.

• Real-time prediction of intensive care unit patient acuity and therapy requirements using state-space modelling
  Authors: Contreras M.; Silva B.; Shickel B.; Davidson A.; Ozrazgat-Baslanti T.; Ren Y.; Guan Z.; Balch J.; Zhang J.; Bandyopadhyay S.; Loftus T.; Khezeli K.; Lipori G.; Sena J.; Nerella S.; Bihorac A.; Rashidi P.
  Published: 2025/8 (journal-article)
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• Development of a versatile chassis for the efficient production of diverse type II polyketides
  Authors: Zou Y.; Wang R.; Liu Z.; Zou Y.; Zeng S.; Fang M.; Chen H.; Wang P.; Xie C.; Deng Z.; Zhang F.; Liu R.; Liu T.
  Published: 2025/8 (journal-article)
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• Reaction-induced regioselective reconstruction of Ni-doped Ce(OH)3/CeO2 enables exceptional activity and selectivity for reverse water-shift reaction
  Authors: Li W.; Liu B.; Guo Q.; Guo W.; Zhang S.; Qu Y.
  Published: 2025/8 (journal-article)
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• ATP allosterically regulates an acyl-CoA oxidase
  Authors: Perez D.; Mondal A.; Xu W.; Baredes V.; Connell H.; Perez A.; Butcher R.
  Published: 2025/8 (journal-article)
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• Uncovering hidden enhancers through unbiased in vivo testing
  Authors: Mannion B.; Tran S.; Plajzer-Frick I.; Novak C.; Afzal V.; Akiyama J.; Sospedra-Arrufat I.; Barton S.; Beckman E.; Garvin T.; Godfrey P.; Godoy J.; Hunter R.; Kato M.; Kosicki M.; Kronshage A.; Lee E.; Meky E.; Pham Q.; von Maydell K.; Zhu Y.; Lopez-Rios J.; Dickel D.; Osterwalder M.; Visel A.
  Published: 2025/8 (journal-article)
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  AbstractChromatin signatures are widely used to identify tissue-specific in vivo enhancers, but their sensitivity and specificity remains unclear. Here we show that many developmental enhancers remain undetectable using currently available chromatin data. In an initial comparison of over 1200 developmental enhancers with tissue-matched chromatin data, 14% (n= 285) lacked canonical enhancer-associated chromatin signatures. To further assess the prevalence of enhancers missed by chromatin profiling approaches, we used a high-throughput transgenic enhancer assay to screen the regulatory landscapes of two key developmental genes at 5 kb resolution, spanning 1.3 Mb of mouse sequence in total. We observed that 23 of 88 (26%) in vivo enhancers discovered by this approach lacked enhancer-associated chromatin signatures in the respective tissue. Our findings suggest the existence of tens of thousands of enhancers that remain undiscovered by currently available chromatin data, underscoring the continued need for expanding resources for enhancer discovery.

• Physical and chemical niche of human growth plate for polarized bone development
  Authors: Xie C.; Li W.; Yao X.; Wu B.; Fang J.; Mao R.; Yan Y.; Meng H.; Wu Y.; Zhang X.; Li R.; Zhang J.; Duan W.; Dai X.; Wang X.; Ouyang H.
  Published: 2025/8 (journal-article)
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• Human cytomegalovirus induces neuronal gene expression through IE1 for viral maturation
  Authors: Kelnhofer-Millevolte L.; Smith J.; Nguyen D.; Wilson L.; Lewis H.; Arnold E.; Brinkley M.; Shin K.; Ahn J.; Kim E.; Kulej K.; Geballe A.; Ramachandran S.; Avgousti D.
  Published: 2025/8 (journal-article)
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• Amorphous polymers separate small organic molecules with switchable selective states
  Authors: Li J.; Liu C.; Yan P.; Chen K.; Jiang Y.; Liu D.; Shan H.; Song X.; Lyu B.; Jiang J.; Soh S.
  Published: 2025/8 (journal-article)
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- Molecular Psychiatry

• Biological correlates of temperament: systematic reviews, empirical studies, and a conceptual framework linking neurotransmitter signaling, intrinsic brain activity, and the hyperthymic-depressive spectrum
  Authors: Chen H.; Martino M.; Dabiri E.; Tamara F.; Sibiya L.; Conio B.; Amore M.; Burnouf T.; Magioncalda P.
  Published: 2025/8 (journal-article)
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• Plasma neurofilament light reflects more severe manifestation of Alzheimer’s disease in men
  Authors: Cheng X.; Wang Z.; He K.; Xia Y.; Wang Y.; Guo Q.; Xie F.; Yuan P.
  Published: 2025/8 (journal-article)
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• Cadherin 11 regulates presynaptic vesicle trafficking and neuronal activity in autism-related brain circuit
  Authors: Cao X.; Jia J.; Li Z.; Guo S.; Duan J.; Ma J.; Yuan X.; Pan Y.
  Published: 2025/8 (journal-article)
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• An amygdala-cortical circuit for encoding generalized fear memories
  Authors: Vincent C.; Aguilar-Alvarez R.; Vanderhoof S.; Mott D.; Jasnow A.
  Published: 2025/8 (journal-article)
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  AbstractGeneralized learning is a fundamental process observed across species, contexts, and sensory modalities that enables animals to use past experiences to adapt to changing conditions. Evidence suggests that the prefrontal cortex (PFC) extracts general features of an experience that can be used across multiple situations. The anterior cingulate cortex (ACC), a region of the PFC, is implicated in generalized fear responses to novel contexts. However, the ACC’s role in encoding contextual information is poorly understood, especially under increased threat intensity that promotes generalization. Here, we show that synaptic plasticity within the ACC and signaling from basolateral amygdala (BLA) inputs during fear learning are necessary for generalized fear responses to novel encountered contexts. The ACC did not encode specific fear to the training context, suggesting this region extracts general features of a threatening experience rather than specific contextual information. Together with our previous work, our results demonstrate that generalized learning about threatening contexts is encoded, in part, within an ascending amygdala-cortical circuit, whereas descending ACC projections to the amygdala drive generalized fear responses during exposure to novel contexts. Our results further demonstrate that schematic learning can occur in the PFC after single-trial learning, a process typically attributed to learning over many repeated learning episodes.

• Acute and chronic stress differentially regulate pain via distinct ensembles in the paraventricular nucleus of hypothalamus
  Authors: Hu S.; Huang J.; Zhang Q.; Yang S.; Wu Z.; Wang Y.; Zhang X.; Wang D.; Ji Y.; Wang H.; Zhu C.; Yang J.; Liu C.; Huang C.; Cao J.; Yang C.
  Published: 2025/8 (journal-article)
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• Interpeduncular GABAergic neuron function controls threat processing and innate defensive adaptive learning
  Authors: Williams E.; Snively L.; O’Meara B.; Jacobs H.; Kolb M.; Zhao-Shea R.; Pavchinskiy R.; Keppler E.; Baratta M.; Tapper A.; Molas S.
  Published: 2025/8 (journal-article)
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  AbstractThe selection of appropriate defensive behaviors in the face of potential threat is fundamental to survival. Equally important is learning to adjust and optimize defensive behaviors when there is no real danger. Despite extensive research on innate threat processing, little is known about the mechanisms by which individuals adapt their defensive behaviors in response to repeated threats that lack real danger. Insight into this process is critical as its dysregulation may contribute to neuropsychiatric conditions, such as anxiety disorders. Here, we used the visual looming stimulus (VLS) paradigm in mice to investigate innate threat processing and adaptive defensive learning. Repeated exposure to VLS over consecutive sessions reduced immediate freezing responses and time spent inside a sheltered area upon VLS events, leading to an increase in exploratory behaviors. Fiber photometry recordings and optogenetic manipulations revealed that VLS innate adaptive defensive learning is associated with reduced recruitment of the midbrain interpeduncular nucleus (IPN), a structure associated with fear and anxiety-related behaviors. Functional circuit-mapping identified a role for select IPN projections to the laterodorsal tegmental nucleus in gating defensive learning. Finally, we uncovered a subpopulation of IPN neurons that express the neuropeptide somatostatin and encode avoidance signals in response to VLS. These results identify critical behavioral signatures of innate defensive responses and a circuit that regulates the essential features of threat processing.

• Brain structure characteristics in children with attention-deficit/hyperactivity disorder elucidated using traveling-subject harmonization
  Authors: Shou Q.; Yamashita M.; Hirano Y.; Yao A.; Li M.; Wang Y.; Kato Y.; Yoshida T.; Matsumoto K.; Tsujikawa T.; Okazawa H.; Tomoda A.; Kagitani-Shimono K.; Mizuno Y.
  Published: 2025/8 (journal-article)
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  AbstractBrain imaging studies for attention-deficit/hyperactivity disorder (ADHD) have not always yielded consistent findings, potentially owing to measurement bias in magnetic resonance imaging (MRI) scanners. This study aimed to elucidate the structural brain characteristics in children with ADHD by addressing measurement bias in multi-site MRI data using the harmonization method, traveling-subject (TS) approach. The MRI data of 14 traveling subjects, 178 typically developing (TD) children, and 116 children with ADHD were collected from multiple sites. The TS method and ComBat were used to correct for measurement bias. Gray matter volumes were estimated using FreeSurfer, and the ADHD and TD groups were compared using mixed-effect models. Compared to raw data, the TS method significantly reduced measurement bias while maintaining sampling bias. In contrast, ComBat effectively reduced measurement bias but also significantly decreased sampling bias. TS-corrected data showed decreased brain volumes in the frontotemporal regions in the ADHD group compared to the TD group. Specifically, significant volumetric reductions were found in the right middle temporal gyrus in children with ADHD (TS-corrected data:β= −0.255, FDR [family discovery rate]p= 0.001). These results demonstrate that the TS method effectively reduces measurement bias across MRI scanners, ensuring reliable findings in multi-site studies. The observed frontotemporal volume reductions in ADHD, especially in the right middle temporal gyrus, highlight the reliability of findings obtained with TS correction.

• Interleukin 13 signaling modulates dopaminergic functions and nicotine reward in rodents
  Authors: Liu X.; Aguirre C.; Yang Q.; Ren J.; Wang L.; Ju F.; Guo H.; Wang J.; Liu L.; Li Z.; He J.; Xu Z.; Shi C.; Cintron-Colon R.; Michel T.; Wood M.; Margetts A.; Pollock T.; Vilca S.; Tuesta L.; Di Angelantonio S.; Basilico B.; De Stefano M.; Xia J.; Wei P.
  Published: 2025/8 (journal-article)
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  AbstractNeuroimmune signals can regulate neuronal function and affect behavior through mechanisms that are not yet fully understood. Here we investigated the action of interleukin 13 (IL-13), a cytokine that can be produced in the brain by both microglia and neurons. We show that dopamine-containing neurons in the ventral tegmental area (VTA) predominantly express the IL-13 receptor alpha 1 (IL-13Rα1) and exhibit presynaptic vesicular localization of neuronal IL-13. Exogenous application of IL-13, or its endogenous mobilization by optogenetics, reduced the activity of VTA dopaminergic neurons and opposed the stimulatory effects of nicotine on these neurons in rodents. These actions required IL-13Rα1, activation of the PI3K/AKT pathway, and functional hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Consistently, local infusion of IL-13 into the VTA markedly reduced nicotine self-administration in rodents. Collectively, these findings demonstrate that IL-13 acts in a neuromodulator-like fashion on mesolimbic dopamine neurons expressing IL-13Rα1. Our data also indicate that IL-13Rα1 signaling regulates the stimulatory actions of nicotine, suggesting a potential role for this neuronal immune signaling in reward processing and the addictive properties of nicotine.

• Computational mechanisms of neuroimaging biomarkers uncovered by multicenter resting-state fMRI connectivity variation profile
  Authors: Yamashita O.; Yamashita A.; Takahara Y.; Sakai Y.; Okamoto Y.; Okada G.; Takamura M.; Nakamura M.; Itahashi T.; Hanakawa T.; Togo H.; Yoshihara Y.; Murai T.; Okada T.; Narumoto J.; Takahashi H.; Takagishi H.; Hosomi K.; Kasai K.; Okada N.; Abe O.; Imamizu H.; Hayashi T.; Koike S.; Tanaka S.
  Published: 2025/8 (journal-article)
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• Anterior insular cortex regulates depression-like and ASD-like behaviors via the differential contribution of two subsets of microglia
  Authors: Zhang Q.; Chen Y.; Xing Y.; Yang M.; Li N.; Jiang X.; Gao H.; Lu S.; Yao J.
  Published: 2025/8 (journal-article)
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• Genomic risk prediction for depression in a large prospective study of older adults of European descent
  Authors: Yu C.; Bakshi A.; Agustini B.; Walker A.; Lin T.; Lotfaliany M.; Williams L.; McNeil J.; Wray N.; Berk M.; Lacaze P.
  Published: 2025/8 (journal-article)
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  AbstractThe extent to which genetic predisposition contributes to late-life depression risk, particularly after age 70, remains unclear, despite the high prevalence of depression in this age group and the variability in risk factors by age. This study investigated the association between a polygenic score (PGS) and depression outcomes, including severity, trajectories of depression, and antidepressant medication use, in a longitudinal cohort of 12,029 genotyped older adults of European descent aged ≥70 years, with no history of diagnosed cardiovascular disease events, dementia, or permanent physical disability at baseline. Participants were followed for a median of 4.7 years. The PGS was derived using the latest Psychiatric Genomics Consortium data for major depression. Depression was defined by the CES-D-10 score thresholds of ≥8 (primary outcome), ≥10, and ≥12 (secondary outcomes), alongside antidepressant medication use and four previously established longitudinal trajectories of depressive symptoms: low (non-depressed), moderate (subthreshold), high (persistent), and initially low but increasing (emerging). Multivariable models were used to examine associations between the PGS (per standard deviation, SD) and outcomes, adjusting for covariates. At baseline, mean participant age was 75.1 years, 54.9% were female, and 9.1% had depression (CES-D-10 ≥ 8). The PGS was significantly associated with baseline depression (OR = 1.23 [1.15–1.31]), incident depression (HR = 1.18 [1.14–1.23]) and antidepressant medication use (OR = 1.39 [1.31–1.47]). Compared with non-depressed participants, the PGS was associated with increasing severity of depression trajectory classes (subthreshold depression OR = 1.15 [1.11–1.20], emerging depression OR = 1.22 [1.13–1.31], persistent depression OR = 1.40 [1.31–1.49]). These findings suggest that the PGS may play an important role in risk stratification for late-life depression.

• Neurobiological subtypes of adolescent depression: a multimodal integration of morphometric similarity network and spatial transcriptomics
  Authors: Wu P.; Kong L.; Zhou Y.; Deng C.; Wang Z.; Shen Y.; Wang L.; Tuo Z.; Liu Y.; Wang Y.; Zhou Y.; Sun Q.; Tang Y.
  Published: 2025/8 (journal-article)
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• PET imaging evidence of HDAC6 suppression in the amygdala across species in PTSD
  Authors: Bonomi R.; Naganawa M.; McRiley D.; Toyonaga T.; LeVasseur B.; Duman C.; Huang Y.; Matuskey D.; Carson R.; Pietrzak R.; Girgenti M.; Cosgrove K.
  Published: 2025/8 (journal-article)
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• The habenula in mood disorders: A systematic review of human studies
  Authors: Fortin J.; Lafleur M.; Parisien C.; Hétu S.
  Published: 2025/8 (journal-article)
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- Neuron

• Direction-selective laterodorsal thalamic nucleus encodes optic flow and turning in spatial navigation
  Authors: Li Z.; Huang J.; Zhang Y.; Su K.; Peng B.; Seo B.; Zhang L.; Tao H.
  Published: 2025/8 (journal-article)
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• Timing matters: Genetic regulation of neuronal maturation in the primate brain
  Authors: Imaizumi K.; Paşca S.
  Published: 2025/8 (journal-article)
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• Highly sensitive TEMPO imaging illuminates the cellular basis of oscillations in the local field potential
  Authors: Gibson E.; Restrepo D.
  Published: 2025/8 (journal-article)
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• Perceptual metacognition beyond confidence
  Authors: Nakamura T.; Lau H.
  Published: 2025/8 (journal-article)
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• Dietary-dependent sensitization of neuronal leptin signaling promotes neural repair after injury via cAMP and gene transcription
  Authors: Chadwick J.; Decourt C.; Müller F.; Maldonado-Lasuncion I.; Serger E.; Kong G.; Zhou L.; Song Y.; Yan Y.; Yuan Z.; Falconieri A.; Liddell P.; Chu L.; Chan W.; Luengo-Gutierrez L.; Palmisano I.; Di Giovanni S.
  Published: 2025/8 (journal-article)
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• The VI-P of the leptomeninges
  Authors: Kim S.; Siegenthaler J.
  Published: 2025/8 (journal-article)
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• Selective removal of astrocytic PERK protects against glymphatic impairment and decreases toxic aggregation of β-amyloid and tau
  Authors: Chen K.; Morizawa Y.; Nuriel T.; Al-Dalahmah O.; Xie Z.; Yang G.
  Published: 2025/8 (journal-article)
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• Nonneuronal contributions to synaptic function
  Authors: Hodebourg R.; Scofield M.; Kalivas P.; Kuhn B.
  Published: 2025/8 (journal-article)
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• Social interaction in mice suppresses breast cancer progression via a corticoamygdala neural circuit
  Authors: Wen H.; Xiong S.; Lou Y.; Yang S.; Sun L.; Yi Y.; Tang B.; Shu Q.; Wang Z.; Yan X.; Wu Y.; Chen P.; Qi X.; Zhang Y.; Dai L.; Xiong Y.; Wu G.
  Published: 2025/8 (journal-article)
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• How the brain shifts between external and internal attention
  Authors: Nobre A.; Gresch D.
  Published: 2025/8 (journal-article)
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• Reconstructed cell-type-specific rhythms in human brain link Alzheimer’s pathology, circadian stress, and ribosomal disruption
  Authors: Hollis H.; Sharma A.; Sheehan P.; Maggi L.; Weber J.; Hammarlund J.; Bennett D.; Menon V.; Musiek E.; Anafi R.
  Published: 2025/8 (journal-article)
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• Constitutive lipid scramblase activity underpins mechanosensitive TMEM63 channelopathies
  Authors: Brynn R.; Poole K.
  Published: 2025/8 (journal-article)
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• Coordination of distinct sources of excitatory inputs enhances motion selectivity in the mouse visual thalamus
  Authors: Fei Y.; Luh M.; Ontiri A.; Ghauri D.; Hu W.; Liang L.
  Published: 2025/8 (journal-article)
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• Distinct molecular patterns in R6/2 HD mouse brain: Insights from spatiotemporal transcriptomics
  Authors: Burns M.; Miramontes R.; Wu J.; Gulia R.; Saddala M.; Lau A.; Quach T.; Reidling J.; Swarup V.; La Spada A.; Lim R.; Thompson L.
  Published: 2025/8 (journal-article)
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• Multimodal analyses reveal genes driving electrophysiological maturation of neurons in the primate prefrontal cortex
  Authors: Gao Y.; Dong Q.; Arachchilage K.; Risgaard R.; Syed M.; Sheng J.; Schmidt D.; Jin T.; Liu S.; Sandoval S.; Knaack S.; Eckholm M.; Chen R.; Guo Y.; Doherty D.; Glass I.; Levine J.; Wang D.; Chang Q.; Zhao X.; Sousa A.
  Published: 2025/8 (journal-article)
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• Competitive integration of time and reward explains value-sensitive foraging decisions and frontal cortex ramping dynamics
  Authors: Bukwich M.; Campbell M.; Zoltowski D.; Kingsbury L.; Tomov M.; Stern J.; Kim H.; Drugowitsch J.; Linderman S.; Uchida N.
  Published: 2025/8 (journal-article)
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• Locus coeruleus activation “resets” hippocampal event representations and separates adjacent memories
  Authors: Clewett D.; Huang R.; Davachi L.
  Published: 2025/8 (journal-article)
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• Structural and functional basis of mechanosensitive TMEM63 channelopathies
  Authors: Zheng W.; Lowry A.; Smith H.; Xie J.; Rawson S.; Wang C.; Ou J.; Sotomayor M.; Fu T.; Yang H.; Holt J.
  Published: 2025/8 (journal-article)
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• Grouping signals in primate visual cortex
  Authors: Franken T.; Reynolds J.
  Published: 2025/8 (journal-article)
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• A neural basis for distinguishing imagination from reality
  Authors: Dijkstra N.; von Rein T.; Kok P.; Fleming S.
  Published: 2025/8 (journal-article)
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• Ion channels in respiratory rhythm generation and sensorimotor integration
  Authors: da Silva Junior C.; Picardo M.; Del Negro C.
  Published: 2025/8 (journal-article)
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• Propagating Motor Cortical Dynamics Facilitate Movement Initiation
  Authors: Balasubramanian K.; Papadourakis V.; Liang W.; Takahashi K.; Best M.; Suminski A.; Hatsopoulos N.
  Published: 2025/8 (journal-article)
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• LRRTM2 Functions as a Neurexin Ligand in Promoting Excitatory Synapse Formation
  Authors: Ko J.; Fuccillo M.; Malenka R.; Südhof T.
  Published: 2025/8 (journal-article)
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• Identification of the velum interpositum as a meningeal-CNS route for myeloid cell trafficking into the brain
  Authors: Hohsfield L.; Kim S.; Barahona R.; Henningfield C.; Mansour K.; Vallejo K.; Tsourmas K.; Kwang N.; Ghorbanian Y.; Angulo J.; Gao P.; Pachow C.; Inlay M.; Walsh C.; Xu X.; Lane T.; Green K.
  Published: 2025/8 (journal-article)
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- Science Advances

• Ultrafast tomograms in a flash
  Authors: Tian L.
  Published: 2025/8 (journal-article)
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  Fourier synthesis optical diffraction tomography encodes hundreds of views per exposure, enabling kilohertz-rate, label-free three-dimensional imaging of complex biological and soft-matter dynamics previously beyond reach.

• Diurnal urban rainfall anomalies across different landscapes
  Authors: Sui X.; Yang Z.; Niyogi D.
  Published: 2025/8 (journal-article)
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  Urbanization influences regional climates and extreme weather. While previous research has documented urban-induced precipitation for specific cities or storm cases, diurnal urban precipitation anomalies across different landscapes remain poorly understood. Analyzing diurnal and seasonal variations of urban precipitation anomalies across 175 US cities, we found strong urban effects on precipitation especially during summer afternoons. Large, inland cities can receive 10% more summer afternoon rainfall, and the pattern varies with urban heat islands and wind conditions. Coastal cities, under the influence of sea-land breeze, experience three times amplified daily urban precipitation enhancements than inland cities. Urban impacts are also noted for mountain cities, affecting their topography-dominated precipitation patterns. With increasing thresholds of extreme precipitation, most US cities experience more intense rainfall compared to their rural backgrounds. This study enhances our understanding of hitherto poorly documented diurnal aspects of urban rainfall through geographically distributed, landscape-specific rainfall anomalies.

• The small-molecule pifithrin-α deactivates ETR1 to repress shade avoidance in Arabidopsis
  Authors: Liang W.; Huang S.; Chen X.; Jiang K.; Gong X.; Guo H.; Li L.
  Published: 2025/8 (journal-article)
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  Shade avoidance syndrome (SAS) commonly occurs in plants sensing shading and the proximity of neighbors, leading to morphological and physiological changes that are detrimental to plant health and consequently crop yield. Controlling SAS could be beneficial for sustainable agriculture. Here, we performed a phenotype-based chemical screening inArabidopsisand identified pifithrin-α (PFT-α) as a compound that suppresses shade-induced hypocotyl elongation and gene expression. Through genetic, biochemical, and molecular approaches, we demonstrated that PFT-α mimics ethylene by deactivating the ethylene receptor 1 (ETR1). Accumulated ethylene-insensitive 3 (EIN3) influences the expression ofphytochrome-interacting factors(PIF4andPIF7) and subsequently inhibits shade-induced hypocotyl elongation. Our findings not only provide molecular insights into SAS but also suggest that PFT-α, acting as a potent ethylene mimic, plays a crucial role in hormone-regulated plant development and holds potential for modulating SAS in agricultural practices.

• Somatic CRISPR tumorigenesis and multiomic analysis reveal a pentose phosphate pathway disruption vulnerability in MPNSTs
  Authors: McGivney G.; Brockman Q.; Borcherding N.; Scherer A.; Rauckhorst A.; Gutierrez W.; Solst S.; Heer C.; Warrier A.; Floyd W.; Kirsch D.; Knepper-Adrian V.; Laverty E.; Roughton G.; Spitz D.; Taylor E.; Dodd R.
  Published: 2025/8 (journal-article)
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  Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive and chemo-resistant sarcomas with poor survival rates. Loss ofCDKN2AorP53following NF1 disruption is a key event in MPNST development. Here, we used CRISPR-Cas9 somatic tumorigenesis in mice to identify transcriptomic and metabolomic features distinguishingCDKN2A- versusP53-deleted MPNSTs. Convergent, multiomic analyses revealed thatCDKN2A-deleted MPNSTs are especially dependent on the pentose phosphate pathway (PPP) and NADPH metabolism for growth and viability. Disruption of glucose-6-phosphate dehydrogenase (G6PD), the PPP rate-limiting enzyme, slowedCDKN2A-deleted MPNST growth and sensitized MPNSTs to standard-of-care chemotherapy. Knockdown of the redox-regulated transcription factor NRF2 slowed MPNST growth and decreased G6PD transcription. Analysis of patient MPNSTs identified a NRF2 gene signature correlating with tumor transformation. Furthermore, G6PD and NRF2 expression in PanCancer TCGA samples correlates with patient survival. This work identifies NRF2-PPP dependency as a targetable vulnerability in these difficult-to-treat MPNSTs, particularly in theNF1/CDKN2A-deleted majority.

• Excess water availability in northern mid-high latitudes contiguously migrated from ocean under climate change
  Authors: Guan Y.; Gu X.; Wang L.; Zhou T.; Xia J.; Jiang D.; Slater L.; Gimeno L.; Pokhrel Y.; Villarini G.; Kug J.; Son S.; Allan R.; Li J.; Gan T.; Liu Y.; Kong D.; Zhang X.; Cui X.
  Published: 2025/8 (journal-article)
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  Terrestrial water availability sustains livelihoods, socioeconomic development, and ecosystems. Despite an understanding of contributions of oceanic moisture to terrestrial hydroclimatic extremes, whether surpluses of terrestrial water availability migrate directly and contiguously from the ocean and the influence of climate change on this process remain unclear. Here, we use a coherent feature-tracking method to identify ocean-to-land water availability surpluses (OWASs), characterized by spatiotemporally contiguous migration of excess atmospheric freshwater (precipitation-minus-evapotranspiration) from ocean to land. Over the past several decades, especially in northern mid-high latitudes (NMHL; above 48°N), OWASs have exhibited longer persistence, wider areal extent, and greater intensity than those developed solely over land. These landward migrations are associated with seasonal Atlantic teleconnection and Pacific circulation shift. Under the business-as-usual scenario, these two processes are projected to be enhanced, markedly increasing OWAS characteristics in NMHL driven by thermodynamic atmospheric responses to future warming. Intensified OWASs may not only help alleviate long-term droughts but also have the potential to accentuate pluvial risks.

• A bioinspired microfluidic wearable sensor for multiday sweat sampling, transport, and metabolic analysis
  Authors: Shin S.; Liu R.; Yang Y.; Lasalde-Ramírez J.; Kim G.; Won C.; Min J.; Wang C.; Fan K.; Han H.; Uwakwe C.; Heng W.; Hsiai T.; Li Z.; FitzGerald J.; Gao W.
  Published: 2025/8 (journal-article)
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  Wearable sweat sensors enable noninvasive real-time biochemical monitoring, holding immense potential for personalized health care applications. However, achieving prolonged and reliable sweat sampling, along with stable biochemical analysis, remains challenging due to inconsistent secretion, rapid evaporation, and the reliance on external stimulation. Here, we present BMS3, a bioinspired microfluidic wearable sweat sensor system designed for multiday continuous metabolic monitoring. BMS3integrates hierarchically graded microchannels and superhydrophobic-superhydrophilic Janus membranes, inspired by pitcher plant trichomes and lotus leaves to enable efficient low volume sweat collection, transport, and renewal. A miniaturized carbachol gel–based iontophoresis module autonomously induces localized sweat secretion. Furthermore, the microfluidic design sustains sweat sampling for over 2 days from a single iontophoresis session, eliminating the need for physical exertion. In vitro and in vivo studies in healthy participants and patients with gout demonstrate BMS3’s capability for continuous metabolic monitoring. By simultaneously tracking uric acid, xanthine, and alcohol levels, it effectively differentiates normal and pathological states while delivering timely therapeutic feedback.

• Classic Maya response to multiyear seasonal droughts in Northwest Yucatán, Mexico
  Authors: James D.; Carolin S.; Breitenbach S.; Hoggarth J.; Lases-Hernández F.; Endsley E.; Curtis J.; Gallup C.; Milbrath S.; Nicolson J.; Rolfe J.; Kwiecien O.; Ottley C.; Iveson A.; Baldini J.; Brenner M.; Henderson G.; Hodell D.
  Published: 2025/8 (journal-article)
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  Protracted droughts may have contributed to sociopolitical upheaval and depopulation of cultural centers in the Maya Lowlands during the Terminal Classic Period (~800 to 1000 CE). Regional proxy climate records suggest multiple prolonged drought episodes during the Terminal Classic. The relationship between drought and response of individual sites, however, remains unclear because of large chronological uncertainties and poor temporal resolution of existing local paleoclimate inferences. We present a subannual rainfall record from northwest Yucatán, Mexico, derived from an annually laminated stalagmite spanning 871 to 1021 CE, with ±6-year age uncertainty. Interpretation of the stalagmite oxygen isotope record is supported by modern rain and drip water monitoring. Precisely dated droughts enable detailed analyses of timing and dynamics of regional human-climate interactions. Despite uncertainties in archaeological chronologies, these results suggest political activity at major northern Maya sites, including Chichén Itzá and Uxmal, declined at different times relative to droughts, implying differential cultural responses to climate stress.

• Transcriptome fingerprinting of aberrant fibroblast activation unlocks effective therapeutics to tackle cardiac fibrosis
  Authors: Cinato M.; Kang R.; Kramar S.; Savchenko L.; Pizzinat N.; Swiader A.; Kel A.; Kalmykov A.; Stelmashenko D.; Martinelli I.; Roncalli J.; Laborde C.; Kunduzova O.
  Published: 2025/8 (journal-article)
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  Aberrant activation of fibroblasts is a pivotal component of cardiac fibrosis predisposing to heart failure. However, the molecular regulation of the functional state of cardiac fibroblasts in fibrosis resolution remains largely unexplored, and therefore, effective antifibrosis therapies are still lacking. By translating mouse transcriptomics to humans, we unlocked common molecular denominators connecting the fibroblast phenotypic state and fibrogenic signaling pathways in cardiac fibrosis. Through the construction of a fibroblast-specific transcriptional gene regulatory network, we found ITGAL and DUSP9 as key druggable targets for human myocardial fibrosis. A computational drug repurposing approach predicted 367 antifibrotic candidate compounds for heart disease. In primary cardiac fibroblasts derived from patients with heart failure, we provided experimental validation of the top 2–ranked repositioned drug candidates and their combination. These innovative approaches facilitate the identification of potential targets and drug candidates for cardiac fibrosis, providing actionable opportunities for clinical translation.

• Sweat-sensitive adaptive warm clothing
  Authors: Jiang X.; Li X.; Zhang H.; Hu Z.; Jia S.; Meng G.; Hsu P.; Guo W.; Zhang Z.
  Published: 2025/8 (journal-article)
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  Thermal regulation in warm clothing is essential for enhancing human comfort in cold environments. However, traditional warm clothing lacks the ability to adapt to dynamic changes in the human body’s microenvironment. Here, we present an adaptive warm cloth, featuring a filling made of a natural bacterial cellulose membrane that responds to human sweating. The cloth’s thickness automatically adjusts from 13 millimeters (under low humidity and no sweating conditions) to 2 millimeters (under high humidity and sweating conditions), expanding the thermal regulation capability by 82.8% compared to traditional warm clothing with an unchanged thickness of 13 millimeters. Modeling results further suggest that deploying this adaptive warm clothing across 20 cities in China could extend the duration of the no thermal stress zone by an average of 7.5 hours. Combining exceptional thermal regulation, high stability, and scalability, this clothing represents a notable supplement to existing thermal management technologies.

• Bioarchitectonics-inspired soft grippers with cutaneous slip perception
  Authors: Su J.; Tan J.; Liu J.; He K.; Wu D.; Lai W.; Cao J.; Phee S.; Magdassi S.; Chen X.
  Published: 2025/8 (journal-article)
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  The growing demand for dexterous and autonomous robotic manipulation highlights the need for advanced sensing and control strategies, particularly for slip prevention. Although soft grippers provide intrinsic compliance and adaptability, their effectiveness is often limited by the lack of real-time sensory feedback and the complexity of soft actuator dynamics. Inspired by human tactile perception, we developed a bioarchitectonics-inspired soft slip sensor with a three-dimensional structure that leverages crack and stress concentration to enhance sensitivity to incipient slip and shear force. Complementarily, a soft gripper with a linear pressure-to-force response was engineered to enable stable and predictable force modulation. The flexible slip sensors were conformally integrated onto the grippers, forming a fully perceptive soft robotic system capable of detecting early-stage slippage and investigating interfacial frictional properties. This integration establishes a closed-loop sensorimotor framework that notably improves the reliability and adaptability of soft robotic grasping across a wide range of real-world applications.

• Structures of MmpL complexes reveal the assembly and mechanism of this family of transporters
  Authors: Zhang Z.; Maharjan R.; Gregor W.; Klenotic P.; Yu E.
  Published: 2025/8 (journal-article)
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  We coexpressed the mycobacterial membrane protein large 5 (MmpL5) transporter and MmpS5 adaptor proteins inMycobacterium smegmatisand defined their structures from detergent-solubilized crude membranes. We observed that MmpL5 presents as a monomer in complex with the cytosolic meromycolate extension acyl carrier protein M (AcpM), where these AcpM-MmpL5 complexes generate regular two-dimensional arrays. We also provide structural information to show thatM. smegmatisMmpL5 assembles as a trimer that interacts with MmpS5 and AcpM to form the tripartite complex AcpM-MmpL5-MmpS5 that spans both the inner and outer membranes of the mycobacterium. In addition, we found that MmpL5 and AcpM are able to form the trimeric AcpM-MmpL5 complex. The structural data reveal that the full-length MmpL5 trimer is capable of spanning the entire mycobacterial cell envelope to transport substrates. However, this assembly requires the presence of MmpS5 to stabilize secondary structural features of the MmpL5 periplasmic subdomains.

• Fourier synthesis optical diffraction tomography for kilohertz rate volumetric imaging
  Authors: Brown P.; Jabbarzadeh N.; Meneses L.; Swanson K.; Pintuff A.; Monakhova E.; Kruithoff R.; Wadhwa N.; Galati D.; Shepherd D.
  Published: 2025/8 (journal-article)
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  Many biological and soft matter processes occur at high speeds in complex three-dimensional (3D) environments, and developing imaging techniques capable of elucidating their dynamics is an outstanding challenge. Here, we introduce Fourier synthesis optical diffraction tomography (FS-ODT), a quantitative phase imaging approach capable of recording the 3D refractive index at kilohertz rates. FS-ODT introduces computational strategies that multiplex tens of illumination angles in a single tomogram, markedly increasing the volumetric imaging rate. We validate FS-ODT on samples of known composition, hindered diffusion of colloids in solution, and the motility of bacterial swimmers. We also integrate FS-ODT into a multimodal microscope combining refractive index imaging with multicolor structured illumination microscopy. FS-ODT is a promising approach for unlocking imaging regimes that have been little explored, including understanding the physical interactions of colloids and microswimmers with their 3D environment and the interplay between these stimuli and the molecular response of biological systems.

• Geographic range shapes influence species richness in global hotspots
  Authors: Sonne J.; Borregaard M.; Colwell R.; Rahbek C.
  Published: 2025/8 (journal-article)
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  The extraordinary richness of species in tropical mountain regions is often attributed to aggregations of small-ranged species, allowing tight spatial packing of their ranges. However, ranges of species in these regions are also distinctly more patchy and elongated than those found in adjacent lowlands. Our global analysis of mainland birds demonstrates that these range shapes augment the spatial variation in species richness. Both the linearity and patchiness of species ranges are most pronounced in aseasonal and topographically complex regions, most notably in the tropical Andes, where these range shapes contribute more to the pattern of species richness than broad-scale variations in range size. Consequently, niche-based processes that govern the spatial configuration of habitats contribute to patterns of species richness in global hotspots over and above the processes that affect species richness through range sizes.

• Topological classification of driven-dissipative nonlinear systems
  Authors: Villa G.; del Pino J.; Dumont V.; Rastelli G.; Michałek M.; Eichler A.; Zilberberg O.
  Published: 2025/8 (journal-article)
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  In topology, averaging over local geometrical details reveals robust global features. These are crucial in physics for understanding quantized bulk transport and exotic boundary effects of linear wave propagation in (meta-)materials. Beyond linear Hamiltonian systems, topological physics strives to characterize open (non-Hermitian) and interacting systems. Here, we establish a framework for the topological classification of driven-dissipative nonlinear systems by defining a graph index for their Floquet semiclassical equations of motion. Our index builds upon the topology of vector flows and encodes the particle-hole nature of excitations around all out-of-equilibrium stationary states. Thus, we uncover the topology of nonlinear resonator’s dynamics under external and parametric forcing. Our framework sheds light on the topology of driven-dissipative phases, including under- to overdamped responses and symmetry-broken phases linked to population inversion. We therefore expose the pervasive link between topology and nonlinear dynamics, with broad implications for interacting topological insulators, topological solitons, neuromorphic networks, and bosonic codes.

• Exploring antibiotic resistance in diverse homologs of the dihydrofolate reductase protein family through broad mutational scanning
  Authors: Romanowicz K.; Resnick C.; Hinton S.; Plesa C.
  Published: 2025/8 (journal-article)
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  Antimicrobial resistance studies often focus on individual protein variants, neglecting broader protein family dynamics. Dihydrofolate reductase (DHFR), a key antibiotic target, has been extensively studied using deep mutational scanning, yet resistance mechanisms across this diverse protein family remain poorly understood. Here, we developed a synthetic metagenomics approach using DropSynth, a scalable gene synthesis platform, to construct a phylogenetically diverse library of 1536 DHFR homologs. These sequences, primarily derived from host-associated metagenomes, represent 759 bacterial species, including many clinically relevant pathogens. A multiplexed in vivo assay tested their ability to restore metabolic function and confer trimethoprim resistance in anEscherichia coli∆folAstrain. Half of the synthetic homologs rescued the phenotype without supplementation, and mutant variants with up to five amino acid substitutions increased rescue rates to 90%, highlighting DHFR’s evolutionary resilience. Broad mutational scanning of DHFR homologs and 100,000 mutants revealed key insights into fitness and resistance, offering the most comprehensive analysis of complementation and inhibitor tolerance to date.

• In situ observation of oxygen ion dynamics in topological phase change memristors through self-assembled interface design
  Authors: Li K.; Zhang J.; Chen Y.; Pan J.; Zheng Y.; Xu S.; Zhao R.; Li M.; Qi R.; Huang R.; Yan Z.; Yu P.; Liu J.; MacManus-Driscoll J.; Yang H.; Li W.
  Published: 2025/8 (journal-article)
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  Resistive switching memory represents a potentially transformative advancement in next-generation nonvolatile memory and neuromorphic technologies. Recently, vertically aligned nanocomposites (VANs) have been proposed to optimize the memristive performance of single-phase memories. However, the microscopic mechanism of dynamic resistive switching in these VAN architectures is still elusive. Here, we built up a VAN structure with brownmillerite SrCoO2.5(BM-SCO) and magnesium oxide (MgO), where the topological phase transformation in BM-SCO provides a well-defined facile vertical path for oxygen ion migration within the vertical interfaces between BM-SCO and MgO phases. Compared with the BM-SCO memristor, the (BM-SCO)0.5:(MgO)0.5VAN memristor exhibits advantages in resistive switching and simulates various synaptic functions, achieving high accuracy in image recognition tasks. Using in situ scanning transmission electron microscopy, we revealed the microscopic mechanism of oxygen ion migration dynamics along the vertical interfaces. Our work substantially advances the understanding of resistive switching mechanism and further demonstrates the great potential of VAN architectures for practical application in high-performance resistive memory.

• Lipid nanoparticles for mRNA delivery in brain via systemic administration
  Authors: Cao D.; Hou X.; Wang C.; Wang S.; Liu Z.; Tian M.; Guo K.; Li H.; Kang D.; Zhong Y.; Xue Y.; Yu C.; Deng B.; Dong Y.
  Published: 2025/8 (journal-article)
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  Efficient delivery of messenger RNA (mRNA) to the brain via systemic administration remains a challenge, primarily due to the blood-brain barrier. To address this challenge, we incorporated SR-57227, a ligand of serotonin [5-hydroxytryptamine type 3 (5-HT3)] receptor, into the design of ionizable lipids to develop lipid nanoparticles (LNPs) for systemic mRNA delivery to the brain. OS4T LNP was identified as an optimized formulation based on multiple assays. Following systemic administration, OS4T LNP achieved over a 50-fold increase in mRNA translation within brain tissues compared to US Food and Drug Administration–approved Onpattro LNPs (DLin-MC3-DMA). In an orthotopic glioblastoma (GBM) mouse model, engineered interleukin-12 mRNA–loaded OS4T LNPs significantly suppressed tumor growth and improved overall survival. This study demonstrates OS4T LNP as a promising platform for brain mRNA delivery and highlights its potential for treating GBM and other central nervous system disorders.

• Tracing the stepwise Darwinian evolution of a plant halogenase
  Authors: Kim C.; Kastner D.; Mitchell A.; Gutierrez M.; Yao J.; Neumann E.; Kulik H.; Weng J.
  Published: 2025/8 (journal-article)
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  Biohalogenation is rare in plant metabolism, with the Menispermaceae’s chloroalkaloid acutumine being an exception. This involves a specialized dechloroacutumine halogenase (DAH) from the iron- and 2-oxoglutarate–dependent dioxygenase (2ODD) family. While DAH is presumed to have evolved from an ancestral 2ODD, how enzyme specialization arises through Darwinian processes remains a fundamental question in understanding metabolic evolution. Here, we investigate the evolutionary history of DAH using the chromosomal-level genome ofMenispermum canadense. Phylogenomic dating and synteny analyses reveal DAH evolution through tandem duplication of an ancestral flavonol synthase (FLS) gene, followed by neofunctionalization and gene loss events. Structural modeling, molecular dynamics, and site-directed mutagenesis identify mutations enabling the catalytic switch from FLS to DAH. This required traversing a complex evolutionary landscape with deep fitness valleys separating intermediate states captured in theM. canadensegenome. Our findings illustrate how enzymatic functions evolve through lineage-specific pathways, reshaping active sites and enabling catalytic mechanism-switching mutations.

• Nanoscale acoustic oscillator for mechanoimmunology: NAOMI
  Authors: He Y.; Jin K.; Pan B.; Li K.; Mai J.; Xu X.; Chen Y.; Ma Z.; Yang K.; Yang S.; Shambaugh K.; Liu M.; Xia J.; Wu Y.; Lee L.; Huang T.
  Published: 2025/8 (journal-article)
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  Mechanoimmunology explores how mechanical forces orchestrate immune responses, offering insights into immune cell functions and the mechanisms underlying mechanotransduction. A critical challenge in this field is the absence of reliable platforms that apply precise, consistent mechanical stimuli to individual cells while enabling reproducible immune activation. Here, we present a nanoscale acoustic oscillator for mechanoimmunology applications: NAOMI. NAOMI features micropatterned pillars that support uniform cell monolayer formation with an integrated acoustic transducer that delivers highly controlled 3D nanoscale oscillations (±1-nanometer deviation) for up to 72 hours. Unlike conventional passive platforms relying on static stiffness or surface topography, NAOMI enables dynamic, programmable stimulation with high precision and reproducibility. Validation studies demonstrate that NAOMI notably enhances mechanical stress intensity and cell displacement, driving robust M1 polarization in macrophages. NAOMI provides a practical and versatile platform for studying mechanoimmunology, offering high precision, stability, and tunability. Its capabilities also position it well to support future research and drive innovative discoveries in the field.

• Submarine ash megabed fed by far-traveled, shoreline-crossing pyroclastic currents from a large explosive volcanic eruption
  Authors: Metcalfe A.; Druitt T.; Pank K.; Kutterolf S.; Preine J.; Kelfoun K.; Hübscher C.; Nomikou P.; Ronge T.; Chiyonobu S.; Koukousioura O.; Woodhouse A.; Beethe S.; Manga M.; McIntosh I.; Tominaga M.; Berthod C.; Chen H.; Clark A.; DeBari S.; Gertisser R.; Johnston R.; Peccia A.; Yamamoto Y.; Bernard A.
  Published: 2025/8 (journal-article)
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  Large explosive volcanic eruptions from island volcanoes deliver vast quantities of ash to the marine environment. While many of the transport pathways are understood, those from shoreline-crossing or submarine pyroclastic currents, and their transformation into water-supported gravity flows, remain poorly constrained. We report the discovery by International Ocean Discovery Program (IODP) deep drilling of a 200-meter-thick ash megabed buried in rift basins of the South Aegean Volcanic Arc. The >73–cubic kilometer ash deposit originates from the Kos Plateau Tuff caldera-forming eruption, which occurred 161 thousand years ago, >120 kilometers to the east. The ash forms a chemically uniform, graded megabed lacking bioturbation, interpreted as having been emplaced by a stream of eruption-fed turbidity currents. Bioclastic debris within the ash provides evidence of widespread destruction of marine ecosystems. Large volcanic eruptions can remodel the seafloor landscape, deposit thick ash turbidites, and destroy marine biota on island arc–wide scales in short-lived, catastrophic events.

• Elusive tropical forest canopy diversity revealed through environmental DNA contained in rainwater
  Authors: Zinger L.; Benoiston A.; Cuenot Y.; Leroy C.; Louisanna E.; Moreau L.; Petitclerc F.; Piatscheck F.; Orivel J.; Richard-Hansen C.; Hansen-Chaffard L.; Suescun U.; Troispoux V.; Boyer F.; Chave J.; Decaëns T.; Fouquet A.; Pansu J.; Raynaud J.; Rougerie R.; Sire L.; Schimann H.; Taberlet P.; Iribar A.
  Published: 2025/8 (journal-article)
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  Exploring the biodiversity hidden in tropical rainforests canopies represents a major frontier in biodiversity research yet remains challenging. Environmental DNA (eDNA) can revolutionize this field as it did already in various ecosystems. Here, we test the hypothesis that eDNA contained in canopy throughfall could be used to monitor this elusive diversity and detect anthropogenic disturbance. Using custom-made, low-cost rain collectors, we sampled rainwash eDNA in a mature Amazonian forest and a nearby tree plantation. We successfully detected eDNA from tropical woody and epiphyte plants, vertebrates (mammals, birds, and amphibians), and insects (e.g., mosquitoes, ants, and beetles). The taxonomic composition and diversity reflected disturbance, with significantly lower diversity in the plantation. Crucially, rainwash eDNA integrated biodiversity over a 10-day period in passive collectors and provided a local signature. This approach has thus potential for establishing a cost-effective monitoring system for tropical moist forest canopies, applicable in impact assessments and sustainable management.

• Data-driven global ocean modeling for seasonal to decadal prediction
  Authors: Guo Z.; Lyu P.; Ling F.; Bai L.; Luo J.; Boers N.; Yamagata T.; Izumo T.; Cravatte S.; Capotondi A.; Ouyang W.
  Published: 2025/8 (journal-article)
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  Accurate modeling of ocean dynamics is crucial for enhancing our understanding of complex ocean circulation processes, predicting climate variability, and tackling challenges posed by climate change. Although great efforts have been made to improve traditional numerical models, predicting global ocean variability over multiyear scales remains challenging. Here, we propose ORCA-DL (Oceanic Reliable foreCAst via Deep Learning), a data-driven three-dimensional ocean model for seasonal to decadal prediction of global ocean dynamics. ORCA-DL accurately simulates the three-dimensional structure of global ocean dynamics with high physical consistency and outperforms state-of-the-art numerical models in capturing extreme events, including El Niño–Southern Oscillation and upper ocean heat waves. Moreover, ORCA-DL stably emulates ocean dynamics at decadal timescales, demonstrating its potential even for skillful decadal predictions and climate projections. Our results demonstrate the high potential of data-driven models for providing efficient and accurate global ocean modeling and prediction.

• Src/Fas2-dependent Ephrin phosphorylation initiates Eph/Ephrin reverse signaling through Rac1 to shape columnar units in the fly brain
  Authors: Wang M.; Han X.; Lee Y.; Takayama R.; Sato M.
  Published: 2025/8 (journal-article)
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  Columns are the morphological and functional units containing multiple neurons in the brain. The molecular mechanisms of column formation are largely unknown. Ephrin/Eph signaling mediates a variety of developmental processes. Ephrin acts as a ligand for Eph to regulate forward signaling, whereas Eph acts as a ligand for Ephrin to regulate reverse signaling. However, whether and how the uni- or bidirectional Ephrin/Eph signaling is involved in column formation remains elusive. In this study, we show that Ephrin and Eph regulate the morphology and location of columnar neurons through bidirectional repulsive signaling. Furthermore, Eph ligand triggers cytoplasmic tyrosine phosphorylation of Ephrin under the control of Src kinases and Fasciclin 2 (Fas2), forming the Ephrin/Src/Fas2 complex to promote reverse signaling through a downstream regulator, Rac1. This study provides the detailed analysis of the molecular interactions involved in column formation using the fly brain as a model.

• Membrane curvature association of amphipathic helix 8 drives constitutive endocytosis of GPCRs
  Authors: Schmidt J.; Herlo R.; Rombach J.; Larsen A.; Stoklund M.; Perslev M.; Nielsen T.; Andersen K.; Herenbrink C.; Lycas M.; Ejdrup A.; Christensen N.; Christensen J.; Salman M.; Herborg F.; Gether U.; Hauser A.; Bassereau P.; Perrais D.; Madsen K.
  Published: 2025/8 (journal-article)
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  Cellular signaling relies on the activity of transmembrane receptors and their presentation on the cellular surface. Their continuous insertion in the plasma membrane is balanced by constitutive and activity-dependent internalization, which is orchestrated by adaptor proteins recognizing semispecific motifs within the receptors’ intracellular regions. Here, we describe a complementary trafficking mechanism for G protein–coupled receptors (GPCRs) that is evolutionary conserved and refined. This mechanism relies on the insertion of their amphipathic helix 8 into the inner leaflet of lipid membranes, orthogonal to the transmembrane helices. These amphipathic helices dictate subcellular localization of the receptors and autonomously drive their endocytosis by cooperative assembly and association with areas of high membrane curvature. The strength of helix 8 membrane insertion propensity quantitatively predicts the rate of constitutive internalization of GPCRs. This discovery advances our understanding of membrane protein trafficking and highlights a principle of receptor-lipid interactions that may have broad implications for cellular signaling and therapeutic targeting.

• N , N -dimethyltryptamine mitigates experimental stroke by stabilizing the blood-brain barrier and reducing neuroinflammation
  Authors: László M.; Vigh J.; Kocsis A.; Porkoláb G.; Hoyk Z.; Polgár T.; Walter F.; Szabó A.; Djurovic S.; Merkely B.; Alpár A.; Frecska E.; Nagy Z.; Deli M.; Nardai S.
  Published: 2025/8 (journal-article)
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  N,N-dimethyltryptamine (DMT) is a psychoactive molecule present in the human brain. DMT is under clinical evaluation as a neuroprotective agent in poststroke recovery. Yet, its mechanism of action remains poorly understood. In a rat transient middle cerebral artery occlusion stroke model, we previously showed that DMT reduces infarct volume. Here, we demonstrate that this effect is accompanied by reduction of cerebral edema, attenuated astrocyte dysfunction, and a shift in serum protein composition toward an anti-inflammatory, neuroprotective state. DMT restored tight junction integrity and blood-brain barrier (BBB) function in vitro and in vivo. DMT suppressed the release of proinflammatory cytokines and chemokines in brain endothelial cells and peripheral immune cells and reduced microglial activation via the sigma-1 receptor. Our findings prove that DMT mitigates a poststroke effect by stabilizing the BBB and reducing neuroinflammation. Such interactions of DMT with the vascular and immune systems can be leveraged to complement current, insufficient, stroke therapy.

• Large-scale maps of altered cortical dynamics in early-stage psychosis are related to GABAergic and glutamatergic neurotransmission
  Authors: Arazi A.; Toso A.; Grent-‘t-Jong T.; Uhlhaas P.; Donner T.
  Published: 2025/8 (journal-article)
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  Psychotic disorders affect GABAergic inhibition and glutamatergic excitation via NMDA receptors across the cerebral cortex. The mechanisms by which these distributed synaptic alterations produce the heterogenous symptoms of psychosis remain poorly understood. Using magnetoencephalographical source imaging, we mapped psychosis-related alterations of various features of intrinsic neural population dynamics across the human cortex. The cortex-wide patterns of these features were highly reproducible and related to the anatomical hierarchy of cortical areas. We found similar changes in these patterns for individuals with a first episode of psychosis and those at clinical high risk for psychosis. Maps of psychosis-induced changes in dynamics resembled the maps of GABA-A receptor densities and of pharmacological GABA-A or NMDA manipulation effects on cortical dynamics in healthy participants. The level of pattern similarity to GABA-A manipulation effects in individual patients correlated with positive symptoms, while the pattern similarity to NMDA effects correlated with negative symptoms. Our results open up a window on the distributed mechanisms of psychotic symptoms.

• Advancing precision photothermal therapy by integrating armored gold nanostars with real-time photoacoustic thermometry and imaging
  Authors: Canning A.; Vu T.; Menozzi L.; Klippel P.; Chen X.; Chen J.; Charity T.; Hoang K.; Yang J.; Jing Y.; Palmer G.; Yao J.; Vo-Dinh T.
  Published: 2025/8 (journal-article)
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  Nanoparticle-mediated photothermal therapy (PTT) is a promising strategy for cancer treatment; however, nanoparticle instability and lack of precise imaging tools for real-time temperature monitoring during therapy and nanoparticle tracking have hindered investigations in animal models. To address these critical issues, we present a theranostic platform that seamlessly integrates armored core–gold nanostar (AC-GNS)–mediated PTT with full-view photoacoustic computed tomography (PACT), enabling nanoparticle tracking and real-time imaging-guided PTT in deep tissues. The AC-GNS platform delivered exceptional photostability and thermal resilience beyond those of conventional nanoparticles while serving as a high-performance contrast agent for PACT and a photothermal transducer for PTT. Integrating AC-GNS–mediated PTT with noninvasive PACT enabled whole-body nanoparticle tracking, PTT treatment monitoring via thermal imaging, and thermal dose determination, culminating in a 100% survival rate in a murine bladder cancer model without long-term treatment-related toxicity. This theranostic platform lays the foundation for broader research applications and provides opportunities for advancing solid tumor treatment and response assessment research.

• Mismatch in reindeer resilience to past and future warming signals ongoing declines
  Authors: Canteri E.; Brown S.; Post E.; Schmidt N.; Nogues-Bravo D.; Fordham D.
  Published: 2025/8 (journal-article)
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  Rangifer tarandus(caribou or reindeer) survived periods of abrupt climatic warming during the last deglaciation but are currently in global decline. Using process-explicit models of likely climate-human-Rangiferinteractions and inferences of demographic change from radiocarbon-dated fossils and ancient DNA, we reconstruct and decipher 21,000 years ofRangiferpopulation dynamics. These high-resolution population reconstructions pinpoint ecological characteristics and life-history traits that most likely enabledRangiferto survive rapid warming events following the Last Glacial Maximum. Projecting these process-driven models into the future reveals that these attributes are unlikely to bufferRangiferagainst wide-scale population declines from expected 21st Century climatic warming. Our findings highlight a need to boost investments in the management and conservation ofRangifer, particularly in North America, where projected losses are expected to exceed 80%. This will not only support the survival of the species and the vital services it renders in Arctic ecosystems, but also help sustain the socioeconomic, cultural, and emotional well-being of manyRangifer-dependent communities.

• Heterogeneous strong asperities and tectonic complexity control irregular cascading ruptures
  Authors: Huang C.; Xu W.; Bürgmann R.; Xie L.; Feng G.; Shan B.; Li Z.; Aoki Y.; Zhang Y.; Zhu J.; Liu X.
  Published: 2025/8 (journal-article)
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  Rupture characteristics and heterogeneity of large earthquakes are essential for seismic hazard assessments. We use relocated aftershocks, geodetic measurements, and seismic waveform data to distinguish contributions from closely separated fault structures of the 2024Mw7.5 Noto earthquake. We find that the initial rupture triggered slip on a complex fault of a preceding swarm and led to bilateral slow rupture there. The earthquake ruptured two fault segments with contrasting dip angles along the eastern and western segments. Aftershocks continued to rupture the preexisting swarm faults. A delayed rupture occurred southwest of the hypocenter, implying that substantial resistance caused by a barrier temporally hindered rupture propagation. Additional stress from surrounding slip eventually overcame the strength of the barrier fault section, leading to a compound rupture. The mainshock triggered a small earthquake swarm, in which the relatively larger events were not followed by abundant aftershocks. Our findings demonstrate the influence of strong asperities and complex geometry in the progression of cascading ruptures.

• Stable isotope evidence for the participation of commoners in Inka khipu production
  Authors: Hyland S.; Lee K.; Koon H.; Laukkanen S.; Spindler L.
  Published: 2025/8 (journal-article)
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  This study presents previously unknown evidence about the social status of Inka-era khipu experts. A lack of physical evidence hinders our understanding of the specialists who made Inka khipus (knotted cords that served as writing). On the basis of primarily Spanish-language colonial chronicles, it is thought that khipus were created exclusively by male bureaucratic elites. We analyzed Inka khipu, KH0631, whose primary cord is composed of human hair. Historically, human hair on a khipu served as a “signature” to indicate the khipu’s creator. Recent advances in elemental analysis–isotope ratio mass spectrometry allowed us to undertake simultaneous carbon, nitrogen, and sulfur measurements from a single KH0631 hair sample, revealing that this individual consumed a diet characteristic of low-ranking commoners. This finding suggests that commoners participated in Inka khipu production.

• An ancient enhancer rapidly evolving in the human lineage promotes neural development and cognitive flexibility
  Authors: Tan K.; Higgins K.; Liu Q.; Wilkinson M.
  Published: 2025/8 (journal-article)
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  The genetic changes driving the evolution of humans since the human-chimpanzee split have been elusive. Here, we report a promising candidate in a chromosomal region linked with neurological defects—17p13.3. We show that this 442-nucleotide sequence—human-accelerated region (HAR) 123—is a conserved neural enhancer that promotes neural progenitor cell (NPC) formation. While present in all mammals, HAR123 has rapidly evolved since humans diverged from chimpanzees. The human and chimpanzee HAR123 orthologs exhibit subtle differences in their neural developmental effects, and the human HAR123 ortholog uniquely regulates many genes involved in neural differentiation. We identified direct targets of the HAR123 enhancer and showed thatHIC1acts downstream of HAR123 to promote human NPC formation. HAR123-knockout mice exhibit a defect in cognitive flexibility and a shift in neural-glia ratio in specific regions of the hippocampus. Our study has implications for neurodevelopmental disorders, which are often accompanied by altered neural-glia ratio and have been linked with HARs.

• Probing and tuning geometric frustration in an organic quantum magnet via elastocaloric measurements under strain
  Authors: Lieberich F.; Saito Y.; Agarmani Y.; Sasaki T.; Yoneyama N.; Winter S.; Lang M.; Gati E.
  Published: 2025/8 (journal-article)
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  Geometric frustration is a key ingredient in the emergence of exotic states of matter, such as the quantum spin liquid in Mott insulators. Although there has been intense interest in experimentally tuning frustration in candidate materials, achieving precise and continuous control has remained a major hurdle—particularly in accessing the properties of the ideally frustrated lattice. Here, we show that large, finely controlled anisotropic strains can effectively tune the degree of geometric frustration in the Mott insulatingκ‐(ET)2Cu2(CN)3—a slightly anisotropic triangular-lattice quantum magnet. Using thermodynamic measurements of the elastocaloric effect, we experimentally map out a temperature-strain phase diagram that captures both the ground state of the isotropic lattice and the less frustrated parent state. Our results provide a benchmark for calculations of the triangular-lattice Hubbard model as a function of frustration and highlight the power of lattice engineering as a route to realizing perfectly frustrated quantum materials.

• Editorial expression of concern
  Authors: Thorp H.
  Published: 2025/8 (journal-article)
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• Fluid dynamical pathways of airborne transmission while waiting in a line
  Authors: Lou R.; Van Mooy M.; Tarditti G.; Monico R.; Mathai V.
  Published: 2025/8 (journal-article)
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  Waiting in a line (or a queue) is an unavoidable social interaction that occurs frequently in public spaces. Despite its wide prevalence and rich parametric variability, few studies have addressed the risks of airborne infection while waiting in a line. Here, we use a combination of laboratory experiments and direct numerical simulations to assess the flow patterns in a simplified waiting line setting. From observations of the transport of breath-like expulsions, we reveal the presence of fluid dynamical counter-currents —due to the competing effects of line kinematics and thermal gradients. Depending on the walking speed, an intermediate temperature range can potentially heighten the infection risks by allowing the breath plume to linger; however, colder and warmer ambients both suppress the spread. Current guidelines of increasing physical separation appear to have a limited impact on reducing aerosol transmission. This work highlights the need for updated transmission mitigation guidelines in settings where physical separation, interaction duration, and periodicity of movements are factors.

• Histone acetylation readers Bdf1 and Yaf9 direct SWR1 remodeler to +1 nucleosome
  Authors: Ranjan A.; Elalaoui E.; Tang X.; Cha J.; Louder R.; Nguyen K.; Ye J.; Bennani M.; Gardner A.; Liu D.; Pugh B.; Wu C.
  Published: 2025/8 (journal-article)
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  The histone variant H2A.Z marking permissive chromatin is deposited by the multicomponent SWR1 chromatin remodeler, which is targeted to nucleosome-free promoters by a DNA length–sensing module. How SWR1 is directed to the flanking acetylated +1 nucleosome, its physiological substrate, has been enigmatic. We show by live-cell, single-molecule tracking that SWR1 subunits Bdf1 and Yaf9 harboring histone acetylation reader domains differentially regulate chromatin binding: Bdf1 promotes SWR1 association, while Yaf9-YEATS slows its dissociation. Notably, single-molecule tracking and genome-wide chromatin immunoprecipitation combined with exonuclease treatment reveal Bdf1 and Yaf9 contributions to global SWR1 targeting and histone exchange at +1 nucleosomes. Our findings highlight the in-cell biochemistry of histone readers and suggest a generalizable, two-stage mechanism wherein acetylated nucleosome interactions initially constrain the three-dimensional diffusion of SWR1 to increase local concentration, followed by stochastic one-dimensional diffusion at nucleosome-depleted regions with directional capture by acetylated +1 nucleosomes.

• Hypersonic acoustic wave control via stealthy hyperuniform phononic nanostructures
  Authors: Diego M.; Hardouin J.; Mazevet-Schargrod G.; Pirro M.; Kim B.; Anufriev R.; Nomura M.
  Published: 2025/8 (journal-article)
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  Controlling hypersonic surface acoustic waves is crucial for advanced phononic devices such as high-frequency filters, sensors, and quantum computing components. While periodic phononic crystals enable precise bandgap engineering, their ability to suppress acoustic waves is limited to specific frequency ranges. Here, we experimentally demonstrate surface acoustic wave control using a hyperuniform arrangement of gold nanopillars on a lithium niobate layer. The hyperuniform structure, exhibiting characteristics of both random and ordered systems, leads to broad-range acoustic transmission reduction and bandgap-like regions of particularly strong suppression. By integrating linear and S-shaped waveguides into the hyperuniform pattern, we achieve efficient waveguiding at frequencies within these bandgaps. Both simulations and experiments confirm high transmission through the waveguides, demonstrating the flexibility of hyperuniform structures to support complex waveguide shapes. These findings provide an alternative approach to overcome limitations of traditional phononic crystals and advance acoustic technologies such as mechanical quantum computing and smartphone filters.

• Identifying a next-generation antimalarial trioxolane in a landscape of artemisinin partial resistance
  Authors: Klope M.; Talukder P.; Blank B.; Chelebieva S.; Chen J.; Fontaine S.; Gonciarz R.; Jaishankar P.; Lee G.; Legac J.; Mathur V.; Narayan A.; Okitwi M.; Orena S.; Settineri N.; Tapia J.; Taremwa Y.; Tumwebaze P.; Vinod A.; Burrows J.; Rosenthal P.; Cooper R.; Renslo A.
  Published: 2025/8 (journal-article)
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  For over two decades, artemisinin-based combination therapy (ACT) has been the standard of care for the treatment of uncomplicated falciparum malaria. However, artemisinin partial resistance (ART-R) is now prevalent in Southeast Asia and has emerged in eastern Africa, threatening ACT efficacy. Artefenomel, a synthetic 1,2,4-trioxolane, exhibits an extended pharmacokinetic exposure profile that predicts for efficacy against ART-R parasites. Unfortunately, the development of artefenomel was halted recently after almost a decade in the clinic. Here, we describe studies of an artefenomel-adjacent chemotype that combines potent in vitro activity against clinical ART-R parasites, an extended pharmacokinetic profile with single-exposure efficacy in a murine malaria model, and enhanced stability in human microsomes and hepatocytes. Overall, our studies reveal a heretofore underexplored trioxolane chemotype with the potential to address ART-R in a next-generation trioxolane development candidate.

• Non-native entanglement protein misfolding observed in all-atom simulations and supported by experimental structural ensembles
  Authors: Vu Q.; Sitarik I.; Jiang Y.; Xia Y.; Sharma P.; Yadav D.; Song H.; Li M.; Fried S.; O’Brien E.
  Published: 2025/8 (journal-article)
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  Several mechanisms are known to cause monomeric protein misfolding. Coarse-grained simulations have predicted an additional mechanism exists involving off-pathway, noncovalent lasso entanglements, which are long-lived kinetic traps and structurally resemble the native state. Here, we examine whether such misfolded states occur in long-timescale, all-atom folding simulations of ubiquitin and λ-repressor. We find that these entangled misfolded states are populated in higher-resolution models. However, because of the small size of ubiquitin and λ-repressor, these states are short-lived. In contrast, coarse-grained simulations of a larger protein, IspE, predict that it populates long-lived misfolded states. Using an Arrhenius extrapolation applied to all-atom simulations, we estimate that these IspE misfolded states have lifetimes similar to the native state while remaining soluble. We further show that these misfolded states are consistent with the structural changes inferred from limited proteolysis and cross-linking mass spectrometry experiments. Our results indicate that misfolded states composed of non-native entanglements can persist for long timescales in both all-atom simulations and experiments.

• Life in the slowest lane: Feeding allometry lowers metabolic rate scaling in the largest whales
  Authors: Blawas A.; Videsen S.; Cade D.; Calambokidis J.; Friedlaender A.; Johnston D.; Madsen P.; Goldbogen J.
  Published: 2025/8 (journal-article)
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  The hypothesized impacts of whale foraging on ocean productivity are ultimately defined by their metabolic rate, but determining energy expenditure for ocean giants remains challenging. The largest baleen whales use a high-drag lunge-feeding strategy that is hypothesized to come at a high energetic cost, thus requiring exceptional calorie intake. We used biologging tags to measure respiratory rates in foraging rorquals and demonstrate that their field metabolic rates are less than half that predicted by prey consumption estimates and by scaling predictions from smaller marine mammals. The relative cost of rorqual foraging decreases with increasing size as larger whales spend disproportionately longer time filtering prey from engulfed water. By decoupling active swimming and filtration, the largest rorquals forage with limited movement costs. The evolution of lunge feeding confers an energetic advantage that is unique among filter feeders and may have provided an evolutionary pathway to the largest body sizes.

• The importance of carbonatite lavas in outgassing Venus’ modern-day atmosphere
  Authors: Trussell A.; O’Rourke J.; Williams D.; Flynn I.; Black B.; Borrelli M.
  Published: 2025/8 (journal-article)
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  Venus diverged from Earth’s evolutionary path through the development of a carbon dioxide (CO2)–dominated atmosphere, although studies dispute whether this atmosphere arose shortly after accretion or after a protracted period of surface habitability. Widespread volcanic features suggest that volcanic outgassing may have played a pivotal role in the transformation of Venus. However, the formation of volcanic units on Venus by basaltic lavas can only outgas a minor fraction of the CO2in the current atmosphere. Here, we model the erosion of long, meandering channels on Venus called canali and show that carbonatite lavas have the unique properties required to erode the canali. Our results suggest that eruption of these carbonatites may have delivered a total mass of CO2comparable to that of the modern atmosphere, resolving challenges to the formation of Venus’ atmosphere within the recent past and suggesting that exoplanets in the “Venus zone” may exhibit the potential for prolonged habitability.

• Erratum for the Research Article “Disruption of BAG3-mediated BACE1 stabilization alleviates neuropathology and memory deficits in a mouse model of Alzheimer’s disease” by L. Xia et al .
  Authors: None
  Published: 2025/8 (journal-article)
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• Time-resolved atomic-resolution Brownian tomography of single nanocrystals reveals size-dependent dynamics
  Authors: Meana-Pañeda R.; Ji C.; Van C.; Reboul C.; Kang S.; Kim S.; Rhee J.; Lee Y.; Ercius P.; Czaja W.; Park J.; Elmlund H.
  Published: 2025/8 (journal-article)
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  Atomic-resolution structure identification of nanocrystals by graphene liquid cell electron microscopy (GLC-EM) has revealed that small, solubilized platinum nanocrystals consist of an ordered crystalline core surrounded by mobile surface atoms, which dissociate during oxidative etching, resulting in distinct temporal structural states. Requirements imposed by the 3D reconstruction algorithm limit the number of structural states that can be resolved. We introduce a regularized 3D reconstruction algorithm that exploits the redundancy inherent in the experimental data, allowing us to improve the time resolution. Our developments provide a comprehensive molecular picture at unprecedented spatial and temporal resolution of the nonlinear, linear, and fluctuating dynamic phenomena that single nanocrystals undergo during the GLC-EM experiment. We determined atomic structures of 66 temporal structural states, extracted from 15 time trajectories of individual nanocrystals. Large (478 to 698 atoms) and small (<300 atoms) nanocrystals show etching that preserves a stable core, whereas mid-sized (351 to 571 atoms) nanocrystals present dynamics that change the coordination of the core.

• A streamlined CRISPR-based test for tuberculosis detection directly from sputum
  Authors: Bell A.; Dunkley O.; Modi N.; Huang Y.; Tseng S.; Reiss R.; Daivaa N.; Davis J.; Vargas D.; Banada P.; Xie Y.; Myhrvold C.
  Published: 2025/8 (journal-article)
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  Mycobacterium tuberculosis(Mtb) is a major threat to global health, and there is an urgent need for affordable, simple tuberculosis (TB) diagnosis in underresourced areas. Here, we combine recombinase polymerase amplification with Cas13a and Cas12a detection to create two parallelized one-pot assays that detect two conserved elements ofMtb(IS6110andIS1081) and a human DNA internal control. These assays are compatible with lateral flow and can be readily lyophilized. Our final assay showed a limit of detection of 69.0 CFU per milliliter forMtbH37Rv and 80.5 CFU per milliliter forMycobacterium bovisBCG in spiked sputum, with no cross-reactivity to diverse bacterial or fungal isolates. Clinical tests on 13 blinded sputum samples revealed 100% (six of six) sensitivity and 100% (seven of seven) specificity compared to culture. SHINE-TB streamlines TB diagnosis from sample to answer by combining amplification and detection while being compatible with lateral flow and lyophilization.

• Anthropogenic warming drives earlier wildfire season onset in California
  Authors: Madakumbura G.; Moritz M.; McKinnon K.; Williams A.; Rahimi S.; Bass B.; Norris J.; Fu R.; Hall A.
  Published: 2025/8 (journal-article)
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  Annual wildfire area in California has rapidly grown in recent decades, with increasingly negative impacts on people. The fire season is also lengthening, with an earlier onset. This trend has been hypothesized to be driven by anthropogenic warming, but it has yet to be quantitatively attributed to climate drivers. Using a comprehensive fire occurrence dataset, we analyze fire season onset and climate controls on its variability and change during 1992–2020 in 13 California ecoregions. Northern California ecoregions show stronger trends toward earlier onset compared to more arid southern California ecoregions. Onset has trended earlier for all but one ecoregion. Interannual variability of onset is dominated by climate variability and its influence on fuel moisture. Trend attribution inferred from onset-climate relationships suggests that anthropogenic warming advanced fire season onset by 6 to 46 days during 1992–2020 in 11 of 13 ecoregions. Continued warming is expected to further promote earlier fire season onsets.

• Pd single atoms guided proton transfer along an interfacial hydrogen bond network for efficient electrochemical hydrogenation
  Authors: Zhao R.; Wang Q.; Yao Y.; Wang R.; Zhao L.; Hu Z.; Kao C.; Chan T.; Li W.; Zheng Q.; Wang J.; Zou X.; Wang K.; Dai J.; Gu X.; Zhang L.
  Published: 2025/8 (journal-article)
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  Electrochemical hydrogenation (ECH) of unsaturated carbon-heteroatom bonds is essential for chemical transformations but is often limited by a barrier-intensive surface hydrogen transfer process. The interfacial hydrogen bond (HB) network offers a promising pathway for proton transfer but requires addressing the challenge of nondirectional proton shuttling in three-dimensional space. Here, we create hydrophilic CuOxislands on Cu foam (CF) and load electron-enriched Pd (Pdδ−) single atoms as proton traps (Pd1-CuOx/CF) to guide a fast proton transfer along a modified HB network to enhance ECH efficiency. During ECH, hydrophilic CuOxislands dissociate H2O into protons and reconstruct the interfacial HB network for facile proton transfer, while the Pdδ−single atoms reorient H2O molecules to electrostatically attract and reduce protons to active hydrogen, enabling efficient substrate hydrogenation. With guided proton transfer, Pd1-CuOx/CF achieves 99% hydrogenation efficiency for C─Cl bonds, outperforming Pd1-CF (69%) and CuOx/CF (57%), and demonstrates high selectivity and Faradaic efficiency in hydrogenating C═O and C≡N bonds to produce valuable chemicals.

• YAP regulates transcriptional programs for layer-specific periosteal expansion during fracture repair
  Authors: Nijsure M.; Tobin B.; Jones D.; Lang A.; Hallström G.; Baitner M.; Tanner G.; Kotsaris G.; Moharrer Y.; Panebianco C.; Seidl E.; Dyment N.; Szeto G.; Wood L.; Boerckel J.
  Published: 2025/8 (journal-article)
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  Bone fracture repair initiates by periosteal expansion. The periosteum is a bilayered tissue composed of inner cambium and outer fibrous layers. Typically quiescent, periosteal progenitor cells proliferate upon fracture; however, the underlying transcriptional mechanisms remain unclear. Here, we show that deletion of the transcriptional regulators, yes-associated protein (YAP) and transcriptional coactivator with PDZ binding motif (TAZ), from Osterix-expressing cells, which reside in the cambium, impairs periosteal expansion. YAP activation increases chromatin accessibility, preferentially at TEA domain transcription factor (TEAD) binding sites, and regulates both cell-intrinsic and cell-extrinsic cellular functions. We identify bone morphogenetic protein 4 (Bmp4) as a YAP-TEAD target gene expressed in the cambium. In YAP/TAZ knockout mice, BMP4 delivery increased periosteal expansion through matrix accumulation and fibrous layer cell proliferation. Conversely, in wild-type mice, BMP4 delivery increased osteogenic activity and angiogenesis. Together, these data identify YAP-mediated transcriptional programs that promote layer-specific periosteal expansion.

• A two-step mechanism for RIG-I activation by influenza virus mvRNAs
  Authors: Pitré E.; Bisht K.; Remick K.; Ghorbani A.; Yewdell J.; Elshina E.; te Velthuis A.
  Published: 2025/8 (journal-article)
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  Influenza A virus (IAV) noncanonical RNAs are bound by retinoic acid–inducible gene I (RIG-I). However, innate immune activation is infrequent and it is not understood why noncanonical IAV RNAs activate RIG-I in a sequence- or RNA structure–dependent manner. We hypothesized that multiple events need to occur before IAV RNA synthesis activates RIG-I and investigated whether RIG-I activation is stimulated by the noncanonical or aberrant transcription of mini viral RNAs (mvRNA), an RNA that is overexpressed in highly pathogenic IAV infections. We find that mvRNAs can cause noncanonical transcription termination through a truncated 5′ polyadenylation signal or a 5′ transient RNA structure that interrupts polyadenylation. The resulting capped complementary RNAs stimulate the release of an mvRNA and complement RIG-I activation in trans. Overall, our findings indicate that sequential rounds of noncanonical or aberrant viral replication and transcription are needed for innate immune signaling by IAV RNA synthesis.

• Tunable phononic quantum interference induced by two-dimensional metals
  Authors: Zhang K.; Maniyara R.; Wang Y.; Jain A.; Wetherington M.; Mai T.; Dong C.; Bowen T.; Wang K.; Rotkin S.; Hight Walker A.; Crespi V.; Robinson J.; Huang S.
  Published: 2025/8 (journal-article)
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  Harnessing quantum interference among bosons provides opportunities due to their longer coherence time than fermions. Fano resonance, an example of quantum interference between discrete and continuous states, is marked by an asymmetric lineshape. While photon-based Fano resonance has enabled high-sensitivity molecule sensing, phonon-based Fano resonance remains underexplored because of ineffective interference between discrete phonons and electronic continuum. In this work, we report phonon-based Fano resonance in a graphene/2D Ag/SiC heterostructure, arising from frequency and lifetime matching between discrete and continuous phonons of SiC. The observed Fano asymmetry is tunable over two orders of magnitude, surpassing previously reported phonon-based systems. The 2D Ag layer restructures the interfacial SiC and facilitates resonant scattering to enhance Fano asymmetry, which is unattainable in conventional Ag. We further demonstrated that this Fano resonance allows ultrasensitive molecule detection at the single-molecule level. Our work highlights phonon-based Fano resonance, opening avenues for engineering quantum interference with phonons.

• A human NK cell progenitor that originates in the thymus and generates KIR ⁺ NKG2A ⁻ NK cells
  Authors: Reiß J.; Ghosh S.; Scheid M.; Graafen L.; Scherenschlich N.; Weinhold S.; Raba K.; Paulusch S.; De Dominico E.; Pham T.; Beyer M.; Laws H.; Niehues T.; Borkhardt A.; Uhrberg M.; Bennstein S.
  Published: 2025/8 (journal-article)
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  KIR+NKG2A−natural killer (NK) cells have the unique ability to detect down-regulation of single HLA-I allotypes, frequently occurring in malignantly transformed and virus-infected cells. We have recently shown that circulating innate lymphoid cells 1 (cILC1s) have the potential to generate such KIR+NKG2A−NK cells, but their developmental origin was unknown. Here, we demonstrate that the development of cILC1 is thymus dependent and identify a putative progenitor of cILC1s in the thymus (thyILC1). Single-cell RNA sequencing analysis revealed a close relationship of thyILC1s to CD34+double-negative thymocytes. Both generated comparable NK cell frequencies, while only thyILC1s could be efficiently differentiated into KIR+NKG2A−NK cells. Last, patients withFOXN1haploinsufficiency, showing congenital thymic hypoplasia, exhibited a profound deficiency of cILC1s but not cILC2s and cILC3s, demonstrating their specific thymus dependency. Together, the data suggest that thyILC1s are the source of a thymus-dependent NK cell differentiation pathway that promotes generation of KIR+NKG2A−NK cells.

• The influence of wildfire on debris flows in a landscape of persistent disequilibrium: Columbia River Gorge, OR, USA
  Authors: Sanders M.; Roering J.; Burns W.; Calhoun N.; Leshchinsky B.
  Published: 2025/8 (journal-article)
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  Extensive debris flow fans emanate from steep catchments in the Columbia River Gorge (CRG), Oregon, a landscape dramatically reshaped by Late Pleistocene megafloods. In 2017, the Eagle Creek Fire burned 200 km2of the CRG, prompting concerns of heightened debris flow activity, yet its impact on hazard potential remains unclear. To assess the fire's effect on 10 CRG catchments, we quantify pre- and postfire debris flow erosion using airborne lidar, imagery, and field observations, as well as long-term (104- to 106-year) erosion from debris fans and volcanic edifice reconstruction. Fan-derived 104-year erosion rates (1 to 9 mm year−1) exceed 106-year rates by 10 to 50 times, suggesting sustained, rapid unraveling of these catchments following the megafloods. Pre- and postfire debris flow erosion rates are consistent with 104-year rates, such that fire-derived erosion accounts for a relatively small fraction of post-megaflood denudation (<10%), implying persistent landscape disequilibrium that manifests as ongoing high hazard potential in the CRG, regardless of wildfire conditions.

• A single-phase epitaxially grown ferroelectric perovskite nitride
  Authors: Choi S.; Jin Q.; Zi X.; Rong D.; Fang J.; Zhang J.; Zhang Q.; Li W.; Xu S.; Chen S.; Hong H.; Ting C.; Wang Q.; Tang G.; Ge C.; Wang C.; Chen Z.; Gu L.; Li Q.; Wang L.; Wang S.; Hong J.; Jin K.; Guo E.
  Published: 2025/8 (journal-article)
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  The integration of ferroelectrics with semiconductors is crucial for developing functional devices, such as field-effect transistors, tunnel junctions, and nonvolatile memories. However, the synthesis of high-quality single-crystalline ferroelectric nitride perovskites has been limited, hindering a comprehensive understanding of their switching dynamics. Here we report the synthesis and characterizations of epitaxial single-phase ferroelectric cerium tantalum nitride (CeTaN3) on both oxides and semiconductors. The polar symmetry of CeTaN3was confirmed by observing the atomic displacement of central ions relative to the center of the TaN6octahedra, as well as through optical second harmonic generation. We observed switchable ferroelectric domains using piezoresponse force microscopy, complemented by the characterization of square-like polarization–electric field hysteresis loops. The remanent polarization of CeTaN3reaches approximately 20 microcoulomb per square centimeter at room temperature, consistent with theoretical calculations. This work establishes a vital link between ferroelectric nitride perovskites and their practical applications, paving the way for next-generation information and energy storage devices.

• Exciton polariton condensation in a perovskite moiré flat band at room temperature
  Authors: Jin F.; Ren J.; Zanotti S.; Cui P.; Zheng H.; Liang J.; Ni J.; Wang Z.; Shi F.; Qiu C.; Chang G.; Liew T.; Su R.
  Published: 2025/8 (journal-article)
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  Moiré superlattices exhibit fascinating moiré flat bands when two layers of van der Waals materials are twisted at specific magic angles, providing unparalleled opportunities to explore unconventional correlated quantum phenomena. Exciton polaritons, hybrid quasiparticles of excitons and photons, have emerged as promising synthetic platforms for exploring moiré physics beyond conventional systems. However, the realization of moiré exciton-polariton flat bands and their condensation remains challenging. Here, we experimentally demonstrate a moiré exciton-polariton flat band with condensation in a perovskite moiré superlattice at room temperature. By engineering a 21.79° magic-angle moiré superlattice potential with enhanced interlayer coupling, we experimentally observe a polaritonic moiré flat band near the corresponding monolayer’s Dirac points position in the perovskite microcavity. Under a nonresonant pulsed excitation, polaritons with proper detuning condense into the moiré flat band at room temperature. Our work provides a unique platform for investigating exotic moiré phenomena and unlocks promising avenues toward advanced polaritonic devices.

• Nonlinear spatial integration allows the retina to detect the sign of defocus in natural scenes
  Authors: Goethals S.; Louboutin A.; Hamlaoui S.; Quetu T.; Virgili S.; Goldin M.; Baranton K.; Marre O.
  Published: 2025/8 (journal-article)
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  Eye growth is regulated by the visual input. Many studies suggest that the retina can detect whether a visual image is focused in front of or behind the back of the eye and modulate eye growth to bring it back to focus. How can the retina distinguish between these two types of defocus? Here, we simulated how eye optics transforms natural images and recorded how the isolated retina responds to different types of simulated defocus. We found that some ganglion cell types could distinguish between an image focused in front of or behind the retina by estimating spatial contrast. Aberrations in the eye optics made spatial contrast, but not luminance, a reliable cue to distinguish these two types of defocus. Our results suggest a mechanism for how the retina can estimate the sign of defocus and provide an explanation for several results aiming at mitigating strong myopia by slowing down eye growth.

• HLF transactivates TFEB to promote gallbladder cancer stem cells’ self-renewal and determines tumor response to distinct therapies
  Authors: Xiang D.; Yang Z.; Gu M.; Xu M.; Liu C.; Liu E.; Liu J.; Wang Y.; Wang H.; Fu J.
  Published: 2025/8 (journal-article)
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  Gallbladder cancer (GBC) is the most common malignancy in the biliary system and lacks biomarkers for personalized therapy. Here, we reported that hepatic leukemia factor (HLF) was highly expressed in gallbladder cancer stem cells (CSCs) and patients with gemcitabine-resistant GBC. Mechanistic study revealed that interleukin-6 receptor (IL-6R) and transcription factor EB (TFEB) are direct target genes of HLF. The IL-6/IL-6R/signal transducer and activator of transcription 3 axis transactivates HLF expression in GBC, forming a positive feedback loop. Functional studies revealed that HLF promoted gallbladder CSCs’ expansion and gemcitabine resistance via TFEB-induced autophagy. In addition, HLF drives TFEB-induced programmed death ligand 1 expression in human tumors and governs tumor immune evasion in a CD8+T cell–dependent manner. Patient cohorts’ analysis suggested that HLF levels in GBCs might determine the distinct responses to chemotherapy and immunotherapy. In conclusion, our findings demonstrated that HLF could act as a driver for gallbladder CSCs’ self-renewal and drug resistance and a biomarker for individualized therapy.

• Isoform-level profiling of m ⁶ A epitranscriptomic signatures in human brain
  Authors: Gleeson J.; Madugalle S.; Wan C.; McLean C.; Bredy T.; De Paoli-Iseppi R.; Clark M.
  Published: 2025/8 (journal-article)
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  The RNA modification N6-methyladenosine (m6A) is highly abundant in human brain and implicated in neurological disorders. Profiling m6A within RNA isoforms is a critical step toward understanding the complex mechanisms that underpin brain function and disease; however, we lack an isoform-level atlas of m6A sites in the brain. We applied Oxford Nanopore direct RNA sequencing (DRS) to three postmortem human brain regions—prefrontal cortex, caudate nucleus, and cerebellum—to simultaneously investigate the transcriptome and epitranscriptome at the isoform level. We identified 57,000 m6A sites within 15,000 isoforms, revealing both isoform- and brain region–specific patterning of m6A modifications. The prefrontal cortex exhibited a distinctive profile of specifically modified isoforms enriched in excitatory neurons and had the highest proportion of unannotated m6A sites. A population of isoforms were hypermodified and associated with excitatory neurons in all brain regions. Our results demonstrate the utility of isoform-level profiling of RNA modifications and provide insights into brain region specificity with implications for development and disease.

• Multiscale mathematical model-informed reinforcement learning optimizes combination treatment scheduling in glioblastoma evolution
  Authors: Liu Z.; Zhang J.; Hong L.; Nie Q.; Sun X.
  Published: 2025/8 (journal-article)
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  Dynamic tumor-microenvironment interactions greatly affect growth and drug resistance, highlighting the importance and challenge of developing mathematical models to optimize treatment schedules. Here, we describe a multiscale mathematical model-informed reinforcement learning (M4RL) framework to simulate dynamic tumor-microenvironment interactions and optimize drug combination scheduling. We first develop a multiscale agent-based model (MSABM) for a critical biological scenario where interactions between tumor-associated macrophages (TAMs) and tumor cells (TCs) underlie immunotherapy resistance in glioblastoma. Next, we learn a surrogate model based on Fokker-Planck equations for the MSABM using a physics-informed neural network approach. We then design a surrogate model–based reinforcement learning method, using an efficient parallel actor-critic algorithm, to predict optimal scheduling of combination treatments. The most effective regimen of dynamic combination of CSF1R inhibitor (targeting TAMs) and IGF1R inhibitor (targeting TCs) is identified and then verified using spatial transcriptomic data. Overall, the M4RL framework introduces a computational approach for characterizing tumor-microenvironment interactions and optimizing dynamic scheduling of drug combinations.

• Coral thermotolerance retained following year-long exposure to a novel environment
  Authors: Roper C.; Suggett D.; Songsomboon K.; Edmondson J.; England H.; Haydon T.; Goyen S.; Duijser C.; Alderdice R.; Voolstra C.; Camp E.
  Published: 2025/8 (journal-article)
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  Active restoration strategies targeting corals with elevated heat tolerance have the potential to enhance reef resistance under a warming climate. While stress-tolerant corals have been documented in extreme systems such as mangrove lagoons, it is critical to assess the ability of these corals to maintain tolerance when moved to a more benign habitat. Here, we translocated corals from a mangrove lagoon to an adjacent reef and evaluated the thermal thresholds of corals from both locations before translocation and after 1 year. We demonstrate that mangrove colonies have higher thermal tolerance than reef corals, and, critically, mangrove colonies exhibited no loss in thermal tolerance following 1-year translocation to a less extreme reef habitat. Up-regulation of genes associated with DNA repair, metabolism, and homeostasis indicates the importance of these pathways in helping mangrove corals mitigate thermal stress. Our findings suggest the use of heat tolerant corals from extreme systems holds promise as part of intervention strategies aiming to increase reef resistance.

• A closed-loop bioelectronic patch for intelligent blood pressure management
  Authors: Zou Y.; Chen Z.; Jin B.; Lyu L.; Xie Y.; Li Y.; Zeng K.; Yan S.; Wu Z.; Chen W.; Liu Y.; Zhao Y.
  Published: 2025/8 (journal-article)
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  Cardiovascular diseases remain a leading cause of mortality due to passive and delayed drug interventions. This study introduces an intelligent blood pressure management system (BPMS) for real-time monitoring and adaptive intervention through a closed-loop framework integrating sensors, control circuits, and microneedle electrodes. A hierarchical microneedle architecture, featuring gold nanoparticle (Au NP) electrocatalysts and copper-nitrogen–doped carbon nanoribbon (Cu-NC NB) nanozymes, selectively catalyzes the in situ generation of nitric oxide (NO) for vasodilation. To enhance NO delivery, an electroosmotic flow (EOF) mechanism extends the diffusion range up to 4 millimeters through a porous microneedle (PMN) array, enabling effective vascular penetration. In vivo studies in rabbits and pigs confirm that BPMS dynamically regulates NO release in response to fluctuating blood pressure, achieving real-time hemodynamic control. This work pioneers a closed-loop strategy for continuous blood pressure monitoring and on-demand vasodilation, offering a transformative approach to the intelligent management of cardiovascular diseases.

• Five thousand years of inequality in the Carpathian Basin
  Authors: Duffy P.; Wilkes F.; Skorna H.; Furholt M.; Dickie C.; Furholt K.; Bilotti G.; Müller J.; Feinman G.
  Published: 2025/8 (journal-article)
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  The emergence of sedentary farming economies, especially in contexts intensified by plow agriculture, has been argued to underpin marked increases in economic inequality and its intergenerational transmission across Eurasia. To assess this presumed causal relationship, we examine relational (burials) and material (house sizes) inequalities in the Carpathian Basin, a large region in central Europe, from the time the first farmers arrived in southeastern Europe through the next five millennia to the Bronze Age. We find that although farming did increase the potentials for both relational and material inequalities, the potential was rarely reached and then only for short durations. We identify a series of leveling mechanisms varying over time, including the removal of material wealth from circulation through the placement in graves, community fission, and investments of surplus labor in infrastructural investments. In the Carpathian Basin, only after at least 5000 years were the intergenerational potentials of material wealth transmissions more broadly realized.

• The recruitment of the A-type cyclin TAM to stress granules is crucial for meiotic fidelity under heat
  Authors: De Jaeger-Braet J.; Hartmann M.; Böttger L.; Yang C.; Hamada T.; Hoth S.; Feng X.; Weingartner M.; Schnittger A.
  Published: 2025/8 (journal-article)
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  Stress granules (SG) are biomolecular condensates that represent an adaptive response of cells to various stresses, including heat. However, the cell type–specific function and relevance of SG formation, especially during reproductive development, are largely not understood. Here, we show that the meiotic A-type cyclin TARDY ASYNCHRONOUS MEIOSIS (TAM) is recruited to SGs in male meiocytes ofArabidopsisafter exposure to heat. We find that the amino terminus of TAM is necessary and sufficient for the localization of proteins to meiotic SGs. Swapping the amino terminus of TAM with the one of its sister protein CYCA1;1 resulted in a separation-of-function allele ofTAM, which prevents the partitioning of TAM to SGs while restoring a wild-type phenotype in atammutant background under nonheat stress conditions. Notably, plants expressing thisTAMversion prematurely terminate meiosis under heat resulting in unreduced gametes. Thus, the formation of TAM-containing SGs is necessary for genome stability under heat stress.

• Atomistic mechanism of noncanonical voltage gating in K _2P channels
  Authors: Aldakul Y.; Schewe M.; Coll-Diez C.; Hwang S.; Baukrowitz T.; Sun H.
  Published: 2025/8 (journal-article)
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  In classical voltage-gated cation channels, the movement of a voltage-sensing domain (VSD) opens a gate in the pore domain. However, two-pore domain K+(K2P) channels lack a VSD and instead rely on K+movement within the selectivity filter (SF) to convert voltage changes into pore opening. To uncover the atomistic basis of voltage gating in TREK K2Pchannels, we integrated large-scale atomistic molecular dynamics simulations with extensive mutagenesis and patch-clamp electrophysiology, including sucrose-based experiments. Simulations revealed an asymmetric stability difference along the SF that results in a water-permeable extracellular side and a watertight intracellular side. Inactivation during inward flux occurs when water penetrates into the inner binding site and halts ion permeation, followed by the unbinding of three K+ions, consistent with gating charge analysis. Our findings provide unprecedented atomistic insights into the C-type inactivation of TREK K2Pchannels and establish a framework for investigating noncanonical voltage gating mechanisms in other ion channels.

• Dual-function polyester nanoparticles for amplified anti-inflammatory effects
  Authors: Heyns I.; Wahab A.; Ganugula R.; Sheikh-Hamad D.; Kumar M.; Arora M.
  Published: 2025/8 (journal-article)
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  This study investigates a dual-acting drug delivery system using naringenin (NAR) as a folate receptor ligand to enhance intestinal uptake and encapsulated NAR for combating inflammation. The dual-acting systems were tested in vitro on cisplatin-induced human kidney–2 cells and in vivo in a mouse model of cisplatin-induced acute kidney injury (AKI). NAR-loaded passive nanoparticles [P2Ns(NAR)] and dual-acting systems [P2Ns-NAR(NAR)] showed notable advantages over unformulated NAR, reducing the required dose by up to 57 and 79%, respectively. These nanoparticles modulated immune responses, restored T cell function, and shifted macrophage polarization from proinflammatory M1 to tissue-repairing M2. In addition, P2Ns-NAR(NAR) alleviated AKI by reducing fibrosis and lowering Toll-like receptor 4 and nuclear factor κB levels in the kidneys. Notably, P2Ns-NAR(NAR) outperformed other formulations, providing a 50% lower effective dose. This study emphasizes the potential of NAR to overcome intestinal barriers and highlights the importance of polymer functionality in delivering effective treatments for inflammatory diseases.

• Combinatorial profiling of multiple histone modifications and transcriptome in single cells using scMTR-seq
  Authors: Wang Y.; Li J.; Malcolm A.; Mansfield W.; Clark S.; Argelaguet R.; Biggins L.; Acton R.; Andrews S.; Reik W.; Kelsey G.; Rugg-Gunn P.
  Published: 2025/8 (journal-article)
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  Profiling combinations of histone modifications identifies gene regulatory elements in different states and discovers features controlling transcriptional and epigenetic programs. However, efforts to map chromatin states in complex, heterogeneous samples are hindered by the lack of methods that can profile multiple histone modifications together with transcriptomes in individual cells. Here, we describe single-cell multitargets and mRNA sequencing (scMTR-seq), a high-throughput method that enables simultaneous profiling of six histone modifications and transcriptome in single cells. We apply scMTR-seq to uncover dynamic and coordinated changes in chromatin states and transcriptomes during human endoderm differentiation. We also use scMTR-seq to produce lineage-resolved chromatin maps and gene regulatory networks in mouse blastocysts, revealing epigenetic asymmetries at gene regulatory regions between the three embryo lineages and identifying Trps1 as a potential repressor in epiblast cells of trophectoderm-associated enhancer networks and their target genes. Together, scMTR-seq enables investigation of combinatorial chromatin landscapes in a broad range of heterogeneous samples, providing insights into epigenetic regulatory systems.

• Light-activated 3D covalent organic framework membranes with adaptive pores for CO ₂ recognition and separation
  Authors: Yin C.; Chen M.; Zhang Z.; Liu K.; Gao J.; Zhao X.; Wu Y.; Wang Y.
  Published: 2025/8 (journal-article)
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  Creation of membrane channels capable of recognizing diverse molecules is desirable for advancing molecular transport and separation, but it remains difficult to precisely control their conformation and achieve dynamic adaption to specific molecules. Here, we demonstrate fine-tuning the pore environment within 3D covalent organic framework (COF) that can precisely control its pore size and polarity to recognize CO2. The pores are integrated with azobenzene units with photo-adaptable trans-to-cis isomerization, enabling dynamic pore size regulation at angstrom scale. Moreover, the isomerization induces drastic changes in intrapore polarity, which exert profound effects on the intermolecular affinity through the dipole-quadrupole interaction. Featuring these dynamic natures, the 3D COF membrane cooperating the size exclusion effect with a molecular recognition ability toward CO2. As a result, light-gating separation experiments show the superior CO2capture performance with a N2/CO2selectivity of 27.6. Theoretical calculations reveal that cis-state azobenzene can reduce the electron transfer barrier from azobenzene to CO2, thereby providing a molecular recognition pathway.

• Acquisition of neural crest promoted thyroid evolution from chordate endostyle
  Authors: Stundl J.; Desingu Rajan A.; Urrutia H.; Leyhr J.; Stundlova J.; Solovieva T.; Haitina T.; Sanchez S.; Musilova Z.; Martik M.; Bronner M.
  Published: 2025/8 (journal-article)
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  The endostyle is an endodermal organ unique to nonvertebrate chordates except for lamprey larvae, where it serves as forerunner to the adult thyroid. Here, we examine whether the acquisition of neural crest in the vertebrate lineage played a role in the elaboration of the endostyle. CM-DiI lineage tracing reveals a neural crest contribution to the endostyle, and CRISPR-Cas9 mutagenesis of key neural crest genes causes endostyle defects including formation of a single rather than bilobed structure. RNA sequencing reveals gene profiles characteristic of embryonic neural crest cells and Schwann cell precursors in the developing endostyle. Contrasting with the prevailing view that the endostyle is an endoderm-derived organ, we propose that the acquisition of the neural crest played a critical step in promoting thyroid evolution from chordate endostyle.

• Integrated horizontal convective PCR system for clinical diagnostics
  Authors: Guo W.; Xu M.; Tao Y.; Liu W.; Zhou H.; Guan X.; Yang R.; Ge Z.; Xue R.; Zhang Z.; Zhou H.; Ren Y.
  Published: 2025/8 (journal-article)
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  Rapid and accurate disease diagnosis in resource-limited settings is critical for optimizing medical resources and controlling epidemic outbreaks. However, developing a point-of-care detection system that is user-friendly, cost-effective, highly accurate, and exhibits strong specificity remains a formidable challenge. Here, we report an integrated horizontal convection PCR system (IHCS) for clinical point-of-care testing, capable of real-time fluorescence detection. IHCS leverages horizontal thermal convection within a capillary to drive sample flow and temperature cycling for nucleic acid amplification, making it suitable for both home use and on-site rapid detection. Capillary action enables swift sample loading, thereby simplifying the overall procedure, and the horizontal thermal convection overcomes the volume limitations inherent in vertical systems. Validation with 130 clinical samples demonstrated that the system successfully detected HBV, SARS-CoV-2, and influenza A virus within 40 min, achieving excellent sensitivity (>96%) and specificity (100%). Overall, the IHCS integrates microfluidics, thermal engineering, and optical sensing and offers a paradigm-shifting solution for point-of-care diagnostics.

• Coherent acoustic frequency comb via floquet engineering of optical tweezer phonon lasers
  Authors: He Y.; Kuang T.; Han X.; Feng Z.; Chen X.; Xiong W.; Jin S.; Tan Z.; Zhang Q.; Luo H.; Jing H.; Xiao G.
  Published: 2025/8 (journal-article)
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  Floquet engineering, featuring time-periodic control of various systems, has enabled observations of many exotic phenomena such as time crystals, breaking of reciprocity symmetry, and exceptional topology. Theoretically, a periodic drive can make the system inherit the time period and generate new harmonics or distort the band structure at the fundamental frequency. Here, by combining such a technique with levitated optomechanics, we present an instructive example of a coherent acoustic frequency comb with microsphere phonon lasers. This work shows that our technique offers the capability of flexibly controlling both the teeth number and the teeth spacing of the resulting coherent acoustic frequency comb. In particular, we confirm that all Floquet-driven comb teeth can reach the truly coherent regime, i.e., satisfying all the characteristic features of phonon lasers. Our work provides a platform to drive the nonlinear phonon laser to a coherent acoustic frequency comb with truly coherent comb teeth.

• A large intraplate hydrogen-rich hydrothermal system driven by serpentinization in the western Pacific: Kunlun
  Authors: Li L.; Zhang H.; Xi S.; Liu C.; Li C.; Zheng J.; Huang J.; Hao Y.; Zhang X.; Sun W.
  Published: 2025/8 (journal-article)
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  The Kunlun hydrothermal system near the Mussau Trench in the western Pacific consists of 20 large round/oval craters of hundreds of meters in diameter. The total area is 11.1 square kilometers, i.e., over a hundred times larger than the Lost City. Four of the larger craters were prospected using the human occupied vehicle Fendouzhe and have steep walls similar to those of kimberlite pipes, with depths of up to 130 meters. Ecosystems have been observed in smaller pits on the bottom of these pipes. Hydrogen concentrations of ~5.9 to 6.8 millimoles per kilogram in hydrothermal fluids have been obtained using in situ Raman spectra. The estimated total hydrogen flux of Kunlun is 4.8 × 1011moles per year, which is >5% of the estimated global submarine abiotic hydrogen flux. Hydrogen-rich, alkaline fluids generated by serpentinization have formed large-scale carbonate rocks within the pipes below the carbonate compensation depth, and both dolomite and calcite have been identified.

• China’s nationwide streamflow decline driven by landscape changes and human interventions
  Authors: Wang K.; Liu X.; Cui P.; Zhang Y.; Xie J.; Liu C.; Gosling S.
  Published: 2025/8 (journal-article)
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  China’s rivers support nearly 20% of the global population and supply freshwater for the world’s largest proportion of industrial output and grain production. Despite their importance, nationwide streamflow changes and their drivers remain unclear because of challenges in accessing observations and disentangling the effects of climate, landscape, and human interventions. By combining data from 1046 hydrological stations with ISIMIP3a reconstructions, we provide a comprehensive national assessment showing that streamflow has declined across more than 70% of stations over the past six decades. Although regional heterogeneity exists, these declines are primarily concentrated in the north and driven by land use and cover change, further exacerbated by water abstraction, diversion, and regulation. In contrast, climate change and variability dominate the increases in streamflow, primarily in the south. Our results provide insights for water managers, helping them understand the multifaceted drivers of hydrological variability and inform the development of infrastructure and ecological projects to mitigate potential risks associated with declining streamflow.

• Soft reconfigurable logic gates with high-frequency electrical switching
  Authors: Xu Y.; Zhang F.; Rothemund P.; Keplinger C.; Xu Z.; Li J.; Zheng Q.; Zhu J.
  Published: 2025/8 (journal-article)
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  The development of functional soft materials has motivated replacing rigid electronics with stretchable logic structures. However, soft logic gates for macroscopic soft robots usually operate at low frequencies (<5 hertz). Here, we present high-frequency soft logic gates based on soft electric switches with ultralow latency (2 milliseconds). Fast switching is achieved using a tailored piezoresistive material—graphite frameworks (GFs)/polydimethylsiloxane (PDMS) and dielectric elastomer actuators (DEAs). The GFs/PDMS strip exhibits a large resistance change within ~0.01% strain, allowing soft logic gates to operate up to 100 hertz. A soft oscillator is further developed using feedback control with a soft NOT gate and achieves autonomous deformation across ~1 to 78 hertz, demonstrating actuation, sensing, and feedback control capabilities. Compared to other soft electrical switches, this scheme also features a compact size (5 cubic centimeter) and low power consumption (0.4 milliwatts). This work enables fast, accurate control for electrostatic soft robots, enhancing their autonomy and interaction capabilities.

• Stressomic: A wearable microfluidic biosensor for dynamic profiling of multiple stress hormones in sweat
  Authors: Tu J.; Yeom J.; Ulloa J.; Solomon S.; Min J.; Heng W.; Kim G.; Dao J.; Vemu R.; Pang M.; Wang C.; Kim D.; Gao W.
  Published: 2025/8 (journal-article)
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  Managing stress is essential for mental and physical health, yet current methods rely on subjective self-assessments or indirect physiological measurements, often lacking accuracy. Existing wearable sensors primarily target a single stress hormone, cortisol, using single-point measurements that fail to capture real-time changes and distinguish between acute and chronic stress. To address this, we present Stressomic, a wearable multiplexed microfluidic biosensor for noninvasive monitoring of cortisol, epinephrine, and norepinephrine in sweat. Stressomic integrates iontophoresis-driven sweat extraction with bursting valve-regulated microfluidic channels for continuous sampling and analysis. Gold nanodendrite–decorated laser-engraved graphene electrodes achieve picomolar-level sensitivity, enabling simultaneous detection of multiple stress hormones. Electrochemical assays and human studies demonstrate that Stressomic reliably tracks hormone fluctuations in response to physical, psychological, and pharmacological stressors. Distinct temporal patterns reveal the dynamic interplay between the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. This platform enables continuous, multiplexed stress profiling, offering opportunities for early detection of maladaptive responses, personalized stress management, and deeper insights into stress biology.

• Erratum for the Research Article “DUX4-r exerts a neomorphic activity that depends on GTF2I in acute lymphoblastic leukemia” by D. Campolungo et al .
  Authors: None
  Published: 2025/8 (journal-article)
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• Ecological similarity governs non-native fish establishment while human pressure and native diversity shape invasion richness
  Authors: Xu M.; Fang M.; Usoof A.; Mandrak N.; Chu C.; Qian H.; Cao Y.; Liu C.; Cuthbert R.; Li S.; Su G.; Tedesco P.; Dick J.; Wei H.; Yu F.; Shu L.; Wang X.; Mu X.; Gu D.
  Published: 2025/8 (journal-article)
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  Biological invasions by non-native fish species pose a major threat to global freshwater ecosystems. However, our understanding of why invaders establish in some communities but not others (i.e., occurrence probability) and why some communities harbor more invaders than others (i.e., invasion richness) remains limited. Here, we combine species- and community-level analyses across taxonomic, phylogenetic, and functional dimensions to investigate both the occurrence probability and invasion richness of exotic and translocated fish species across nearly 3000 North American freshwater fish communities. We found that ecological similarity between non-native and native species primarily governed non-native fish establishment, with invaders more likely to succeed when closely related to native species. In contrast, invasion richness was largely promoted by human pressure, while native diversity reduced richness specifically for translocated species. Additionally, both the occurrence and richness of invaders increased toward lower latitudes. Together, these findings highlight the distinct yet complementary roles of environmental filtering, human activities, and biotic interactions in shaping freshwater fish invasions.

• Deep manifold learning reveals hidden developmental dynamics of a human embryo model
  Authors: Chen K.; Qin K.; Na J.; Gao G.; Yang C.; Fu J.
  Published: 2025/8 (journal-article)
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  In this study, postimplantation human epiblast and amnion development are modeled using a stem cell–based embryoid system. A dataset of 3697 fluorescent images, along with tissue, cavity, and cell masks, is generated from experimental data. A computational pipeline analyzes morphological and marker expression features, revealing key developmental processes such as tissue growth, cavity expansion, and cell differentiation. To uncover hidden developmental dynamics, a deep manifold learning framework is introduced. This framework uses an autoencoder to project embryoid images into a twenty-dimensional (20D) latent space and models the dynamics using a mean-reverting stochastic process of mixed Gaussians. The approach accurately captures phenotypic changes observed at discrete experimental time points. Moreover, it enables the generation of artificial yet realistic embryoid images at finer temporal resolutions, providing deeper insights into the progression of early human development.

• Cryogenic electron tomography reveals helical organization of lipoprotein lipase in storage vesicles
  Authors: Gunn K.; Wheless A.; Calcraft T.; Kreutzberger M.; El-Houshy K.; Egelman E.; Rosenthal P.; Neher S.
  Published: 2025/8 (journal-article)
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  Lipoprotein lipase (LPL) is a triglyceride lipase that is contained in intracellular vesicles in an inactive storage form before secretion, but the precise structural details have not yet been resolved. Using cryo–electron tomography (cryo-ET), we observe that LPL exists inside of storage vesicles as a filament with an 11-nanometer diameter and is packed in these vesicles in two distinct patterns. Next, we solved a 4.2-Å resolution cryo–electron microscopy (cryo-EM) structure of this 11-nanometer LPL filament using purified protein. The filament is made of repeating pairs of LPL molecules with occluded active sites, rendering the LPL inactive. The comparison of the in situ subtomogram average and the in vitro cryo-EM structure indicates that the previously uncharacterized physiological storage form of LPL is an inactive filament.

• Simultaneous imaging of bidirectional guided waves probes arterial mechanical anisotropy, blood pressure, and stress synchronously
  Authors: Jiang Y.; Li G.; Hu K.; Ma S.; Zheng Y.; Jiang M.; Zhang Z.; Wang X.; Cao Y.
  Published: 2025/8 (journal-article)
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  Arterial biomechanical indicators have long been recognized as fundamental contributors to the physiology and pathology of cardiovascular systems. Probing multiple biomechanical parameters of arteries simultaneously throughout the cardiac cycle is highly important but remains challenging. Here, we report a method to quantify arterial anisotropic stiffness, arterial wall stresses, and local blood pressure in a single measurement. With programmed ultrasound excitation and imaging, arterial axial and circumferential guided waves were simultaneously induced and measured in the longitudinal view. Then, a mechanical model was proposed to quantitatively predict the correlation of arterial guided waves with arterial biomechanical parameters. Our experimental design and biomechanical model enable an elastography method to assess temporal variations in blood pressure, bidirectional stiffness, and mechanical stresses in arterial walls. In vivo experiments were performed on healthy young, normotensive older, and hypertensive older volunteers. The results demonstrate that our method can find applications in understanding aging of cardiovascular system and diagnosis of cardiovascular diseases.

• Digital light processing of photoresponsive and programmable hydrogels
  Authors: Dhand A.; Kirkpatrick B.; Garay-Sarmiento M.; Nelson B.; Miksch C.; Meurer-Zeman B.; Zlotnick H.; Mandal A.; Lee J.; Cione J.; Bowman C.; Anseth K.; Burdick J.
  Published: 2025/8 (journal-article)
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  Light-mediated manipulation of hydrogel physicochemical properties is attractive for numerous applications, yet the processing of such hydrogels via vat photopolymerization [e.g., digital light processing (DLP)] is challenging as photoresponsive chemistries may be consumed during printing. Here, we report a facile strategy to DLP print hydrogels that combines short light exposures to set the shape of a printed object and complementary dark polymerization to continue the reaction of macromers without disturbing photoresponsive groups. Postprinting, hydrogels are then programmed using single- or multiphoton light and photoinitiator-free reactions: tetrazole-alkene click reaction (for photofunctionalization), dithiolane ring-opening polymerization (for photostiffening), ando-nitrobenzyl cleavage (for photosoftening). We demonstrate the versatility of this approach through applications that include the patterning of ligands to direct cell-material interactions, four-dimensional shape morphing, and bottom-up construction of multiscale models, including microscale perfusable channels. This approach provides access to highly tunable 3D-printed photoresponsive hydrogels for a range of soft matter applications.

• Soluble N-terminal region of prion protein causes rapid neurodegeneration in prion disease
  Authors: Yan R.; Zhang Y.; Zhang J.; Zhang X.; Han Y.; Wang M.; Wang D.; Huang S.; Liu W.; Shi Q.; Dong X.; Zou W.; Li Z.; Ma J.
  Published: 2025/8 (journal-article)
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  Rapid neurodegeneration distinguishes prion disease from other neurodegenerative disorders. Notably, normal prion protein (PrPC) is essential for prion-induced rapid neurodegeneration, but the underlying mechanism remains unknown. Here, we show that the unstructured N-terminal region of PrPCinduces rapid and lethal neurodegeneration in mice, accompanied by the hallmark of prion disease, spongiosis. The neurotoxic N-terminal PrP is soluble, associates peripherally with lipid membranes, and induces neurotoxicity only when a critical threshold is exceeded. Both the N-terminally localized KKRPKP sequence and octarepeats contribute to neurotoxicity, with KKRPKP being essential. Without it, the N-terminal PrP is innocuous but exacerbates either neurodegeneration caused by N-terminal PrP or neurodegeneration in prion disease induced by intracerebral prion inoculation in mice. Our findings establish that soluble N-terminal PrP causes rapid neurodegeneration in prion disease and is a target for intervention.

• More comprehensive cell profiling to understand normal and disease states
  Authors: Huynh H.; Chen H.
  Published: 2025/8 (journal-article)
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  Single-cell multitargets and mRNA sequencing enable the simultaneous profiling of transcriptome and up to six histone modifications in individual cells.

• Positive-going hybrid indicators for voltage imaging in excitable cells and tissues
  Authors: Liu S.; Ling J.; Xie B.; Zhang Y.; Peng L.; Yang L.; Yu Y.; Lin J.; Tang C.; Chen Z.; Zou P.
  Published: 2025/8 (journal-article)
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  Membrane potential dynamics are crucial to the physiology of electrically excitable cells, such as neurons, cardiomyocytes, and pancreatic islet cells. Fluorescence voltage indicators have enabled the visualization of electrical activities at the single-cell level across large cell populations. However, most existing indicators have a negative fluorescence-voltage response, resulting in a high background signal when cells are at their resting state. To reduce background interference during voltage imaging, we developed a positive-going hybrid voltage indicator (HVI+), which has lower intensity at the resting state and becomes brighter upon membrane depolarization. HVI+-Cy3b exhibits a remarkable voltage sensitivity of 55% ΔF/F0per 100 mV, enabling accurate reporting of action potential waveforms in beating cardiomyocytes and neurons. In addition, by combining HVI+-Cy3b with HVI-Cy3b, we demonstrate the capability to simultaneously assess the effects of glucose on the spike activities of two cell types in pancreatic islets.

• A sonoelectric niche for noninvasive intervertebral disc regeneration via targeted cell cycle modulation
  Authors: Zhang X.; Liang H.; Liao Z.; Tong B.; Wu D.; Ma L.; Lei J.; Zhou X.; Zhu D.; Ou Z.; Wei J.; Tan L.; Yang C.
  Published: 2025/8 (journal-article)
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  Cell cycle regulation is pivotal for tissue regeneration yet remains challenging in degenerative microenvironments. We engineered a sonosensitive conductive hydrogel incorporating polypyrrole-encapsulated porphyrin derivatives {[Tetrakis (4-carboxyphenyl) porphyrin (TCPP)]@PPy} to regulate cell cycle dynamics. Upon ultrasound irradiation, TCPP@PPy generates free electrons, establishing a controlled microcurrent within degenerative tissues. This sonoelectric niche induces nucleus pulposus cell (NPC) membrane depolarization, activating calcium voltage-gated channels (Cav) to drive Ca2+influx. Subsequent calcium- and calmodulin-dependent protein kinase I activation up-regulates cyclin-dependent kinases CDK1/CDK2, forming a sonoelectricity–ion–kinase axis that stimulates NPC proliferation and anabolism. Concurrently, ultrasound-responsive borate ester bonds in the hydrogel amplify reactive oxygen species scavenging, counteracting oxidative stress–induced NPC ferroptosis. In a goat model of intervertebral disc degeneration, ultrasound-guided hydrogel implantation alleviated degenerative progression by synergistically reactivating cell cycle progression and suppressing oxidative damage. This strategy demonstrates a noninvasive, dual-targeted approach to regulate degenerative microenvironments through spatiotemporal control of sonoelectric and biochemical cues, offering a translatable strategy for tissue regeneration therapies.

• Lead isotopic evidence for an old and rapid lunar magma ocean
  Authors: Zhang Y.; Sheng S.; Wang S.; Li Q.; Hua J.; Li S.; Li X.
  Published: 2025/8 (journal-article)
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  The Moon’s early history remains enigmatic, with intensive debate over the timing and duration of the lunar magma ocean (LMO) and its consequences on the early thermal and chemical evolution of the Moon. Here, we report a lead-lead isochron age of 4406.1 ± 3.2 million years ago (Ma) with an extraordinarily high initial lead (Pb) composition (HIP) for a lunar meteorite Northwest Africa 14729. The HIP at ~4406 Ma implies Pb isotopic evolution from an early-formed, high-μ (238U/204Pb > 5000) reservoir that is genetically linked to the last remaining liquid of the LMO called urKREEP. This requires that lunar primordial differentiation was completed within approximately 150 million years (Myr) after the Solar System’s formation.

• An energy-embodied paralleled liquid manipulation for equipment-free, quantitative multiplexed liver function monitoring
  Authors: Liang C.; Zhao J.; Wei P.; Wei K.; Jiang H.
  Published: 2025/8 (journal-article)
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  Comprehensive liver function monitoring is vital for liver damage diagnoses. However, multiplexed testing with clinical accuracy often requires paralleled liquid manipulation to avoid reagent interference and nonspecific adsorption, making it restricted to centralized facilities and specialists. Here, we report an equipment-free, quantitative, and multiplexed point-of-care testing (POCT), the energy-embodied POCT (EE-POCT). The driving energy (pressured gas) and liquid reagents are embodied in separate rigid-flexible chambers through a mechanical pressure sensing mechanism to achieve a paralleled, interference-free, and multiple-reagent operation with no need for external equipment. The EE-POCT achieves quantitative results for nine liver-related indicators from 180 microliters of whole blood within 4 minutes. Validated with 103 clinical specimens, it shows high concordance with a clinical gold standard analyzer (Pearson coefficients >0.9). The EE-POCT platform not only advances liver health diagnostics but also sets a precedent for developing versatile, accessible medical technologies that can significantly affect global health outcomes.

• Heparan sulfate fine-tuned interleukin-1 (IL-1) signaling inhibits insulin secretion of grafted pancreatic islets
  Authors: Wrublewsky S.; Rother S.; Pohlemann F.; Radanovic T.; Junker F.; Boewe A.; Schunk S.; Roma L.; Ruiz-Gómez G.; Pisabarro M.; MacDonald P.; Menger M.; Laschke M.; Ampofo E.
  Published: 2025/8 (journal-article)
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  Islet-resident macrophages contribute to hypoxia-induced islet cell death during pancreatic islet transplantation. However, their specific role during this process remains elusive. Here, we report that interleukin-1α (IL-1α) and IL-1β are released by islet-resident macrophages, resulting in the suppression of insulin secretion. This may be due to a decreased inflammation-driven expression of pancreatic and duodenal homeobox 1 (PDX-1) and MafA in β cells. Islet-resident macrophages release significantly less IL-1α when compared to IL-1β. However, both cytokines inhibit insulin expression and secretion to a comparable extent. We identified heparan sulfate on the islet surface, which acts as a “molecular glue” potentiating the inhibitory action of IL-1α on insulin expression via specific binding to IL-1 receptor (IL-1R). In vivo analyses revealed that the loss of IL-1 signaling in isolated islets accelerates their revascularization and, thus, enhances their endocrine function. These findings indicate that heparan sulfate fine-tuned IL-1 signaling crucially determines the outcome of islet transplantation.

• Allele frequency selection and no age-related increase in human oocyte mitochondrial mutations
  Authors: Arbeithuber B.; Anthony K.; Higgins B.; Oppelt P.; Shebl O.; Tiemann-Boege I.; Chiaromonte F.; Ebner T.; Makova K.
  Published: 2025/8 (journal-article)
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  Mitochondria, cellular powerhouses, harbor DNA [mitochondrial DNA (mtDNA)] inherited from the mothers. mtDNA mutations can cause diseases, yet whether they increase with age in human oocytes remains understudied. Here, using highly accurate duplex sequencing, we detected de novo mutations in single oocytes, blood, and saliva in women 20 to 42 years of age. We found that, with age, mutations increased in blood and saliva but not in oocytes. In oocytes, mutations with high allele frequencies were less prevalent in coding than noncoding regions, whereas mutations with low allele frequencies were more uniformly distributed along the mtDNA, suggesting frequency-dependent purifying selection. Thus, mtDNA in human oocytes is protected against accumulation of mutations with aging and having functional consequences. These findings are particularly timely as humans tend to reproduce later in life.

• Inapparent virus infections differentially affect honey bee flight
  Authors: Kaku N.; Jankauski M.; Doyle B.; Collins C.; Flenniken M.
  Published: 2025/8 (journal-article)
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  Honey bee colony deaths are associated with viruses, which frequently do not cause morphological symptoms in adult bees. To assess the impact of these inapparent infections, we measured flight performance as a proxy for honey bee health. We hypothesized that deformed wing virus (DWV) and/or sacbrood virus (SBV) would reduce flight performance and that coinfections would have compounding, negative impacts. We identified virus-specific effects; bees with DWV flew shorter distances at slower speeds, whereas bees with SBV flew greater distances at higher speeds. Bees with high virus loads expressed moreheat shock protein 90, and SBV-infected bees expressed moreoctopamineβ-2 receptor(Oβ-2R).Oβ-2Rbinds octopamine, a “fight or flight” molecule, stimulating metabolic activity, neuromuscular transmission, and movement. To examine relationships between virus infection, octopamine, and flight, we compared the flight performance of DWV-infected bees with octopamine treatment and demonstrated that octopamine negated DWV-associated flight impairment. These findings have organismal-, colony-, and ecosystem-level implications.

• AND-1 is a critical regulator of R-loop dynamics and a target to overcome endocrine resistance
  Authors: Li Z.; Peng Y.; Chiang H.; Gao Y.; Chu C.; Zhang Y.; Mughal M.; Liu C.; Li R.; Pei H.; Zhu W.
  Published: 2025/8 (journal-article)
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  R-loops are three-stranded DNA/RNA hybrids that are essential for various cellular pathways. However, when dysregulated, they lead to genomic instability and numerous human diseases. R-loops are tightly regulated, with RNase H1 acting as a key enzyme responsible for resolving DNA/RNA hybrids. Here, we identify the DNA-binding protein AND-1 as an essential factor in R-loop regulation through directly binding to R-loop structures, where it enhances the recruitment of RNase H1 and stimulates its endonuclease activity. We also provide in vivo evidence that R-loop accumulation occurs in the mammary gland tissue of AND-1–deficient mice. Furthermore, we demonstrate that inhibition of AND-1 decreasesESR1expression by disrupting R-loop regulation at the enhancer region of theESR1gene in estrogen receptor–positive (ER+) breast cancer cells, thereby overcoming resistance to aromatase inhibitors. Collectively, our findings reveal a mechanism by which AND-1 modulates R-loop dynamics and present a promising therapeutic strategy to combat endocrine resistance in breast cancer.

• In situ–formed immunotherapeutic hydrogel containing sphingosine-1-phosphate for enhanced lung cancer immunotherapy
  Authors: Shen H.; Deng Q.; Chen Z.; Zhang Q.; Zhou X.; Chen Q.; Fan J.
  Published: 2025/8 (journal-article)
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  Limited infiltration of immune cells within tumors restricts the therapeutic efficiency of immune checkpoint blockades. Herein, we discover that sphingosine-1-phosphate (S1P) is down-regulated in patients with lung cancer who do not respond to PD-1/PD-L1 therapy. Our findings indicate that S1P gradient enhances the migration and viability of immune cells and promotes the polarization of macrophages toward the M1 phenotype primarily through mitochondrial reactive oxygen species–activated nuclear factor κB and Janus kinase–signal transducers and activators of transcription signaling pathways. To capitalize on these findings, we used a biodegradable sodium alginate hydrogel as a delivery system for the sustained and sequential release of S1P and anti–PD-L1 (αPDL1). In vivo studies demonstrated that S1P-αPDL1@Gel effectively inhibited tumor growth and reduced the recurrence of local tumors after surgery. Additionally, the hydrogel significantly enhanced the infiltration of dendritic cells, M1 macrophages, CD4+T cells, and CD8+T cells. S1P-αPDL1@Gel holds a promising therapeutic strategy for remodeling the immunosuppressive tumor microenvironment.

• Elucidating the characteristics and clonal evolutionary trajectory of influenza neuraminidase broadly reactive B cell
  Authors: Lin C.; Yang Q.; Huang L.; Wang X.; Zhang Z.
  Published: 2025/8 (journal-article)
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  Influenza virus neuraminidase (NA) is receiving increasing attention as a target for universal flu vaccines. Several broad NA inhibition monoclonal antibodies (BImAbs) targeting the highly conserved enzymatic pocket have been previously described. However, the molecular characteristics, clonal evolutionary trajectory, and B cell sources of BImAbs remain poorly understood. Here, using NA-mutant probes, we comprehensively profiled the immune signatures of NA-specific memory B cells (MBCs) from a healthy individual with NA cross-inhibition activity. From the NA-specific MBC repertoires, we identified a series of NA BImAbs with molecular features characterized by long HCDR3 regions with an “xxxDRxxx” motif, which exhibited broad inhibition against diverse influenza NAs. Clonal lineage tracing revealed that BImAbs followed a clonal evolutionary trajectory encompassing classical MBC (cMBC) and atypical MBC (aMBC). Both cMBC- and aMBC-derived BImAbs displayed similar inhibition against influenza NA. These findings enhance our understanding of the development of NA BImAbs and provide a foundation for the rational design of NA-based universal flu vaccines.

• Low-dose metformin requires brain Rap1 for its antidiabetic action
  Authors: Lin H.; Lu W.; He Y.; Fu Y.; Kaneko K.; Huang P.; De la Puente-Gomez A.; Wang C.; Yang Y.; Li F.; Xu Y.; Fukuda M.
  Published: 2025/8 (journal-article)
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  Metformin is the most commonly prescribed antidiabetes drug, yet its precise mechanism of action remains controversial. Previous studies have suggested that metformin acts peripherally by reducing hepatic glucose output and altering gut functions. Here, we report a neural mechanism via the small guanosine triphosphatase Ras-related protein 1 (Rap1). Mice with forebrain-specificRap1knockout exhibited resistance to the antidiabetic effects of low-dose metformin while remaining sensitive to other antidiabetic agents. Centrally administered metformin inhibited brain Rap1 and reduced hyperglycemia. Conversely, forced activation of brain Rap1 increased glycemia and abolished the glycemic effect of metformin. Metformin activated a specific subset of neurons in the ventromedial hypothalamic nucleus (VMH) that requires Rap1. Both loss-of-function and gain-of-function studies suggest that VMH Rap1 is indispensable for the antidiabetic effects of metformin. These findings highlight the VMH Rap1 pathway as a critical mediator of metformin action.

• Morphology– and adhesion–dual biomimetic nanovaccine boosts antigen cross-presentation through subcellular transport regulation
  Authors: Wang Z.; Zhou H.; Su Q.; Qiu Q.; Deng W.; Zhang M.; Xu Z.; Li J.; Xiao J.; Duan X.
  Published: 2025/8 (journal-article)
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  In situ tumor vaccines have immense potential for immunotherapy because they generate whole tumor–derived antigens (TDAs) to activate antitumor immune responses. However, the rapid degradation and clearance of the released TDAs severely hinder subsequent antigen presentation and the final efficacy of the in situ vaccine. Here, we synthesized gold nanoxanthium coated with polydopamine (AuNX-PDA) to mimic the morphological and biological adhesion properties of xanthium and mussels, respectively. AuNX-PDA facilitated effective absorption of released TDAs after near-infrared II photothermal treatment and delivery of the absorbed TDAs to the endoplasmic reticulum and Golgi apparatus of dendritic cells for cross-presentation, thereby activating CD8+T cells for efficient tumor-specific immunity. The nanovaccine (NV) significantly inhibited irradiated primary tumors and nonirradiated distant tumors by producing robust antitumor immune responses in B16F10 melanoma and 4T1 breast cancer mouse models. These findings highlight the potency of morphology– and adhesion–dual biomimetic NVs in whole-tumor vaccine therapy.

• Violation of Bell inequality with unentangled photons
  Authors: Wang K.; Hou Z.; Qian K.; Chen L.; Krenn M.; Aspelmeyer M.; Zeilinger A.; Zhu S.; Ma X.
  Published: 2025/8 (journal-article)
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  Violation of local realism via Bell inequality—a profound and counterintuitive manifestation of quantum theory that conflicts with the prediction of local realism—is viewed to be intimately linked with quantum entanglement. Experimental demonstrations of such a phenomenon using quantum entangled states are among the landmark experiments of modern physics and paved the way for quantum technology. Here, we report the violation of the Bell inequality that cannot be described by quantum entanglement in the system but arises from quantum indistinguishability by path identity, shown by the multiphoton frustrated interference. By analyzing the measurement of four-photon frustrated interference within the standard Bell-test formalism, we find a violation of Bell inequality by more than four SDs. Our work establishes a connection between quantum correlation and quantum indistinguishability, providing insights into the fundamental origin of the counterintuitive characteristics observed in quantum physics.

• A scalable ultra-long-acting tenofovir phosphonate prodrug sustains HBV suppression
  Authors: Raut S.; Das S.; Bybee G.; Chava H.; Ogunnaike M.; Wang W.; Pathania A.; Hanson B.; Le N.; Cohen S.; Gendelman H.; Poluektova L.; Edagwa B.; Osna N.
  Published: 2025/8 (journal-article)
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  Long-acting (LA) extended-release formulations are revolutionizing treatment and prevention of HIV infection. However, none of the existing LA therapies are active against hepatitis B virus (HBV), a common coinfection with HIV. Managing coinfection requires therapy to be effective against both viruses. Notable candidates are tenofovir (TFV) prodrugs. We have previously developed an LA TFV through a modified lipophilic ProTide strategy. Given the process chemistry challenges presented by amino acid chiral centers in ProTides, a simplified lipophilic amino acid–free crystalline phosphonate prodrug of TFV (M5TFV) has been created. Intramuscular injections of M5TFV nanosuspension (NM5TFV) were well tolerated in Sprague-Dawley rats and HBV transgenic mice. Notably, single doses at 200 and 400 milligrams per kilogram TFV equivalents produced >2.5 log10reduction in HBV DNA beyond 2 months in transgenic mice. Reductions of covalently closed circular DNA were seen in hepatocyte-like cells. These promising findings support further development of NM5TFV as an ultra-LA formulation.

• T _H 17 cells regulate chemokine expression in epithelial cells through C/EBPβ and dictate host sensitivity to colitis and cancer immunity
  Authors: Xing C.; Duan T.; Li L.; Chen L.; Zhang P.; Du Y.; Liu S.; Annaparthi N.; Wang S.; Qian C.; Wang H.; Wang R.
  Published: 2025/8 (journal-article)
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  TH17 cells play a critical role in inflammation, cancer development, and antitumor immunity in a context-dependent manner, but detailed mechanisms and their downstream signaling events remain poorly understood. Here, we describe that TH17 cytokines strongly inhibit expression of critical chemokines in epithelial tissues, which leads to blocking infiltration of proinflammatory immune cells into the colon, rendering resistance to DSS-induced colitis and colon cancer. We show that key chemokine expression dictates the sensitivity of WT mice to DSS treatment. Mechanistically, we identified C/EBPβ and STAT3 as negative regulators of key chemokine expression following IL-17 and IL-22 stimulation. Knockout of either C/EBPβ or STAT3 in mouse epithelial cells abolished the protective function of TH17 cytokines and converted resistant to sensitive phenotype. C/EBPβ ablation in cancer cells markedly enhanced chemokine expression, thus sensitizing cancer cells for anti–PD-1 immunotherapy. Overall, our findings have identified a previously unrecognized critical gap between TH17 cytokines, epithelial chemokine expression, and immune cell infiltration through a C/EBPβ-mediated pathway.

• Glia-derived noncanonical fatty acid binding protein modulates brain lipid storage and clearance
  Authors: Yin J.; Chen H.; Grigsby-Brown A.; He Y.; Cotten M.; Short J.; Dermady A.; Lei J.; Gibbs M.; Cheng E.; Zhang D.; Long C.; Tabet J.; Xu L.; Zhong T.; Abzalimov R.; Haider M.; Sun R.; He Y.; Zhou Q.; Tjandra N.; Yuan Q.
  Published: 2025/8 (journal-article)
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  Glia-derived secretory factors are essential for brain development, physiology, and homeostasis, with their dysfunction linked to a variety of neurological disorders. Through genetic and biochemical approaches, we identified odorant binding protein 44a (Obp44a), a noncanonical α-helical fatty acid binding protein (FABP) highly expressed inDrosophilacentral nervous system glia. Obp44a binds long-chain fatty acids and shuttles between glia and neurons, acting as a secretory lipid chaperone and scavenger to support lipid storage, efflux, and redox homeostasis. Notably, Obp44a is recruited to apoptotic cells and injured axons, especially when glial engulfment is impaired, demonstrating its role in lipid waste management and clearance of cellular debris during development and in pathological states. Our findings highlight FABPs’ importance in regulating brain lipid dynamics and neuronal response to stress and injury. By visualizing FABP function in vivo, this study provides insights into how defective lipid regulation may contribute to neuronal stress and disease progression.

• Deciphering photocurrent mechanisms at the nanoscale in van der Waals interfaces for enhanced optoelectronic applications
  Authors: Xu D.; Liu Q.; Liang B.; Yu N.; Ma X.; Xu Y.; Taniguchi T.; Ding C.; Lake R.; Yan R.; Liu M.
  Published: 2025/8 (journal-article)
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  Integrated photodetectors are vital for their high speed, sensitivity, and low power consumption, with photocurrent driven by the photovoltaic and photothermoelectric (PTE) effects. At the nanoscale, these mechanisms overlap, complicating their separate evaluation. We introduce a 3D photocurrent nanoimaging technique to map these effects in a MoS2-Au Schottky photodiode, revealing a PTE-dominated region extending hundreds of nanometers from the electrode edge, enabled by weak electrostatic forces in two-dimensional materials. Unexpectedly, adding high–thermal conductivity hexagonal boron nitride enhances the PTE response by laterally redirecting heat, aligning thermal gradients with Seebeck coefficient variations, and boosting local conductance. This technique advances optoelectronic applications and deepens insights into light-matter interactions in low-dimensional systems, offering a powerful tool for designing efficient nanoscale photodetectors.

• Topology-driven design of bianisotropic metasurfaces through knot particles
  Authors: Goshen N.; Mazor Y.
  Published: 2025/8 (journal-article)
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  Bianisotropic metasurfaces enable advanced electromagnetic wave manipulation through magnetoelectric coupling. Here, we demonstrate how knot particles enable single-layer bianisotropic control using their inherent topology. Leveraging their geometric properties, we examine three-dimensional (3D) wire configurations characterized by the knot winding numbers (p,q), generating balanced electric and magnetic responses. Through multipole analysis, we demonstrate efficient polarization rotation with high transmission for different knot-particle topologies. We explore the knot-particle topologies required to achieve matched polarization rotation and derive simple design rules for the knot parameters without resorting to numerical optimization. The microscopic polarizability tensors and macroscopic susceptibilities reveal that the trefoil knot exhibits strong chiral bianisotropic behavior through its magnetoelectric coupling tensor. We implement knot-particle metasurfaces using advanced 3D printing, which realizes the full 3D geometry of the wires. We present simplified flat designs suitable for printed circuit board fabrication that preserve the essential symmetry enabling the bianisotropic properties.

• A wearable spatiotemporal controllable ultrasonic device with amyloid-β disaggregation for continuous Alzheimer’s disease therapy
  Authors: Zou F.; Liu Y.; Luo Y.; Xu T.
  Published: 2025/8 (journal-article)
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  The rising prevalence of Alzheimer’s disease (AD) due to an aging population has made the search for effective treatments more urgent than ever. Previous studies have demonstrated that continuous ultrasound can depolymerize amyloid proteins, offering potential relief from AD. In this study, we present a portable, fully integrated wearable ultrasound system designed to promote amyloid protein depolymerization. The system comprises a flexible honeycomb ultrasonic array patch, a flexible printed circuit, and an interactive terminal control system to facilitate the treatment process. Our results demonstrate that the system effectively reduces amyloid proteins in the brain, improves cognitive function in a familial Alzheimer’s disease (FAD) mouse model, enhances microglial phagocytosis of amyloid-β plaques, and shifts microglia polarization from M1 to M2. These changes contribute to a mitigated inflammatory environment in the brain. This innovative approach may pave the way for noninvasive, personalized treatments for AD, potentially transforming therapeutic strategies in neurodegenerative disorders.

• Identification of distinct epitopes in dipeptidyl peptidase-4 inhibitor–associated bullous pemphigoid
  Authors: Mai S.; Mai Y.; Ujiie I.; Izumi K.; Natsuga K.; Nishie W.; Ujiie H.
  Published: 2025/8 (journal-article)
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  Bullous pemphigoid (BP) is a common autoimmune skin disorder caused by autoantibodies targeting BP180. Recent evidence shows that dipeptidyl peptidase-4 inhibitors (DPP4i), used in diabetes management, can induce BP (DPP4i-BP). DPP4i-BP differs from typical BP in its genetic, clinical, and immunological features, but methods to specifically detect DPP4i-BP autoantibodies have been unavailable. This study used enzyme-linked immunosorbent assay with “domain-swapped BP180” proteins to identify autoantibodies in DPP4i-BP, which targeted BP180 regions from the seventh noncollagenous domain to the fourth collagenous domain (NC7-Col4). These epitopes were associated with DPP4i-BP–specific human leukocyte antigen class II peptide epitopes. Notably, the duration of DPP4i intake before BP onset was significantly shorter in patients with anti–NC7-Col4 autoantibodies than those without them. Measuring the autoantibodies enabled the early diagnosis of DPP4i-BP before epitope spreading. Furthermore, anti–NC7-Col4 autoantibodies were detected in some patients with diabetes taking DPP4i without BP, suggesting that these assays may offer potential tools for early identification of at-risk individuals.

• Precise rewiring of corticospinal axons and spinal interneurons via near-infrared optogenetics for spinal cord injury treatment
  Authors: Ji Z.; Yan J.; Li C.; Sun Y.; Wang S.; Tao J.; Liu J.; Liu Y.
  Published: 2025/8 (journal-article)
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  To date, precise restoration of proper connections between posttrauma axons and neurons following spinal cord injury (SCI) remains a substantial challenge. Here, we developed glutamate-linked upconversion nanoparticles (Glu-UCNP) to facilitate optogenetic control of axonal sprouting in SCI mice. After being specifically uptaken by the postsynaptic interneurons innervated by corticospinal tract (CST) axons, Glu-UCNP not only serves as internal light transducers that convert near-infrared light to visible light but also acts as nanobeacons that guide axonal sprouting toward postsynaptic neurons of glutamatergic synapses. This in situ optogenetic modulation successfully demonstrated the restoration of spinal motor circuits by rebuilding functional connections between CST axons and postsynaptic interneurons. It was corroborated by live-cell recording, immunofluorescence staining, in vivo Ca2+imaging, and pellet-reaching tests. Transcriptome sequencing further elucidated the molecular network changes underlying this optogenetic modulation. These findings highlight the potential therapeutic applications of optogenetic modulation in the reassembly of neural circuits after SCI.

• The ISW1 and CHD1 chromatin remodelers suppress global nucleosome dynamics in living yeast cells
  Authors: Xu Z.; Prajapati H.; Eriksson P.; Clark D.
  Published: 2025/8 (journal-article)
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  The budding yeast genome is globally accessible to DNA methyltransferases in living cells, unlike in isolated nuclei, where it is mostly inaccessible. Here, we assess the roles of the RSC, ISW1, and CHD1 adenosine 5′-triphosphate–dependent chromatin remodelers in generating nucleosome dynamics in vivo. We compare DNA methylation rates in wild-type cells and chromatin remodeler mutants by normalizing nuclear methylation rates to the nonnucleosomal mitochondrial DNA methylation rate in each strain. Depletion of both Isw1 and Chd1 increases the normalized methylation rate, suggesting that these remodelers act together to suppress nucleosome dynamics. Separate depletion of Isw1, Chd1, or Rsc8 has little effect. A decaying sine wave model used to fit nucleosome phasing data shows that nucleosome dynamics decrease with distance from the promoter in an Isw1/Chd1-dependent manner. Furthermore, the TFIIIB and TFIIIC transcription factors exhibit differential dynamics at transfer RNA genes in vivo. Our analysis provides insight into nucleosome and transcription factor dynamics in vivo.

• Better and faster decisions by larger fish shoals in the wild
  Authors: Pacher K.; Bierbach D.; Sevinchan Y.; Vollmoeller C.; Juarez-Lopez A.; Jiménez-Jiménez J.; Krause S.; Wolf M.; Romanczuk P.; Arias-Rodríguez L.; Krause J.
  Published: 2025/8 (journal-article)
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  Studies on collective cognition provide many examples of how the efficient spread of information within groups leads to benefits with increasing group size. However, little is known if groups also amplify maladaptive information such as false alarms and whether such costs reduce possible benefits. Here, we investigated wild fish shoals responding collectively with escape dives when attacked by birds. We analyzed the collective response in reaction to bird attacks and similar but harmless flybys as a function of shoal size. Larger shoals increasingly detected predator attacks (i.e., true positives), while their response facing harmless flybys (i.e., false alarms) remained constant. Furthermore, decision time decreased with increasing shoal size. Larger shoals were thus able to simultaneously overcome two major trade-offs inherent in solitary decision-making: the trade-off between true and false positives and the trade-off between speed and accuracy. Our findings set the stage for the next generation of studies investigating the mechanisms underlying collective decision-making.

• Biomimetic targeted self-adaptive nanodrug for inflammation optimization and AT2 cell modulation in precise ARDS therapy
  Authors: Chen C.; He D.; Li X.; Ou Z.; Wang H.; Shou Z.; Wang L.; Mao Z.; Qi X.; Deng J.
  Published: 2025/8 (journal-article)
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  Acute respiratory distress syndrome (ARDS) is a lethal respiratory condition, while effective pharmacological treatments remain elusive. We identified the decreased mechanical capacity and impaired proliferation of alveolar type 2 (AT2) epithelial cells in the inflammatory environment as the primary contributors to respiratory failure of ARDS. A biomimetic, self-adaptive, 7,8-dihydroxyflavone–loaded hollow mesoporous cerium oxide coated with a platelet membrane (HCeOx-D@PM) was developed for precise ARDS therapy. HCeOx-D@PM comprises a platelet membrane (PM) shell for targeted delivery to injured lungs and an HCeOxcore, which enables high drug loading, efficient reactive oxygen species (ROS) scavenging, and penetration of the alveolar-capillary barrier. Initially, HCeOx-D@PM suppresses the inflammation and mitigates the adverse effects of lesions on AT2 cell by scavenging accumulated ROS. It then adaptively releases 7,8-dihydroxyflavone in response to cysteine–aspartic acid protease 3 activation, facilitating AT2 cell proliferation and notably improving survival rates in vivo, offering a promising advancement in the precise treatment of respiratory diseases.

• Origami exoskeletons for enhanced soft robotic manipulation
  Authors: Fu K.; Wu X.; Yu S.; Zhang Q.; Yang Y.; Xu T.; Yao W.; Yi T.; Li H.; Chen Y.; Zhang X.; Chen X.
  Published: 2025/8 (journal-article)
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  Soft robots are characterized by ultraflexible electromechanical structures that are capable of large deformations and movements. However, the challenge of generating the high output forces necessary for manipulation persists because of the low Young’s moduli of soft materials, which limit their effectiveness in tasks such as carrying, grasping, and providing support. Inspired by shrimp exoskeletons, we designed an origami exoskeleton that features flexible-rigid arrangements and mechanical multistability. This design offers high stiffness in stable states while allowing for long-stroke transitions, making it suitable for integration with soft actuators to balance deformability and load-bearing capacity. With advantages such as high compressibility and rapid integration, these exoskeleton-enhanced arms have promising applications when mounted on unmanned ground and aerial vehicles, facilitating large-scale dexterous manipulation with the necessary load capacities. For existing soft arms, the proposed origami exoskeleton enhances the potential for manipulation within their original design framework.

• Tailored sliding ferroelectricity for ultrahigh fatigue resistance in stacked trilayer MoS ₂ crystals
  Authors: Fan A.; Zhang Q.; Yang Z.; Li L.; Li M.; Zhang K.; Gao J.; Wu F.; Wu M.; Geng D.; Hu W.
  Published: 2025/8 (journal-article)
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  Fatigue-resistant ferroelectric materials in two-dimensional systems are crucial for next-generation electronic devices, but the relationship between stacking configurations and ferroelectric behavior remains underexplored. Here, we synthesize trilayer MoS2crystals with three noncentrosymmetric stacking configurations (AAA, AAB, and ABB) using a thermal gradient chemical vapor deposition strategy. Notable variations in room-temperature ferroelectricity are observed, with polarization strength following the order AAA > AAB > ABB, up to 0.110 microcoulombs per square centimeter. The total stress time for AAA, AAB, and ABB configurations is 106seconds under a 10-microsecond pulse width. We also identify an oscillatory feature between stacking configurations and ferroelectric polarization in multilayer systems. This work establishes a distinctive paradigm for designing robust, high-performance ferroelectric materials, unlocking scalable solutions for next-generation memory and electronic applications.

• BACH2 drives the development and function of group 2 innate lymphoid cells
  Authors: Liu G.; Wang Y.; Yi X.; Wang J.; Zhang J.; Feng X.; Wang H.; Chen C.; Liu Q.; Wang J.; Zhou J.
  Published: 2025/8 (journal-article)
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  Group 2 innate lymphoid cells (ILC2s) represent one of the major drivers of allergic inflammation; however, the precise mechanisms governing the development and function of ILC2s remain unknown. Here, we show that the transcription factor BACH2 was abundantly expressed and epigenetically activated in ILC2s and their progenitors. Conditional ablation of BACH2 diminished the ability of ILC2 progenitors to differentiate into ILC2s. Integration of the scRNA-seq, ATAC-seq, and CUT&Tag-seq techniques revealed that BACH2 modulated the transcriptional profiles and epigenetic landscapes of ILC2 progenitors. Furthermore, BACH2 ablation compromised the functionality of ILC2s, resulting in a resolution of allergic airway inflammation. Notably, the different binding sites of BACH2 in ILC2s and TH2 cells suggested that BACH2 binds to IRF4 to control the function of ILC2, underscoring its context-specific effects on allergic airway inflammation. These findings shed promising light on the importance of BACH2 in type 2 immunity and its multifaceted role in asthma.

• Tailoring tin-based perovskite crystallization via large cations and pseudo-halide anions for high mobility and high stable transistors
  Authors: Wu Y.; Yuan F.; Yang S.; Li E.; Wang W.; Liu Y.; Yang X.; Wen J.; Hua L.; Yang Y.; Lei Y.; Chu J.; Li W.
  Published: 2025/8 (journal-article)
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  Tin-based perovskites, renowned for their eco-friendliness, intrinsic high hole mobility, and low effective mass, hold great potential for p-type thin-film transistors (TFTs). However, their propensity for rapid crystallization and oxidation severely limits stability and carrier mobility. Here, we strategically enhance perovskite TFT performance by incorporating 2-thiopheneethylamine thiocyanate (TEASCN) into 3D tin-based perovskites. The induction of the pseudo-halide SCN−into a bilayer quasi-2D perovskite intermediate phase, combined with the strong interaction between sulfur-bearing thiophene rings (TEA+) and Sn-I octahedra, effectively reorients perovskite crystallization while inhibiting Sn2+oxidation and reducing trap density. Consequently, TEASCN-based TFTs achieve an average hole mobility of more than 60 square centimeters per volt per second and an on/off current ratio surpassing 108, standing out among state-of-the-art p-type perovskite TFTs. Furthermore, unencapsulated devices preserve 84% of their initial mobility after 30 days in an N2atmosphere, underscoring their remarkable stability. This work opens a straightforward path toward high-mobility and highly stable tin-based perovskite transistors.

• Observation of quantum Darwinism and the origin of classicality with superconducting circuits
  Authors: Zhu Z.; Salice K.; Touil A.; Bao Z.; Song Z.; Zhang P.; Li H.; Wang Z.; Song C.; Guo Q.; Wang H.; Mondaini R.
  Published: 2025/8 (journal-article)
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  The transition from quantum to classical behavior is a central question in modern physics. How can we rationalize everyday classical observations from an inherently quantum world? Quantum Darwinism offers a compelling framework to explain this by proposing that the environment redundantly encodes information about a quantum system, leading to the objective reality. Here, by leveraging cutting-edge superconducting quantum circuits, we observe the highly structured branching quantum states that support classicality and the saturation of quantum mutual information, establishing a robust verification of quantum Darwinism and the underlying geometric structure of quantum states. Additionally, we propose a particular class of observables that can be used as a computationally and experimentally inexpensive quantifier to probe quantum-to-classical transitions. Our investigation delves into how the quantum effects are inaccessible to observers, allowing only classical properties to be detected. It experimentally demonstrates the physical framework through which everyday classical observations emerge from underlying quantum principles and paves the way to settling the measurement problem.

• Tracking bioturbation through time: The evolution of the marine sedimentary mixed and transition layers
  Authors: Tarhan L.; Pippenger K.; Cribb A.; Zill M.; Phelps W.; Droser M.; Bottjer D.; Clapham M.
  Published: 2025/8 (journal-article)
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  The physical, biogeochemical, and ecological properties of the modern seafloor are extensively shaped by the activities of burrowing and sediment-mixing animals, processes collectively known as bioturbation. Bioturbation is primarily recorded by homogenized sediments of the seafloor mixed layer and the underlying transition layer of discrete burrows. Although these two zones can be readily measured today, there has been limited understanding of how the mixed and transition layers evolved over the Phanerozoic since animals first began to extensively colonize the seafloor. Here, we provide a record for the depths of the sedimentary mixed and transition layers through the Phanerozoic. We find that although deepening of the sediment mixed layer spanned hundreds of millions of years, a deep transition layer was established as early as the Cambrian and did not further deepen until the Mesozoic—trajectories reflecting evolutionary radiations, changes in nutrient cycling, and alleviation of oxygen stress.

• Paleoseismic activity in the moon’s Taurus-Littrow valley inferred from boulder falls and landslides
  Authors: Watters T.; Schmerr N.
  Published: 2025/8 (journal-article)
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  The Taurus-Littrow valley offers a unique opportunity to analyze surface changes due to seismic activity on the lunar surface. Ground acceleration from moonquakes has triggered landslides and boulder falls in the valley. The formation and growth of the Lee-Lincoln thrust fault is a likely source of the moonquakes. Here, we estimate the ground acceleration and quake magnitude for four boulders and one landslide: all sampled by Apollo 17 astronauts. These features all have exposure ages that establish the approximate timing of the moonquakes. Our analysis suggests that the structural relief of the Lee-Lincoln fault scarp is the result of multiple coseismic slip events with a minimum body wave magnitudeMwof ~2.9 to 3.3. The formation and growth of thousands of such globally distributed young thrust faults, through multiple coseismic events, suggest that the Moon has a history of widespread strong shallow moonquakes. Shallow moonquakes from likely active faults may pose a potential hazard to long-term outposts.

• Hospitalization risk and burden for cause-specific cardiovascular diseases following tropical cyclones: A multicountry study
  Authors: Huang W.; Yang Z.; Zhang Y.; Vogt T.; Park J.; Yu W.; Xu R.; Hales S.; Hundessa S.; Otto C.; Yu P.; Liu Y.; Ju K.; Lavigne E.; Ye T.; Wen B.; Wu Y.; Zhang Y.; Kliengchuay W.; Tantrakarnapa K.; Guo Y.; Kim H.; Phung D.; Ritchie E.; Li S.
  Published: 2025/8 (journal-article)
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  The indirect health risks of tropical cyclones (TCs), the costliest climate extremes, remain unclear, with cardiovascular diseases (CVDs) being a major contributor. We applied two-stage time-series analysis to 6.54 million CVD hospitalizations across six countries/territories (Canada, New Zealand, South Korea, Taiwan, Thailand, and Vietnam) between 2000 and 2019 to quantify the long-term risks and burden of CVD hospitalizations following TCs. Hospitalization risks for cause-specific CVDs consistently increased following TC exposure, generally peaking around 2 months postexposure and dissipating by 6 months. Overall, each additional TC day was associated with a 13% (95% confidence interval, 7 to 19%) increase in CVD hospitalizations in 6 months following TCs. Particularly high TC-attributable burden was found for ischemic heart diseases and stroke, especially among males, individuals aged 20 to 59 years, and those with higher levels of socioeconomic deprivation. The TC-attributable proportions of CVD hospitalizations showed decreasing trends in less deprived populations and increasing trends in more deprived populations from 2000 to 2019.

• Machine learning-assisted exploration of multidrug-drug administration regimens for organoid arrays
  Authors: Yakavets I.; Kheiri S.; Cruickshank J.; Hickman R.; Rakhshani F.; Aldeghi M.; Rajaonson E.; Young E.; Aspuru-Guzik A.; Cescon D.; Kumacheva E.
  Published: 2025/8 (journal-article)
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  Combination therapies enhance the therapeutic effect of cancer treatment; however, identifying effective interdependent doses, durations, and sequences of multidrug administration regimens is a time- and labor-intensive task. Here, we integrated machine learning, automation, and large microfluidic arrays of cancer spheroids or patient-derived organoids formed in a tissue-mimetic hydrogel to achieve notable acceleration of the discovery of effective multidrug administration regimens. For the clinically approved drug combination, we found a sequential administration regimen leading to a substantial reduction in the total drug dose, in comparison with concurrent drug supply, both at comparable drug efficacy. For the drugs that are currently under clinical development, we found a synergistic effect of concurrently administered drugs and showed that the synergy diminishes for the sequential drug supply. The developed strategy holds promise for the discovery of effective combination therapies for advanced cancer treatment, including personalized chemotherapies.

• The β ₂ -adrenergic receptor ( Adrb2 ) entrains circadian gene oscillation and CD8 ⁺ T cell differentiation in response to virus infection
  Authors: Sharma D.; Kohlbach K.; Maples R.; Farrar J.
  Published: 2025/8 (journal-article)
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  Adaptive immune cells are regulated by circadian rhythms both under steady state conditions and during responses to infection. Cytolytic CD8+T cells display variable responses to infection depending upon the time of day of exposure. However, the neuronal signals that entrain these cyclic behaviors remain unknown. Immune cells express various neurotransmitter receptors, and we demonstrate that selective deletion of the β2-adrenergic receptor (Adrb2) gene perturbs the normal diurnal oscillation of clock gene expression in CD8+T cells, such asPer2andBmal1. Consequently, their time-of-day–dependent response to vesicular stomatitis virus was dysregulated, and the diurnal development of CD8+T cells into variegated populations of memory/effectors was altered in the absence of ADRB2 signaling. The diurnal fluctuations in T cell phenotypes were a distinct developmental process, independent of migration kinetics within the spleen. Thus,Adrb2directly entrains core clock gene oscillation and regulates T cell developmental responses to virus infection as a function of time of day of pathogen exposure.

• Circularly polarized thermal emission driven by chiral flatbands in monoclinic metasurfaces
  Authors: Sun K.; Yang B.; Cai Y.; Kivshar Y.; Han Z.
  Published: 2025/8 (journal-article)
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  Achieving circularly polarized thermal emissions with high spatiotemporal coherence using planar structures has long been considered to be elusive. Here, we use nonlocal metasurfaces with monoclinic lattices that break mirror symmetry to efficiently achieve circularly polarized thermal emissions with both high temporal and spatial coherence. We design a chiral metasurface based on waveguide arrays with periodically shifted segments that have a saddle-shaped chiral and high-Qdispersion band. The parabolic shape along one direction ensures minimum involvement of spatial/Fourier components at each frequency, thereby achieving circularly polarized thermal emission with high spatial coherence. Meanwhile, the flatband behavior along the other direction allows the use of a slot-shaped spatial filter and a mid-infrared lens to collect emissions from large-area metasurfaces, thus improving power collection efficiency without affecting temporal coherence. Our experiments demonstrate circularly polarized thermal emissions with high temporal coherence (Q> 200) and very large circular dichroism (~0.8).

• Ultrasound matrix imaging for 3D transcranial in vivo localization microscopy
  Authors: Bureau F.; Denis L.; Coudert A.; Fink M.; Couture O.; Aubry A.
  Published: 2025/8 (journal-article)
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  Transcranial ultrasound imaging is usually limited by skull-induced attenuation and high-order aberrations. By using contrast agents such as microbubbles in combination with ultrafast imaging, not only can the signal-to-noise ratio be improved, but super-resolution images down to the micrometer scale of the brain vessels can also be obtained. However, ultrasound localization microscopy (ULM) remains affected by wavefront distortions that limit the microbubble detection rate and hamper their localization. In this work, we show how ultrasound matrix imaging, which relies on the prior recording of the reflection matrix, can provide a solution to these fundamental issues. As an experimental proof of concept, an in vivo reconstruction of deep brain microvessels is performed on three anesthetized sheep. The compensation of wave distortions is shown to markedly enhance the contrast and resolution of ULM. This experimental study thus opens up promising perspectives for a transcranial and nonionizing observation of human cerebral microvascular pathologies, such as stroke.

• A pan-respiratory virus attachment inhibitor with high potency in human airway models and in vivo
  Authors: Mathez G.; Silva P.; Carlen V.; Deloizy C.; Prompt C.; Hubart A.; Rocha-Pereira J.; Galloux M.; Le Goffic R.; Stellacci F.; Cagno V.
  Published: 2025/8 (journal-article)
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  Respiratory viruses can cause severe infections, often leading to hospitalization or death, and pose a major pandemic threat. No broad-spectrum antiviral is currently available. However, most respiratory viruses use sialic acid or heparan sulfates as attachment receptors. Here, we report the identification of a pan-respiratory antiviral strategy based on mimicking both glycans. We synthesized a modified cyclodextrin that simultaneously mimics heparan sulfate and sialic acid. This compound demonstrated broad-spectrum antiviral activity against important human pathogens: parainfluenza virus 3, respiratory syncytial virus, influenza virus H1N1, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition, the compound is active against avian strains of influenza virus, revealing its importance for pandemic preparedness. The compound retains broad-spectrum activity in ex vivo models of respiratory tissues and in vivo against respiratory syncytial virus and influenza virus, using prophylactic and therapeutic strategies. These findings contribute to the development of future treatments and preventive measures for respiratory viral infections.

• Indirect genetic effects among neighbors promote cooperation and accelerate adaptation in a small-scale human society
  Authors: Martin J.; Beheim B.; Gurven M.; Kaplan H.; Stieglitz J.; Trumble B.; Hooper P.; Cummings D.; Eid Rodriguez D.; Jaeggi A.
  Published: 2025/8 (journal-article)
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  Explaining the rapid evolution of human cooperation and its role in our species’ biodemographic success remains a major evolutionary puzzle. To address this challenge, we tested a social drive hypothesis, which predicts that social plasticity and social selection in human groups cause indirect genetic effects that accelerate the adaptation of fitness, promoting population growth via feedback between the environmental causes and evolutionary consequences of cooperation. Using Bayesian multilevel models to analyze fertility data from a small-scale society, we demonstrate that density- and frequency-dependent indirect genetic effects on fitness promote the evolution of cooperation among neighboring women, increasing the rate of contemporary adaptation by ~5×. Our results show how interactions between the genetic and socioecological processes shaping cooperation in reproduction can drive rapid growth and social evolution in human populations.

• North American bird declines are driven by reductions in common species
  Authors: Dupont G.; Dobson A.
  Published: 2025/8 (journal-article)
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  Biodiversity loss continues to occur globally. However, the long-term dynamics of the redistribution of abundance within declining communities remain poorly resolved. We quantitatively dissected the major decline of North American bird abundance by rigorously analyzing 38,854 surveys that quantify over half a century of annual dynamics for 648 populations of 244 bird species from six regions, each encompassing 140,000 to 370,000 km2. Despite regional variation in geography, habitat, and species composition, a consistent pattern emerges: Biodiversity loss predominantly stems from declines in the most abundant bird species, whereas less abundant species show increases. We demonstrate that species once abundant and near their carrying capacity have declined, while less abundant species farther from their carrying capacity have increased. A path analysis identifies the key role played by anthropogenic land-use changes in causing the observed declines. Conservation efforts should place stronger emphasis on the abundance of common species as a central ecological indicator.

• GPR161 mechanosensitivity at the primary cilium drives neuronal saltatory migration
  Authors: Paillard T.; Allam A.; Doulazmi M.; Hautefeuille M.; Fouquet C.; Sarde L.; Stoufflet J.; Messaoudi S.; Spassky N.; Nédélec S.; Dusart I.; Trembleau A.; Isabelle Caillé N/A.
  Published: 2025/8 (journal-article)
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  The saltatory migration of neurons is essential for brain formation. Whether mechanical stimuli regulate this process is unknown. Here, we show that the primary cilium acts as a mechanical sensor through GPR161. Using an ex vivo neuronal migration model and microfluidic assays, we demonstrate that fluid shear stress induces migration via the mechanoreceptor GPR161 at the primary cilium, with its mechanosensitive helix 8 being essential. We demonstrate that GPR161 activates a recently discovered cAMP/PKA signaling pathway leading to the phosphorylation of NDE1, a dynein complex regulator, and microtubule organization to regulate migration. These findings unveil a critical role of mechanosensation in neuronal migration, regulating the rhythmicity of migration, in concert with the externalization/internalization dynamics of the primary cilium.

• Energy filtering–induced ultrahigh thermoelectric power factors in Ni ₃ Ge
  Authors: Garmroudi F.; Di Cataldo S.; Parzer M.; Coulter J.; Iwasaki Y.; Grasser M.; Stockinger S.; Pázmán S.; Witzmann S.; Riss A.; Michor H.; Podloucky R.; Khmelevskyi S.; Georges A.; Held K.; Mori T.; Bauer E.; Pustogow A.
  Published: 2025/8 (journal-article)
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  Traditional thermoelectric materials rely on low thermal conductivity to enhance their efficiency but suffer from inherently limited power factors. Innovative pathways to optimize electronic transport are thus crucial. Here, we achieve ultrahigh power factors in Ni3Ge-based systems through an unconventional thermoelectric materials design principle. When overlapping flat and dispersive bands are engineered to the Fermi level, charge carriers can undergo intense interband scattering, yielding an energy filtering effect similar to what has long been predicted in certain nanostructured materials. Via a multistep DFT-based screening method developed here, we find a family of L12-ordered binary compounds with ultrahigh power factors up to 11 mW m−1K−2near room temperature, which are driven by an intrinsic phonon-mediated energy filtering mechanism. Our comprehensive experimental and theoretical study of these intriguing materials paves the way for understanding and designing high-performance scattering-tuned metallic thermoelectrics.

• Formation control between leader and migratory follower tissues allows coordinated growth
  Authors: Kawanishi T.; Sushida T.; Tsai T.; Takeda H.; Megason S.
  Published: 2025/8 (journal-article)
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  Coordinated growth of multiple tissues is fundamental to shaping our body, but the underlying mechanisms remain underexplored. In zebrafish embryos, midline tissues composed of the notochord, floorplate, and hypochord elongate synchronously with their lengths aligned. We show that floorplate and hypochord cells collectively migrate posteriorly along the nascent notochord extracellular matrix as it extends posteriorly, maintaining the tripartite configuration. Fibroblast growth factor-mediated migration in a spatially graded manner causes cell stretching, which triggers Yap-dependent proliferation and controls floorplate and hypochord growth. Supported by mathematical modeling, we further suggest that their growth is fine-tuned by mechanical tethering to the notochord via cadherin 2 at the posterior end. We propose that the notochord instructs and sustains the tripartite formation via leader-follower formation control, a strategy from engineering that spatially organizes multiple agents to coordinate the growth of the midline tissues.

• A century of anthropogenic perturbations impact genomic signatures of the iconic migratory Atlantic cod
  Authors: Helmerson C.; Durant J.; Hoff S.; Brieuc M.; Berg P.; Jorde P.; Maurstad M.; Bradbury I.; Kjesbu O.; Godiksen J.; Stenseth N.; Star B.; Jakobsen K.; Jentoft S.
  Published: 2025/8 (journal-article)
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  Anthropogenic stressors have led to marked ecosystem perturbations, including population declines and shifts in habitat range for key marine fish species. Understanding how these changes affect genome-wide characteristics, causing long-term evolutionary responses, is still in its infancy. Genome-wide retrospective assessment of the iconic migratory Atlantic cod (Gadus morhua) from the Barents Sea, unraveled varying degree of admixture with the nonmigratory coastal ecotype throughout the 20th century, and intriguingly more intensified during recent decades. These genomic changes were supported by an increased number of individuals displaying the heterozygous state of the chromosomal inversion coupled to migratory behavior in Atlantic cod. Ecological models and genome-wide scans identified that some of the observed frequency shifts, coupled to neural development, metabolic, and growth regulation, covaried with intensified fisheries, reduced generation time, and ocean warming. Our results demonstrate how anthropogenic perturbations impact the dynamics between two well-known ecotypes of Atlantic cod and thus, their genomic signatures, with potential implications for future management programs.

• Time of proto-Earth reservoir formation and volatile element depletion from ⁵³ Mn- ⁵³ Cr chronometry
  Authors: Kruttasch P.; Mezger K.
  Published: 2025/8 (journal-article)
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  The53Mn-53Cr chronometry of Solar System materials constrains the early chemical evolution of the protoplanetary disk, which is critical for planet formation. Mn/Cr ratios in carbonaceous chondrites and the bulk silicate Earth indicate that meteorite parent bodies and Earth have variable depletions in volatile elements compared to the bulk Solar composition. This depletion is a consequence of the local temperature decreasing as a function of heliocentric distance before planetesimal accretion. Back-tracking the present-day ε53Cr composition of the hypothetical proto-Earth fraction shows that the cessation of Mn-Cr fractionation from the bulk Solar composition occurred no later than ~3 Ma after CAI formation, similar to disk regions of carbonaceous chondrites at greater heliocentric distances. The timing of limited solid-gas interaction due to the dissipation of gas from the protoplanetary disk caused the cessation of Mn-Cr fractionation and provides a lower limit on its lifetime.

• Revealing European-wide ecosystem strategies to drought from space
  Authors: Chen Q.; Timmermans J.; van Bodegom P.
  Published: 2025/8 (journal-article)
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  Ecosystems are threatened by increasing droughts under climate change. A multitude of plant physiological regulation processes determine the overall drought resistance of ecosystems. So far, these physiological strategies to resist drought are poorly understood at large scales across different ecosystem types because the detection of these physiological regulation processes is mostly limited to in situ measurements on individual plants. In this study, by using high-resolution remote sensing data, we evaluated drought strategies of different ecosystem types throughout Europe by evaluating three key physiological regulation aspects (evapotranspiration, water content, and carbon regulation) based on their associated vegetation attributes. We found that different ecosystem types show divergent responses in these physiological attributes, suggesting different optimization strategies with respect to water saving versus spending, water content stabilizing versus fluctuating, and leaf conserving versus shedding strategies facing drought. These drought strategies from remote sensing provide timely ecosystem response information, facilitating earth system model predictions and aiding the protection against future droughts at large scales.

• Static three-dimensional structures determine fast dynamics between distal loci pairs in interphase chromosomes
  Authors: Shi G.; Shin S.; Thirumalai D.
  Published: 2025/8 (journal-article)
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  Live-cell imaging experiments have shown that the distal dynamics between enhancers and promoters are unexpectedly rapid and incompatible with standard polymer models. The discordance between the compact static chromatin organization and dynamics is a conundrum that violates the expected structure–function relationship. We developed a theory to predict chromatin dynamics by accurately determining three-dimensional (3D) structures from static Hi-C contact maps or fixed-cell imaging data. Using the calculated 3D coordinates, the theory accurately forecasts experimentally observed two-point chromatin dynamics. It predicts rapid enhancer–promoter interactions and uncovers a scaling relationship between two-point relaxation time and genomic separation, closely matching recent measurements. The theory predicts that cohesin depletion accelerates single-locus diffusion while significantly slowing relaxation dynamics within topologically associating domains. Our results demonstrate that chromatin dynamics can be reliably inferred from static structural data, reinforcing the notion that 3D chromatin structure governs dynamic behavior. This general framework offers powerful tools for exploring chromatin dynamics across diverse biological contexts.

• Erratum for the Research Article “The Summer North Atlantic Oscillation, Arctic sea ice, and Arctic jet Rossby wave forcing” by C. K. Folland et al .
  Authors: None
  Published: 2025/8 (journal-article)
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• Noise-enhanced stability in synchronized systems
  Authors: Shi Z.; Lv Q.; Fu M.; Wang X.; Huang Z.; Wei X.; Amabili M.; Huan R.
  Published: 2025/8 (journal-article)
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  Synchronization underpins coherence in natural and engineered systems, unifying dynamics and countering noise while remaining vulnerable to disturbances threatening the stability and risking desynchronization. Here, we present a counterintuitive approach: harnessing noise to dilute the energy of unwanted fluctuations from external disturbances, thereby enhancing stability while preserving synchronization through the system’s inherent noise suppression at the synchronized frequency. Through experiments with micromechanical oscillators and macroscale rotors, combined with stochastic averaging analysis, we show that this noise dilution effect improves synchronization efficiency, bolsters resistance to interference, and enhances long-term frequency stability. These findings position white noise of appropriate intensity as a dilution element for mitigating unwanted disturbances, providing previously unidentified insights into stability and resilience in complex synchronized systems.

• Dynamics of proximity-induced magnetism at cobalt/molecular interfaces
  Authors: Strohsack J.; Shumilin A.; Zhao H.; Jecl G.; Kabanov V.; Benini M.; Rakshit R.; Dediu V.; Rogers M.; Ozdemir S.; Cespedes O.; Parlak U.; Cinchetti M.; Mertelj T.
  Published: 2025/8 (journal-article)
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  Interfacing ferromagnetic metals with organic molecules is a versatile strategy to control key parameters in magnetic and spintronic technologies. Hybridization between the metal’s surface d orbitals and molecular p orbitals profoundly alters both the interfacial molecular layer and adjacent metal interface atomic layers, causing substantial changes in the magnetic properties of metal/molecule heterostructures. While magnetic modifications within the metallic layer are relatively well understood, the interfacial magnetism remains elusive. Using ultrafast time-resolved magneto-optical spectroscopy, we investigate the magnetic dynamics in such heterostructures and identify a distinct interfacial magnetic component that appears universal across various cobalt/molecule combinations. Our findings reveal a highly anisotropic magnetic layer localized at the interface, which has remained undetected in static measurements. This interfacial layer likely originates from strong chemical modifications in the cobalt surface induced by chemisorbed molecules. These results underscore the crucial role of molecular chemisorption in shaping interfacial magnetic properties, offering further opportunities for tuning functionalities in molecule-based spintronic devices.

• Ultrahigh-density nested polar nanovortices with independently controllable conduction for ferroelectric memristor
  Authors: Taazayet W.; Wang J.; Zhang Y.; Qu S.; Yang H.; Fan Y.; Han H.; Ma J.; Shao R.; Huang H.; Nan C.
  Published: 2025/8 (journal-article)
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  Ferroelectric vortices have received much attention in the past decade due to their functionalities and potential applications in nanoelectronics. However, most of the vortices fabricated in the nanoislands have a size of more than a hundred nanometers, which limits the miniaturization of electronic devices. Here, we show the realization of a high-density vortex lattice with ~10- to 20-nanometer size in ultrathin bismuth ferrite/barium titanate bilayer by strain engineering. The obtained vortex shows a nested structure, e.g., an outer center-type structure with a nested inner ring included, which is well supported by piezoelectric force microscopy, transmission electron microscopy, and phase-field simulations. The nested vortex structure is not only more stable than the center-type vortex structure but also exhibits controllable multistate conduction with low energy consumption (<100 zeptojoules, e.g., 10−19joules), good stability (>1 year), and high endurance. This is of great interest for high-density [~2 terabits per square inch (3100 terabits per square meter)] ferroelectric memristor conception for neuromorphic computing.

• High-elongation, water-weldable, and fully degradable biomass foams fabricated via oven drying
  Authors: Chang Y.; Tian Y.; Wang J.; Zhao J.; Chen L.; Kang S.; Lu Q.; He X.; Zhang Q.
  Published: 2025/8 (journal-article)
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  Biomass-based foams present a promising alternative to conventional plastic foams. However, many reported biomass-based foams are composed of nondegradable components and are mechanically weak and brittle. We proposed a hybrid biomass-driven foaming strategy that used specially designed cellulose nanofibers and sodium caseinate to synergistically create stable wet foams and form gas-impermeable bubble interfaces to prevent structural collapse during oven drying. The foams exhibited high tensile stress (~400 kPa) comparable to that of brittle foams and had excellent ductility, with an elongation of 137.0%. The foams also displayed outstanding cyclic elastic behavior, retaining more than 90% of their compressive stress after 100 cycles. In addition, the foams were water-weldable, recovering 87.3% of their original tensile stress and nearly 100% of their elongation, allowing them to be tailored into customized geometric structures. A roll-to-roll casting process was used to produce continuous foam rolls, demonstrating successful scalability. This study provides an advanced formulation for fabricating fully degradable biomass-based foams with superior mechanical properties.

• Quantifying effects of solar power adoption on CO ₂ emissions reduction
  Authors: Biswas A.; Qiu M.; Braun D.; Dominici F.; Mork D.
  Published: 2025/8 (journal-article)
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  We quantify the effect of solar power adoption in reducing carbon dioxide (CO2) emissions from the US electricity sector using 5 years of Energy Information Administration data, starting 1 July 2018. By tailoring a distributed lag statistical model, we estimate the immediate and time-lagged effects of increased solar generation on reducing CO2emissions within a region. Our analysis highlights how solar adoption in one region affects CO2emissions in neighboring regions, emphasizing the potential for collaborative efforts. We estimate that a 15% increase in solar generation is associated with an annual reduction of 8.54 million metric tons (MMT) of CO2emissions, contributing 12.38% toward the yearly target of 69 MMT CO2reductions needed to cut 1380 MMT of CO2in 20 years, as per the Environmental Protection Agency rule on fossil fuel power plants. This study offers insights for policymakers and stakeholders in achieving CO2reduction targets through increased solar generation.

• Control and synchronization of rapid nanoscale DNA heat engine by local heating
  Authors: Wang K.; Hardikar A.; Chen W.; Huang Q.; Guo B.; Zhu G.; Ni H.; Sha R.; Seeman N.; Chaikin P.
  Published: 2025/8 (journal-article)
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  To further activate devices based on DNA nanotechnology, we introduce an approach that notably enhances both the speed and force of DNA powered machines and artificial hinge machine. A microheater, with millisecond response, heats or recools DNA origami constructs, hybridizing or dehybridizing sticky ends. Because anything within 20 micrometers of the heater equilibrates to a programmed temperature change in milliseconds, sticky ends of a compound DNA origami machine can open and close synchronously and operate cooperatively, in phase, additively increasing the drive force compared to single pair of sticky ends DNA machine (the six-helix bundle DNA origami hinge machine). In our demonstrations, we fold and unfold two square origami with 10 pairs of complementary sticky ends to drive a bead on the end of a rod like origami to speeds exceeding 30 micrometers per second. Our device envisions the creation of complex, synchronized DNA machines.

• CeyeHao: AI-driven microfluidic flow programming with hierarchically assembled obstacles and receptive field–augmented neural network
  Authors: Yang Z.; Jiang Z.; Lin H.; Fan X.; Wu C.; Lam E.; So H.; Shum H.
  Published: 2025/8 (journal-article)
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  Microfluidic fabrication technologies are increasingly used to produce functional anisotropic microstructures for broad applications. However, the limited flow manipulation methods hinder the production of intricate microstructure morphologies. In this work, we introduce CeyeHao, an artificial intelligence–driven flow programming methodology for designing microchannels to perform unprecedented flow manipulations. In CeyeHao, microchannels containing hierarchically assembled obstacles are constructed, offering more than double flow transformation modes and immense configurability compared to state-of-the-art methods. An AI model, CEyeNet, predicts the transformed flow profiles, reducing computation time by up to 2700 folds and achieving up to 97 and 90% accuracy with simulated and experiment results. CeyeHao facilitates microchannel design in both human-guided and automatic modes, enabling creation of flow morphologies with highly regulated geometries and elaborate artistic patterns, along with precise topology manipulation of multiple streams. The superior flow manipulation capability of CeyeHao can facilitate broad applications from complex microstructure fabrication to precise reaction control.

• A trehalase-derived MAMP triggers LecRK-V–mediated immune responses in Arabidopsis
  Authors: Iino E.; Kadota Y.; Maki N.; Sato K.; Ono E.; Ishihama N.; Rugen-Hankey M.; Wei S.; Ngou B.; Kumakura N.; Schmid M.; den Akker S.; Suzuki T.; Uehara T.; Shirasu K.
  Published: 2025/8 (journal-article)
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  Plant-parasitic nematodes (PPNs) cause major agricultural losses worldwide, yet the molecular basis of plant immunity against these pathogens remains poorly understood. To investigate how plants recognize PPNs, we aimed to identify microbe-associated molecular patterns (MAMPs) from nematodes and the corresponding plant immune components. Because of the limited availability of material from obligate PPNs, we usedCaenorhabditis elegans, a free-living nematode, as a MAMP source.C. elegansextract activated MAMP-triggered immune responses inArabidopsisCol-0. Through chromatography-based purification, we identified a secreted trehalase and pinpointed a conserved peptide region essential for its MAMP activity. A corresponding peptide from root-knot nematode trehalase enabled the identification of lectin receptor kinases LecRK-V.5 and LecRK-V.6 as key components in immune induction. Notably, this peptide region is conserved across some phytophagous insects and fungal pathogens, with LecRK-Vs required for immune responses to these peptides, highlighting the role of LecRK-V–mediated mechanism for broad-spectrum pathogen detection via trehalase-derived peptides.

• eIF2A regulates cell migration in a translation-independent manner
  Authors: Jungfleisch J.; Mestre-Farràs N.; Gómez-Riera R.; Pourcelot O.; Bertrand E.; Halidi N.; Gebauer F.
  Published: 2025/8 (journal-article)
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  The RNA-binding protein eukaryotic translation initiation factor 2A (eIF2A) is an alternative translation initiation factor shown to drive tumor formation by facilitating translation from near-cognate initiation codons. Here, we uncover a function for eIF2A in regulating cell migration in a manner independent of overt control of translation. Using a melanoma cell model consisting of nontumoral melanocytic Mel-ST cells and their metastatic counterpart obtained byH-Rastransformation, we unexpectedly find minimal effects of eIF2A depletion on translation. Interactome studies identified centrosomal proteins as major binding partners of eIF2A. We found that eIF2A colocalizes with the centrosome, enhances centrosome composition, and promotes centrosome orientation during cell migration. Migration requires the C-terminal disordered region of eIF2A, involved in mRNA binding. Interaction with mRNA, however, does not require ongoing translation. These findings reveal a role for eIF2A in centrosome dynamics beyond its traditional function in translation.

• Flexoelectric manipulation of ferroelectric polarization in self-strained tellurium
  Authors: Yan Y.; Liang X.; Wang L.; Zhang Y.; Zhou J.; Wang W.; Zhang Z.; Zhou Y.; Firdous I.; Lai Z.; Wang W.; Xie P.; Xiong Y.; Daoud W.; Fan Z.; Shin D.; Yang Y.; Lu Y.; Zeng X.; Meng Y.; Ho J.
  Published: 2025/8 (journal-article)
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  Beyond conventional ferroelectric compounds, the realization of single-element ferroelectricity expands the scope of ferroelectric materials and diversifies polarization mechanisms. However, strategies for manipulating ferroelectric dipoles in elemental ferroelectrics remain underexplored, limiting their broader applications. Here, we introduce a universal flexoelectric manipulation strategy to tune the ferroelectric and piezoelectric polarization of one-dimensional self-strained tellurium (Te) ferroelectrics. A substantial flexoelectric field of 9.55 microcoulombs per square centimeter was observed in self-strained Te, inducing a polarization rotation of 18°, comparable to the typical 15° rotation in ferroelectric PbTiO3compounds. This substantial polarization rotation enhances ferroelectric coercivity by 165% and piezoelectric responses by 75% compared to unstrained Te. Moreover, the flexoelectric manipulation of ferroelectric polarization demonstrated improved energy harvesting performance at the device level, surpassing most existing counterparts. Our findings highlight the crucial role of flexoelectricity-ferroelectricity coupling in developing high-performance single-element electromechanical devices and ferroelectronics.

• GTP hydrolysis triggers membrane remodeling by AMPH-1
  Authors: Gai W.; Wang Y.; Martin B.; Zhang J.; Carr C.; Rye H.
  Published: 2025/8 (journal-article)
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  Membrane-enclosed transport carriers return biological molecules from the recycling endosome to the plasma membrane using a mechanism that is not well understood. InCaenorhabditis elegans, the formation of carriers from the recycling endosome requires the amphiphysin protein AMPH-1. Recently, we found that purified AMPH-1 is sufficient for tubulation and vesiculation of liposomes in a mechanism that is regulated by guanine nucleotides. Here, we propose a model linking guanosine 5′-triphosphate (GTP) binding and hydrolysis to the membrane binding and tubulation required for transport carrier formation. We find that GTP binding stabilizes interactions between AMPH-1 and the membrane through amphipathic, amino-terminal α helices, which are found at the tips of the arc-shaped, homodimeric structure. By contrast, in the posthydrolysis, guanosine diphosphate–bound state, these helices are repositioned to interact with the amino-terminal helices of other homodimers, to form an oligomeric AMPH-1 lattice that tubulates the membrane, in preparation for carrier formation by membrane fission.

• Temperature extremes impact mortality and morbidity differently
  Authors: Gould C.; Heft-Neal S.; Heaney A.; Bendavid E.; Callahan C.; Kiang M.; Graff Zivin J.; Burke M.
  Published: 2025/8 (journal-article)
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  Increased temperature-related mortality is expected to significantly contribute to future economic damages from climate change, with declines in cold-related deaths outweighed by increases in heat-related deaths. While temperature-mortality relationships are well-documented, the effects of climate change on morbidity are less understood. Using data on emergency department (ED) visits, hospital admissions, mortality, and daily temperatures across California from 2006 to 2017, we find distinct differences in the temperature-response functions of these health outcomes, influenced by age distribution and underlying causes of morbidity and mortality. These differential responses fundamentally shape the burden of future climate change: We project that while future warming will increase ED visits, mortality will decrease due to fewer cold extremes. These results underscore the need to quantify temperature-morbidity responses to fully understand and anticipate the health impacts of climate change and suggest that local declines in mortality due to warming can mask economically meaningful increases in temperature-driven morbidity and health care utilization.

• Magnetically induced magnetosome chain (MAGiC): A biogenic magnetic-particle-imaging tracer with high performance and navigability
  Authors: Li L.; Zhao C.; Zhao Z.; Han D.; Liao Y.; Liu Y.; Liu S.; Jia X.; Tian J.; Liu Q.; Feng X.; Tian J.
  Published: 2025/8 (journal-article)
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  Magnetic particle imaging (MPI) enables real-time, sensitive, and quantitative visualization of tracer distribution, augmenting the capability of in vivo imaging technologies. Previous MPI tracer research has predominantly focused on superparamagnetic nanoparticles, whose suboptimal sigmoidal magnetization curves limit their spatial resolution. Here, we introduce the magnetically induced magnetosome chain (MAGiC), a superferromagnetic MPI tracer, demonstrating a 25-fold improvement in resolution in the excitation direction and an order of magnitude improvement in signal intensity compared to the commercial tracer VivoTrax+. Under a gradient field of 4 tesla per meter, the resolution in the excitation direction reached 80 micrometers. Furthermore, MAGiC can be accurately manipulated using magnetic fields, making it an MPI-trackable microrobot. We have elucidated the mechanisms underlying MAGiC’s superior performance and validated its effectiveness in vitro and in vivo. As a high-performance MPI tracer and microrobot, MAGiC holds tremendous potential for various applications, such as cell tracking, image-guided drug delivery, and therapeutic interventions.

• LARGE protein drives activity-induced homeostatic resetting
  Authors: Seo B.; Kim H.; Tuong C.; Kim H.; Dustov F.; Lee S.; Choi S.; Kang M.
  Published: 2025/8 (journal-article)
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  In the brain, memory can be coded as relative differences in synaptic strength produced by Hebbian plasticity [e.g., long-term potentiation (LTP)]. However, changes in neuronal activity, including the saturation of synaptic strength by the positive-feedback nature of Hebbian plasticity, could deteriorate the encoded memory. Homeostatic plasticity is thought to contribute to the stability of the encoded memory by maintaining the relative differences in synaptic strength against persistent destabilizing changes in neuronal activity. However, it remains unclear how and when these two types of plasticity work together in the context of memory. Here, we have demonstrated that LARGE, a protein associated with intellectual disability, drives homeostatic resetting several hours after LTP by down-regulating AMPA-receptor trafficking via the Golgi apparatus. LARGE deficiency impairs long-term memory formation in mice. Our study reveals a potential molecular mechanism underlying the stability of memory mediated by cross-talk between Hebbian and homeostatic plasticity.

• Laser writing of spin defects in polymers
  Authors: Qin Y.; Guo H.; Wu D.; Ma Y.; Li X.; Wen H.; Li Z.; Ma Z.; Tian H.; Tang J.; Liu J.
  Published: 2025/8 (journal-article)
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  Technologies based on quantum effects of spin defects, such as computation, communication, sensing, and anticounterfeiting, have developed rapidly. However, limited by specific crystal structure required for spin defects, wide extension of their application faces challenges. A notable challenge is fabricating spin defects in general-purpose, low-cost amorphous materials such as polymers. Here, we propose an in situ laser–induced fabrication strategy of spin defects from polymers based on manipulation of main and side chains of polymers (MMSCP). By using 17 laser parameters and 8 polymers, we successfully fabricated silicon carbide spin defects derived from material mismatches. ODMR contrast and linewidth are consistently above 0.15% and below 54 megahertz, respectively. Benefiting from minimal damage of laser direct writing and stable covalent bonding, MMSCP effectively fabricates spin defects in manufactured microfluidic devices, cardiac patches, and medicine bottles and applies them to sensing and anticounterfeiting. Overall, MMSCP represents a paradigm that revolutionizes the application scheme of spin defects.

• Spinal motor neuron development and metabolism are transcriptionally regulated by nuclear factor IA
  Authors: Gauberg J.; Jenkins S.; Moreno K.; Jayaraman K.; Abumeri S.; Salazar A.; Meharena H.; Glasgow S.
  Published: 2025/8 (journal-article)
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  Neural circuits governing all motor behaviors in vertebrates rely on the proper development of motor neurons and their precise targeting of limb muscles. Transcription factors are essential for motor neuron development, regulating their specification, migration, and axonal targeting. While transcriptional regulation of the early stages of motor neuron specification is well established, much less is known about the role of transcription factors in the later stages of maturation and muscle targeting. Defining the molecular mechanisms of these later stages is critical for elucidating how motor circuits are constructed. Here, we demonstrate that the transcription factor nuclear factor IA (NFIA) is required for motor neuron positioning, axonal branching, and neuromuscular junction formation. Moreover, we find that NFIA is required for proper mitochondrial function and adenosine triphosphate production, providing an important link between transcription factors and metabolism during motor neuron development. Together, these findings underscore the critical role of NFIA in instructing the assembly of spinal circuits for movement.

• Neuronal Reg3β/macrophage TNF-α–mediated positive feedback signaling contributes to pain chronicity in a rat model of CRPS-I
  Authors: Nie H.; Liu B.; Yin C.; Dong Z.; Pan Y.; Li P.; Hu Q.; Wang J.; Tai Y.; Shao X.; Tian G.; Wang C.; Fang J.; Liu B.
  Published: 2025/8 (journal-article)
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  Complex regional pain syndrome type I (CRPS-I) develops after an initial injury. It causes prolonged pain that persists beyond the usual expected time for tissue healing. Mechanisms underlying pain chronicity of CRPS-I remain unknown. Here, we identified the presence of long-lasting infiltration of macrophages in local dorsal root ganglia (DRG) of a rat model of CRPS-I. We demonstrate that regenerating islet-derived 3β (Reg3β) is specifically produced by DRG neurons upon model establishment and functions as an important signaling molecule to drive proinflammatory macrophage infiltration in local DRG. Infiltrated macrophages produce TNF-α, which causes hyperexcitability of nociceptive DRG neurons and reciprocally promotes Reg3β overexpression and secretion from DRG neurons to recruit more macrophages. Our work reveals a positive feedback signaling conveyed by neuronal Reg3β/macrophage TNF-α that contributes to neuroinflammation in DRG, resulting in persistent pain in a rat model of CRPS-I. This finding provides insights into the neuroimmune interaction in local DRG that contributes to pain chronicity of CRPS-I.

• Childhood nutritional stress and later-life health outcomes in medieval England: Evidence from incremental dentine analysis
  Authors: DeWitte S.; Beaumont J.; Walter B.; Towers J.; Brennan E.
  Published: 2025/8 (journal-article)
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  Numerous studies have revealed links between prenatal/early-life stress and elevated morbidity and risks of mortality later in life. Given the number of subsistence crises in medieval England, this study uses stable isotopic, demographic, and paleopathological data from human skeletal remains (n= 275) to assess associations between early-life nutritional stress and health outcomes before, during, and after the Black Death in London and rural Lincolnshire approximately 1000 to 1540 CE. Our results suggest that survivors of early-life nutritional stress were resilient with respect to causes of death in childhood, adolescence, and early adulthood. Ultimately, however, early-life nutritional stress was associated with the presence of skeletal biomarkers of stress and elevated mortality in middle and late adulthood in the medieval period, consistent with models from developmental biology. We find that the prevalence of nutritional stress increased before the Black Death and decreased afterward. Understanding the long-term consequences of early-life nutritional stress can offer insights on the health trajectories of historical populations.

• Erratum for the Research Article “Brain injury accelerates the onset of a reversible agerelated microglial phenotype associated with inflammatory neurodegeneration” by R. Ritzel et al .
  Authors: None
  Published: 2025/8 (journal-article)
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• Structural determinants of G protein subtype selectivity at the serotonin receptor 5-HT1A
  Authors: Warren A.; Zilberg G.; Abbassi A.; Abraham A.; Yang S.; Wacker D.
  Published: 2025/8 (journal-article)
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  Activation of the serotonin receptor 5-HT1A has been shown to regulate mood and cognition, making 5-HT1A an important target in the treatment of anxiety, depression, and psychosis. Although the receptor signals through inhibitory G proteins, more work is necessary to understand differences in transducer coupling and its relation to functional activity. To develop a molecular understanding of the differences underlying transducer coupling and activation, we performed structure-activity relationship studies of 5-HT1A with distinct G proteins. Through a combination of in vitro assays, we identified a potent partial agonist that selectively engages a G protein subtype. We further investigated the differences in G protein engagement at 5-HT1A with cryo–electron microscopy, determining structures of 5-HT1A bound to distinct ligands and G protein subtypes. Combined with subsequent structure-guided mutagenesis and signaling assays, our studies uncover both orthosteric and allosteric determinants of agonist-specific stimulation of distinct transducers.

• Insights into the genetic basis of bilateral head asymmetry in a scale-eating cichlid fish
  Authors: Tian X.; Li M.; Meyer A.
  Published: 2025/8 (journal-article)
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  Almost all animals are bilaterally symmetrical, and only rarely is this universality broken and maintained as a stable polymorphism. One such case isPerissodus microlepis, a scale-eating cichlid fish endemic to Lake Tanganyika. This species is polymorphic with left- or right-headed morphs, each specialized for scraping scales from the opposite side of their prey. This polymorphism is stably maintained around a 50:50 ratio and is likely driven by negative frequency–dependent selection, a classic form of balancing selection. Using a genome-wide dataset, including a de novo haplotype-resolved reference genome, whole-genome sequences, and microcomputed tomography scans of 102 individuals, we identified 72 genetic loci linked to head asymmetry. Nearby genes are enriched for roles in symmetry establishment, facial morphology, and nervous system function, with evidence suggesting that balancing selection maintains this diversity. Our study expands our understanding of the genetic basis of head asymmetry and provides candidate genes for further research.

• Ambient catalyst-free conversion of methane to methanol by water radical cations
  Authors: Zhang X.; Su R.; Duan M.; Chen X.; Jia B.; Chingin K.; Balabin R.; Wang J.; Zhang W.; Zhang X.; Chen H.
  Published: 2025/8 (journal-article)
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  Methane combustion contributes 30% to global warming, making its conversion to cleaner chemicals a critical challenge. Here, we report a catalyst-free ambient conversion of methane to methanol with a remarkable yield exceeding 650 millimoles per hour and a high conversion rate of ~35%, achieved using in situ–generated water dimer radical cations,(H2O)2+·, in a specially designed batch reactor operating under mild conditions. In a single run, the reactor was typically operated for 10 minutes. The atom efficiency for hydrogen in our approach for methanol synthesis is ~67%. Hydrogen gas is the by-product, produced at a rate of over 2 millimoles per hour. Compared to the previously reported catalytic methods, our production yields are up by between 102and 106times depending on the literature method. This breakthrough enables clean, energy-efficient methane conversion without unwanted oxidation by-products, offering substantial environmental and economic benefits beyond combustion.

• Revealing rhythm categorization in human brain activity
  Authors: Barbero F.; Lenc T.; Jacoby N.; Polak R.; Varlet M.; Nozaradan S.
  Published: 2025/8 (journal-article)
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  Humans across cultures show an outstanding capacity to perceive, learn, and produce musical rhythms. These skills rely on mapping the infinite space of possible rhythmic sensory inputs onto a finite set of internal rhythm categories. What is the nature of the brain processes underlying rhythm categorization? We used electroencephalography to measure brain activity as human participants listened to a continuum of rhythmic sequences characterized by repeating patterns of two interonset intervals. Using frequency and representational similarity analyses, we show that brain activity does not merely track the temporal structure of rhythmic inputs but, instead, produces categorical representation of rhythms. These neural rhythm categories arise automatically, independent of any motor- or timing-related tasks, yet exhibit strong similarity with categorization observed in overt behavior. Together, these results and methodological advances constitute a critical step toward understanding the biological roots and diversity of musical behaviors across cultures.

• Virtual staining of label-free tissue in imaging mass spectrometry
  Authors: Zhang Y.; Huang L.; Pillar N.; Li Y.; Li Y.; Migas L.; Van de Plas R.; Spraggins J.; Ozcan A.
  Published: 2025/8 (journal-article)
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  Imaging mass spectrometry (IMS) enables untargeted, highly multiplexed mapping of molecular species in biological tissue with unparalleled chemical specificity and sensitivity. However, most IMS platforms lack microscopy-level spatial resolution and cellular morphological contrast, necessitating subsequent histochemical staining, microscopic imaging, and advanced image registration to correlate/link molecular distributions with specific tissue features and cell types. We present a diffusion model–based virtual histological staining approach that enhances spatial resolution and digitally introduces cellular morphological contrast into mass spectrometry images of label-free human tissue. Blind testing on human kidney tissue demonstrated that the virtually stained images of label-free samples closely match their histochemically stained counterparts (with periodic acid–Schiff staining), showing high concordance in identifying key renal pathology structures despite using IMS data with 10-fold larger pixel size. Additionally, our approach uses optimized noise sampling during the diffusion model’s inference to achieve reliable and repeatable virtual staining. We believe this virtual staining method will open avenues for IMS-based biomedical research.

• Climate change drives shifts in straddling fish stocks in the world’s ocean
  Authors: Palacios-Abrantes J.; Santos B.; Frölicher T.; Reygondeau G.; Sumaila U.; Wabnitz C.; Cheung W.
  Published: 2025/8 (journal-article)
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  Climate-induced distribution changes are particularly challenging for fisheries targeting fish populations shared between exclusive economic zones (EEZs) and the high seas, known as straddling stocks. Here, we combine multiple datasets and ecosystem modeling to identify the presence of straddling stocks worldwide and consider the management implications of climate change–driven shifts. We identify 347 straddling stocks across 67 species, including both highly migratory and less mobile species. Our results suggest that regardless of the climate change scenario, at least 37% and 54% of stocks are projected to shift between EEZs and the high seas, by 2030 and 2050, respectively. More stocks are expected to shift toward the high seas, and highly migratory stocks are projected to shift across Regional Fisheries Management Organizations (RFMOs). Coastal states and RFMOs require to revise governance frameworks to support sustainable and equitable adaptation to shifting stocks. Developing such strategies requires cooperation between management bodies within EEZs and the high seas.