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Neuronal morphology governs how neurons connect, integrate, and process information, offering critical insights into the functional architecture of the brain. Characterizing the three-dimensional (3D) morphology of individual neurons is key not only for mapping circuit connectivity but also for understanding the cellular diversity that emerges during development. Neural organoids are valuable models of human brain development and disease, yet their morphological complexity remains poorly characterized despite advances in single-cell transcriptomics. Here, we use 3D confocal imaging and manual reconstruction of 735 neurons to analyze forebrain (dorsal and ventral) and thalamic (dorsal and ventral) organoids, as well as forebrain, thalamic, and corticothalamic assembloids. We find that organoids and assembloids exhibit distinct morphologies resembling fetal brain neurons, including immature pyramidal-like, double-bouquet, and bushy-like neurons. Interregional assembloids show greater neuronal morphological complexity than individual organoids, with more extensive dendritic branching, longer projections, and diverse soma shapes. Corticothalamic assembloids further display features of emerging connectivity. We observe dendritic spines with excitatory and inhibitory profiles and varicosities, indicative of maturing synaptic architecture. Together, our work makes an initial effort in describing the diversity of neuronal morphology in human neural organoids and assembloids. It further establishes structural phenotyping as a critical dimension for validating human neural models and underscores their value for modeling morphofunctional disorders.
in bioRxiv: Neuroscience on 2025-10-25 00:00:00 UTC.
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Although clinical and experimental evidence highlight the role of the thalamus in voluntary movement production, the involvement of the thalamus in complex motor tasks such as speech production remains to be elucidated. The present study examined neural activity within the bilateral thalamus in 13 participants (seven females) with essential tremor undergoing awake deep brain stimulation implantation surgery, using three speech tasks of varied complexity [vowel vocalization, a diadochokinetic task (DDK), and sentence repetition]. Low-frequency neural activity (delta/theta band) activity was significantly increased during sentence and DDK compared with vowel vocalization in the bilateral motor thalamus and, to a lesser extent, increased for sentence repetition compared with DDK. Moreover, there was prominent prespeech beta band activity, with a greater decrease in the power of beta activity for sentence compared with DDK and vowel vocalization. The greater low-frequency activity in more complex speech tasks may reflect the allocation of additional cognitive resources to monitor the execution of speech motor plans through cortico–thalamo–cortical pathways in a temporally precise manner. The greater decrease in the power of beta activity prior to the onset of sentence repetition may imply greater involvement of the bilateral thalamus in the planning of complex speech tasks. These findings provide new insights into the role of the bilateral thalamus in speech production and may have clinical implications for neurological disorders that affect speech production.
in eNeuro on 2025-10-24 16:30:41 UTC.
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Aberrant dopamine transmission is a hallmark of several psychiatric disorders. Dopamine neurons in the ventral tegmental area (VTA) display distinct activity states that are regulated by discrete afferent inputs. For example, burst firing requires excitatory input from the mesopontine tegmentum, while dopamine neuron population activity, defined as the number of spontaneously active dopamine neurons, is thought to be dependent on inhibitory drive from the ventral pallidum (VP). Rodent models used to study psychiatric disorders, such as psychosis, consistently exhibit elevated dopamine neuron population activity, due to decreased tonic inhibition from the VP. However, it remains unclear whether the VP can modulate all dopamine neurons or if only a specific subset of VTA dopamine neurons receive innervation from the VP to be recruited as required. This knowledge is critical for understanding dopamine regulation in normal and pathological conditions. Here, we used in vivo electrophysiology in male and female rats to record VTA dopamine neurons inhibited by electrical stimulation of the VP. Specifically, VP stimulation inhibited ~22% of spontaneously active dopamine neurons; however, activation of the ventral hippocampus, a modulator of VTA population activity, increased the proportion to ~48%. This increase suggests that VP selectively modulates a subset of dopamine neurons that can be recruited by afferent activation. Anterograde monosynaptic tracing revealed that approximately half of the VTA dopamine neurons receive input from the VP. Taken together, we demonstrate that a subset of VTA dopamine neurons receives monosynaptic input from the VP, providing valuable information regarding the regulation of VTA neuron activity.
in eNeuro on 2025-10-24 16:30:41 UTC.
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by Jeremy Charlier, Zeinab Sherkatghanad, Vladimir Makarenkov
Transfer learning has emerged as a powerful tool for enhancing predictive accuracy in complex tasks, particularly in scenarios where data is limited or imbalanced. This study explores the use of similarity-based pre-evaluation as a methodology to identify optimal source datasets for transfer learning, addressing the dual challenge of efficient source-target dataset pairing and off-target prediction in CRISPR-Cas9, while existing transfer learning applications in the field of gene editing often lack a principled method for source dataset selection. We use cosine, Euclidean, and Manhattan distances to evaluate similarity between the source and target datasets used in our transfer learning experiments. Four deep learning network architectures, i.e. Multilayer Perceptron (MLP), Convolutional Neural Networks (CNNs), Feedforward Neural Networks (FNNs), and Recurrent Neural Networks (RNNs), and two traditional machine learning models, i.e. Logistic Regression (LR) and Random Forest (RF), were tested and compared in our simulations. The results suggest that similarity scores are reliable indicators for pre-selecting source datasets in CRISPR-Cas9 transfer learning experiments, with cosine distance proving to be a more effective dataset comparison metric than either Euclidean or Manhattan distances. An RNN-GRU, a 5-layer FNN, and two MLP variants provided the best overall prediction results in our simulations. By integrating similarity-based source pre-selection with machine learning outcomes, we propose a dual-layered framework that not only streamlines the transfer learning process but also significantly improves off-target prediction accuracy. The code and data used in this study are freely available at: https://github.com/dagrate/transferlearning_offtargets.
in PLoS Computational Biology on 2025-10-24 14:00:00 UTC.
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by Hao Zhu, Donna K. Slonim
A major challenge in working with single-cell RNA sequencing data is the prevalence of “dropout,” when some transcripts’ expression values are erroneously not captured. Addressing this issue, which produces zero-inflated count data, is crucial for many downstream data analyses including the inference of gene regulatory networks (GRNs). In this paper, we introduce two novel contributions. First, we propose Dropout Augmentation (DA), a simple but effective model regularization method to improve resilience to zero inflation in single-cell data by augmenting the data with synthetic dropout events. DA offers a new perspective to solve the “dropout” problem beyond imputation. Second, we present DAZZLE, a stabilized and robust version of the autoencoder-based structure equation model for GRN inference using the DA concept. Benchmark experiments illustrate the improved performance and increased stability of the proposed DAZZLE model over existing approaches. The practical application of the DAZZLE model on a longitudinal mouse microglia dataset containing over 15,000 genes illustrates its ability to handle real-world single cell data with minimal gene filtration. The improved robustness and stability of DAZZLE make it a practical and valuable addition to the toolkit for GRN inference from single-cell data. Finally, we propose that Dropout Augmentation may have wider applications beyond the GRN-inference problem. Project website: https://bcb.cs.tufts.edu/DAZZLE.
in PLoS Computational Biology on 2025-10-24 14:00:00 UTC.
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by Fabiano Baroni, Ben D. Fulcher
Neuronal activity is organized in collective patterns that are critical for information coding, generation, and communication between neural populations. These patterns are often described in terms of synchrony, oscillations, and phase relationships. Many methods have been proposed for the quantification of these collective states of dynamic neuronal organization. However, it is difficult to determine which method is best suited for which experimental setting and research question. This choice is further complicated by the fact that most methods are sensitive to a combination of synchrony, oscillations, and other factors; in addition, some of them display systematic biases that can complicate their interpretation. To address these challenges, we adopt a highly comparative approach, whereby spike trains are represented by a diverse library of measures. This enables unsupervised or supervised analysis in the space of measures, or in that of spike trains. We compile a battery of 122 measures of synchrony, oscillations, and phase relationships, complemented with 9 measures of spiking intensity and variability. We first apply them to sets of synthetic spike trains with known statistical properties, and show that all measures are confounded by extraneous factors such as firing rate or population frequency, but to different extents. Then, we analyze spike trains recorded in different species—rat, mouse, and monkey—and brain areas—primary sensory cortices and hippocampus—and show that our highly comparative approach provides a high-dimensional quantification of collective network activity that can be leveraged for both unsupervised and supervised characterization of firing patterns. Overall, the highly comparative approach provides a detailed description of the empirical properties of multineuron spike train analysis methods, including practical guidelines for their use in experimental settings, and advances our understanding of neuronal coordination and coding.
in PLoS Computational Biology on 2025-10-24 14:00:00 UTC.
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by Victor Hugo Mello, Jiri Wald, Thomas C Marlovits, Pablo Sartori
Proteins carry out cellular functions by changing their structure among a few conformations, each characterised by a different energy level. Therefore, structural changes, energy transformations, and protein function are intimately related. Despite its central importance, this relationship remains elusive. For example, while many hexameric ATPase motors are known to function using a hand-over-hand alternation of subunits, how energy transduction throughout the assembly structure drives the hand-over-hand mechanism is not known. In this work, we unravel the energetic basis of hand-over-hand in a model AAA+ motor, RuvB. To do so, we develop a general method to compute the residue-scale elastic pseudoenergy due to structure changes and apply it to RuvB structures, recently resolved through cryo-EM. This allows us to quantify how progression through RuvB’s mechanochemical cycle translates into residue-scale energy transduction. In particular, we find that DNA binding is associated with overcoming a high energy barrier. This is possible through inter-subunit transmission of energy, and ultimately driven by nucleotide exchange. Furthermore, we show how this structure-inferred energetic quantification can be integrated into a non-equilibrium model of AAA+ assembly dynamics, consistent with single-molecule biophysics measurements. Overall, our work elucidates the energetic basis for the hand-over-hand mechanism in RuvB’s cycle. Furthermore, it presents a generally applicable methodology for studying the energetics of conformational cycles in other proteins, allowing to quantitatively bridge data from structural biology and single-molecule biophysics.
in PLoS Computational Biology on 2025-10-24 14:00:00 UTC.
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by Weifan Wang, Xueyan Niu, Liyuan Liang, Tai-Sing Lee
A ubiquitous phenomenon observed along the ventral stream of the primate hierarchical visual system is the suppression of neural responses to familiar stimuli at the population level. The observation of the suppression of the neural response in the early visual cortex (V1 and V2) to familiar stimuli that are multiple times larger in size than the receptive fields of individual neurons implicates the plausible development of recurrent circuits for encoding these global stimuli. In this work, we investigated the neural mechanisms of familiarity suppression and showed that a recurrent neural circuit based on Hebbian learning, consisting of neurons with small and local receptive fields, can develop to encode specific global familiar stimuli robustly as a result of familiarity training. We proposed that the learned recurrent circuit implements a manifold transform. The recurrent circuit compresses the dimensions of nuisance variations of a familiar image in the neural response manifold relative to the dimensions for discriminating different familiar stimuli, resulting in increased robustness of the global stimulus representation against noise and other irrelevant perturbations. We demonstrate that a recurrent circuit implements the manifold transform using a mixed strategy of locally linear and globally nonlinear computations, where the local linear computation selectively redistributes recurrent gain to enhance concept discrimination. These results provide testable predictions for neurophysiological experiments.
in PLoS Computational Biology on 2025-10-24 14:00:00 UTC.
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by Huijuan Zhou, Jun Chen, Xianyang Zhang
Microbiome sequencing data are inherently sparse and compositional, with excessive zeros arising from biological absence or insufficient sampling. These zeros pose significant challenges for downstream analyses, particularly those that require log-transformation. We introduce BMDD (BiModal Dirichlet Distribution), a novel probabilistic modeling framework for accurate imputation of microbiome sequencing data. Unlike existing imputation approaches that assume unimodal abundance, BMDD captures the bimodal abundance distribution of the taxa via a mixture of Dirichlet priors. It uses variational inference and a scalable expectation-maximization algorithm for efficient imputation. Through simulations and real microbiome datasets, we demonstrate that BMDD outperforms competing methods in reconstructing true abundances and improves the performance of differential abundance analysis. Through multiple posterior samples, BMDD enables robust inference by accounting for uncertainty in zero imputation. Our method offers a principled and computationally efficient solution for analyzing high-dimensional, zero-inflated microbiome sequencing data and is broadly applicable in microbial biomarker discovery and host-microbiome interaction studies.
in PLoS Computational Biology on 2025-10-24 14:00:00 UTC.
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by Etienne Gosselin, Sophie Bagur, Sara Jamali, Jean-Luc Puel, Jérôme Bourien, Brice Bathellier
Early studies on orientation selectivity in the visual cortex have suggested that sensory systems generate new feature representations at specific processing stages. Many observations challenge this view, but in the absence of systematic, multistage measurements, the logic of how feature tuning emerges remains elusive. Here, using a generic approach based on representational similarity analysis with a noise-corrected population metric, we demonstrate in the mouse auditory system that feature representations evolve gradually with, in some cases, major, feature-specific improvements at particular stages. We observe that single frequency tuning is already fully developed in the cochlear nucleus, the first stage of processing, while tuning to higher-order features improves up to the auditory cortex, with major steps in the inferior colliculus for amplitude modulation frequency or noise bandwidth tuning and in the cortex for frequency modulation direction and for complex sound identity or direction. Moreover, we observe that intensity tuning is established in a feature-ependent manner, earlier for pure frequencies than for more complex sounds. This indicates that auditory feature computations are a mix of stepwise and gradual processes which together contribute to decorrelate sound representations.
in PLoS Biology on 2025-10-24 14:00:00 UTC.
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by Robin Rondon, Théaud Hezez, Julien Richard Albert, Shinichiro Hayashi, Bernadette Drayton-Libotte, Gloria Gonzalez Curto, Frédéric Auradé, Elie Balloul, Claire Dugast-Darzacq, Frédéric Relaix, Pascale Gilardi-Hebenstreit, Vanessa Ribes
Understanding how transcription factors regulate organized cellular diversity in developing tissues remains a major challenge due to their pleiotropic functions. We addressed this by monitoring and genetically modulating the activity of PAX3 and PAX7 during the specification of neural progenitor pools in the embryonic spinal cord. Using mouse models, we show that the balance between the transcriptional activating and repressing functions of these factors is modulated along the dorsoventral axis and is instructive to the patterning of spinal progenitor pools. By combining loss-of-function experiments with functional genomics in spinal organoids, we demonstrate that PAX-mediated repression and activation rely on distinct cis-regulatory genomic modules. This enables both the coexistence of their dual activity in dorsal cell progenitors and the specific control of two major differentiation programs. PAX promote H3K27me3 deposition at silencers to repress ventral identities, while at enhancers, they act as pioneer factors, opening and activating cis-regulatory modules to specify dorsal-most identities. Finally, we show that this pioneer activity is restricted to cells exposed to BMP morphogens, ensuring spatial specificity. These findings reveal how PAX proteins, modulated by morphogen gradients, orchestrate neuronal diversity in the spinal cord, providing a robust framework for neural subtype specification.
in PLoS Biology on 2025-10-24 14:00:00 UTC.
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Aim This study aims to compare the isokinetic strength of the Hamstrings against the Quadriceps for Football, Cricket, and Tennis among semi-professional athletes. Methodology An observational, cross-sectional study was conducted with the inclusion of participants between 18-40 years, both males and females having an active athlete profile playing Football, Cricket, and Tennis as semi-professional (competing in inter-collegiate, national-level tournaments in the UAE). The minimum duration for each sport was one hour per day and three to five times per week. A total of 66 participants were enrolled, with 22 participants in each group. The ISOMOVE isokinetic device was used to assess the strength of dynamically contracting Quadriceps concentrically against eccentric contraction of the Hamstring muscles to determine the functional ratio (H/Q ratio). Results Age-wise distribution of players showed predominant male participants with 77.3% of players in Football, 68.2% in Cricket, and 59.1% in Tennis. The comparison for the mean peaks of isokinetic strength for functional ratio suggested a statistically significant difference between the three sports (Football p<0.001, Cricket p=0.006, Tennis p =0.003). The findings suggested that the highest H/Q ratio was found in Football players with a mean value of 0.51±0.07, followed by Cricket and Tennis with a mean of 0.48±0.08 and 0.42±0.05, respectively (p<0.05). Conclusion The isokinetic strength testing for H/Q ratio was found to be higher in Football players, followed by Cricket and Tennis players for semi-professional athletes. The study concluded that the functional H/Q ratio varies between three similar sports as the demand on the target muscle would specifically vary. Thus, semi-professional players who play multiple games should consider enhancing FR for the Hamstring to the Quadriceps, besides the strength and training specific to sports, to avoid the risk of injuries.
in F1000Research on 2025-10-24 09:13:22 UTC.
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Human papillomavirus (HPV) is a common sexually transmitted infection that can lead to HPV-related cancers such as cervical cancer and other cancers such as anal, vaginal, and penile cancer. HPV rarely produces symptoms and cannot be cured or treated; therefore, vaccination is essential to protect against HPV and HPV-related diseases. However, young Aboriginal and Torres Strait Islander (hereafter, respectfully, ‘Aboriginal’) people are not receiving their HPV vaccine dose, resulting in missed opportunities to be protected from HPV-related cancers. Health promotion is a critical way to empower people to take ownership over and control their health and is a core function of public health. One way to deliver health promotion is through social media platforms. In recent COVID-19 times, we have seen the effect of social media on public health messaging, both positive and harmful. In particular, Instagram influencers have had a profound impact on pro- and anti-vaccination messages. Aboriginal adolescents aged 13-15 years old have strong engagement with social media platforms. Combining co-created health promotion messages with local ‘micro-Influencers’ is a novel way to improve HPV vaccination rates. The overall aim of this project is to improve the rates of HPV vaccination amongst young Aboriginal people. We will achieve this through: i) co-creation of health promotion messages, ii) developing and delivering a social media campaign and iii) evaluating the effectiveness of the campaign through an interrupted time-series design. We hypothesise that the co-creation of health promotion messages with young Aboriginal people and their families and utilising the skills of micro-Influencers to engage and influence their followers will result in improvements HPV vaccination rates amongst this population.
in F1000Research on 2025-10-24 09:10:08 UTC.
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Background The use of ensemble learning has been crucial for improving predictive accuracy in healthcare, especially with regard to critical diagnostic and classification problems. Ensemble models combine the strengths of multiple ML models and reduce the risk of misclassification, which is important in healthcare, where accurate predictions impact patient outcomes. Methods This study introduces the Gradient-Based Weight Optimized Ensemble Model (GBWOEM), an advanced ensemble technique that optimizes the weights of five base models: Decision Tree Classifier (DTC), Random Forest Classifier (RFC), Logistic Regression (LR), Multi-Layer Perceptron (MLP), and K-Nearest Neighbours (KNN), through optimizing the weights. Two variants, GBWOEM-R (random weight initialization) and GBWOEM-U (uniform weight initialization), were proposed and tested on five healthcare-related datasets: breast cancer, Pima Indians Diabetes Database, diabetic retinopathy debrecen, obesity level estimation based on physical condition and eating habits, and thyroid diseases. Results The test accuracy of the proposed models increased to 0.48-8.26% over the traditional ensemble models, such as Adaboost, Catboost, GradientBoost, LightGBM, and XGBoost. Performance metrics, including ROC-AUC analyses, confirmed the model’s efficacy in handling imbalanced data, highlighting its potential for advancing predictive consistency in healthcare applications. Conclusion The GBWOEM model improves the predictive accuracy and offers a reliable solution for healthcare applications even when dealing with the imbalance data. This strategy has the potential to ensure patient outcomes and diagnostic consistency in healthcare settings.
in F1000Research on 2025-10-24 09:01:35 UTC.
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This study introduces a robust numerical method for addressing the fourth-order Fisher-Kolmogorov reaction-diffusion equation, employing a combination of quintic Hermite splines and Richardson extrapolation. The proposed technique effectively transformed the original equation into a system of linear and nonlinear equations, achieving sixth-order convergence in space and fourth-order convergence in time. A thorough stability analysis confirmed the unconditional stability of the method, ensuring that the numerical solutions remained accurate throughout various perturbation scenarios. Extensive numerical experiments validated the performance of the method, revealing significant improvements in accuracy compared to existing approaches. The findings underscore the applicability of the method in mathematical biology and related fields, where the precise modelling of dynamic processes is crucial. Overall, this study contributes to the advancement of numerical techniques for complex differential equations, demonstrating enhanced reliability and precision in computational simulations.
in F1000Research on 2025-10-24 08:57:27 UTC.
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Science Advances, Volume 11, Issue 43, October 2025.
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Science Advances, Volume 11, Issue 43, October 2025.
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Science Advances, Volume 11, Issue 43, October 2025.
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Science Advances, Volume 11, Issue 43, October 2025.
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Science Advances, Volume 11, Issue 43, October 2025.
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Science Advances, Volume 11, Issue 43, October 2025.
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Science Advances, Volume 11, Issue 43, October 2025.
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Science Advances, Volume 11, Issue 43, October 2025.
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Science Advances, Volume 11, Issue 43, October 2025.
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Science Advances, Volume 11, Issue 43, October 2025.
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Science Advances, Volume 11, Issue 43, October 2025.
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Science Advances, Volume 11, Issue 43, October 2025.
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Science Advances, Volume 11, Issue 43, October 2025.
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Science Advances, Volume 11, Issue 43, October 2025.
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Science Advances, Volume 11, Issue 43, October 2025.
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Science Advances, Volume 11, Issue 43, October 2025.
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Science Advances, Volume 11, Issue 43, October 2025.
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Science Advances, Volume 11, Issue 43, October 2025.
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Science Advances, Volume 11, Issue 43, October 2025.
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Science Advances, Volume 11, Issue 43, October 2025.
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Science Advances, Volume 11, Issue 43, October 2025.
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Science Advances, Volume 11, Issue 43, October 2025.
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Science Advances, Volume 11, Issue 43, October 2025.
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Science Advances, Volume 11, Issue 43, October 2025.
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Science Advances, Volume 11, Issue 43, October 2025.
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Science Advances, Volume 11, Issue 43, October 2025.
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Science Advances, Volume 11, Issue 43, October 2025.
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Science Advances, Volume 11, Issue 43, October 2025.
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Science Advances, Volume 11, Issue 43, October 2025.
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Science Advances, Volume 11, Issue 43, October 2025.
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Science Advances, Volume 11, Issue 43, October 2025.
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Zhang et al. reveal that BST2-positive border astrocytes regulate astrocyte-microglia interactions after stroke. Genetic or antibody blockade of BST2 reduces these interactions and improves early functional outcomes, highlighting BST2 as a therapeutic target for brain repair.
in Neuron: In press on 2025-10-24 00:00:00 UTC.
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This study isolates extracellular vesicles and particles (EVPs) from hepatocellular carcinoma (HCC) cells. Biophysical and proteomic analyses demonstrate that sEVs and exomeres are distinctive entities. GALNS and MAN2B1 are identified as potential EM markers. HCC-derived EMs promote oncogenesis via several mechanisms, including PI3K/AKT/mTOR activation, cell cycle progression, and lipidomic dysregulation.
in Cell Reports: Current Issue on 2025-10-24 00:00:00 UTC.
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Sethi et al. define a molecular role for the ATP-dependent chromatin remodeler EP400, a core subunit of the NuA4 HAT complex, in preventing CENP-A mislocalization for chromosomal stability. Cells defective for EP400 function cause mislocalization of CENP-A to non-centromeric regions in a DAXX-dependent manner, leading to CIN phenotypes.
in Cell Reports: Current Issue on 2025-10-24 00:00:00 UTC.
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Tan et al. reveal that Bacillus velezensis biofilms accumulate Fe on roots, serving as Fe reservoirs to make Fe more accessible to the host plant. The bacterial siderophore bacillibactin plays a dual role by promoting Fe accumulation in the biofilms and activating plant Fe-deficiency responses.
in Cell Reports: Current Issue on 2025-10-24 00:00:00 UTC.
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Nature, Published online: 24 October 2025; doi:10.1038/d41586-025-03415-8
Scientists ‘draw’ crystal patterns using laser light.
in Nature on 2025-10-24 00:00:00 UTC.
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Nature, Published online: 24 October 2025; doi:10.1038/d41586-025-03421-w
Lessons learnt from research into the body’s internal clock could be key to unlocking blissful slumber.
in Nature on 2025-10-24 00:00:00 UTC.
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Nature, Published online: 24 October 2025; doi:10.1038/d41586-025-03368-y
A previously unknown strain left a stamp on modern varieties of the world’s most popular sugar source.
in Nature on 2025-10-24 00:00:00 UTC.
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Nature, Published online: 24 October 2025; doi:10.1038/d41586-025-03507-5
Andrew Robinson reviews five of the best science picks.
in Nature on 2025-10-24 00:00:00 UTC.
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Nature, Published online: 24 October 2025; doi:10.1038/d41586-025-03491-w
Beijing wants to double down on advanced semiconductor technologies, artificial intelligence and basic research.
in Nature on 2025-10-24 00:00:00 UTC.
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Nature, Published online: 24 October 2025; doi:10.1038/d41586-025-03508-4
Nobel prizewinner who helped to improve scientific relations between China and the United States.
in Nature on 2025-10-24 00:00:00 UTC.
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Nature, Published online: 24 October 2025; doi:10.1038/d41586-025-03390-0
Nature asked researchers who use artificial intelligence how its propensity for people-pleasing affects their work — and what they are doing to mitigate it.
in Nature on 2025-10-24 00:00:00 UTC.
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Nature, Published online: 24 October 2025; doi:10.1038/d41586-025-03487-6
Remains of some of the 300,000 soldiers who died on the retreat from Moscow reveal two bacterial diseases that probably added to the death count.
in Nature on 2025-10-24 00:00:00 UTC.
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Nature, Published online: 24 October 2025; doi:10.1038/d41586-025-03259-2
The real thing.
in Nature on 2025-10-24 00:00:00 UTC.
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Nature, Published online: 24 October 2025; doi:10.1038/d41586-025-03440-7
Nature surveyed scientists about their favourite cinematic moments to celebrate the International Year of Quantum Science and Technology.
in Nature on 2025-10-24 00:00:00 UTC.
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Nature Photonics, Published online: 24 October 2025; doi:10.1038/s41566-025-01783-1
Performance of solid-state triplet fusion upconversion films is enhanced by surface plasmons, intensity threshold is reduced by a factor of 17 and external quantum efficiency is enhanced by a factor of 19. A white-emitting organic light-emitting diode featuring upconverted blue emission—rather than blue electroluminescence—is demonstrated, with a colour rendering index of up to 86.2.
in Nature Photomics on 2025-10-24 00:00:00 UTC.
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Nature Communications, Published online: 24 October 2025; doi:10.1038/s41467-025-65418-3
Author Correction: Float-stacked graphene–PMMA laminate
in Nature Communications on 2025-10-24 00:00:00 UTC.
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Nature Communications, Published online: 24 October 2025; doi:10.1038/s41467-025-65397-5
Retraction Note: DNA-PK inhibition synergizes with oncolytic virus M1 by inhibiting antiviral response and potentiating DNA damage
in Nature Communications on 2025-10-24 00:00:00 UTC.
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Nature Communications, Published online: 24 October 2025; doi:10.1038/s41467-025-64460-5
Functional group interconversion, a pivotal synthetic technique for precise editing of molecular building blocks, is rare when facilitated by energy transfer catalysis. Herein, the authors report two instances of photochemical rearrangement of isonitriles, facilitated by energy transfer catalysis under visible light.
in Nature Communications on 2025-10-24 00:00:00 UTC.
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Nature Communications, Published online: 24 October 2025; doi:10.1038/s41467-025-64541-5
Candidate PET ligands targeting pathological TDP-43 aggregates are characterized by Vokali and colleagues in a series of human tissue, cell/animal model, and non-human primate experiments. Their preclinical data suggests favorable specificity and pharmacokinetic profiles of their two candidate tracers, which could translate into a disease-specific biomarker in TDP-43 proteinopathies.
in Nature Communications on 2025-10-24 00:00:00 UTC.
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Nature Communications, Published online: 24 October 2025; doi:10.1038/s41467-025-64554-0
The authors report lensless holography lithography with diffraction-limited resolution by proposing a phase-probability shaping mechanism to suppress speckle noise efficiently.
in Nature Communications on 2025-10-24 00:00:00 UTC.
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Nature Communications, Published online: 24 October 2025; doi:10.1038/s41467-025-64415-w
Tuning the electronic properties of nanocatalysts by doping them with uniformly dispersed hetero-metal atoms is an effective way to improve catalytic performance. Here, the authors show that weakening the Cu–O bond energy in CuO nanocatalysts boosts the efficiency of NH₃ oxidation.
in Nature Communications on 2025-10-24 00:00:00 UTC.
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Nature Communications, Published online: 24 October 2025; doi:10.1038/s41467-025-64071-0
Here, the authors report that Pseudomonas aeruginosa virulence in Drosophila is not immediate upon infection, but instead it is acquired through a priming process elicited by N-acetyl-glucosamine (NAG) that involves a morphological switch.
in Nature Communications on 2025-10-24 00:00:00 UTC.
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Nature Communications, Published online: 24 October 2025; doi:10.1038/s41467-025-64184-6
Volatile organic compounds are important analytes in medical diagnostics, with aldehydes forming a characteristic subclass. Here, the authors report that covalent nanopore sensing enables the targeted detection of aldehydes in mixtures through reversible thiol–aldehyde chemistry, offering a route to portable and low-cost analysis.
in Nature Communications on 2025-10-24 00:00:00 UTC.
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Scientific Data, Published online: 24 October 2025; doi:10.1038/s41597-025-05970-1
An HD-EEG Database to dissect Somatosensory Awareness from Task Relevance and Report
in Nature scientific data on 2025-10-24 00:00:00 UTC.
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Scientific Data, Published online: 24 October 2025; doi:10.1038/s41597-025-04980-3
Panel Data on Perceived Electoral Legitimacy using Two Independent Samples
in Nature scientific data on 2025-10-24 00:00:00 UTC.
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Scientific Data, Published online: 24 October 2025; doi:10.1038/s41597-025-05973-y
Annotated IFCB plankton images from the Mediterranean Sea
in Nature scientific data on 2025-10-24 00:00:00 UTC.
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Scientific Data, Published online: 24 October 2025; doi:10.1038/s41597-025-05974-x
A seven-year monitoring on fish community around the Qigu Lagoon located on the southwest coast of Taiwan
in Nature scientific data on 2025-10-24 00:00:00 UTC.
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Scientific Data, Published online: 24 October 2025; doi:10.1038/s41597-025-05913-w
A chromosome-level genome assembly of Myrmica angulata (Hymenoptera: Formicidae)
in Nature scientific data on 2025-10-24 00:00:00 UTC.
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Scientific Data, Published online: 24 October 2025; doi:10.1038/s41597-025-05963-0
The community acquired pneumonia endotypes and phenotypes dataset
in Nature scientific data on 2025-10-24 00:00:00 UTC.
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Scientific Data, Published online: 24 October 2025; doi:10.1038/s41597-025-05966-x
SIGNAL: Dataset for Semantic and Inferred Grammar Neurological Analysis of Language
in Nature scientific data on 2025-10-24 00:00:00 UTC.
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Communications Biology, Published online: 24 October 2025; doi:10.1038/s42003-025-08958-0
Motion sickness, a common response to unnatural motion, varies widely among individuals. A review of recent findings highlights the gut’s active role, including its brain-body pathways potentially driving pathophysiology and hinting at a more complex model than previously thought.
in Nature communications biology on 2025-10-24 00:00:00 UTC.
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The epigenetic adaptation of innate immune cells to inflammatory stimuli, or trained immunity, represents an evolutionarily conserved feature of host defense. Recent advances have revealed that such adaptations can occur at the level of hematopoietic stem and progenitor cells, resulting in long-lasting epigenetic reprogramming of the immune system. However, a comprehensive mechanistic understanding of these processes remains incomplete, limiting our capacity to predict or therapeutically manipulate the adaptive capacity of hematopoiesis. In this review, we survey the current literature to support a model of hematopoietic memory whose stimulus-specific nuances are shaped by specific cytokine environments and driven by the combinatorial activity of key transcription factors. Comparative analyses underscore the evolutionary conservation and essential biological roles of these factors, suggesting that trained immunity may reflect the strategic repurposing of ancient transcriptional programs for the purpose of enhancing host defense.
in eLife on 2025-10-24 00:00:00 UTC.
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The blood-brain barrier (BBB) interferes with the treatment of central nervous system disorders owing to the complexity of its structure and restrictive function. Thus, it is challenging to develop central nervous system drug delivery strategies. Specific mode electroacupuncture (EA) stimulation can effectively open the BBB in rats. Here, we used single-cell RNA sequencing (scRNA-seq) to comprehensively map the cell population in the Sprague-Dawley rat cerebral cortex. We identified 23 cell subsets and eight types of cells in the brain by cell annotation. scRNA-seq revealed transcriptional changes in the cerebral cortex under EA. Our findings offer valuable insights into the molecular and cellular modifications in the brain resulting from EA intervention and serve as a resource for drug delivery across healthy and diseased states. Innovative approaches to enhance BBB opening will lead to more effective therapeutic plans and enhanced drug delivery.
in eLife on 2025-10-24 00:00:00 UTC.
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Theoretical neurodevelopmental models implicate increases in dopamine (DA) function and limitations in neurocognitive control in risk-taking behavior, including substance use, during the transition from adolescence to adulthood. However, developmental relationships between DA, neurocognitive control, and the emergence of substance use are poorly understood. Here, we tested the role of basal ganglia tissue iron, reflecting DA neurophysiology, as well as impulsivity and inhibitory control in longitudinal developmental trajectories of substance use. We leveraged the National Consortium on Alcohol and NeuroDevelopment in Adolescence and Adulthood (NCANDA-A) cohort, a large, multisite longitudinal neuroimaging study of 807 participants (baseline ages 12-22 years old, 50% female, 1-9 annual visits per participant, 6164 sessions total). Substance use, inhibitory control, and tissue iron increased non-linearly during adolescence into young adulthood, concurrent with decreases in impulsivity. Non-linear Growth Mixture Models identified four common trajectories of substance use: low (no- or low levels of use across visits; 30% of participants), youth peak (peak use in adolescence/young adulthood followed by declines; 26%), adolescent increasing (early, steep linear increases in use from adolescence into adulthood; 17%), and adult increasing (low use in adolescence, followed by late linear increases into adulthood; 26%). We show that increased substance use was associated with a phenotype of high impulsivity, low inhibitory control, and low basal ganglia tissue iron, particularly in early adolescence in individuals who displayed youth peak patterns in substance use trajectories. These findings highlight that early developmental differences in DA-related neurobiology and associated impulsivity and cognitive control shape distinct trajectories of adolescent substance use, underscoring adolescence as a critical window for the early identification and implementation of neurodevelopmentally sensitive interventions for substance use disorders.
in bioRxiv: Neuroscience on 2025-10-24 00:00:00 UTC.
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Lipid abnormalities are emerging as key pathogenic mechanisms in neurodegenerative diseases such as Alzheimer's, Parkinson's and Lewy body dementia. Astrocytes in the brain provide APOE proteins and influence neuronal metabolism and health. Using live cell imaging and objective neurite imaging techniques, we show that following induction of cellular lipid (cholesterol and triglycerides) load by inhibiting the lysosomal cholesterol transport protein NPC1 in human neuron-astrocyte co-cultures, that human astrocytes CRISPR edited to be either APOE3 or 4 variants have different effects on rescuing dystrophic neurites, where axons and dendrites of nerve cells become disfigured. APOE3, but not APOE4 or APOEKO, astrocytes prevented cholesterol and lipid induced neurite damage in APOE4 neurons. In the media of APOE3 co-cultured astrocytes with neurons the HDL-like particles were larger and presumably more lipidated than equivalent APOE4 co-cultures. This discovery highlights that living APOE3 astrocytes control key biological mechanisms by physiologically enhancing lipid cellular homeostasis, that can rescue lipid-induced neurite structural abnormalities relevant to Alzheimer's disease and neurodegenerative diseases.
in bioRxiv: Neuroscience on 2025-10-24 00:00:00 UTC.
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Vocal production is a complex behavior across the animal kingdom that relies on coordinated motor and auditory networks. However, the contribution of sensory areas in vocal control remains poorly understood. Here, we investigated vocalization-related activity in a major auditory processing area in the mammalian brain, the auditory cortex. We recorded neuronal spike rates in an audio-vocal specialist, the bat Carollia perspicillata, which emits vocalizations to echolocate and for social communication. We found distinct spike patterns encoding echolocation and communication calls several hundred milliseconds before vocal onset. Neuronal activity not only contained information about the vocalization category, but also reflected temporal complexity, specifically the syllable amount in a communication sequence. These vocalization-specific firing patterns were dependent on the neuron's frequency receptive field. Our results indicate that single neurons in the auditory cortex not only process acoustic information but also encode the class and temporal structure of future vocal output.
in bioRxiv: Neuroscience on 2025-10-24 00:00:00 UTC.
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Microglia-neuron interactions play a central role in a variety of central nervous system disorders. Technologies using human induced pluripotent stem cells (hiPSCs) have been developed to model human brain cells with the goal to understand their function. To effectively study neuro-immune crosstalk and investigate microglial contributions to neuronal network development and function, both microglia and neurons should co-mature allowing for long-term interactions throughout their differentiation. Here, we present a co-maturation protocol that robustly generates glutamatergic neuronal networks containing human iPSC-derived microglia. We validated the long-term co-cultures using single-cell transcriptomics, imaging and neuronal activity readouts. We show that astrocytes were required for long-term survival of microglia and for their integration into neuronal networks. Our co-maturation approach induced the typical ramified microglia morphology and characteristic microglia-neuron interactions. Homeostatic markers like P2RY12 and TMEM119 and neuronal remodeling associated genes were upregulated compared to microglia monocultures, highlighting the necessity of the environment to generate and maintain the context-dependent microglia signature in vitro. In this manuscript, we include the full optimization process of our co-maturation approach, a comprehensive description of the protocol, practical guidelines and troubleshooting tips. Our co-maturation model provides a powerful tool to assess the role of human microglia in modulating neuronal function and development in health and disease.
in bioRxiv: Neuroscience on 2025-10-24 00:00:00 UTC.
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Humans make over a hundred thousand eye movements daily to gather visual information. But what determines where we look? Current computational models typically link gaze behaviour to visual features of isolated images, but we know that eye movements are also strongly shaped by cognitive goals: Observers gather information that helps them to understand, rather than just represent, the world. Within this framework, observers should focus more on information that updates one's understanding of the environment, and less on what is purely visually salient. Here we tested this hypothesis using a free-viewing paradigm of narratives where we experimentally manipulated the meaningfulness of temporal context by either presenting pictures in a coherent, i.e. correct, order, or in a temporally shuffled order. We developed a novel approach to quantify which visual information is semantically salient (i.e., important for understanding): we separately obtained language narratives for images in stories, and computed the contextual surprisal of visual objects using a large language model. The ability of this semantic saliency model in explaining gaze behaviour was compared to a state-of-the art model of visual saliency (DeepGaze-II). We found that individuals looked relatively more often and more quickly at semantically salient objects when images were presented in coherent compared to shuffled order. In contrast, visual salience did not better account for gaze behaviour in coherent than shuffled order. These findings highlight how internal contextual models guide visual sampling and demonstrate that language models could offer a powerful tool for capturing gaze behavior in richer, meaningful settings.
in bioRxiv: Neuroscience on 2025-10-24 00:00:00 UTC.
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Growing evidence suggests that synaptic weights in the brain follow heavy-tailed distributions, yet most theoretical analyses of recurrent neural networks (RNNs) assume Gaussian connectivity. We systematically study the activity of RNNs with random weights drawn from biologically plausible Levy alpha-stable distributions. While mean-field theory for the infinite system predicts that the quiescent state is always unstable---implying ubiquitous chaos---our finite-size analysis reveals a sharp transition between quiescent and chaotic dynamics. We theoretically predict the gain at which the finite system transitions from quiescent to chaotic dynamics, and validate it through simulations. Compared to Gaussian networks, finite heavy-tailed RNNs exhibit a broader gain regime near the edge of chaos, namely, a slow transition to chaos. However, this robustness comes with a tradeoff: heavier tails reduce the Lyapunov dimension of the attractor, indicating lower effective dimensionality. Our results reveal a biologically aligned tradeoff between the robustness of dynamics near the edge of chaos and the richness of high-dimensional neural activity. By analytically characterizing the transition point in finite-size networks---where mean-field theory breaks down---we provide a tractable framework for understanding dynamics in realistically sized, heavy-tailed neural circuits.
in bioRxiv: Neuroscience on 2025-10-24 00:00:00 UTC.
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Multidisciplinary evidence support a neurodevelopmental origin for schizophrenia, yet the mechanistic translation of known risk factors remains poorly understood. In this study, we leverage multi-lineage, forebrain-patterned organoids derived from monozygotic twins discordant for schizophrenia, integrating single-cell transcriptomic and epigenomic profiling to uncover disease-associated gene expression and chromatin accessibility topics. By constructing fate probability maps, we identify an accelerated developmental trajectory emerging from a distinct, schizophrenia-associated radial glia cell state, and reveal unique interactions among schizophrenia risk genes through unbiased multimodal analyses. Further, we confirm that schizophrenia-enriched states persist in differentiated lineages and disrupt synaptic programs, accompanied by molecular and cellular phenotypes mimicking observed disease pathology. Collectively, our findings delineate an early disruption in forebrain development, providing novel mechanistic insights into the origins of schizophrenia risk.
in bioRxiv: Neuroscience on 2025-10-24 00:00:00 UTC.
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Stathmin-2 (STMN2) is a microtubule associated protein that plays a role in the stability of microtubules of axons in the nervous system of animals. In this study we generated a novel zebrafish STMN2 knockout (KO) model. STMN2 is represented by two genes in the zebrafish genome: stmn2a and stmn2b. Using the CRISPR/Cas9 mutagenic system we selected founder fish lines harbouring frameshift mutations in both genes and bred these together to generate a double stmn2a and stmn2b KO model. Using these models, we observed increased developmental lethality in our double stmn2a and stmn2b KO model and impaired motor function at larval stages of development. Examination of the larval neuromuscular junction (NMJ) revealed a slight increase in the number of orphaned NMJs in trunk musculature as well as a reduction in amplitude of miniature endplate currents in our double stmn2a and stmn2b KO model. In a final series of experiments, we show impaired ventral root axon regrowth following transection in double stmn2a and stmn2b KO larvae. Our findings suggest that while not essential for motor axon development, loss of stmn2a and stmn2b expression perturbs the assembly of zebrafish NMJs during development resulting in a minor motor phenotype and impairs that ability to regenerate motor axons following injury.
in bioRxiv: Neuroscience on 2025-10-24 00:00:00 UTC.
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The dentate gyrus (DG) is thought to play a key role in the formation of dissociable memory representations for similar contexts. Neurons in the dentate gyrus (DG) receive highly processed spatial and nonspatial sensory information from the medial and lateral entorhinal cortices, respectively. Changes in spatially tuned firing patterns of DG place cells occur after spatial changes to an environment, but the degree to which DG place cells respond to ethologically relevant nonspatial stimuli is largely unknown. Spatial and nonspatial information is thought to be transmitted to the DG during discrete local field potential events called dentate spikes. Here, we tested the extent to which different spatial and nonspatial stimuli modulate place cell firing patterns and dentate spike dynamics. We performed extracellular recordings of DG place cells and local field potentials in rats of both sexes exploring a familiar spatial environment, in which social stimuli and nonsocial odors of varying ethological relevance were presented, and a novel spatial environment. As expected, DG place cells exhibited different firing patterns between familiar and novel environments. Remarkably, a small population of DG place cells changed their firing patterns when social but not nonsocial stimuli were presented in a familiar environment. Additionally, the occurrence of dentate spikes associated with lateral entorhinal cortex inputs increased during exploration of social but not nonsocial stimuli. Altogether, these results suggest that the DG preferentially responds to social stimuli at neuronal and network levels, providing novel insights into how spatial and nonspatial information is integrated in the DG.
in bioRxiv: Neuroscience on 2025-10-24 00:00:00 UTC.
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Central nervous system development requires parallel but interrelated processes of neural circuit assembly and vascularization. Intersecting between these two processes, the cell-adhesion G-protein coupled receptor Adgrl2 is expressed in select neuron populations where it has been found to localize and control the assembly of specific synaptic sites. Further, Adgrl2 is found to be expressed in select non-neuronal brain cells, where it is restricted to endothelial cells. Testing for Adgrl2 function in these cells, here we find that endothelial cell specific Adgrl2 deletion results in an impairment in cerebrovascular integrity. To understand how it might be possible for Adgrl2 to function independently in neuronal and endothelial contexts, we analyzed single-cell RNA sequencing datasets for differences in transcriptional identity between these cell classes. Doing so, we find that expression of Adgrl2 mRNA is subject to robust cell type-specific alternative splicing, resulting in distinct isoforms being produced in neurons compared to endothelial cells. Investigating the functional implication of this cell type-specific alternative splicing, we find that forced expression of the neuronal isoform of Adgrl2 in endothelial cells leads to alterations in cerebrovasculature properties. Morphologically, endothelial cells with the non-native neuronal Adgrl2 isoform induce the formation of ectopic glutamatergic synaptic contacts onto endothelial cells, indicating alternations in the cell-cell recognition process. Functionally, in direct contrast to endothelial Adgrl2 deletion, this genetic expression switch instead enhances blood brain barrier integrity. This overly restricted cerebrovascular function results in dysregulation of blood to cerebrospinal fluid homeostasis, enlargement of brain ventricles, and a higher likelihood in the development of hydrocephalus neurological disorder. As such, alternative splicing serves as a cell type specific mechanism that provides isoform specific Adgrl2 for discerning functions controlling neural circuit assembly and cerebrovascular homeostasis.
in bioRxiv: Neuroscience on 2025-10-24 00:00:00 UTC.
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Adeno-associated viruses (AAVs) are the vector of choice for gene delivery to the nervous system. While AAVs have a strong safety profile, recent studies show that AAV causes dendritic loss and synaptic weakening in mouse somatosensory cortex, impacts that are prevented by systemic administration of blockers of Toll-like receptor 9 (TLR9), an innate immunoreceptor that detects unmethylated cytosine-guanine (CpG) motifs. However, TLR9 blockers are immunosuppressive and costly. To realize AAV's full potential, it is critical to identify strategies to protect neurons without compromising immunity. Here we find that partially depleting CpG motifs from the AAV genome prevents AAV-induced dendritic loss and synaptic weakening. CpG depletion of transgene and intronic regions via codon-optimized synonymous mutations was protective and did not impair transgene expression in vivo. To facilitate the production and use of lower-CpG AAVs, we created a web-facing application, CpG-Assist Tool (CpG-AT), which allows researchers to quantify the CpG content of any sequence, explore the CpG content of commonly used AAV components, and generate CpG-depleted coding and non-coding sequences. This study identifies CpG depletion as a practical strategy to prevent AAV-induced neural circuit disruption, and provides tools to facilitate CpG reduction to enhance the safety and efficacy of AAV-mediated gene delivery.
in bioRxiv: Neuroscience on 2025-10-24 00:00:00 UTC.
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Remembering the temporal order of events is critical for episodic memory, allowing us to link individual events into sequences. While the medial temporal lobe and prefrontal cortex are essential for this process, the underlying neural mechanisms remain poorly understood. Here we characterized the representation of order information at the level of single neurons and field potentials recorded from human neurosurgical patients watching naturalistic videos of everyday events and later recalling the order and content of the events depicted. We found order-selective cells (OSCs) in the human hippocampus, amygdala, and orbitofrontal cortex that responded selectively to specific event orders, independent of event content or absolute time. OSCs exhibited transient theta phase precession following their preferred order during both memory encoding and retrieval, the strength of which predicted participants' order memory accuracy. During retrieval, OSC spike timing relative to theta varied with the relative position of their preferred event within the recalled event sequence, enabling selective retrieval of relevant events. These findings reveal a neural substrate for representing, encoding into and retrieving from memory absolute and relative ordinal relationships between discrete events. OSCs tile temporal space into discrete ordinal positions, thereby weaving episodic experiences into coherent temporal narratives.
in bioRxiv: Neuroscience on 2025-10-24 00:00:00 UTC.
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Understanding the neural mechanisms underlying disorders of consciousness (DoC) remains a major challenge, particularly in distinguishing limited awareness in minimally conscious state (MCS) and complete unawareness in unresponsive wakefulness syndrome, also coined vegetative state (UWS/VS). In this multicentre study, we fitted a biophysically informed corticothalamic neural field model to high-density EEG data from two large independent datasets, comprising 203 UWS patients, 270 MCS patients and 74 healthy controls. We then used the fitted parameters to simulate EEG time series on a per-subject basis and compared empirical and simulated complexity metrics. The model reliably captured the spectral features across different states of consciousness and revealed reduced corticothalamic integrity in DoC patients that was more pronounced in UWS than in MCS, supporting the mesocircuit hypothesis. Furthermore, the simulated EEG reproduced the complexity patterns of the empirical recordings, with permutation entropy emerging as a sensitive marker capable of distinguishing between MCS and UWS for both real and simulated time series.
in bioRxiv: Neuroscience on 2025-10-24 00:00:00 UTC.
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De novo CSNK2B variants are strongly associated with autism spectrum disorder (ASD) and early-onset epilepsy, yet in vivo therapeutic evidence and translatable biomarkers remain limited. We generated Csnk2b haploinsufficient (Csnk2b+/-) mice that recapitulate core clinical features: ASD-like social and cognitive deficits, heightened anxiety, spontaneous seizures, cortical and hippocampal structural compromise, and reduced PV-interneuron density with impaired cortical inhibition. Neonatal brain-wide AAV-PHP.eB-mediated CSNK2B replacement (hsyn or CAG promoters, retro-orbital P3) restored cortical/hippocampal structure, normalized neuronal numbers, prolonged survival, and ameliorated seizures and ASD-like behaviors with comparable efficacy across promoters. Critically, treatment also corrected quantitative EEG signatures that are directly deployable in human trials: theta and gamma band power were normalized, theta/gamma (and beta/gamma) ratios recovered, and inter-areal coherence and gamma-band effective connectivity were restored, indicating re-established excitation/inhibition balance and large-scale network coordination. These EEG endpoints constitute a compact, noninvasive biomarker panel of target engagement and physiological efficacy that can be harmonized with clinical EEG to support dose finding, early decision-making, and longitudinal monitoring in CSNK2B gene-therapy trials. Together, our data provide preclinical proof-of-concept that early AAV-mediated CSNK2B replacement is therapeutically effective and nominate band-limited EEG metrics as translational readouts to accelerate first-in-human studies for CSNK2B-linked neurodevelopmental disorders.
in bioRxiv: Neuroscience on 2025-10-24 00:00:00 UTC.
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The primate visual system is a hierarchical network of brain areas that transform retinal inputs into rich percepts. According to efficient neural coding principles, basic visual features such as orientation, which are already represented in early visual areas, should not be redundantly encoded in higher areas like V4 and inferotemporal (IT) cortex. We tested this hypothesis by quantifying orientation representation throughout the entire visual stream using functional Magnetic Resonance Imaging (fMRI) and multivoxel pattern analysis (MVPA) in macaque monkeys watching full-field gratings. Contrary to predictions from efficient coding, we found robust orientation information along the entire visual ventral stream from V1 to IT cortex. Orientation information was distributed in cortical and representational space, especially in IT. Voxels with multivariate responsiveness to faces, objects, and bodies carried more orientation information than highly category-selective voxels. They also displayed stronger connectivity within IT and with upstream areas V1-V4. These finding suggests the existence of functional "hubs" that integrate low- and high-level features through enhanced connectivity. This phenomenon generalized to deep convolutional neural network models with high brain similarity, underscoring the importance of hub-like units in hierarchical processing of complex inputs. Together, our results show that orientation re-emerges in IT cortex not through redundancy but as a computational byproduct of functional diversity and connectivity, propounding the existence of "hub" neurons that may support flexible, integrative visual processing beyond object recognition.
in bioRxiv: Neuroscience on 2025-10-24 00:00:00 UTC.
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The promiscuous ligand cannabidiol (CBD) shows promise as an analgesic, but its complex pharmacodynamics has made it difficult to identify its mechanism(s) of action. Numerous putative CBD receptors including cannabinoid receptors CB1 and CB2, as well as Trpv1 and Trpa1, the receptors for capsaicin and mustard-oil (AITC) respectively, have been proposed to contribute to CBD-mediated analgesia. Larval zebrafish have several attributes that lend themselves to inquiries into the biology of nociception. The neural circuits underlying nociception in zebrafish larvae are highly analogous to those found in higher vertebrates. Notably, the small size and optical clarity of zebrafish enable holistic evaluation of analgesic function utilizing behavioral and imaging platforms. Here we report that in larval zebrafish CBD serves both anti- and pro-nociceptive functions. Utilizing place aversion assays as a proxy for nociception, we found that low concentrations of CBD inhibit aversion to noxious chemical stimuli including AITC and acetic acid. Counterintuitively, we found that higher concentrations of CBD potentiated nocifensive behavior as measured by enhanced thermal aversion and increased locomotion. Knockdown of Trpa1b eliminated the algogenic effects of CBD while having no effect on its analgesic properties, as it abolished trpa1b+ sensory neuron responses to CBD, CBD-evoked thermal hypersensitivity, and increased locomotion in Trpa1b-null animals. Strikingly, CBD profoundly inhibited thermal aversion to noxious heat in Trpa1b-null animals but not in wildtype animals, indicating that CBD-mediated Trpa1b activation can oppose the analgesic properties of CBD. These studies provide a framework to investigate the genetic and neural substrates of CBD-mediated analgesia and nociception.
in bioRxiv: Neuroscience on 2025-10-24 00:00:00 UTC.
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Sequential sampling models of choice, such as the drift-diffusion model (DDM), are frequently fit to empirical data to account for a variety of effects related to accuracy/consistency, response time (RT), and sometimes confidence. However, no model in this class has been shown to account for the phenomenon known as choice-induced preference change, wherein decision makers tend to rate options higher after they choose them and lower after they reject them (and often choose the option that they had initially rated lower). Studies have reported choice-induced preference change for many decades, and the principal findings are robust. The resulting spreading of alternatives (SoA) in terms of their subjective value ratings is incompatible with traditional sequential sampling models, which consider the rated values of the options to be stationary throughout choice deliberation. Here, we propose that extending the basic DDM to incorporate independent attributes into the drift rate can allow this class of model to account for SoA. Critically, the extended model assumes that choice deliberation does not always involve the same set of attributes as is involved in individual evaluations of the same options. We show that this model can generate SoA (while simultaneously accounting for consistency and RT), as well as the relationships between SoA and choice difficulty, attribute disparity, and RT previously reported in the literature.
in bioRxiv: Neuroscience on 2025-10-24 00:00:00 UTC.
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The bladder is innervated by a complex network of sensory neurons that detect and transmit mechanical and chemical signals to the central nervous system, regulating both urine storage and voiding, as well as mediating sensations of bladder fullness and pain. While stretch-sensitive afferents within the bladder wall are known to monitor filling, the contribution of stretch-insensitive afferents that reside within the bladder mucosa to bladder sensation and function remains unclear. Here, we establish a novel mouse model of selective bladder mucosal afferent denervation using intravesical instillation of resiniferatoxin (RTX) to define the functional roles of these fibres in health and disease. We assessed the impact of mucosal denervation on sensory nerve activity and bladder function in healthy mice and in a model of urinary tract infection (UTI) induced by acute bacterial challenge with uropathogenic E. coli. We show that mucosa-innervating afferents do not influence bladder distension responses or voiding function under healthy conditions. In contrast, during UTI, these afferents become hypersensitive and serve as critical drivers of infection-induced pelvic pain and urinary frequency, responses that contribute to enhanced bacterial clearance. Together, these findings identify bladder mucosal afferents as key sensors of pathogenic challenge and reveal a previously unrecognised mechanism that drives behavioural responses to reduce the burden and extent of UTI.
in bioRxiv: Neuroscience on 2025-10-24 00:00:00 UTC.
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The study of inter-individual variability in animal behaviors during cognitive processes is crucial to better grasp the emergence of personality traits in healthy animals. Social experiences occurring at adolescence can affect the expression of the behavioural variability as it is a critical period of brain and cognitive plasticity. Here, we asked how individual variability of social profiles is shaped at adolescence and whether the profiles are associated with regional brain metabolites and gene expressions in the adult brain. At adolescence we determined a 'dominant' profile expressing more dominance, a 'submissive' profile expressing more submission and an 'explorer' profile showing more novelty exploration than social interaction. Adolescent social behaviors are conserved at adulthood. Our data suggest that dominance tendencies already present at adolescence are likely to stabilize throughout life, thus shaping future social behaviors. Our results show that social profiles are not related to sex and life environment. However, being more dominant, interactive and socially motivated shape dopaminergic olfactory activity at adolescence. Also, showing the explorer or submissive profiles is associated with an opposite serotonin pattern in the cerebellum, but a similar kynurenine pattern in the prefrontal cortex and cerebellum, thus pointing toward major neurotransmitter systems in key regions for brain health. This work opens new perspectives on the importance of studying social profiles early in life and the individual neurobiological associated features that could potentially predict individual vulnerability.
in bioRxiv: Neuroscience on 2025-10-24 00:00:00 UTC.
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Chronic consumption of drugs of abuse increases sensitivity of the dynorphin/kappa opioid receptor (KOR) stress system, which reduces striatal dopamine signaling and promotes drug taking. However, there is mixed evidence on how KOR-modulation of dopamine affects operant behavior in the absence of addiction. To address this gap, we injected dLight1.2 in the nucleus accumbens of male and female C57BL/6J mice and trained them to self-administer sucrose. Mice were injected with the KOR agonist U50,488H, with or without the KOR antagonist aticaprant, prior to each session. U50,488H did not affect dopamine responses during the lever press and did not alter total presses or consumption. The primary effects of KOR activation were to delay initiation of lever pressing, and to diminish the rapid ramp-up in dopamine seen before lever presses. The first lever press of each session was preceded by the largest dopamine ramp; however, ramp size did not correlate with latency under any condition. We further tested whether KOR-modulation of dopamine ramps affects behavior throughout the session. We found that the total amount of dopamine activity 10 seconds before the lever press predicted when the next lever press would occur, specifically after U50,488H injection. When the phasic peaks were subtracted from this to quantify a slower dopamine ramp, time to the next lever press could be predicted and this effect was strongest after U50,488H injection. As U50,488H reduces basal dopamine signaling, we propose that dopamine ramps prior to behavior have a larger signal-to-noise ratio during KOR activation. This relatively greater increase in dopamine from baseline could increase the salience of the decision to perform reward-associated actions, which may play a role in habitual behaviors like drug taking.
in bioRxiv: Neuroscience on 2025-10-24 00:00:00 UTC.
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The precise development of the visual system is driven by retinal waves, which are bursts of spontaneous activity that propagate across retinal neurons in a wave-like fashion. In mice, retinal waves begin embryonically and continue until eye opening at the end of the second postnatal week. During this time, the mechanisms for generating and propagating retinal waves are changing, thus causing retinal waves to exhibit highly dynamic spatiotemporal properties from one day to the next. Critically, the spatiotemporal properties of retinal waves have been shown to instruct the development of the visual system, including eye-specific segregation, retinotopic mapping, direction selectivity, and potentially retinal vascularization. Currently, there is no method for the automatic detection and high-throughput analysis of the spatiotemporal properties of retinal waves. To overcome this barrier, we have created a toolbox to automatically detect retinal waves and analyze their spatiotemporal properties from data collected using multielectrode arrays or calcium imaging. We apply this toolbox to enrich our understanding of retinal waves. First, we recapitulate and uncover novel dynamic spatiotemporal properties of retinal waves in the first two postnatal weeks. Second, we apply this toolbox on ultra long physiological recordings to demonstrate that the spatiotemporal properties of waves change throughout the day in an age-dependent manner. Third, we demonstrate that this toolbox can detect waves in the presence of pharmacological agents that increase the baseline firing of neurons, potentially enabling the discovery of novel factors that perturb retinal waves and visual development. Our toolbox is an intuitive interface that provides a systemized method to segregate and analyze retinal waves and other wave-like data.
in bioRxiv: Neuroscience on 2025-10-24 00:00:00 UTC.
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Objective. We investigate the possibility to disrupt motor activity via premotor and parietal cortex stimulation, by inducing cortical silent periods (cSPs) in the voluntarily activated upper limb. Methods. We analyzed data from 17 subjects with normal brain function, using navigated TMS (nTMS) on individual MR anatomies. We applied single-pulse biphasic stimulation at 120% of resting motor threshold (rMT) in blocks of 30 stimulations on each spot of a 10-16 point grid covering the inferior parietal and frontal lobes in the dominant hemisphere while participants performed voluntary submaximal contraction. Electromyography (EMG) was recorded bilaterally from intrinsic hand muscles. Results. We observed cSPs not preceded by a MEP in the contralateral hand in 16/17 participants. The maximum overlap, of individual areas where such MEP-independent cSPs could be evoked, corresponded to the ventral precentral gyrus (MNI coordinates: [x=-57, y=7, z=33]). In a subset of stimulus sites, MEP-independent cSPs were bilateral, with contralateral predominance. Canonical short-latency MEPs were observed in all patients, with maximum overlap over the primary motor cortex. We also observed rare contralateral long-latency (> 23 ms) MEP-like responses from peri-Rolandic TMS. Conclusions. MEP-independent cSPs are systematically elicitable in healthy participants They likely reflect interference with premotor representations of ongoing movements. They offer a novel possibility to investigate higher-order motor functions in the experimental and clinical neurosciences.
in bioRxiv: Neuroscience on 2025-10-24 00:00:00 UTC.
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Background: Ischemic stroke is a leading cause of mortality and disability worldwide, yet therapeutic options remain limited. Preclinical models play a crucial role in understanding stroke pathophysiology and evaluating potential treatments. This study aimed to provide a comprehensive characterization of the temporal evolution of ischemic injury induced by malonate intracerebral injection using multiparametric magnetic resonance imaging (MRI) combined with histological and molecular analysis. Methods: Focal ischemic lesions were induced by malonate injection in the striatum of rats. Lesion volume was monitored using T2-weighted MRI at multiple time points (Day 1, D7, D14, D28, and D56). Water content, reflecting vasogenic edema, was assessed via apparent diffusion coefficient (ADC) measurements, while vascular alterations were evaluated using blood volume fraction (BVF), vessel radius, and oxygen saturation (StO2). Blood-brain barrier (BBB) permeability was quantified through gadolinium-enhanced MRI. Molecular analyses by RT-qPCR were conducted to assess oxidative stress, inflammation, and angiogenesis-related gene expression. Immunohistological staining was performed to investigate neuronal loss, astrocytic activation, and vascular remodeling. Results: MRI analysis showed a significant and progressive decrease in lesion volume. Water content increased from D4 onward. Ischemic injury significantly altered vascular function, leading to increased vessel radius and BVF while reducing tissue oxygenation. BBB permeability was elevated at D7 and D56, accompanied by increased claudin-1 and aquaporin-1 expression. Molecular analysis revealed an upregulation of inflammatory markers (IL-6, TGF-{beta}, NF-{kappa}B), oxidative stress response genes (SOD1, Nrf1), and impaired angiogenesis with increased Ang1/Ang2 but reduced VEGF/VEGFR1. Immunohistological analysis demonstrated neuronal loss, astrocytic activation, and vascular remodeling, characterized by increased ZO-1 and ColI-IV expression. Conclusion: The observed changes in lesion volume, vascular function, inflammation, oxidative stress, and angiogenesis highlight key mechanisms underlying post-stroke recovery. These findings emphasize the importance of long-term monitoring in preclinical stroke models and may contribute to the development of novel therapeutic strategies.
in bioRxiv: Neuroscience on 2025-10-24 00:00:00 UTC.
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Purpose: Retinal ganglion cell (RGC) loss in glaucoma occurs in a large fraction of patients even after intraocular pressure (IOP) is reduced. Mitochondrial dysfunction is a key mechanism that links elevated IOP to RGC degeneration. We tested whether HDAP2, a novel high-density aromatic peptide that binds cardiolipin to stabilize mitochondrial membranes, can protect RGCs in the DBA/2J mouse model. Methods: DBA/2J mice received HDAP2 (3 mg/kg, intraperitoneally, every other day) starting at 4 months of age for 8 months. IOP was measured each month to track pressure exposure. RGC survival was assessed by counting RBPMS-stained cells in retinal wholemounts and optic nerve axons in semithin toludine blue-stained sections. Results: HDAP2-treated retinas had about 49% more RGCs than untreated retinas at similar pressure exposures (p = 0.0063; F(2,59) = 5.524). At mild IOP exposure, HDAP2 preserved 58% more RGCs compared with untreated retinas, and at high IOPs, RGC survival was 180% greater. Kaplan Meier analysis indicated that HDAP2 increased the threshold for severe RGC loss by 29 mmHg and reduced the chance of developing severe RGC degeneration by a factor of 4.6. Optic nerve axons from treated retinas were also well preserved, with axon morphologies appearing indistinguishable from controls. Axon size distributions did not change significantly among the treatment groups, suggesting that protection by HDAP2 was similar among RGC subtypes. Conclusions: HDAP2 preserved both RGCs and axons in a pressure-dependent manner and increased tolerance to IOP. These results suggest that HDAP2 may complement pressure-lowering therapy, including for normal-tension and treatment-refractory glaucoma.
in bioRxiv: Neuroscience on 2025-10-24 00:00:00 UTC.
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It has recently been discovered that physiological crosstalk exists between human retinas. Accordingly, visual stimulation of one retina elicited a neurovascular coupling (NVC) response of the contralateral retina in about 30% of individuals. The functional significance of this feature in health and disease remains unknown. Here, we asked the question whether inter-retina crosstalk predicts the nature of neurovascular coupling in the brain. To test this hypothesis, we assessed BOLD fMRI (blood-oxygen-level-dependent functional magnetic resonance imaging signal) in healthy individuals and a disease model of neurovascular coupling, type 1 diabetes. We used three visual paradigms: a Threshold speed and Sub-maximum speed discrimination tasks, and flicker stimulation. The presence or absence of inter-retinal coupling was predictive of the time course of the cortical hemodynamic response, either during the initial or late phases. The presence of interocular coupling predicted larger BOLD responses. Diabetic patients with interocular coupling showed a very similar profile to the healthy group. In sum, we identified a direct relationship between interocular physiological coupling and cortical hemodynamic responses, suggesting that this NVC response may serve as a disease biomarker in diabetes.
in bioRxiv: Neuroscience on 2025-10-24 00:00:00 UTC.
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Peripheral parasympathetic ganglia lie adjacent to their target organs; their dysfunction contributes to diseases like atrial fibrillation. Due to their challenging accessibility for primary culture, we provide a step-by-step protocol to generate parasympathetic neurons from human induced pluripotent stem cells (hiPSC). They reproduce numerous native physiological features: cholinergic and autonomic markers, functional nicotinic receptors and electrophysiological properties. We also describe a co-culture system with hiPSC-atrial cardiomyocytes allowing neuromodulation of cardiomyocyte activity and offering a platform for drug discovery and disease modelling.
in bioRxiv: Neuroscience on 2025-10-24 00:00:00 UTC.
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The insular cortex integrates interoceptive and exteroceptive information to mediate bodily homeostasis, emotion, learning, and potentially consciousness. However, the cellular and circuit substrates governing the insula and other associative cortices are poorly understood compared to primary cortices. Here, we quantify the dendritic morphology together with electrical properties, local inputs, and/or projections of 1,093 insular pyramidal neurons. These neurons are mapped onto a quantitative anatomical model of the insula based on a Nissl-staining coordinate framework. Using improved algorithms, we define 21 morphological, 12 electrical, and 9 input neuronal types, and identify several morphological and input types that are unique to the insula. Further, we find that morphological properties constrain and often predict inputs, electrical properties, or projection targets. Several morphological types are differentially distributed between the functionally distinct anterior and posterior insula, providing the substrates for a quantitative demarcation between the anterior and posterior insular subregions. Surprisingly, certain neuronal types receive intra-insular inputs originating far beyond canonical cortical columns. Functionally, these connections bridge a long-range thalamus-to-amygdalar circuit that potentially links sensory information to valence. Our work establishes a structure-and-function foundation for investigating the insular cortex.
in bioRxiv: Neuroscience on 2025-10-24 00:00:00 UTC.
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In this work, we introduce a method for mapping the spatial entropy of functional brain network community structure images in brain space. Entropy maps indicate the extent to which the network communities present in a local area are ordered or disordered. We demonstrate how spatial entropy can be quantified for each voxel in the brain according to the network community affiliations of surrounding voxels. This process results in interpretable maps of brain network entropy. We show that local entropy decreases in predictable brain regions during working memory and music-listening tasks. We suggest that these regional entropy reductions reflect self-organization of neural processes in support of functionally localized cognitive tasks. Analyses in this work provide a framework for future analyses of spatial entropy in complex networks that can be mapped to Euclidean space, both within the brain and in other contexts.
in bioRxiv: Neuroscience on 2025-10-24 00:00:00 UTC.
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Animals experience cyclical environmental changes, such as seasons, that require physiological adjustments to support different behaviors. Although many behaviors occur only during specific periods, some species, like Gymnotus omarorum, display territorial aggression year-round, making them valuable models to study seasonal plasticity in the mechanisms maintaining stable behavioral outputs. G. omarorum is a teleost fish in which neuroestrogens have been shown to play a key role in non-breeding aggression. Here, we quantified circulating hormone levels and gene expression in the social behavior network of wild breeding and non-breeding individuals. During the non-breeding season, both sexes exhibited elevated circulating androgen levels, providing potential substrates for local estrogen synthesis. Consistently, brain aromatase and estrogen receptor expression were also upregulated, suggesting an increased capacity for local estrogen synthesis and signaling. Our findings provide the first evidence in a teleost of seasonal plasticity in the mechanisms underlying territorial aggression. Comparisons with birds and mammals reveal both shared and lineage-specific strategies, highlighting common endocrine principles while revealing the evolutionary diversity of solutions to maintain a stable behavioral phenotype across changing seasonal contexts.
in bioRxiv: Neuroscience on 2025-10-24 00:00:00 UTC.
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Incorporating Indigenous knowledge into Technical and Vocational Education and Training (TVET) is recognized as one of the key strategies to support culturally responsive and inclusive education. In the sections that follow, we draw upon current international literature and studies to identify approaches with respect to embedding Indigenous knowledge into TVET curricula - strategies and challenges; outcomes. Eighty-five peer-reviewed articles between 2020 and 2025 were reviewed according to PRISMA 2020, concentrating on pedagogical models and methods, curriculum construction process, community involvement and student performance. The outcomes reveal that effective integration is grounded on culturally relevant teaching resources and active engagement with indigenous communities, along with traditional knowledge systems coupling to technical skills. Some of the challenges involve institutionalized barriers, a lack of teacher training and resources can restrict the ways in which we see Indigenous perspectives incorporated in meaningful ways. Notwithstanding these obstacles, there is evidence that students who experience Indigenous knowledge in TVET display higher levels of cultural awareness and identity formation, and engagement with learning; their communities are more empowered to participate in education. The review emphasizes the necessity for an overall framework and policies supporting sustainable integration, and advises that long-term effects on employability, social inclusion and community development be investigated in future studies. By highlighting the importance of Indigenous knowledge in TVET, this study adds to discussions on culturally-responsive pedagogical practice and offers practical advice for educators, policy makers and researchers aiming to improve TVET practices across the world.
in F1000Research on 2025-10-23 17:29:41 UTC.
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In the contemporary digital landscape, social media platforms have radically reshaped consumer-brand interactions, with Instagram emerging as a pivotal channel for luxury brand marketing. This study investigates the adoption of luxury products through Instagram by integrating psychological, social, and demographic predictors with advanced analytical methodologies. Utilizing a comprehensive dataset of 205 respondents, we examine how Instagram engagement metrics—such as time spent on the platform, influencer marketing, sponsored advertisements, and interactive content—impact consumer adoption behaviours. Employing multiple statistical techniques including multiple linear regression, logistic regression, and path analysis, alongside machine learning models like Support Vector Machines (SVM) and decision trees, we identify the primary drivers of purchase intention and brand trustworthiness in the luxury context. Notably, while surface-level engagement metrics show limited predictive power, factors such as brand trust, prestige, uniqueness, and personalized recommendations have strong influences on consumer purchase intention. The SVM model accurately predicts adoption likelihood with 87% accuracy, underscoring the efficacy of psychological and social variables as discriminators. Additionally, sentiment analysis of qualitative feedback reveals predominantly positive consumer attitudes toward Instagram marketing strategies. Our findings highlight the nuanced role of brand-related psychological constructs and demographic variables in shaping luxury product adoption, offering actionable insights for marketers aiming to optimize Instagram’s potential in luxury branding. This integrative approach advances both theoretical understanding and practical applications, reinforcing the importance of authenticity, emotional connection, and targeted psychographic segmentation in luxury digital marketing.
in F1000Research on 2025-10-23 17:27:13 UTC.
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Background Leprosy, or Hansen’s disease, is a chronic infectious disease that primarily affects the skin and peripheral nervous system, often leading to disabilities, including trophic ulcers (TU). The role of vitamin D and vitamin D receptor (VDR) gene polymorphisms in the development of TU among leprosy patients remain unclear. Objective This study aims to investigate the differences in serum 25-hydroxyvitamin D [25(OH)D] levels and the frequency of VDR gene FokI polymorphism between leprosy patients with and without TU, and to evaluate their association with the occurrence of TU. Methods This Institutional Review Board-approved, single-center, observational, analytic case-control study will enroll adult leprosy patients from the Dermatology and Venereology Clinic at Dr. Cipto Mangunkusumo Hospital in Jakarta, Indonesia. Participants will be divided into cases (patients with TU) and controls (patients without TU). Serum 25(OH)D levels will be measured using a chemiluminescence immunoassay, and FokI polymorphism detection is conducted through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. A total of 82 participants (41 cases and 41 controls) will be recruited. Statistical analysis will be performed to evaluate the differences and associations. Results Data collection commenced in March 2024 and was completed in September 2024, during the Indonesia’s dry season. Data analysis and reporting are expected to be finalized by January 2025. Discussion The findings of this study will enhance the current understanding of the role of the vitamin D axis in the development of TU among leprosy patients. This could lead to new therapeutic strategies, such as vitamin D supplementation or personalized medicine based on genetic profiling, potentially reducing the burden of TU among leprosy patients.
in F1000Research on 2025-10-23 17:04:47 UTC.
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Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) is a key RNA-binding protein involved in alternative splicing, mRNA transport, and local translation processes essential for neuronal development and synaptic plasticity. Here we have characterized eight hnRNP A2/B1 commercial antibodies for western blot, immunoprecipitation, and immunofluorescence using a standardized experimental protocol based on comparing read-outs in knockout cell lines and isogenic parental controls. These studies are part of a larger, collaborative initiative seeking to address antibody reproducibility issues by characterizing commercially available antibodies for human proteins and publishing the results openly as a resource for the scientific community. While the use of antibodies and protocols vary between laboratories, we encourage readers to use this report as a guide to select the most appropriate antibodies for their specific needs.
in F1000Research on 2025-10-23 16:36:28 UTC.
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Epileptic seizures involve the brain transitioning from a resting state to an abnormal state of synchronized bursting, akin to a bifurcation in dynamical systems where a parameter shift triggers a qualitative change in behavior. A comprehensive model was previously developed that used dynamical equations capable of simulating 16 "dynamotypes" of seizures that span the full range of theoretical first-order dynamics. The current work is a tool to understand and implement this model with the goal of generating a wide range of synthetic seizures. We present a dynamical atlas of all 16 possible onset–offset bifurcation combinations, each characterized by distinct features in simulated EEG-like recordings. We include a tutorial and graphical user interphase that generates diverse simulated seizures. In addition, we include methods to add realistic noise and filtering effects to enhance their resemblance to human EEG data. This toolbox has two purposes: it is a practical, educational demonstration of the dynamical principles underlying seizure bifurcations, and it provides the algorithms necessary to produce large numbers of realistic, diverse seizure patterns that have similar noise and filtering characteristics as human EEG. This generative model can aid in training seizure detection algorithms, understanding brain dynamical behavior for clinicians, and exploring the impact of noise on EEG recordings and detection algorithms.
in eNeuro on 2025-10-23 16:30:27 UTC.
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Most statistical inferences in neuroscience and psychology are based on frequentist statistics, which rely on sampling distributions: the long-run outcomes of multiple experiments, given a certain model. Yet, sampling distributions are poorly understood and rarely explicitly considered when making inferences. In this tutorial and commentary, I demonstrate how to use simulations to illustrate sampling distributions to answer simple practical questions: for instance, if we could run thousands of experiments, what would the outcome look like? What do these simulations tell us about the results from a single experiment? Such simulations can be run a priori, given expected results, or a posteriori, using existing datasets. Both approaches can help make explicit the data generating process and the sources of variability; they also reveal the large uncertainty in our experimental estimation and lead to the sobering realization that, in most situations, we should not make a big deal out of results from a single experiment. Simulations can also help demonstrate how the selection of effect sizes conditional on some arbitrary cutoff (p ≤ 0.05) leads to a literature filled with false positives, a powerful illustration of the damage done in part by researchers’ over-confidence in their statistical tools. The tutorial focuses on graphical descriptions and covers examples using correlation analyses, proportion data, and response latency data. All the figures and numerical values in this article can be reproduced using code available at https://github.com/GRousselet/sampdist.
in eNeuro on 2025-10-23 16:30:27 UTC.
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by Ernesto Tavares-Neto, Marcel Aguilella-Arzo, Vicente M. Aguilella
Electrostatic interactions are crucial for protein structure and function, especially in mesoscopic protein channels where ion selectivity is largely governed by the protein’s electrostatic properties. Understanding the protonation state of ionizable residues across pH values —often described by their pKa— is key to linking structure and function. However, experimental pKa determination is challenging, typically carried out using Nuclear Magnetic Resonance only in a limited number of membrane proteins. Thus, computational methods are the primary alternative. Constant pH Molecular Dynamics (CpHMD) simulation is one of the most accurate pKa prediction methods in proteins that contain many charged residues since it captures the coupling between conformational dynamics and residue protonation. Here we study the charge state of a general diffusion porin, OmpF, in which protons exert a crucial regulation of the channel discrimination of small inorganic ions as well as antibiotic translocation. We compare different pKa prediction methods, using CpHMD as a benchmark, and discuss the somewhat unusual titration of several acidic residues. The most widely used pKa prediction methods, though effective for globular proteins, fall short for membrane-embedded channels either because they were trained using pKa measurements in globular proteins or because of a poor description of the lipidic environment.
in PLoS Computational Biology on 2025-10-23 14:00:00 UTC.
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by Jiawen Chang, Zhuda Yang, Changsong Zhou
The spatiotemporal patterns of neural dynamics are jointly shaped by directed structural interactions and heterogeneous intrinsic features of the neural components. Despite well-developed methods for estimating directionality in network connections from network of homogeneous nodes, how local heterogeneity impacts on directionality estimation remains poorly understood. In particular, the role of excitatory-inhibitory interactions in shaping network directionality and how these interactions should be incorporated into reconstruction frameworks remain largely unexplored. Here, we present a novel reconstruction framework that simultaneously estimates effective heterogeneity across network nodes and asymmetric network connections from neural activity and symmetric connection, both are assessible in experimental data, validated using macaque cortical connectivity data and several circuit models. We found that the estimated local heterogeneity remains consistent across various forms of parameterized local circuit heterogeneity. Furthermore, we demonstrated and quantified how hidden local inhibitory populations only modify within-region connection strengths, elucidating the functional equivalence between dynamics of excitatory-inhibitory networks and purely observing excitatory networks when estimating effective heterogeneity and asymmetry. Finally, we demonstrated the sampling interval effect in estimating network interactions with respect to the sampling resolution. Together, our results not only provide a unified framework for evaluating relative functional contributions of local heterogeneity and asymmetry to overall system dynamics but also reveal the fundamental limitations and scaling principles in reconstructing neural circuit connectivity from experimental observations.
in PLoS Computational Biology on 2025-10-23 14:00:00 UTC.
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by Krutika Patidar, Ashlee N. Ford Versypt
The progression of diabetic kidney disease is often characterized by early dysfunction of glomerular endothelial cells, including alterations in fenestration size and number linked to impaired glomerular filtration. However, the cellular mechanisms regulating fenestrations in glomerular endothelial cells remain poorly understood due to limitations in existing in vitro models, challenges in imaging small fenestrations in vivo, and inconsistencies between in vitro and in vivo findings. This study used a logic-based protein-protein interaction network model with normalized Hill functions for dynamics to explore how glucose-mediated signaling dysregulation impacts fenestration dynamics in glomerular endothelial cells. Key drivers of fenestration loss and size changes were identified by incorporating signaling pathways related to actin remodeling, myosin light chain kinase, Rho-associated kinase, calcium, and VEGF and its receptors. The model predicted how hyperglycemia in diabetic mice leads to significant fenestration loss and increased size of fenestrations. Glycemic control in the pre-diabetic stage mitigated signaling dysregulation but was less effective as diabetic kidney disease developed and progressed. The model suggested alternative disease intervention strategies to maintain the integrity of the fenestration structure, such as targeting Rho-associated kinase, VEGF-A, NFκB, and actin stress fibers.
in PLoS Computational Biology on 2025-10-23 14:00:00 UTC.
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by Yiyuan Teresa Huang, Zenas C. Chao
Our brain uses prior experience to anticipate the timing of upcoming events. This dynamic process can be modeled using a hazard function derived from the probability distribution of event timings. However, the contexts of an event can lead to various probability distributions for the same event, and it remains unclear how the brain integrates these distributions into a coherent temporal prediction. In this study, we create a foreperiod sequence paradigm consisting of a sequence of paired trials, where in each trial, participants respond to a target signal after a specified time interval (i.e., foreperiod) following a warning cue. The prediction of the target onset in the second trial can be based on two probability distributions: the unconditional probability of the second foreperiod and its conditional probability given the foreperiod in the first trial. These probability distributions are then transformed into hazard functions to represent the unconditional and conditional temporal predictions. The behavioral model incorporating both predictions and their mutual modulation provides the best fit for reaction times to the target signal, indicating that both temporal statistics are integrated to make predictions. We further show that electroencephalographic source signals are also best reconstructed when integrating both predictions. Specifically, the unconditional and conditional predictions are encoded separately in the posterior and anterior brain regions, and integration of these two types of predictive processing requires a third region, particularly the right posterior cingulate area. Our study reveals brain networks that integrate multilevel temporal information, offering insight into the hierarchical predictive coding of time.
in PLoS Biology on 2025-10-23 14:00:00 UTC.
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by Hongyang Wu, Sayaka Eno, Kyoko Jinnai, Ayako Abe, Kokoro Saito, Yoh Maekawa, Darren W. Williams, Nobuhiro Yamagata, Shu Kondo, Hiromu Tanimoto
Neurons can adjust synaptic output according to the postsynaptic partners. However, the target-specific regulation of synaptic structures within individual neurons in the central nervous system remains unresolved. Applying the CRISPR/Cas9-mediated split-GFP tagging, we visualized the endogenous active zone scaffold protein, Bruchpilot (Brp), in specific cells. This technology enabled the spatial characterization of the presynaptic scaffolds only within the Kenyon cells (KCs) of the Drosophila mushroom bodies. We found the patterned accumulation of Brp among the compartments of axon terminals, where a KC synapses onto different postsynaptic neurons. Mechanistically, the localized octopaminergic projections along γ KC terminals regulate this compartmental Brp heterogeneity via Octβ2R and cAMP signaling. We further found that physiological stress, such as food or sleep deprivation reorganizes this intracellular pattern in an octopamine-dependent manner. Such concurrent regulation of local active zone assemblies thus suggests how the mushroom bodies integrate changing physiological states.
in PLoS Biology on 2025-10-23 14:00:00 UTC.
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by Kazuo L. Nakamura, Karen Zhang, Mario R. Mestre, Matías Rojas-Montero, Seth L. Shipman
Retrons are bacterial immune systems that protect a bacterial population against phages by killing infected hosts. Retrons typically comprise a reverse transcriptase (RT), a template noncoding RNA that is partially reverse transcribed into RT-DNA, and a toxic effector. The reverse transcriptase (RT), noncoding RNA, and RT-DNA complex sequester the toxic effector until triggered by phage infection, at which point the toxin is released to induce cell death. Due to their ability to produce single-stranded DNA in vivo, retrons have also been engineered to produce donor templates for genome editing in both prokaryotes and eukaryotes. However, the current repertoire of experimentally characterized retrons is limited, with most retrons sourced from clinical and laboratory strains of bacteria. To better understand retron biology and natural diversity, and to expand the current toolbox of retron-based genome editors, we developed a pipeline to isolate retrons and their bacterial hosts from a variety of environmental samples. Here, we identify seven new retron systems, each isolated from a different host bacterium. We characterize DNA production by these retrons and test their ability to defend against a panel of Escherichia coli phages. We find that two of these retrons are disrupted by other elements, in one case a group II intron and in another a separate defense system, yet both retrons still produce RT-DNA. For two other retrons, we further unravel their mechanism of defense by identifying the phage genes responsible for triggering abortive infection. Finally, we engineer these retrons for genome editing in E. coli, demonstrating their potential use in a biotechnological application.
in PLoS Biology on 2025-10-23 14:00:00 UTC.
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Background Performance monitoring is essential for enhancing academic staff productivity and institutional accountability in higher education. In Uganda, private chartered universities face challenges in implementing effective performance monitoring systems. This study examines the types and effectiveness of these systems in private chartered universities in Western Uganda. Methods The study was guided by Fayol’s Administrative Management Theory and Vroom’s Expectancy Theory. A concurrent triangulation mixed-methods design was employed. Quantitative data were collected from 386 academic staff using structured questionnaires, while qualitative data were gathered through in-depth interviews with 10 academic deans from four selected universities. Ethical approval was obtained from institutional review boards and the Uganda National Council for Science and Technology (SS3145ES). Descriptive statistics, correlation, and regression analyses were used to analyze quantitative data, while thematic analysis was used for qualitative responses. Results Findings indicate that various performance monitoring tools are in use, including student evaluations, peer reviews, and supervisory assessments. However, their application is often inconsistent, with limited feedback loops and weak integration into staff development initiatives. Quantitative analysis revealed a moderate positive correlation between effective performance monitoring and academic staff performance (r = 0.48, p < 0.05). Regression analysis showed that performance monitoring accounted for 21.3% of the variance in staff performance. Conclusions While performance monitoring tools are present in private chartered universities in Western Uganda, their inconsistent implementation undermines their effectiveness. Strengthening the integration of monitoring outcomes into professional development and decision-making processes could enhance academic staff performance. These findings underscore the need for systematic policy enforcement and capacity-building in performance management practices within the sector.
in F1000Research on 2025-10-23 10:12:18 UTC.
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Proceedings of the National Academy of Sciences, Volume 122, Issue 43, October 2025.
SignificanceMicroglial-mediated neuroinflammation is strongly implicated in the development and progression of Alzheimer’s disease (AD). Here we demonstrate that human induced pluripotent stem cell (iPSC)-microglia (iMG) employ voltage-gated proton ...
in PNAS on 2025-10-23 07:00:00 UTC.
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Proceedings of the National Academy of Sciences, Volume 122, Issue 43, October 2025.
SignificanceAnimal movement is shaped by the continuous interaction between motor actions and sensory feedback. This process is challenging due to time delays, which can have destabilizing effects, and the constantly varying relationship between motor ...
in PNAS on 2025-10-23 07:00:00 UTC.
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Proceedings of the National Academy of Sciences, Volume 122, Issue 43, October 2025.
SignificanceCarbon dioxide (CO2) emitted by human hosts is a critical cue that mosquitoes use for host detection, yet the nanoscale three-dimensional (3D) structure of their CO2-sensing neurons and associated cells remains unclear. Elucidating the anatomy ...
in PNAS on 2025-10-23 07:00:00 UTC.
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Science, Volume 390, Issue 6771, October 2025.
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Science, Volume 390, Issue 6771, October 2025.
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Science, Volume 390, Issue 6771, October 2025.
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Science, Volume 390, Issue 6771, October 2025.
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Science, Volume 390, Issue 6771, October 2025.
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Science, Volume 390, Issue 6771, October 2025.
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Science, Volume 390, Issue 6771, October 2025.
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Science, Volume 390, Issue 6771, October 2025.
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Science, Volume 390, Issue 6771, Page 342-342, October 2025.
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Science, Volume 390, Issue 6771, Page 341-341, October 2025.
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Science, Volume 390, Issue 6771, Page 386-389, October 2025.
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Science, Volume 390, Issue 6771, Page 381-385, October 2025.
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Science, Volume 390, Issue 6771, Page 377-380, October 2025.
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Science, Volume 390, Issue 6771, Page 367-370, October 2025.
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Science, Volume 390, Issue 6771, Page 400-404, October 2025.
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Science, Volume 390, Issue 6771, Page 390-393, October 2025.
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Science, Volume 390, Issue 6771, Page 361-366, October 2025.
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Science, Volume 390, Issue 6771, Page 405-410, October 2025.
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Science, Volume 390, Issue 6771, Page 371-376, October 2025.
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Science, Volume 390, Issue 6771, Page 356-360, October 2025.
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Science, Volume 390, Issue 6771, Page 394-399, October 2025.
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Science, Volume 390, Issue 6771, Page 414-414, October 2025.
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Science, Volume 390, Issue 6771, Page 348-349, October 2025.
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Science, Volume 390, Issue 6771, Page 332-333, October 2025.
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Science, Volume 390, Issue 6771, Page 333-334, October 2025.
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Science, Volume 390, Issue 6771, Page 335-336, October 2025.
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Science, Volume 390, Issue 6771, Page 336-337, October 2025.
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Science, Volume 390, Issue 6771, Page 343-344, October 2025.
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Science, Volume 390, Issue 6771, Page 344-344, October 2025.
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Science, Volume 390, Issue 6771, Page 343-343, October 2025.
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Science, Volume 390, Issue 6771, Page 327-331, October 2025.
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Science, Volume 390, Issue 6771, Page 318-319, October 2025.
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Science, Volume 390, Issue 6771, Page 320-321, October 2025.
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Science, Volume 390, Issue 6771, Page 321-322, October 2025.
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Science, Volume 390, Issue 6771, Page 322-323, October 2025.
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Science, Volume 390, Issue 6771, Page 324-324, October 2025.
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Science, Volume 390, Issue 6771, Page 325-325, October 2025.
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Science, Volume 390, Issue 6771, Page 326-326, October 2025.
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Science, Volume 390, Issue 6771, Page 338-340, October 2025.
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Science, Volume 390, Issue 6771, Page 347-349, October 2025.
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Wang et al. reveal a neuroanatomical and functional crosstalk between cholinergic enteric neurons and sensory neurons of the dorsal root ganglia that mediates colonic interoception. While this pathway typically elicits non-aversive reflexes under physiological conditions, inflammatory colitis triggers plasticity that transforms its output to promote aversive behaviors.
in Neuron: In press on 2025-10-23 00:00:00 UTC.
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Xu et al. report that intratumoral Citrobacter enrichment correlates with poor overall survival in pancreatic cancer patients. An intratumoral Citrobacter freundii strain metabolizes 5-fluorouracil (5-FU) into inactive products via PreTA. Gimeracil, an inhibitor of human dihydropyrimidine dehydrogenase, preserves 5-FU efficacy by blocking PreTA activity.
in Cell Reports: Current Issue on 2025-10-23 00:00:00 UTC.
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Ras mutations drive tumorigenesis yet persist in normal tissues. Elliot et al. explore this paradox, finding that HRASG12V induces bifurcating cell fates in the zebrafish larval epidermis, with lamc2+krt18+ cancer stem cell-like cells emerging from permissive cells at the preneoplastic stage and expressing neutrophil-modulating cytokines that instigate reciprocal tumor-supportive crosstalk.
in Cell Reports: Current Issue on 2025-10-23 00:00:00 UTC.
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Waschina et al. explored how multi-strain probiotic supplementation influenced the gut microbiome and metabolome in very-low-birth-weight infants at high risk of late-onset sepsis. Probiotics promote colonization with beneficial microbes and reduce antibiotic-resistant pathobionts. Late-onset sepsis is associated with lower levels of key fermentation products (lactate and acetate) of probiotics.
in Cell Reports: Current Issue on 2025-10-23 00:00:00 UTC.
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Gao et al. reveal that the metabolic interactions of gut microbial community are driven by the key competitive and cooperative microbiota, which are potentially associated with non-human primate health. The study improves our understanding of the complex interactions in microbial community, providing potential avenues to therapeutic implications.
in Cell Reports: Current Issue on 2025-10-23 00:00:00 UTC.
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Rodriguez et al. employ bioinformatic analyses to discover effectors involved in the virulence of the understudied human fungal pathogen Histoplasma and uncover an expansion of knottins (inhibitor cystine knot proteins). Their algorithms are broadly applicable to other organisms and uncover virulence effectors with diverse predicted structures.
in Cell Reports: Current Issue on 2025-10-23 00:00:00 UTC.
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(Cell Reports 44, 115103, January 28, 2024)
in Cell Reports: Current Issue on 2025-10-23 00:00:00 UTC.
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Nature, Published online: 23 October 2025; doi:10.1038/d41586-025-03441-6
A deep-learning design sidesteps the need for time-consuming drug-screening.
in Nature on 2025-10-23 00:00:00 UTC.
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Nature, Published online: 23 October 2025; doi:10.1038/d41586-025-03281-4
Researchers welcome the initiative, but say it doesn’t go far enough to capture the nuance of researcher productivity and impact.
in Nature on 2025-10-23 00:00:00 UTC.
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Nature, Published online: 23 October 2025; doi:10.1038/d41586-025-03496-5
mRNA vaccines seem to ‘rev up’ the immune system to boost immunotherapy. Plus, a rare meteorite has been recovered from the Moon and the mysterious transition between wakefulness and sleep.
in Nature on 2025-10-23 00:00:00 UTC.
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Nature, Published online: 23 October 2025; doi:10.1038/d41586-025-03381-1
A theoretical study suggests that gravity could have quantum effects without itself being a quantum theory. Other researchers aren’t so sure.
in Nature on 2025-10-23 00:00:00 UTC.
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Nature, Published online: 23 October 2025; doi:10.1038/d41586-025-03466-x
Florida’s primary reef-building corals have been declared ‘functionally extinct’ — prompting a shift in conservation strategies.
in Nature on 2025-10-23 00:00:00 UTC.
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Nature, Published online: 23 October 2025; doi:10.1038/d41586-025-03467-w
Civets enrich coffee beans they eat and excrete with two fatty acids often used in dairy products, study finds.
in Nature on 2025-10-23 00:00:00 UTC.
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Nature Neuroscience, Published online: 23 October 2025; doi:10.1038/s41593-025-02087-x
The brain is constantly monitoring the systems in the body. Here the authors use 7 Tesla functional magnetic resonance imaging to map a large-scale brain system for body regulation in humans, including brainstem nuclei, and confirm many monosynaptic connections traced in nonhuman animals.
in Nature Neuroscience on 2025-10-23 00:00:00 UTC.
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Nature Neuroscience, Published online: 23 October 2025; doi:10.1038/s41593-025-02067-1
Sheehan et al. have characterized the circadian translatomes of astrocytes and microglia in the mouse cortex in the context of amyloid pathology or aging, revealing cell- and disease-specific reprogramming of neurodegeneration-related pathways.
in Nature Neuroscience on 2025-10-23 00:00:00 UTC.
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Nature Reviews Neuroscience, Published online: 23 October 2025; doi:10.1038/s41583-025-00981-8
Itch has an important role as a somatosensory defensive mechanism. In this Review, Sun synthesizes CNS circuits underlying itch signal processing and its modulation in the spinal cord, transmission of processed itch information to the brain for encoding, and evoked sensory and affective components from the perception of itch.
in Nature Reviews on 2025-10-23 00:00:00 UTC.
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Nature Methods, Published online: 23 October 2025; doi:10.1038/s41592-025-02858-1
A recently proposed Hodge Laplacian model has advanced single-cell multimodal data analysis by providing highly reliable results for complex multi-branching trajectories.
in Nature Methods on 2025-10-23 00:00:00 UTC.
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Nature Methods, Published online: 23 October 2025; doi:10.1038/s41592-025-02870-5
PHLOWER leverages single-cell multimodal data to infer complex, multi-branching cell differentiation trajectories.
in Nature Methods on 2025-10-23 00:00:00 UTC.
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Nature Physics, Published online: 23 October 2025; doi:10.1038/s41567-025-03066-6
A study shows that the nucleation of vortices in dipolar supersolids can be revealed by the onset of rotational synchronization.
in Nature Physics on 2025-10-23 00:00:00 UTC.
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Nature Physics, Published online: 23 October 2025; doi:10.1038/s41567-025-03065-7
Supersolids combine superfluid and crystal order and their response to external driving remains unclear. Now it is shown that, in a dipolar supersolid, rotation induces synchronization of the crystal motion via vortex nucleation.
in Nature Physics on 2025-10-23 00:00:00 UTC.
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Scientific Data, Published online: 23 October 2025; doi:10.1038/s41597-025-06139-6
Author Correction: GERDA: The German Election Database
in Nature scientific data on 2025-10-23 00:00:00 UTC.
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Communications Biology, Published online: 23 October 2025; doi:10.1038/s42003-025-08965-1
Targeted lipid nanoparticle supplementation in Acropora spathulata enhances larval swimming, settlement, and juvenile resilience, revealing critical roles of sterols and fatty acids in early life-stage fitness of corals.
in Nature communications biology on 2025-10-23 00:00:00 UTC.
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Communications Biology, Published online: 23 October 2025; doi:10.1038/s42003-025-09015-6
The spider Cheiracanthium punctorium evolved defensive venom rich in CSTX peptides and PLA2 enzymes. These components arose via gene duplication, fusion, and convergence, reflecting how similar ecological pressures shape venom evolution.
in Nature communications biology on 2025-10-23 00:00:00 UTC.
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Communications Biology, Published online: 23 October 2025; doi:10.1038/s42003-025-08989-7
The small protein MicN functions as an anti-sigma factor of RpoS, playing a crucial role in Salmonella survival within macrophages by modulating bacterial metabolism.
in Nature communications biology on 2025-10-23 00:00:00 UTC.
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The transition from prebiotic chemistry to living systems requires the emergence of a scheme for enzyme-free genetic replication. Here, we analyze a recently proposed prebiotic replication scenario, the so-called Virtual Circular Genome (VCG) [Zhou et al., RNA 27, 1-11 (2021)]: Replication takes place in a pool of oligomers, where each oligomer contains a subsequence of a circular genome, such that the oligomers encode the full genome collectively. While the sequence of the circular genome may be reconstructed based on long oligomers, monomers and short oligomers merely act as replication feedstock. We observe a competition between the predominantly error-free ligation of a feedstock molecule to a long oligomer and the predominantly erroneous ligation of two long oligomers. Increasing the length of long oligomers and reducing their concentration decreases the fraction of erroneous ligations, enabling high-fidelity replication in the VCG. Alternatively, the formation of erroneous products can be suppressed if each ligation involves at least one monomer, while ligations between two long oligomers are effectively prevented. This kinetic discrimination (favoring monomer incorporation over oligomer–oligomer ligation) may be an intrinsic property of the activation chemistry, or can be externally imposed by selectively activating only monomers in the pool. Surprisingly, under these conditions, shorter oligomers are extended by monomers more quickly than long oligomers, a phenomenon that has already been observed experimentally [Ding et al., JACS 145, 7504-7515 (2023)]. Our work provides a theoretical explanation for this behavior and predicts its dependence on system parameters such as the concentration of long oligomers. Taken together, the VCG constitutes a promising scenario of prebiotic information replication: It could mitigate challenges in non-enzymatic copying via template-directed polymerization, such as short lengths of copied products and high error rates.
in eLife on 2025-10-23 00:00:00 UTC.
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Signatures of consciousness are found in spectral and temporal properties of neuronal activity. Among these, spatiotemporal complexity after a perturbation has recently emerged as a robust metric to infer levels of consciousness. Perturbation paradigms remain, however, difficult to perform routinely. To discover alternative paradigms and metrics, we systematically explore brain stimulation and resting-state activity in a whole-brain model. We find that perturbational complexity only occurs when the brain model operates within a specific dynamical regime, in which spontaneous activity produces a large degree of functional network reorganizations referred to as being fluid. The regime of high brain fluidity is characterized by a small battery of metrics drawn from dynamical systems theory and predicts the impact of consciousness-altering drugs (Xenon, Propofol, and Ketamine). We validate the predictions in a cohort of 15 subjects at various stages of consciousness and demonstrate their agreement with previously reported perturbational complexity, but in a more accessible paradigm. Beyond the facilitation in clinical use, the metrics highlight complexity properties of brain dynamics in support of the emergence of consciousness.
in eLife on 2025-10-23 00:00:00 UTC.
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The evolutionary expansion of extracellular matrix (ECM) molecules has been crucial for the establishment of cell adhesion and the transition from unicellular to multicellular life. Members of the early diverging metazoan phylum Cnidaria offer an exceptionally rich perspective into the metazoan core adhesome and its original function in developmental and morphogenetic processes. Here, we present the ensemble of ECM proteins and associated factors for the starlet sea anemone Nematostella vectensis based on in silico prediction and quantitative proteomic analysis of decellularized mesoglea from different life stages. The integration of the matrisome with single-cell transcriptome atlases shows that gastrodermal cells are the primary producers of Nematostella’s complex ECM, confirming the homology of the cnidarian inner cell layer with bilaterian mesoderm. The transition from larva to polyp is marked by an upregulation of metalloproteases and basement membrane components including all members of an unusually diversified SVEP1/Polydom family, suggesting massive epithelial remodeling. The enrichment of Wnt/PCP pathway factors during this process further indicates directed cell rearrangements as a key contributor to the polyp’s morphogenesis. Mesoglea maturation in adult polyps involves wound response proteins indicating shared molecular patterns in growth and regeneration. Our study identifies conserved matrisomal networks that coordinate transitions in Nematostella’s life history.
in eLife on 2025-10-23 00:00:00 UTC.
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People are remarkably self-focused, disproportionately choosing to think about themselves relative to other topics. Self-focus can be adaptive, helping individuals fulfill their needs. It can also be maladaptive, with self-focus a risk and maintenance factor for internalizing disorders like depression. Yet, the drive to focus on the self remains to be fully characterized. We discovered a brain pattern that when spontaneously brought online during a quick mental break predicts the desire to focus on oneself just a few seconds later. In Study 1 (19 female and 13 male human subjects), we identified a default network neural signature from pr-trial activity that predicts multiple indicators of self-focus within our sample. In Study 2 (588 female and 498 male human subjects), we applied our neural signature to independent resting-state data from the Human Connectome Project. We found that individuals who score high on internalizing, a form of maladaptive self-focus, similarly move in and out of this pattern during rest, suggesting a systematic trajectory toward self-focused thought. This is the first work to "decode" the bias to focus on the self and paves the way toward stopping maladaptive self-focus in its course.
in Journal of Neuroscience on 2025-10-22 16:30:34 UTC.
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in Journal of Neuroscience on 2025-10-22 16:30:34 UTC.
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The purpose of this study was to investigate how Sphingosine-1-phosphate (S1P) signaling regulates glial phenotype, neuroprotection, and reprogramming of Müller glia (MG) into neurogenic MG-derived progenitor cells (MGPCs) in the adult male and female mouse retina. We found that S1P-related genes were dynamically regulated following retinal damage. S1pr1 (S1P receptor 1) and Sphk1 (sphingosine kinase 1) are expressed at low levels by resting MG and are rapidly upregulated following acute damage. Overexpression of the neurogenic bHLH transcription factor Ascl1 in MG downregulates S1pr1, and inhibition of Sphk1 and S1pr1/3 enhances Ascl1-driven differentiation of bipolar-like cells. Treatments that activate S1pr1 or increase retinal levels of S1P initiate proinflammatory NFB signaling in MG, whereas treatments that inhibit S1pr1 or decreased levels of S1P suppress NFB signaling in MG. Conditional knock-out (cKO) of S1pr1 in MG, but not Sphk1, enhances the accumulation of immune cells in damaged retinas. cKO of S1pr1 promotes the survival of ganglion cells, whereas cKO of Sphk1 promotes the survival amacrine cells in damaged retinas. Consistent with these findings, pharmacological treatments that inhibit S1P receptors or inhibit Sphk1 have protective effects upon inner retinal neurons. We conclude that the S1P signaling pathway is activated in MG after damage and this pathway restricts the accumulation of immune cells, impairs neuron survival, and suppresses the reprogramming of MG into neurogenic progenitors in the adult mouse retina.
in Journal of Neuroscience on 2025-10-22 16:30:34 UTC.
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During cortical development, oligodendrocyte precursor (OPC) attachment and detachment to microvessels play a crucial role in their positioning and differentiation. In the developing brain, endothelial cells are regionally diverse, and previous studies showed a peak in cortical endothelial NMDA receptor (eNMDAR) expression during perinatal life, coinciding with OPC migration along microvessels. This raises the hypothesis that eNMDAR might influence the fate of vessel-associated OPC. In this study, a Grin1lox/lox/VeCadCre mouse model was used to investigate in females and males the effects of endothelial GluN1 invalidation (eNMDAR–/–) on (1) positioning and differentiation of cortical oligodendrocytes and myelination, (2) OPC/microvessel association and endothelial MMP9-like activity, and (3) motor activity. Results showed that, from postnatal days (P) 2 to P15, PDGFRα expression was increased in eNMDAR–/– mice and returned to wild-type levels by P45. CNPase and MBP expression was reduced at P15 and remained low in adult eNMDAR–/– mice. Histological analysis revealed no change in OPC–microvessel association, but positioning was altered with increased density in layers VI and V at P15. Myelination was impaired, as evidenced by thinner corpus callosum, reduced myelin sheath thickness, and higher g-ratio. Axonal mitochondria density was significantly increased. Functional tests revealed that glutamate could not stimulate endothelial MMP9-like activity in eNMDAR–/– mice. Molecular, histological and functional changes were linked to sensorimotor disabilities. At P45, despite the absence of observable myelination defects, locomotor impairments persisted, suggesting that early OPC differentiation disruption contributes to lasting motor dysfunction. These findings offer new insights into OPC vulnerability in human preterm infants.
in Journal of Neuroscience on 2025-10-22 16:30:34 UTC.
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Alcohol use disorders (AUDs) are complex phenomena governed by genetics, neurophysiology, environment, and societal structures. New methods to understand the underlying neurogenetics are valuable for designing personalized interventional strategies. Here, we used a two-choice self-administration zebrafish assay to isolate the function of nicotinic acetylcholine receptor subunit alpha3 (chrna3) in alcohol response. Juvenile zebrafish, of either sex, prior to complete sex differentiation, were examined in this study. They exhibited a biphasic response when self-administering alcohol that transitioned from attraction to aversion within minutes, suggesting they can regulate exposure to alcohol. This inverted U-shaped self-administration mirrored the effect alcohol has on shoaling behavior. Exposure to low concentration of alcohol reduced anxiety-like behaviors, while sedative effects became prominent at higher concentrations resulting in reduced locomotion and uncoordinated swimming. In contrast, these responses are blunted in chrna3 mutants. They exhibited prolonged alcohol self-administration and increased gregariousness. Transcriptomic analyses suggest that glutamatergic and GABAergic neurotransmission alongside cholinergic signaling is impacted in the mutant brains. Our results thus suggest that chrna3 dysfunction has a systemic change with an increase in alcohol tolerance being one effect. These findings also highlight the use of nonrodent alternatives to understand the neurogenetics of development of AUD.
in Journal of Neuroscience on 2025-10-22 16:30:34 UTC.
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Nonsense-mediated mRNA decay (NMD) is a conserved RNA surveillance mechanism that degrades transcripts with premature termination codons (PTCs) and fine-tunes gene expression by targeting RNA transcripts with other NMD inducing features. This study demonstrates that conditional knock-out of Smg5, a key NMD component, in oligodendrocyte lineage cells disrupts the degradation of PTC-containing transcripts, including aberrant variants of the RNA-binding protein Hnrnpl. The loss of SMG5 in both sexes of mice impaired oligodendrocyte differentiation, reduced myelin gene expression, and led to thinner myelin sheaths and compromised motor function in mice. Mechanistically, HNRNPL was shown to regulate the alternative splicing of myelin-associated genes Mag and Nfasc and promote oligodendrocyte differentiation. These findings reveal that SMG5-mediated NMD ensures RNA processing fidelity essential for proper oligodendrocyte development and CNS myelination.
in Journal of Neuroscience on 2025-10-22 16:30:34 UTC.
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Following injury, the peripheral nervous system (PNS) exhibits remarkable regenerative capacity, whereas the central nervous system (CNS) has limited regenerative potential. This difference is partially attributed to distinct postinjury myelin breakdown. However, the underlying mechanisms driving this disparity remain unclear. By comparing the expression profiles of injured peripheral and central nerves in adult male and female C57BL/6J mice, we identified insulin-like growth factor-binding protein 2 (IGFBP2) as a key regulator that determines the differences in myelin breakdown between the injured PNS and CNS. Schwann cell-derived IGFBP2 in the injured PNS promotes myelin breakdown and facilitates axonal regeneration. Furthermore, through lipidomics, we identify ceramide, a sphingolipid regulated by ceramide synthase 6 in injured nerves, as playing a critical role in IGFBP2-mediated myelin breakdown. Conversely, minimal IGFBP2 expression is observed in the injured CNS, contributing to the limited myelin breakdown and axon regeneration in injured CNS. These findings provide insights into the divergent regenerative potential of the PNS and CNS and unveil IGFBP2 and ceramide as promising targets for promoting CNS regeneration after injury.
in Journal of Neuroscience on 2025-10-22 16:30:34 UTC.
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The paraventricular thalamic nucleus (PVT) integrates subcortical signals related to arousal, stress, addiction, and anxiety with top-down cortical influences. Increases or decreases in PVT activity exert profound, long-lasting effects on behavior related to motivation, addiction, and homeostasis. Yet the sources of its subcortical excitatory and inhibitory afferents, their distribution within the PVT, and their integration with layer-specific cortical inputs remain unclear. Using transgenic male and female mice selective for GABAergic and glutamatergic neurons, or for different cortical layers, we found that the input organization of PVT is unique among thalamic nuclei. PVT received subcortical GABAergic and glutamatergic inputs from multiple, distinct hypothalamic and brainstem regions. Most regions provided either excitatory or inhibitory afferents; however, subcortical inputs with dual components have also been found. Most of these subcortical inputs selectively targeted the core region of the PVT that contained large number of densely packed calretinin-positive (CR+) neurons. Cortical afferents to PVT displayed layer-specific segregation. Layer 5 neurons of the medial prefrontal cortex preferentially innervated the CR+ core, whereas layer 6 input was more abundant in the transition zone between PVT and the mediodorsal nucleus. These findings demonstrate extensive convergence of excitatory and inhibitory inputs from diverse subcortical sources, selectively, in a sharply delineated CR+ core region of PVT which is also under strong top-down control from layer 5. This unique organization may explain why the CR+ PVT core serves as a critical bottleneck in the subcortex–cortex communication involved in affective behavior.
in Journal of Neuroscience on 2025-10-22 16:30:34 UTC.
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At the glutamatergic synapses between rod photoreceptors and ON-type bipolar cells (BCs), neurotransmitter is detected by the postsynaptic metabotropic glutamate receptor mGluR6. This receptor forms trans-synaptic interactions with ELFN1, a presynaptic cell adhesion molecule expressed in rods, and ELFN1 is important for mGluR6 localization at BC dendritic tips. Here, we show that in mice of either sex lacking mGluR6, the presynaptic localization of ELFN1 is disrupted. In rods of mGluR6 null mice, ELFN1 is still restricted to the axon terminal spherules but is only partially colocalized with synapses. The ELFN1 localization defect is rescued by expressing mGluR6-EGFP in ON-BCs. In vitro binding experiments demonstrated that the leucine-rich repeat (LRR) and LRR C-terminal cap (LRRCT) regions of the ELFN1 extracellular domain (ECD) are necessary and sufficient for binding to all of the Group 3 mGluRs, including mGluR6. ELFN1-flag expressed in rods of wild-type mice is correctly localized at presynapses, colocalizing with the postsynaptic marker TRPM1 in the outer plexiform layer. Deletion of the LRRCT domain abolished trafficking of ELFN1-flag to rod spherules, whereas deletion of other parts of the ELFN1 ECD did not prevent axonal trafficking or correct presynaptic localization. Our results demonstrate bidirectional mutual regulation of presynaptic enrichment of ELFN1 and postsynaptic enrichment of mGluR6 at photoreceptor synapses.
in Journal of Neuroscience on 2025-10-22 16:30:34 UTC.