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DNA pioneer James Watson has died ― colleagues wrestle with his legacy
Nature, Published online: 08 November 2025; doi:10.1038/d41586-025-03380-2
The co-discoverer of the structure of DNA helped to strengthen a US research institute and wrote a classic textbook, but also earned a reputation for racist and sexist comments.in Nature on 2025-11-08 00:00:00 UTC.
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Layer-Specific Glutamatergic Inputs and Parvalbumin Interneurons Modulate Early Life Stress-Induced Alterations in Prefrontal Glutamate Release during Fear Conditioning in Pre-adolescent Rats
Exposure to early life stress (ELS) can exert long-lasting impacts on emotional regulation. The corticolimbic system including the basolateral amygdala (BLA), ventral hippocampus (vHIP), and the medial prefrontal cortex (mPFC) plays a key role in fear learning. Using the limited bedding paradigm (LB), we examined the functional consequences of ELS on excitatory and inhibitory tone in the prelimbic (PL) mPFC after fear conditioning in rats. In adults, LB exposure enhanced in vivo glutamate release in the PL mPFC during fear conditioning in male, but not female offspring. In contrast, the glutamate response to fear conditioning was diminished in LB-exposed pre-adolescent males, but not females. We investigated whether reduced glutamatergic inputs and/or elevated inhibitory tone might contribute to the diminished glutamate response in the mPFC following LB in pre-adolescent male rats. Indeed, we found that LB exposure specifically increased the activation of PV, but not SST interneurons in layer V, but not layer II/III of the PL mPFC in fear-exposed pre-adolescent males. Presynaptic glutamate release probability was reduced by LB exposure in layer V, but increased in layer II/III of the PL mPFC. These functional changes might be related to the LB-induced alterations in the bilaminar distribution of BLA and vHIP projections to the PL mPFC we observed in pre-adolescent males. Overall, our findings suggest that ELS modifies glutamate release and PL mPFC function during fear conditioning in a sex- and age-dependent fashion, likely through layer-specific shifts in excitation/inhibition balance.
in eNeuro on 2025-11-07 17:30:18 UTC.
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A Bioscience Educators Purpose in a Modern World
Higher education (HE) is undergoing rapid transformation, shaped as a result of the COVID-19 pandemic, the expansion of digital learning, and the increasing presence of artificial intelligence (AI). For educators, these shifts raise important questions about their evolving purpose and responsibilities. In this commentary, we reflect on the role of bioscience educators in the United Kingdom, highlighting the enduring need for human connection, empathy, and belonging in teaching, alongside the integration of digital tools. We discuss changing student motivations, the necessity of flexible and inclusive learning environments, and the balance between traditional practices and innovative pedagogies. Practical training, active learning, and responsible engagement with emerging technologies remain central to equipping students with transferable skills such as adaptability, critical thinking, and resilience. We argue that while digital innovations can enhance accessibility and engagement, they cannot replace the uniquely human dimensions of teaching. Ultimately, bioscience educators must embrace their dual role as facilitators and lifelong learners, modeling curiosity, vulnerability, and inclusivity to empower students to thrive in an increasingly complex world.
in eNeuro on 2025-11-07 17:30:18 UTC.
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Tourette syndrome research highlights from 2024 [version 3; peer review: 2 approved, 1 approved with reservations]
We summarize research reports from 2024 relevant to Tourette syndrome, which the authors consider the most important or interesting. This working draft aims to submit this content for publication around the beginning of 2025 in the yearly Tourette Syndrome Research Highlights series on F1000Research. The authors welcome article suggestions and thoughtful feedback from readers, who can add a comment by clicking on the rectangular comment box icon to the left of the LOG IN link at the top of this page. For private comments, you can reach us by email (andreas.hartmann@aphp.fr or kevin@wustl.edu).in F1000Research on 2025-11-07 16:19:56 UTC.
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Income Inequality, Governance Quality, and Political Engagement: A Cross-country Analysis of Disparities and Democratic Participation [version 2; peer review: 1 approved with reservations]
Background Whether income inequality erodes citizens’ (VA) depends on institutional context. We examine how integrity—proxied by Control of Corruption (CC)—conditions the inequality–voice link across developed and developing democracies. Methods We assemble a harmonised, unbalanced 10-country panel (2003–2022) with VA as outcome and a parsimonious set of regressors: lagged Gini, lagged poverty, lagged GDP-per-capita growth, CC, Political Stability, and Gini×CC. We test cross-sectional dependence, serial correlation, and stationarity (IPS/CADF). Given mixed orders of integration and no panel cointegration in Westerlund tests with bootstrap p-values, our main specification is first-difference two-way fixed effects with country-clustered inference. A dynamic Augmented Anderson–Hsiao (AAH) estimator provides robustness. Multicollinearity among governance pillars is addressed via diagnostics (VIF) and a parsimonious design. Heterogeneity is assessed via separate models for developed and developing groups. Results Diagnostics indicate cross-sectional and AR(1) dependence; VA, Gini, poverty, and CC behave as I(1), while growth and stability are I(0); Westerlund fails to reject no cointegration (bootstrap p≈0.51 across Gt/Ga/Pt/Pa). In Δ two-way FE, CC is a robust positive correlate of VA, whereas the main Gini effect is small/unstable; the Gini×CC term shows that integrity conditions the inequality–voice link. In developed countries, higher integrity attenuates the (marginally) negative association of inequality with VA (interaction >0). In developing countries, integrity amplifies a negative inequality–VA association as CC improves (interaction <0). The AAH model confirms high persistence in VA (lag ≈0.70, p<0.001), a positive CC effect (≈0.33, p≈0.02), and a borderline negative Gini×CC interaction (p≈0.08). Conclusions The political impact of inequality is context-dependent and integrity-mediated. Control of Corruption consistently emerges as the institutional dimension most tightly linked to citizens’ voice, while inequality’s association with VA hinges on governance quality and differs by development group. Absent cointegration, findings are interpreted as short-run within-country associations. Policy should pair inequality-reducing reforms with integrity-building measures to safeguard VA.in F1000Research on 2025-11-07 15:50:57 UTC.
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Sixth Annual BCM Hackathon on Structural Variation and Pangenomics [version 1; peer review: awaiting peer review]
Background Structural variants (SVs) and metagenomics remain challenging areas in genomics, requiring new tools and collaborative solutions. Hackathons provide a rapid, team-based approach to prototyping and innovation. Methods In August 2024, 48 scientists from six continents convened at Baylor College of Medicine for the Sixth Structural Variant Codeathon. Participants worked in interdisciplinary teams over three days, using public datasets and cloud-based infrastructure to design and implement computational tools. Results Eight projects were developed, addressing topics such as tandem repeat annotation, structural variant discovery, benchmarking, pangenome visualization, and machine learning applications. Each project produced open-source software, with repositories openly available on GitHub and archived on Zenodo. Conclusions The hackathon fostered global collaboration and generated reproducible, community-driven tools. These outputs provide new resources for structural variation and metagenomics research and demonstrate the effectiveness of hackathons in advancing genomic science.in F1000Research on 2025-11-07 15:41:35 UTC.
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Quantifying microbial interactions based on compositional data using an iterative approach for solving generalized Lotka-Volterra equations
by Yue Huang, Tianqi Tang, Xiaowu Dai, Fengzhu Sun
Understanding microbial interactions is fundamental for exploring population dynamics, particularly in microbial communities where interactions affect stability and host health. Generalized Lotka-Volterra (gLV) models have been widely used to investigate system dynamics but depend on absolute abundance data, which are often unavailable in microbiome studies. To address this limitation, we introduce an iterative Lotka-Volterra (iLV) model, a novel framework tailored for compositional data that leverages relative abundances and iterative refinements for parameter estimation. The iLV model features two key innovations: an adaptation of the gLV framework to compositional constraints and an iterative optimization strategy combining linear approximations with nonlinear refinements to enhance parameter estimation accuracy. Using simulations and real-world datasets, we demonstrate that iLV surpasses existing methodologies, such as the compositional LV (cLV) and the generalized LV (gLV) model, in recovering interaction coefficients and predicting species trajectories under varying noise levels and temporal resolutions. Applications to the lynx-hare predator-prey, Stylonychia pustula-P. caudatum mixed culture, and cheese microbial systems revealed consistency between predicted and observed relative abundances showcasing its accuracy and robustness. In summary, the iLV model bridges theoretical gLV models and practical compositional data analysis, offering a robust framework to infer microbial interactions and predict community dynamics using relative abundance data, with significant potential for advancing microbial research.in PLoS Computational Biology on 2025-11-07 14:00:00 UTC.
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HAPP: High-accuracy pipeline for processing deep metabarcoding data
by John Sundh, Emma Granqvist, Ela Iwaszkiewicz-Eggebrecht, Lokeshwaran Manoharan, Laura J. A. van Dijk, Robert Goodsell, Nerivania N. Godeiro, Bruno C. Bellini, Johanna Orsholm, Piotr Łukasik, Andreia Miraldo, Tomas Roslin, Ayco J. M. Tack, Anders F. Andersson, Fredrik Ronquist
Deep metabarcoding offers an efficient and reproducible approach to biodiversity monitoring, but noisy data and incomplete reference databases challenge accurate diversity estimation and taxonomic annotation. Here, we introduce a novel algorithm, NEEAT, for removing spurious operational taxonomic units (OTUs) originating from nuclear-embedded mitochondrial DNA sequences (NUMTs) or sequencing errors. It integrates ‘echo’ signals across samples with the identification of unusual evolutionary patterns among similar DNA sequences. We also extensively benchmark current tools for chimera removal, taxonomic annotation and OTU clustering of deep metabarcoding data. The best performing tools/parameter settings are integrated into HAPP, a high-accuracy pipeline for processing deep metabarcoding data. Tests using CO1 data from BOLD and large-scale metabarcoding data on insects demonstrate that HAPP significantly outperforms existing methods, while enabling efficient analysis of extensive datasets by parallelizing computations across taxonomic groups.in PLoS Computational Biology on 2025-11-07 14:00:00 UTC.
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Evaluation of risk factors for ocular morbidities and its impact on the lives of medical students: An academic collateral. [version 1; peer review: awaiting peer review]
Background One billion people worldwide have preventable vision impairment. Ocular morbidities are a significant problem in the public health sector, especially among medical students. The study objectives were to identify the prevailing ocular morbidities and evaluate the risk factors and their impact on students’ lifestyles and academics. Methods A cross-sectional study was conducted among 312 undergraduate medical students over 6 months. Data were collected through a structured questionnaire and analysed to identify the prevalence, associated risk factors, and consequences of ocular morbidities. Results 64.7% were suffering from ocular morbidities. Headache was a predominant symptom in students with (51.7%) and without (39.1%) ocular morbidities. The most common ocular morbidity was myopia (84.3%). 18.7% of students perceived that ocular morbidity had restricted them from participating in activities or applying for specific job posts. The evaluation of various risk factors inferred that ocular morbidity was associated with family history, early age onset of the condition, lighting, posture while reading, screen time, and a vitamin A-rich diet. Conclusion The study concluded that the most prevalent ocular morbidity was refractive error, with myopia being the highest among medical students, and it has adversely impacted the students’ lifestyle and academics, underscoring the need for early detection, preventive strategies, and health education interventions.in F1000Research on 2025-11-07 11:23:34 UTC.
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Innovations in Inventory Management to Improve the Profitability of Local SMEs [version 2; peer review: 1 approved with reservations, 1 not approved]
Background Efficient inventory management is a critical internal capability for ensuring the financial sustainability of micro and small enterprises, especially in emerging economies affected by post-pandemic disruptions. In Bagua, Peru, MSMEs often lack digitised control systems, leading to frequent stock imbalances, rushed purchases at high prices, and lower profitability; a deeper understanding of inventory practices that drive financial performance can contribute to more informed and strategic decision-making. Method This quantitative, descriptive, and explanatory study examined the effects of four components of inventory management—control, valuation methods, control records, and measurement—on profitability; a convenience sample of 83 MSMEs yielded 200 valid responses from key personnel involved in inventory decisions; A 21-item Likert scale validated by experts was applied, and the data were analysed using descriptive statistics and multiple linear regression in SPSS v27. Profitability indicators included return on assets (ROA), gross margin (GM), and return on equity (ROE). Results All dimensions of the inventory showed moderate levels of implementation (means: 2.37–2.62 on a five-point scale). The regression model demonstrated satisfactory predictive power (R2 = 0.402; F = 32.81; p < 0.001). Inventory measurement was the strongest and only highly significant predictor of profitability (β = 0.383; p < 0.001), followed by inventory control, with a smaller but significant contribution (β = 0.257; p = 0.013). Inventory valuation methods and control records did not show statistically significant direct effects (p > 0.40). Conclusion The findings highlight that decision-oriented measurement practices, supported by systematic control, are essential factors for the financial performance of micro and small enterprises; investment in digital monitoring tools, replenishment based on key performance indicators, and staff training could improve operational and financial efficiency; due to its cross-sectional design and localised context, future studies should incorporate longitudinal data and broader geographical comparisons to strengthen generalisation and explore possible mediation pathways between accounting-oriented practices and profitability.in F1000Research on 2025-11-07 10:50:24 UTC.
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Oral Health Policy Assessment in the WHO Eastern Mediterranean Region: A Scoping Review Protocol [version 1; peer review: awaiting peer review]
Background Although preventable and treatable, oral diseases affect nearly half of the world’s population, driven by limited accessibility and equity in oral healthcare services, and lack of integration of oral health into noncommunicable diseases (NCDs) and universal health coverage (UHC) agendas. The World Health Organization (WHO) Global Strategy and Action Plan on Oral Health 2023–2030 (WHOOH) emphasizes the importance of embedding oral health in national health systems and policies. Evidence-informed oral health policies (OHPs) can help reduce disease burden, improve access, and address inequalities. However, in the WHO Eastern Mediterranean Region (WHO EMR) (hereafter, EMR), current policies have not achieved meaningful impact, constrained by barriers that require comprehensive analysis and systematic evaluation. This review aims to systematically identify and assess OHPs and barriers and facilitators influencing their creation, dissemination, implementation, monitoring, and evaluation (CDIM&E). Methods A systematic search was developed for Ovid MEDLINE, and also used to search Embase, Cochrane Library, and Epistemonikos. It will also be applied to global and regional databases, covering January 2014 to December 2024 without language restrictions. Additional searches will be conducted on government websites (e.g., ministries of health) to capture OHPs. Eligible documents will include official and up-to-date national OHPs, and research or policy-related documents reporting barriers to and facilitators for the CDIM&E of OHPs. Independent reviewers will perform screening and data extraction using DistillerSR. Quantitative data will be analyzed in R Studio using descriptive statistics, while qualitative data will undergo thematic analysis in NVivo. Discussion Advancing evidence-informed OHPs in the EMR requires mapping existing national policies, evaluating their alignment with WHOOH targets, and understanding the barriers and facilitators for their CDIM&E. This review’s findings may help and support ministries of health, chief dental officers, academic institutions, and regional interest-holders to inform policy dialogue and support collective efforts to achieve the WHOOH targets. Registration The protocol is registered with the Open Science Framework (OSF): https://doi.org/10.17605/OSF.IO/DQ6E4.in F1000Research on 2025-11-07 10:48:43 UTC.
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Analysis of skin mycobiota associated with alopecia in captive cynomolgus macaques (Macaca fascicularis) based on Oxford Nanopore Technologies [version 1; peer review: awaiting peer review]
Backgrounds Alopecia in captive non-human primates (NHPs) is a major animal welfare concern in many primate facilities. Some studies suggested that the mycobiome, considered fungal communities in specific areas, could influence the pathogenesis of alopecia. However, the pathogenesis mechanism of alopecia in cynomolgus macaques is poorly known. Objectives This study aims to investigate the association between alopecia and skin mycobiota in cynomolgus macaques. Methods Skin swab samples were collected from five areas where alopecia is common (arm, dorsal, head, leg, and ventral areas) of 47 healthy and 50 alopecic macaques. The samples were extracted for DNA. Oxford Nanopore Technologies (ONT) was applied to explore the skin mycobiota based on full-length Internal Transcribed Spacer (ITS) sequencing. Results Our findings showed that alpha and beta diversities significantly differed between alopecic and healthy macaques among the five areas. Wallemia sebi was associated with alopecia in the arm. Furthermore, Candida albicans, Rhodotorula mucilaginosa, Exophiala dermatitidis, and Candida parapsilosis were prevalent in the dorsal and head areas. Moreover, Aspergillus penicillioides was dominant in the dorsal and ventral areas. Pseudozyma sp., Moesziomyces antarcticus, and Cladosporium dominicanum were uniquely found in the head area. Apiotrichum domesticum was highly observed in the leg and ventral areas. Lastly, Cladosporium halotolerans was uniquely detected in the ventral area. Conclusion These microorganisms may be associated with the development of alopecia in cynomolgus macaques. These findings might be useful for biomedical research and therapeutic management strategies of animal health in primate facilities in the future.in F1000Research on 2025-11-07 10:44:35 UTC.
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Needs and Wants as Relational Dynamics: A Marxist and Activity-Theoretical Framework [version 1; peer review: awaiting peer review]
This work presents a Marxist and activity-theoretical framework for understanding needs and wants as relational dynamics rather than fixed hierarchies. Drawing on the works of Marx, Engels, Gramsci, Mao Zedong, and Silvia Federici, alongside cultural-historical activity theory from Vygotsky, Leontyev, Rubinstein, Engeström, and Bedny, it conceptualizes needs as historically and socially produced relations between living beings and their modes of life. Integrating perspectives on emotion (Holodynski, Ratner, Roth, Burkitt) and biological agency (Michael Levin, Richard Lewontin), it examines how needs emerge ontogenetically, phylogenetically, and collectively, mediated by objects, tools, and cultural practices. The chapter emphasizes the material, symbolic, and pragmatic dimensions of mediation, showing how needs evolve through co-production of organisms and environments. Latin American veterinary and public health case studies illustrate the interplay of human, animal, and ecological needs in contexts such as companion animal care, livestock production, pest control, and wildlife conservation. By synthesizing socio-historical, psychological, emotional, biological, and ecological dimensions, the framework provides a holistic basis for analyzing and transforming how needs and wants are defined, aligned, and fulfilled in practice.in F1000Research on 2025-11-07 10:41:33 UTC.
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Toxicology Study and MMP-1 and COL1A1 Expression of Malang Green Apple Juice Fermented by Lactobacillus plantarum DAD-13 and Saccharomyces cerevisiae Fermipan on Human Fibroblast: Potential Modality of Anti-aging [version 1; peer review: awaiting peer rev
Background Continuous exposure to sunlight and pollution without adequate protection can damage skin, making it prone to premature aging. One of the natural ingredients for anti-aging is antioxidant. Malang green apple (Malus sylvestris Mill) contains bioactive compounds that can act as antioxidants, but its use is still limited to only as food ingredient. Furthermore, some studies show the potency of fruit fermentation to increase these bioactive compounds. Thus, this study is a preliminary study to examine the anti-aging potency of fermented Malang green apples. Methods Human foreskin fibroblasts were treated with fermented Malang green apple juice extract (FAJ) by Lactobacillus plantarum DAD-13 and Saccharomyces cerevisiae Fermipan and its unfermented (AJ) for 24, 48, and 72 hours. Cell viability was measured using the MTT assay and collagen deposition was measured using the Sirius red staining method. The expression of matrix metalloproteinase 1 (MMP-1) and collagen type 1 alpha 1 chain (COL1A1) was measured in fibroblasts after treatment with extracts. Results Cell viability and collagen deposition of fibroblasts tended to be higher after 48 h of extract exposure. Fibroblasts that received FAJ 62.5 μg/mL showed higher cell viability than negative control (p <0.05) and FAJ 31.25 μg/mL showed higher collagen deposition than negative control (p <0.05) at 48 hours of extract exposure. AJ and FAJ also decreased MMP-1 gene expression. They showed a significant decrease in MMP-1 levels (p <0.01) compared to the untreated group, whereas they showed increased expression of COL1A1 at low concentrations. There was no significant difference in the gene expression between FAJ and AJ. Conclusions Our results indicated that Malang green apple juice extract affected fibroblast cell viability, collagen deposition, MMP-1, and COL1A1 gene expression. Better results were obtained at lower concentrations. Exposure of lower concentrations of FAJ to skin fibroblasts for 48 h resulted in better results.in F1000Research on 2025-11-07 10:39:29 UTC.
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Stability through plasticity: Finding robust memories through representational drift
Proceedings of the National Academy of Sciences, Volume 122, Issue 45, November 2025.
SignificanceAlthough synaptic and neuronal changes are often associated with learning, many such changes occur without learning or forgetting in a phenomenon known as representational drift. Previous studies suggest that multiple synaptic configurations ...in PNAS on 2025-11-07 08:00:00 UTC.
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MDFIC2 is a PIEZO channel modulator that can alleviate mechanical allodynia associated with neuropathic pain
Proceedings of the National Academy of Sciences, Volume 122, Issue 45, November 2025.
SignificanceDespite the known importance of the PIEZO2 mechanosensitive channel to innocuous touch, proprioception, mechanical pain, and interoception, direct modulators are still underexplored. Here, we identify MDFIC2, a sensory neuron–enriched ...in PNAS on 2025-11-07 08:00:00 UTC.
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l-Fucose is a candidate monosaccharide neuromodulator and mitigates Alzheimer’s synaptic deficits
Science Advances, Volume 11, Issue 45, November 2025.
in Science Advances on 2025-11-07 08:00:00 UTC.
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Quantifying widespread hydrothermal chimneys on the East Pacific Rise flanks between 9°43′ and 57′N
Science Advances, Volume 11, Issue 45, November 2025.
in Science Advances on 2025-11-07 08:00:00 UTC.
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Peptide-MHC–targeted retroviruses enable in vivo expansion and gene delivery to tumor-specific T cells
Science Advances, Volume 11, Issue 45, November 2025.
in Science Advances on 2025-11-07 08:00:00 UTC.
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A network of basolateral amygdala projection neurons contributes to stress-induced activation of the hypothalamic-pituitary-adrenal axis
Science Advances, Volume 11, Issue 45, November 2025.
in Science Advances on 2025-11-07 08:00:00 UTC.
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Terahertz antiferromagnetic dynamics induced by ultrafast spin currents
Science Advances, Volume 11, Issue 45, November 2025.
in Science Advances on 2025-11-07 08:00:00 UTC.
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Alveolar macrophages initiate the spatially targeted recruitment of neutrophils after nanoparticle inhalation
Science Advances, Volume 11, Issue 45, November 2025.
in Science Advances on 2025-11-07 08:00:00 UTC.
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Human stem cell-derived β cells expressing an optimized CD155 reduce cytotoxic immune cell function for application in type 1 diabetes
Science Advances, Volume 11, Issue 45, November 2025.
in Science Advances on 2025-11-07 08:00:00 UTC.
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PLAMseq enables the proteo-genomic characterization of chromatin-associated proteins and protein interactions in a single workflow
Science Advances, Volume 11, Issue 45, November 2025.
in Science Advances on 2025-11-07 08:00:00 UTC.
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Functional divergence of tandem duplicate SCPL acyltransferase genes reveals convergent evolution of chicoric acid biosynthesis
Science Advances, Volume 11, Issue 45, November 2025.
in Science Advances on 2025-11-07 08:00:00 UTC.
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Dynamically autofocused 3D pulsed laser micromachining enables advanced 3D bioelectronics
Science Advances, Volume 11, Issue 45, November 2025.
in Science Advances on 2025-11-07 08:00:00 UTC.
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Attenuated LMCT photocatalysis enables C─H allylation of methane and other gaseous alkanes
Science Advances, Volume 11, Issue 45, November 2025.
in Science Advances on 2025-11-07 08:00:00 UTC.
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Pfs230 domain 12 is a potent malaria transmission–blocking vaccine candidate
Science Advances, Volume 11, Issue 45, November 2025.
in Science Advances on 2025-11-07 08:00:00 UTC.
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Hug fans or follow celebrities? How nationalism is reinforced on Chinese social media
Science Advances, Volume 11, Issue 45, November 2025.
in Science Advances on 2025-11-07 08:00:00 UTC.
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Oligo-CALL: A next-generation barcoding platform for studying resistance to targeted therapy
Science Advances, Volume 11, Issue 45, November 2025.
in Science Advances on 2025-11-07 08:00:00 UTC.
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Mothers facing greater environmental adversity experience increased costs of reproduction
Science Advances, Volume 11, Issue 45, November 2025.
in Science Advances on 2025-11-07 08:00:00 UTC.
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The role of universities in society
Science Advances, Volume 11, Issue 45, November 2025.
in Science Advances on 2025-11-07 08:00:00 UTC.
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Concurrent selection of internal goals and external sensations during visual search
Science Advances, Volume 11, Issue 45, November 2025.
in Science Advances on 2025-11-07 08:00:00 UTC.
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NAD+ reverses Alzheimer’s neurological deficits via regulating differential alternative RNA splicing of EVA1C
Science Advances, Volume 11, Issue 45, November 2025.
in Science Advances on 2025-11-07 08:00:00 UTC.
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Source framing triggers systematic bias in large language models
Science Advances, Volume 11, Issue 45, November 2025.
in Science Advances on 2025-11-07 08:00:00 UTC.
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Endogenic heat at Enceladus’ north pole
Science Advances, Volume 11, Issue 45, November 2025.
in Science Advances on 2025-11-07 08:00:00 UTC.
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Energy landscape–engineered iontronics enable artificial thermoreceptors for augmented bioinspired thermosensation
Science Advances, Volume 11, Issue 45, November 2025.
in Science Advances on 2025-11-07 08:00:00 UTC.
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Engineered probiotic restores GLP-1 signaling to ameliorate fiber-deficiency exacerbated colitis
Science Advances, Volume 11, Issue 45, November 2025.
in Science Advances on 2025-11-07 08:00:00 UTC.
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DKK3-LRP1 complex and a chemical inhibitor regulate Aβ clearance in models of Alzheimer’s disease
Science Advances, Volume 11, Issue 45, November 2025.
in Science Advances on 2025-11-07 08:00:00 UTC.
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Structural basis of herpesvirus helicase-primase inhibition by pritelivir and amenamevir
Science Advances, Volume 11, Issue 45, November 2025.
in Science Advances on 2025-11-07 08:00:00 UTC.
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Stretchable complementary integrated electronics based on elastic dual-type transistors
Science Advances, Volume 11, Issue 45, November 2025.
in Science Advances on 2025-11-07 08:00:00 UTC.
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Electrical excitation of self-hybridized exciton polaritons in a van der Waals antiferromagnet
Science Advances, Volume 11, Issue 45, November 2025.
in Science Advances on 2025-11-07 08:00:00 UTC.
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Calcium-based synaptic and structural plasticity link pathological activity to synaptic reorganization in Parkinson’s disease
Science Advances, Volume 11, Issue 45, November 2025.
in Science Advances on 2025-11-07 08:00:00 UTC.
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Agreement, polarization, or both? Americans’ views of universities
Science Advances, Volume 11, Issue 45, November 2025.
in Science Advances on 2025-11-07 08:00:00 UTC.
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Issue Information
in Journal of Comparative Neurology on 2025-11-07 06:40:41 UTC.
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Structure in noise: Recurrent connectivity shapes neural variability to balance perceptual and cognitive demands in the human brain
Does neural variability reflect random noise or a feature that benefits adaptive behavior? Using intracranial recordings in humans, Terlau et al. demonstrate that neural variability results from the recurrent connectivity structure along the cortical hierarchy, which supports the spatiotemporal unfolding from perceptual to cognitive processing.in Neuron: In press on 2025-11-07 00:00:00 UTC.
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Human cortical dynamics of auditory word form encoding
Zhang, Leonard, et al. use high-density direct human brain recordings to reveal how the superior temporal gyrus (STG) detects word boundaries in natural speech and encodes whole auditory word forms. Neural populations dynamically reflect properties of the whole-word units listeners perceive in continuous, connected speech.in Neuron: In press on 2025-11-07 00:00:00 UTC.
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Large sharp-wave ripples promote hippocampo-cortical memory reactivation and consolidation during sleep
Robinson et al. found that the reactivation of experience-related neural ensemble patterns in hippocampus and cortex during sleep is specifically associated with a subset of large SWRs. Closed-loop optogenetic boosting of SWRs during post-task sleep enhanced ensemble reactivation in the hippocampus and prefrontal cortex and improved memory performance in mice.in Neuron: In press on 2025-11-07 00:00:00 UTC.
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Fat knows its limits: Creatine kinases keep adipocytes in check
The prevalence of obesity has led to significant interest in identifying the molecular mediators of adipose tissue expansion. In a recent issue of Cell Reports, Renzi and colleagues reveal a new mechanism by which creatine kinase B (CKB) regulates de novo lipogenesis in white adipocytes.in Cell Reports: Current Issue on 2025-11-07 00:00:00 UTC.
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The pan-cancer mutational landscape of MLL3 and its impact on prognosis and immunochemotherapy
MLL3 is frequently mutated across cancers. Liu et al. reveal that these mutations are associated with enhanced immune infiltration, predicting improved survival and immunochemotherapy response in endometrial and colon cancers, while Mll3 ablation in mouse models confirms its role in promoting anti-tumor immunity.in Cell Reports: Current Issue on 2025-11-07 00:00:00 UTC.
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Genetic mapping and predictive modeling of paralog synthetic lethality
Synthetic lethal paralogs have long been known, yet most paralog interactions are untested. Flister et al. report a screen of 36,648 known human paralog pairs. These data combined with a meta-analysis of 462 pairs across 49 cell models revealed insights into the molecular underpinnings of context-dependent synthetic lethality.in Cell Reports: Current Issue on 2025-11-07 00:00:00 UTC.
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ID1 boosts antiviral immunity by countering PRMT5-mediated STING methylation
Li et al. report that ID1 sustains STING activation and innate immunity by blocking PRMT5-STING binding, thereby preventing PRMT5-mediated methylation at Arg281 of STING. The PRMT5 inhibitor EPZ015666 enhances STING activation by suppressing PRMT5, providing a therapeutic candidate for antiviral treatment.in Cell Reports: Current Issue on 2025-11-07 00:00:00 UTC.
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A retrograde, non-canonical integrated stress response cascade maintains synaptic strength under amino acid deprivation
Mori and colleagues show that the integrated stress response (ISR) cascade triggered in the postsynaptic muscle of the Drosophila larval neuromuscular junction (NMJ) by acute amino acid restriction maintains baseline presynaptic release. This ATF4-independent, non-canonical ISR cascade enhances translation of Still life (Sif) and promotes neurotransmitter output at the NMJ.in Cell Reports: Current Issue on 2025-11-07 00:00:00 UTC.
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Therapeutic VEGFC treatment provides protection against traumatic-brain-injury-driven tauopathy pathogenesis
How traumatic brain injury (TBI) mechanistically contributes to neurodegenerative disease remains poorly understood. Marco et al. find that therapeutic viral vector-based delivery of VEGFC recuperates meningeal lymphatic drainage deficits post-TBI and protects against severe development of tauopathy, neurodegeneration, and cognitive decline in the PS19 mouse model of tauopathy.in Cell Reports: Current Issue on 2025-11-07 00:00:00 UTC.
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Situating the salience and parietal memory networks in the context of multiple parallel distributed networks using precision functional mapping
(Cell Reports 44, 115207; January 28, 2025)in Cell Reports: Current Issue on 2025-11-07 00:00:00 UTC.
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Surprise ‘tail’ found on an iconic galaxy may rewrite its history
Nature, Published online: 07 November 2025; doi:10.1038/d41586-025-03665-6
First image from Vera C. Rubin telescope reveals a previously unnoticed feature of galaxy M61 that may explain its mysterious properties.in Nature on 2025-11-07 00:00:00 UTC.
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A host of ‘exocomets’ swarms a distant star
Nature, Published online: 07 November 2025; doi:10.1038/d41586-025-03518-2
Dimming of the starlight from RZ Piscium reveals that 24 unseen bodies are whizzing around the star.in Nature on 2025-11-07 00:00:00 UTC.
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Preprint site arXiv is banning computer-science reviews: here’s why
Nature, Published online: 07 November 2025; doi:10.1038/d41586-025-03664-7
The repository is taking steps to tackle a surge in low quality, AI-generated content.in Nature on 2025-11-07 00:00:00 UTC.
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Pressure to publish is rising as research time shrinks, finds survey of scientists
Nature, Published online: 07 November 2025; doi:10.1038/d41586-025-03623-2
Researchers feel that pressures to publish are increasing, but the time and resources available to do research are decreasing, according to a survey by Elsevier.in Nature on 2025-11-07 00:00:00 UTC.
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Outside the window
Nature, Published online: 07 November 2025; doi:10.1038/d41586-025-03600-9
A life well lived.in Nature on 2025-11-07 00:00:00 UTC.
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How scientists exposed to other people’s trauma find support
Nature, Published online: 07 November 2025; doi:10.1038/d41586-025-03485-8
Vicarious trauma is an occupational risk for some researchers. But there are strategies to cope.in Nature on 2025-11-07 00:00:00 UTC.
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International PhD student numbers in US hold steady — for now
Nature, Published online: 07 November 2025; doi:10.1038/d41586-025-03653-w
Trend flies in face of Trump-administration policies, but could yet see a rapid decrease, especially in science fields.in Nature on 2025-11-07 00:00:00 UTC.
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Dock, prime, deliver while shrinking — and repeat
Nature Reviews Neuroscience, Published online: 07 November 2025; doi:10.1038/s41583-025-00995-2
Both full-collapse fusion and the more transient ‘kiss-and-run’ fusion are shown to occur at hippocampal synapses, with the kiss-and-run form involving vesicle shrinkage in between ‘kissing’ and ‘running’.in Nature Reviews on 2025-11-07 00:00:00 UTC.
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Room-temperature spin-layer locking of exciton–polariton nonlinearities in a WS2 microcavity
Nature Photonics, Published online: 07 November 2025; doi:10.1038/s41566-025-01786-y
A room-temperature double-layer WS2 microcavity is used to explore spin anisotropy and tune it with interlayer spacing.in Nature Photomics on 2025-11-07 00:00:00 UTC.
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Stabilizing high-efficiency perovskite solar cells via strategic interfacial contact engineering
Nature Photonics, Published online: 07 November 2025; doi:10.1038/s41566-025-01791-1
Engineering the perovskite–electrical contact interface with sodium heptafluorobutyrate reduces interfacial defects and improves charge transport in perovskite solar cells. Functionalized devices deliver a certified power conversion efficiency of 26.96%, which is fully retained after 1,200 h of continuous operation under 1-sun illumination.in Nature Photomics on 2025-11-07 00:00:00 UTC.
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Genome-wide bacterial genetic interaction mining by dual Tn-seq
Nature Methods, Published online: 07 November 2025; doi:10.1038/s41592-025-02921-x
Genome-wide bacterial genetic interaction mining by dual Tn-seqin Nature Methods on 2025-11-07 00:00:00 UTC.
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Scaling up sequence searching
Nature Methods, Published online: 07 November 2025; doi:10.1038/s41592-025-02922-w
Scaling up sequence searchingin Nature Methods on 2025-11-07 00:00:00 UTC.
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Poison frogs
Nature Methods, Published online: 07 November 2025; doi:10.1038/s41592-025-02885-y
Endowed with formidable chemical defenses, spectacular coloration and diverse parental care strategies, poison frogs are a powerful comparative model for understanding how ecology, genetics and neurobiology intersect to shape the evolution of physiology and behavior.in Nature Methods on 2025-11-07 00:00:00 UTC.
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Imaging the genome in motion
Nature Methods, Published online: 07 November 2025; doi:10.1038/s41592-025-02920-y
TRACK-IT offers a live-cell 3D genome imaging tool to study genome motion across different genomic scales and chromatin states.in Nature Methods on 2025-11-07 00:00:00 UTC.
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Monod: model-based discovery and integration through fitting stochastic transcriptional dynamics to single-cell sequencing data
Nature Methods, Published online: 07 November 2025; doi:10.1038/s41592-025-02832-x
Monod fits biophysically motivated models to single-cell transcriptomics data, empowering multifaceted and integrative insights of gene expression dynamics, stochasticity and regulation.in Nature Methods on 2025-11-07 00:00:00 UTC.
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nELISA: a high-throughput, high-plex platform enables quantitative profiling of the inflammatory secretome
Nature Methods, Published online: 07 November 2025; doi:10.1038/s41592-025-02861-6
nELISA miniaturizes the sandwich immunoassay and transforms it into a massively scalable platform for quantitative proteomics.in Nature Methods on 2025-11-07 00:00:00 UTC.
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Functional significance of opioid receptor homomers and heteromers
Nature Communications, Published online: 07 November 2025; doi:10.1038/s41467-025-64693-4
A new structural dynamics analysis provides an explanatory bridge between apparently divergent results in the field of opioid receptor oligomerization and, by extension, in the broader field of class A G protein-coupled receptor oligomerization.in Nature Communications on 2025-11-07 00:00:00 UTC.
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The marine phosphorus cycle driven by an unlikely microbe
Nature Communications, Published online: 07 November 2025; doi:10.1038/s41467-025-64456-1
Phosphorus availability is vital to ocean ecosystem functioning. Analyses of global seawater samples combined with laboratory experiments reveal the Alteromonas bacteria as a surprising regulator of the marine phosphorus cycling.in Nature Communications on 2025-11-07 00:00:00 UTC.
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Multifunctionally diverse alkaline phosphatases of Alteromonas drive the phosphorus cycle in the ocean
Nature Communications, Published online: 07 November 2025; doi:10.1038/s41467-025-64455-2
This study shows that Alteromonas is a key driver of phosphorus recycling in the ocean and that its alkaline phosphatases are multifunctional—with different families coexisting in one genome by adopting distinct functions and secretion strategies.in Nature Communications on 2025-11-07 00:00:00 UTC.
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The nerve center of organ engineering
Nature Communications, Published online: 07 November 2025; doi:10.1038/s41467-025-64801-4
As tissue engineering has developed it has become apparent that multiple inputs are needed to fully replicate tissues, neuronal-axonal networks are an important part of this. In this review, the authors explore the advances in biomanufacturing and multi cell techniques aiming to generate tissues with integrated neuronal networks.in Nature Communications on 2025-11-07 00:00:00 UTC.
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Turbulent isopycnal mixing dominates thermohaline transformations of intermediate ocean waters
Nature Communications, Published online: 07 November 2025; doi:10.1038/s41467-025-64806-z
Based on deep ocean observations, temperature and salinity transformations along density surfaces, which do not disturb the ocean dynamics, are more important than their across density equivalents.in Nature Communications on 2025-11-07 00:00:00 UTC.
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Reference genome and population genomic analyses reveal insight into herbicide tolerance in Avena fatua L.
Nature Communications, Published online: 07 November 2025; doi:10.1038/s41467-025-64825-w
Avena fatua (wild oat) is a herbicide resistant weed species for many crops worldwide. Here, the authors report its genome assembly, reveal evolutionary history through population genetics analyses, and identify expanded GST genes in conferring herbicide resistance.in Nature Communications on 2025-11-07 00:00:00 UTC.
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Deep learning models simultaneously trained on multiple datasets improve base-editing activity prediction
Nature Communications, Published online: 07 November 2025; doi:10.1038/s41467-025-65200-5
CRISPR base editing enables the precise introduction of single-nucleotide mutations in the genome. Here, authors generated new adenine/cytosine base editor dataset and proposed a deep-learning model CRISPRon-BE for base editor efficiency prediction, thereby enhancing base editing applications.in Nature Communications on 2025-11-07 00:00:00 UTC.
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Electrochemical deutero-(di)carboxylations for the preparation of deuterium-labeled medicinal building blocks
Nature Communications, Published online: 07 November 2025; doi:10.1038/s41467-025-64818-9
The metal cations released from sacrificial anodes during reductive electrosynthetic reactions are widely believed to not affect reaction outcomes. Here, the authors disclose an electrochemical deutero-(di)carboxylation that relies on anodically generated Mg2+ cations to achieve selectivity in both the site and amount of deuteration.in Nature Communications on 2025-11-07 00:00:00 UTC.
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Quantum light steers photoelectrons
Nature Physics, Published online: 07 November 2025; doi:10.1038/s41567-025-03092-4
When driven by nonclassical light, photoemission from a needle tip reveals signatures of strong-field physics, opening up opportunities to control matter and to engineer the building blocks of quantum technologies.in Nature Physics on 2025-11-07 00:00:00 UTC.
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Fractional quantization in insulators from Hall to Chern
Nature Physics, Published online: 07 November 2025; doi:10.1038/s41567-025-03072-8
This Review describes the concepts behind generalized quantum Hall effects that can take place without a magnetic field, and summarizes recent experimental manifestations of these phenomena in twisted two-dimensional materials and few-layer graphene.in Nature Physics on 2025-11-07 00:00:00 UTC.
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Quantum light drives electrons strongly at metal needle tips
Nature Physics, Published online: 07 November 2025; doi:10.1038/s41567-025-03087-1
The common description of strong-field light–matter interaction neglects the quantum-optical nature of the driving field. Now signatures of strong-field photoemission appear in electron energy spectra when driving with non-classical light.in Nature Physics on 2025-11-07 00:00:00 UTC.
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A high-density diffuse optical tomography dataset of naturalistic viewing
Scientific Data, Published online: 07 November 2025; doi:10.1038/s41597-025-06041-1
A high-density diffuse optical tomography dataset of naturalistic viewingin Nature scientific data on 2025-11-07 00:00:00 UTC.
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A large electroencephalogram database of freewill reaching and grasping tasks for brain machine interfaces
Scientific Data, Published online: 07 November 2025; doi:10.1038/s41597-025-06039-9
A large electroencephalogram database of freewill reaching and grasping tasks for brain machine interfacesin Nature scientific data on 2025-11-07 00:00:00 UTC.
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Chromosome-scale genome assembly and annotation of Saccharina sculpera
Scientific Data, Published online: 07 November 2025; doi:10.1038/s41597-025-06033-1
Chromosome-scale genome assembly and annotation of Saccharina sculperain Nature scientific data on 2025-11-07 00:00:00 UTC.
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A multi-regional input-output database linking Chinese subnational regions and global economies
Scientific Data, Published online: 07 November 2025; doi:10.1038/s41597-025-06040-2
A multi-regional input-output database linking Chinese subnational regions and global economiesin Nature scientific data on 2025-11-07 00:00:00 UTC.
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Building morphologies of the USA structures database; a gauntlet feature set
Scientific Data, Published online: 07 November 2025; doi:10.1038/s41597-025-05925-6
Building morphologies of the USA structures database; a gauntlet feature setin Nature scientific data on 2025-11-07 00:00:00 UTC.
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The composition and structure of the outer kinetochore KMN complex is conserved across kingdoms
Communications Biology, Published online: 07 November 2025; doi:10.1038/s42003-025-09120-6
Affinity purification in Arabidopsis identified all key subunits of the outer kinetochore KMN complex. Functional analyses revealed a striking conservation of its composition and organization across kingdoms, underscoring its deep evolutionary origin.in Nature communications biology on 2025-11-07 00:00:00 UTC.
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Kinetoplast DNA structure, RNA editing patterns and small respiratory Complex I in Trypanosoma musculi
Communications Biology, Published online: 07 November 2025; doi:10.1038/s42003-025-08883-2
Mitochondrial kDNA and RNA editing in Trypanosoma musculi are associated with a small Complex I, providing insights into mitochondrial metabolism and kDNA dynamics in trypanosomes.in Nature communications biology on 2025-11-07 00:00:00 UTC.
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Cross-platform motif discovery and benchmarking to explore binding specificities of poorly studied human transcription factors
Communications Biology, Published online: 07 November 2025; doi:10.1038/s42003-025-08909-9
Cross-platform benchmarking of DNA binding specificity models highlights top-performing motif discovery methods and demonstrates the potential of advanced models to capture alternative binding modes of human transcription factors.in Nature communications biology on 2025-11-07 00:00:00 UTC.
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Roles of the membrane-binding motif and the C-terminal domain of RNase E in localization and diffusion in E. coli
In Escherichia coli, RNase E, a central enzyme in RNA processing and mRNA degradation, contains a catalytic N-terminal domain, a membrane-targeting sequence (MTS), and a C-terminal domain (CTD). We investigated how MTS and CTD influence RNase E localization, diffusion, and function. Super-resolution microscopy revealed that ~93% of RNase E localizes to the inner membrane and exhibits slow diffusion similar to polysomes. Comparing the native amphipathic MTS with a transmembrane motif showed that the MTS confers slower diffusion and stronger membrane binding. The CTD further slows diffusion by increasing mass but unexpectedly weakens membrane association. RNase E mutants with partial cytoplasmic localization displayed enhanced co-transcriptional degradation of lacZ mRNA. These findings indicate that variations in the MTS and the presence of the CTD shape the spatiotemporal organization of RNA processing in bacterial cells, providing mechanistic insight into how RNase E domain architecture influences its cellular function.in eLife on 2025-11-07 00:00:00 UTC.
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Rhythmic sampling and competition of target and distractor in a motion detection task
It has been suggested that the visual system samples attended information rhythmically. Does rhythmic sampling also apply to distracting information? How do attended information and distracting information compete temporally for neural representations? We recorded electroencephalography (EEG) from participants who detected instances of coherent motion in a random-dot kinematogram (RDK; the target), overlayed on different categories (pleasant, neutral, and unpleasant) of affective images from the International Affective Picture System (IAPS) (the distractor). The moving dots were flickered at 4.29 Hz, whereas the IAPS pictures were flickered at 6 Hz. The time course of EEG spectral power at 4.29 Hz was taken to index the temporal dynamics of target processing. The spatial pattern of the EEG spectral power at 6 Hz was similarly extracted and subjected to a moving-window MVPA decoding analysis to index the temporal dynamics of processing pleasant, neutral, or unpleasant distractor pictures. We found that (1) both target processing and distractor processing exhibited rhythmicity at ~1 Hz and (2) the phase difference between the two rhythmic time courses was related to task performance, i.e., relative phase closer to π predicted a higher rate of coherent motion detection whereas relative phase closer to 0 predicted a lower rate of coherent motion detection. These results suggest that (1) in a target-distractor scenario, both attended and distracting information were sampled rhythmically and (2) the more target sampling and distractor sampling were separated in time within a sampling cycle, the less distraction effects were observed, both at the neural and the behavioral level.in eLife on 2025-11-07 00:00:00 UTC.
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Fronto-Hippocampal Synchronization in Rapid Spatial Learning in Humans
Achieving goals in real-life situations - from fetching a glass of water to landing a dream job - often requires planning based on experience and executing a sequence of actions. Neurophysiological research in animal models has indicated that the orbitofrontal cortex (OFC) mediates relationships between memory, actions, and outcomes and the hippocampus and other medial temporal lobe (MTL) regions are known to be critical for rapid learning, but little is known about how these areas interact to support rapid learning and retrieval of goal-directed action sequences in humans. Here, we leverage a rare opportunity to investigate human OFC gamma oscillations and examine the coordination between the OFC and MTL during a continuous multi-step task that requires applying recently acquired experience to guide behavior. We used multisite intracranial electroencephalography (iEEG) recordings while participants searched for a hidden goal in an animated game to study neural activity in both brain areas during goal-directed behavior. Hippocampal ripples - brief high-frequency oscillations reflecting synchronized neuronal firing - are known to support memory consolidation during sleep, but their role during active memory retrieval and updating remains unclear. We found that OFC gamma activity was modulated by both memory demands and ripples in the hippocampus and adjacent structures. Notably, ripple-coupled OFC gamma during exploration was associated with subsequent task performance. We propose that hippocampal ripples mark a narrow window, supporting hippocampal-cortical communication required for successful goal encoding for future behaviors.in bioRxiv: Neuroscience on 2025-11-07 00:00:00 UTC.
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Plateau potentials are instructive signals for behavioral timescale synaptic plasticity in the neocortex
Learning occurs via the adjustment of synaptic weights across a variety of timescales. The mechanisms supporting these processes, from single-shot to iterative learning, are unclear. The prevailing model in the neocortex, spike-timing dependent plasticity (STDP), requires many pairings of precisely coordinated activity. This is difficult to reconcile with single-shot learning in behaving animals. In hippocampus, an alternative form of plasticity driven by plateau potentials (behavioral timescale synaptic plasticity; BTSP) alters synaptic weights in a single trial to reorganize spatial representations. Here we show that layer 5 pyramidal neurons (L5 PNs) of mouse primary visual cortex (V1) exhibit highly prevalent plateau potentials that drive single-shot changes in sensory representations. Spontaneously occurring and experimentally induced plateaus rapidly and persistently modified L5 PN responses to visual stimuli. In acute slices, plateau potentials drove synapse-specific plasticity with few repetitions across seconds-long pairing intervals. Our results demonstrate that plateau potentials in the neocortex rapidly reshape neuronal representations through BTSP. This instructive form of plasticity provides a mechanism for dynamic adjustment of neocortical synaptic weights to support rapid learning.in bioRxiv: Neuroscience on 2025-11-07 00:00:00 UTC.
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Computational mechanisms for temporal integration in the anterior claustrum
The claustrum, with its extensive reciprocal connections to nearly all cortical regions, has long been hypothesized as a key hub for integrating diverse cognitive, sensory and motor information. However, despite its anatomical connectivity, whether and how it functionally integrates different inputs to generate coherent representations has remained unclear. Here, we developed a recurrent neural network (RNN) trained via supervised learning on behavioral metrics of delayed escape--a task that requires inference-based escape behavior and depends critically on anterior claustral activity. A subset of RNN neurons exhibited dynamics similar to those of anterior claustral neurons during this behavior. These neurons formed a recurrent cluster, a structure supported by in vitro stimulation experiments in claustral brain slices. We analyzed the computational properties of this claustrum-like cluster via dimensionality reduction of population activity. The network showed nonlinear integration of temporally distributed inputs and increased synergistic information. Rather than settling into attractors, integrated information was dynamically encoded along continuously evolving neural trajectories. Notably, the evolving trajectories that reflected dynamic integration in the RNN model matched those approximated in claustral recordings, suggesting the models biological plausibility. We propose that the anterior claustrum dynamically integrates task-relevant input signals over time and broadcasts the evolving representation to downstream brain regions capable of reading and interpreting it in a context-dependent manner.in bioRxiv: Neuroscience on 2025-11-07 00:00:00 UTC.
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Basolateral Amygdala Projections to the Prelimbic Cortex Suppress the Motivational Value of Reward-Associated Cues
Reward-associated cues drive reward-seeking behaviours, with different cue types taking on distinct associative meanings. In instrumental settings, discriminative stimuli (DSs) signal when a response will produce reward, while conditioned stimuli (CSs) are paired with reward delivery after responding. Basolateral amygdala (BLA) projections are known to mediate CS-guided reward seeking, but their role in DS-guided behaviour remains unclear despite DSs being uniquely effective in triggering reward seeking. Here, we used optogenetic stimulation of BLA projections to the nucleus accumbens (NAc) core or prelimbic cortex (PrL) to probe their causal involvement in DS- and CS-guided sucrose seeking. Female and male rats learned to lever press during DS+ trials to obtain sucrose paired with a CS+, and to withhold responding during DS- trials where sucrose was unavailable. We then assessed sucrose seeking evoked by response-independent DS+ and CS+ presentations, without sucrose. The DS+ prompted the greatest increases in lever pressing, acting as a strong Pavlovian conditioned excitor. Cue-paired photostimulation of BLA[->]NAc core or BLA[->]PrL projections did not alter this effect. In a test of instrumental responding for conditioned reinforcement, rats lever pressed most for DS+ and CS+ presentations, with no effect of cue-type, indicating that the two cues gained comparable conditioned reinforcing value. While cue-paired photostimulation of BLA[->]NAc core neurons had no impact, photostimulation of BLA[->]PrL projections suppressed instrumental responding for both the DS+ and CS+. These findings reveal the BLA[->]PrL pathway as a key regulator that constrains control over behaviour by reward-associated cues, making them less desirable and reducing their motivational effects.in bioRxiv: Neuroscience on 2025-11-07 00:00:00 UTC.
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Distributed Population Coding and Memory Consolidation in the Cerebellar Cortex and Dentate Nucleus
The cerebellum contributes to associative learning, yet how cortical and nuclear populations interact during memory formation remains unclear. We recorded single neurons from Purkinje cells (PCs) in Crus I/II and from the dentate nucleus (DN) in monkeys learning a visuomotor association. Both populations encoded the association in a temporally distributed manner spanning stimulus onset to movement. Once learning was consolidated, DN population activity preceded that of PCs, suggesting a progressive transfer of information from the cerebellar cortex to the nuclei, where long-term memory traces are stabilized. Spike-time analyses revealed that temporal regularity and bursts provide coding dimensions independent of firing rate and dynamically modulated across learning. These temporal features likely facilitate plasticity during acquisition and stabilize network dynamics after consolidation. Together, the results identify the dentate nucleus as an active site of memory consolidation and highlight distributed, ensemble-level mechanisms underlying cerebellar learning and predictive control.in bioRxiv: Neuroscience on 2025-11-07 00:00:00 UTC.
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Next-generation enhancer AAVs for selective interspecies targeting of midbrain dopaminergic neurons
To enable genetic access without genetically engineered animals, we developed and benchmarked enhancer-AAVs for selectively targeting dopamine (DA) neurons across mice and marmosets. 12 DA enhancer candidates were nominated through integrated single-nucleus RNA-seq/ATAC-seq analysis of marmoset ventral midbrain tissue. We identified two leads (cjDAE8, cjDAE4) by systemic AAV delivery and dual-color fluorescence screening in mice. Local co-injection of both AAVs in marmoset confirmed DA-restricted expression, with cjDAE8 exhibiting higher specificity. However, antibody amplification of reporter fluorescence exposed weakly labeled off-target cells (leaky expression). We therefore engineered next-generation AAV backbones for cjDAE8 to strengthen expression while limiting leakiness. Quantitative histology comparing natural versus antibody-amplified fluorescence defined AAV doses for achieving both high efficiency and greater than 90-95% specificity of DA neuron labeling across injection routes. We demonstrate applications for (i) retrograde targeting of projection-defined DA populations in marmoset, (ii) fiber-photometric recording of divergent DA-axonal dynamics in mouse striatal subregions, and (iii) driving optogenetic VTA DA self-stimulation. Our results provide a resource for interspecies DA targeting and two practical guidelines: backbone context critically shapes enhancer performance, and antibody-amplified readouts rigorously assesses specificity.in bioRxiv: Neuroscience on 2025-11-07 00:00:00 UTC.
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A unified model of short- and long-term plasticity: Effects on network connectivity and information capacity
Activity-dependent synaptic plasticity is a fundamental learning mechanism that shapes connectivity and activity of neural circuits. Existing computational models of Spike-Time-Dependent Plasticity (STDP) model long-term synaptic changes with varying degree of biological details. A common approach is to neglect the influence of short-term dynamics on long-term plasticity, which may represent an oversimplification for certain neuron types. Thus, there is a need for new models to investigate how short-term dynamics influence long-term plasticity. To this end, we introduce a novel phenomenological model, the Short-Long-Term STDP (SL-STDP) rule, which directly integrates short-term dynamics with postsynaptic long-term plasticity. We fit the new model to layer 5 visual cortex recordings and study how the short-term plasticity affects the firing rate frequency dependence of long-term plasticity in a single synapse. Our analysis reveals that the pre- and postsynaptic frequency dependence of the long-term plasticity plays a crucial role in shaping the self-organization of recurrent neural networks (RNNs) and their information processing through the emergence of sinks and source nodes. We applied the SL-STDP rule to RNNs and found that the neurons of SL-STDP network self-organized into distinct firing rate clusters, stabilizing the dynamics and preventing connection weights from exploding. We extended the experimentation by including homeostatic balancing, namely weight normalization and excitatory-to-inhibitory plasticity and found differences in degree correlations between the SL-STDP network and a network without the direct coupling between short-term and long-term plasticity. Finally, we evaluated how the modified connectivity affects networks' information capacities in reservoir computing tasks. The SL-STDP rule outperformed the uncoupled system in majority of the tasks and including excitatory-to-inhibitory facilitating synapses further improved information capacities. Our study demonstrates that short-term dynamics-induced changes in the frequency dependence of long-term plasticity play a pivotal role in shaping network dynamics and link synaptic mechanisms to information processing in RNNs.in bioRxiv: Neuroscience on 2025-11-07 00:00:00 UTC.
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Emotional Semantic Meaning Enhances Neural Tracking of Conversations Through Context-Sensitive Modulation of Auditory - Language Areas
Engagement in interaction arises through the continuous monitoring of conversation content, allowing individuals to prioritize information that is most relevant to them. Emotional salience of semantic content may play a key role in guiding this attentional engagement. By combining audiovisual 'Cocktail-party' - paradigm with source-localized magnetoencephalography and encoding-decoding models, we examined how emotional salience and narrative coherence shape cortical tracking of concurrent dialogues. Our results showed that emotional salience strengthened neural tracking of attended but not ignored conversations. This enhancement unfolded nonlinearly across the conversational arc, peaking early when the dialogue was coherent and later when incoherent. Cortical temporal response functions revealed latency-specific effects: emotional salience amplified early sensory encoding under uncertainty in auditory and language networks, whereas late semantic integration in these areas was driven by salience alone. These results indicate that emotional meaning dynamically modulates predictive engagement in speech, acting as a high-level relevance signal that sharpens attentional selection and semantic integration moment by moment across conversational turns.in bioRxiv: Neuroscience on 2025-11-07 00:00:00 UTC.
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Disruption in Patterning in the Whisker-to-Barrel Cortex Pathway Alters Behavior
Mice use their whiskers to convey sensory information, navigate and explore their environment. We investigated the behavioral impact of the disruption of somatotopic patterning along the whisker-to-barrel pathway utilizing two mouse models: Barrelless (BRL) mice, an adenylyl cyclase 1 variation, in which somatotopic patterning is absent in the barrel cortex and Prrxl1-/- mice, a genetic knockout in which patterning is disrupted along the entire lemniscal pathway. A textured novel object recognition test was conducted to investigate whisker-dependent discriminatory behavior, an open field test was conducted to investigate exploratory behavior. Results were compared to an outbred strain (CD-1) and demonstrated that BRL mice were able to discriminate, whereas Prrxl1-/- mice were unable to discriminate between textures, and that both strains exhibited increased anxiety. Exploratory and locomotor behavior increased in BRL mice but decreased in Prrxl1-/- mice. Together, the results suggest that somatotopy may be related to behavioral phenotype.in bioRxiv: Neuroscience on 2025-11-07 00:00:00 UTC.
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Ketamine and Psilocybin Differentially Impact Sensory Learning During the Mismatch Negativity
Ketamine and psilocybin show potential as therapies for various mental illnesses, including major depressive disorder. However, further investigation into their neural mechanisms is required to understand their effects on the brain. By combining computational modelling with electroencephalography (EEG), we examine the effects of ketamine and psilocybin on hierarchical sensory pwPE learning in the context of the auditory mismatch negativity, an event-related potential consistently shown to be reduced under psychotomimetic interventions. We employed a Bayesian framework and re-analyzed a previously acquired EEG dataset (Schmidt et al., 2012) by modelling single-trial EEG data using the Hierarchical Gaussian Filter. Using a placebo-controlled within-subject crossover design, healthy subjects were administered either S-ketamine or psilocybin during an auditory roving paradigm of pure sinusoidal tones. Our findings elucidate distinct neural impacts of ketamine and psilocybin on sensory learning: ketamine led to a larger reduction in the effect of sensory precision compared to placebo from 207 to 316 ms peaking at 277 ms in the frontal central channels, while psilocybin showed no significant effect. Both drugs reduced the expression of belief precision between 160 to 184 ms, peaking at 172 ms. For higher-level volatility pwPEs, ketamine reduced the expression at 312 ms while psilocybin had a null effect. For perception of elementary imagery, ketamine had a greater effect than psilocybin on sensory and volatility precision, while psilocybin had a greater effect on volatility pwPEs. Our findings suggest hallucinogens have distinct effects on sensory learning that could inform tailored therapies for major depression.in bioRxiv: Neuroscience on 2025-11-07 00:00:00 UTC.
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On the mechanism of calcium permeability and magnesium block in NMDA receptors - a central molecular paradigm in neuroplasticity
Neuroplasticity is a fundamental cellular mechanism underlying learning and memory formation and is primed by the coincidental detection of neurotransmitter release from the presynapse and the subsequent calcium influx upon voltage change in the postsynaptic membrane (Bliss and Collingridge, 1993). Molecular assemblies that achieve these events are N-methyl-D-aspartate receptors (NMDARs), which bind the neurotransmitter glutamate and a co-agonist, either glycine or D-serine, and allow Ca2+ influx upon relief of the Mg2+ channel blockade by membrane depolarization. However, the molecular basis governing Ca2+ permeability and Mg2+ blockade in NMDAR remains limited. Here, we demonstrate that Ca2+ permeation through the narrow constriction of the cation selectivity filter involves partial dehydration, as evidenced by multiple Ca2+ binding sites captured using single-particle cryo-electron microscopy (cryo-EM). In contrast, Mg2+ binds outside of the selectivity filter through the water network by remaining hydrated, thereby serving as a channel blocker. Furthermore, we show that the lipid network around the selectivity filter influences the stability of Mg2+ binding. Our study details the critical transmembrane chemistry of NMDAR for initiating neuroplasticity.in bioRxiv: Neuroscience on 2025-11-07 00:00:00 UTC.
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Distinct Mechanisms of Surround Modulation for Dynamic Natural Scenes in Motion- and Scene-Selective Cortex
Surround modulation refers to changes in neural responses to a central stimulus induced by its surrounding context, which can manifest as either suppression or facilitation. Although this phenomenon is well established for simple stimuli, its underlying neural mechanism during natural scene perception remains unclear. Using fMRI, we examined how motion congruence and categorical similarity between central and surrounding scenes shape surround modulation across the visual hierarchy. Central and surrounding scenes systematically varied in categorical similarity (identical exemplar, different exemplar of the same basic-level category, different basic-level category, or different superordinate category) and in motion direction (same or opposite direction). Neural responses were measured in primary visual cortex (V1), motion-selective cortex (hMT$+$), and scene-selective occipital and parahippocampal place areas (OPA and PPA). hMT$+$ showed robust motion-dependent surround suppression, which was stronger for same-direction motion. In contrast, V1 showed surround facilitation across all conditions, which was reduced when center and surround were identical and moved in the same direction, consistent with sensitivity to physical similarity. OPA and PPA primarily exhibited facilitation. Multivariate decoding between center-only and center-surround conditions complemented these findings, revealing motion-dependent surround modulation in hMT$+$, and category-dependent surround modulation in OPA and PPA. Across the visual hierarchy, surrounding scene context thus systematically attenuates redundant input or enhances informative differences: from low-level facilitation in V1 to motion-dependent suppression in hMT$+$ and category-dependent modulation in scene-selective regions.in bioRxiv: Neuroscience on 2025-11-07 00:00:00 UTC.
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From Atoms to Neuronal Spikes: A Multi-Scale Simulation Framework
Understanding how molecular events in ion channels impact neuronal excitability, as derived from the calculation of the time course of the membrane potentials, can help elucidate the mechanisms of neurological disease-linked mutations and support neuroactive drug design. Here, we propose a multi-scale simulation approach which couples molecular simulations with neuronal simulations to predict the variations in membrane potential and neural spikes. We illustrate this through two examples. First, molecular dynamics simulations predict changes in current and conductance through the AMPAR neuroreceptor when transitioning from the wild-type protein to certain disease-associated variants. The results of these simulations inform morphologically detailed models of cortical pyramidal neurons, which are simulated using the Arbor framework to determine neural spike activity. Based on these multiscale simulations, we suggest that disease associated AMPAR variants may significantly impact neuronal excitability. In the second example, the Arbor model is coupled with coarse-grained Monte Carlo gating simulations of voltage-gated (K+ and Na+) channels. The predicted current from these ion channels altered the membrane potential and, in turn, the excitation state of the neuron was updated in Arbor. The resulting membrane potential was then fed back into the Monte Carlo simulations of the voltage-gated ion channels, resulting in a bidirectional coupling of current and membrane potential. This allowed the transitions of the states of the ion channels to influence the membrane potentials and vice versa. Our simulations also included the crucial - so far unexplored - effects of the composition of the lipid membrane embedding the ion channels on the membrane potential and revealed a significant impact of temperature on the neuronal excitability. Our combined approaches predicted membrane potentials consistent with electrophysiological recordings and established a multi-scale framework linking the atomistic perturbations to neuronal excitability.in bioRxiv: Neuroscience on 2025-11-07 00:00:00 UTC.
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Offline Reconstruction of Diffusion MRI Acquisitions for Comparison Between Complex PCA-based and AI-based Denoising
Purpose: Optimal diffusion MRI (dMRI) reconstruction for image denoising is often unavailable from scanner reconstruction. In this work we make available an offline reconstruction pipeline for GE dMRI acquisitions, giving access to complex, unfiltered dMRI data. Furthermore, we compare the efficacy of GE HealthCare's AIR-Recon DLTM (ARDL), a proprietary convolutional neural network-based reconstruction and denoising approach, to open-source patch-based MPPCA and NORDIC denoising methods on high-resolution dMRI data. Methods: We developed an end-to-end offline dMRI reconstruction pipeline for GE HealthCare acquisitions, building on and augmenting the Orchestra software development kit and validated its output against scanner reconstruction. We used it to compare MPPCA, NORDIC and ARDL denoising approaches, considering underlying metrics reflecting noise variance and noise floor suppression, such as the signal dynamic range and ADC in highly anisotropic areas, noise variance in maximally-suppressed dMRI signal and downstream measurements, such as fibre orientation estimation and white matter tractography. Results: Our validated offline reconstruction starts from single-channel complex k-space data and allows channel combination, support of various in-plane/out-of-plane accelerations and partial Fourier reconstruction methods and retrospectively switching filters off. Unlike scanner reconstruction, our pipeline provides access to complex dMRI data, allowing denoising in the complex domain, which showed superior noise floor suppression compared to magnitude constrained denoising. Comparisons across denoising methods suggest improved spatial resolution, contrast-to-noise and more robust fibre orientation estimation when using patch-based approaches compared to ARDL. Conclusion: We found significant gains in dMRI data quality when using the proposed offline reconstruction pipeline, allowing denoising to occur in the complex domain, both for reducing noise-induced variance and bias. MPPCA and NORDIC (4D patch based) outperformed ARDL (2D) in terms of spatial resolution, reduction of noise-floor bias and variance.in bioRxiv: Neuroscience on 2025-11-07 00:00:00 UTC.
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Complex environmental cycles reveal evolution of circadian activity waveform and thermosensitive timeless splicing
Circadian clocks synchronise physiological and behavioural rhythms to environmental cycles such as light and temperature. In nature, temperature cycles lag light cycles, with the extent of lag varying seasonally. Thus, the extent of this delay is an essential aspect of seasonal cues. Yet, the combined effects of light and temperature cycles on circadian systems remain poorly understood. Using a series of environmental cycles with varying degrees of lag between temperature and light, we examined the response of circadian activity to complex environments and show that morning and evening activity exhibit differential temperature sensitivity in Drosophila melanogaster. We find that the expression of temperature-induced timeless splice variants is modulated by light cycles as well as the degree of lag between temperature and light. We also reveal rhythmic expression of the timeless splicing regulator Psi. Furthermore, we leveraged a laboratory-selection approach to reveal that the differential temperature sensitivity of morning and evening activity evolves upon selection. We observed selection-dependent differences in temporal expression of timeless splice variants thus linking circadian gene splicing to behavioural plasticity. Thus, our integrated behavioural, molecular, and evolutionary approach advances the understanding of how circadian systems integrate seasonal cues.in bioRxiv: Neuroscience on 2025-11-07 00:00:00 UTC.
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High-throughput imaging of GABA fluorescence as a functional assay for variants in the neurodevelopmental gene, SLC6A1
Pathogenic variants in SLC6A1, which encodes GABA Transporter 1 (GAT-1), are associated with developmental delay, autism, epilepsy (e.g., epilepsy with myoclonic astatic seizures [EMAS]), and possibly schizophrenia. Functional assays to establish pathogenicity of human variants is a key limiting factor in the clinical interpretation of genetic findings. Methods based on radioactive [3H]-GABA uptake come with significant regulatory concerns, cost, and workflow complexity, which could be resolved by an alternate assay. To address this issue, we developed a high-content fluorescence imaging assay of GAT-1-mediated GABA uptake using a genetically encoded GABA sensor, iGABA-Snfr. We demonstrated that pathogenic variants strongly reduced uptake (mean, -89.4% [95% CI, -71.5% to -107.3%]). Some variants of uncertain significance (VUS) were associated with reduced GABA uptake (G111R, S459R, V511M; mean, -101.2% [95% CI -81.1% to -121.3%]), whereas others showed only mild reduction (R211C, R566H, F242V, R419C; mean, -33.6% [95% CI -17.2% to -50.1%]), supporting variant reclassification. Variant-specific effects on iGABA were highly correlated with the results of the radioactive [3H]-GABA assay (R2=0.8095, p<0.0001). The molecular chaperone 4-phenylbutyric acid (4PBA) was associated with ~35% increase in iGABA. This non-radioactive assay is suitable for functional validation and high-throughput screening to identify positive modulators of GAT-1.in bioRxiv: Neuroscience on 2025-11-07 00:00:00 UTC.
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A silent Kv channel subunit shapes PV neuron action potential waveform and short-term synaptic plasticity during high-frequency firing
Fast-spiking parvalbumin-positive (PV) neurons provide precisely timed, context-dependent inhibition within cortical circuits. PV neuron firing properties are specialized among cortical neurons, suggesting that they express a unique complement of ion channels. Here, we identify the PV-specific silent voltage-gated potassium (Kv) channel subunit Kv6.4 (encoded by Kcng4) as a modulator of both intrinsic and synaptic properties. Kv6.4 does not form functional channels on its own but assembles with Kv2 subunits to create heterotetrameric channel complexes. Kcng4 expression is enriched within a distinct Pvalb-expressing subclass in primary somatosensory (S1) and motor (M1) cortex and emerges during postnatal development. Kv6.4 depolarizes the interspike and threshold potentials, broadens action potentials (APs), increases AP height, and decelerates the AP upstroke. These changes in AP waveform enhance GABA release probability and paired-pulse depression at synapses made by PV onto pyramidal (PYR) neurons. The effects of Kv6.4 loss are amplified during high-frequency firing, within the physiological range of fast-spiking PV neurons, likely due to altered repolarization dynamics that accumulate across successive APs. These findings are thus consistent with the function of Kv6.4 in modifying Kv2-mediated delayed rectifier currents. Hence, Kv6.4 tunes the temporal precision of PV inhibitory output, a feature that may be critical for stable excitation-inhibition ratios and adaptive circuit function underlying learning and behavior.in bioRxiv: Neuroscience on 2025-11-07 00:00:00 UTC.
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The Median Preoptic Nucleus is a Key Site for Estradiol Regulation of Sleep-Wake Behaviors in Females Rats
Study Objectives: Women experience more sleep disruptions than men, particularly during hormonal transitions such as puberty, pregnancy, and menopause. This study investigated the role of estradiol (E2) in regulating sleep-wake behavior in female rats and identified the brain regions involved. Methods: Using an exogenous E2 replacement model in ovariectomized rats, we assessed changes in sleep-wake patterns via EEG/EMG telemetry. The effects of E2 and progesterone, selective estrogen receptor agonists, and direct brain infusions of E2 and receptor antagonists were evaluated. Results: E2 administration increased wakefulness, reduced non-rapid eye movement (NREM) and rapid eye movement (REM) sleep, and decreased NREM slow-wave activity (SWA), predominantly during the dark phase. These effects required both estrogen receptor alpha (ER) and beta (ER{beta}) activation and were mediated by estrogen receptor signaling within the median preoptic nucleus (MnPO). Direct infusion of E2 into the MnPO was sufficient to replicate systemic effects, while local infusion of the pure estrogen receptor antagonist ICI 182,780 (Fulvestrant) attenuated them. Progesterone did not augment estradiol actions, and males showed no sleep-wake changes in response to E2, highlighting sex-specific mechanisms.in bioRxiv: Neuroscience on 2025-11-07 00:00:00 UTC.
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Connecting a P300 speller to a large language model
The advent of large-language models (LLMs) offers a transformative approach for improving the performance of brain-computer interface (BCI) spellers. We propose a novel framework that leverages the contextual understanding of LLMs to compensate for imperfect BCI decoding. Using existing P300 speller data, we simulated a system where users select letters to form words, generating text with characteristic spelling errors. This output is then processed by an LLM, which corrects the errors, a task that becomes more effective when the model considers full-sentence context. Our findings suggest that this synergy can accelerate communication rates by relaxing the need for high single-character accuracy. Beyond speed, integrating an LLM transforms the BCI into an intelligent agent, capable of acting as a discussant and assistant, thereby enriching the user experience.in bioRxiv: Neuroscience on 2025-11-07 00:00:00 UTC.
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Attentional reconfiguration during acute and sustained fear
BACKGROUND: Fear is a fundamental survival mechanism that both enhances the chances of survival by rapid detection and adaptive responses to potential threat and by optimizing sensory input and cognitive processing. Here we used naturalistic design with eye tracking to map the spatiotemporal dynamics of attention and arousal during fearful events with slow and fast temporal dynamics. METHODS: 21 participants watched a full-length horror movie while their eye-movements were recoded with eye tracker. Moment-to-moment intensity of sustained fear as well as the onsets of the jump scares (acute fear) were annotated and used to predict gaze parameters (fixation duration & counts, blink frequency, saccade amplitude, pupil size and intersubject synchronization of gaze position). RESULTS: Acute fear events led to shortening of fixation duration, suppression of blinking, as well as increase of fixation count, saccade amplitude, and pupil size. Sustained fear was in turn associated with increased pupil size and decrease in blinking and saccade amplitude. These effects remained significant when controlling for luminosity. CONCLUSIONS: During natural vision both acute and sustained fear cause rapid reconfiguration, state dependent and individual changes in visual attention prioritizing that is accompanied by increased affective arousal. Keywords: Emotion, fear, attention, pupillometry, eye-trackingin bioRxiv: Neuroscience on 2025-11-07 00:00:00 UTC.
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Metabolic Dysfunction Underlying Fatigue in Multiple Sclerosis: Elevated Lactate and Impaired Post-Exercise Creatine Response in the Anterior Cingulate Cortex
Background: Multiple Sclerosis (MS) is characterised by altered brain metabolism and increased chronic perceived fatigue. However, the relationship between brain metabolites, fatigue, and physical task effects in MS remains unclear. This study investigated brain metabolite concentrations (glutamate + glutamine (Glx), lactate, and total creatine (tCr)) in the anterior cingulate cortex (ACC), a region involved in interoceptive processing, before and after a physical task. Methods: Twenty-two people with MS (pwMS) and 22 controls underwent Magnetic Resonance Spectroscopy before and after fatiguing wrist extension tasks. Linear mixed models analysed group differences and exercise-induced metabolite changes. Results: PwMS showed higher ACC lactate concentrations than controls at rest and post-exercise (F = 7.08, p = 0.011, 95% CI[0.033, 0.228]). No significant Glx differences were observed. A significant group x exercise interaction for tCr occurred (F = 4.63, p = 0.037, 95% CI[0.027, 0.581]), with tCr decreasing post-exercise in controls (t = 3.09, p = 0.02) but remaining stable in pwMS. Changes in lactate correlated moderately with perceived effort in pwMS (r = 0.51, p = 0.04). Conclusions: This study provides novel evidence of metabolic differences in pwMS, characterised by elevated lactate and stable post-exercise tCr, suggesting altered energy metabolism potentially linked to mitochondrial dysfunction.in bioRxiv: Neuroscience on 2025-11-07 00:00:00 UTC.
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Distinctive Functionality of Semantic Hubs: Evidence from Semantic Dementia
Semantic cognition relies on a distributed network with multiple candidate hub regions that bind multimodal conceptual information. While the anterior temporal lobe (ATL) is widely regarded as a core semantic hub, the roles of other candidate regions such as the fusiform gyrus (FFG) and posterior middle temporal gyrus (pMTG) remain debated, particularly regarding verbal and non-verbal semantic processing within the same sensory modality. This study examined 33 patients with semantic dementia and 20 healthy controls using a comprehensive behavioral battery (word and picture versions of the Pyramid and Palm Trees Test and a word picture verification task) combined with multimodal neuroimaging, including voxel based morphometry, diffusion-weighted imaging, and resting-state fMRI. Partial correlation and commonality analyses revealed that (1) the left ATL selectively underpins abstract verbal semantic processing, (2) the left FFG contributes to general semantic processing across verbal and non-verbal stimuli, (3) and the left pMTG plays a critical role in integrating verbal and non verbal semantic information. White matter tracts linking the left ATL and FFG to the right ATL significantly predicted semantic integration performance, underscoring the importance of inter hemispheric structural connectivity. Functional measures in contralateral regions, including amplitude of low frequency fluctuation (ALFF) in the right FFG and degree centrality (DC) in the right pMTG, also predicted integration outcomes, suggesting compensatory network reorganization. These findings highlight functional specialization among semantic hubs and underscore the importance of multimodal, cross-hemispheric approaches for understanding the neural architecture of semantic representation.in bioRxiv: Neuroscience on 2025-11-07 00:00:00 UTC.
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Regulation of miR-219 and its target RalGPS dictates acute synaptic plasticity at the Drosophila neuromuscular junction
RNA regulatory mechanisms mediate adaptive responses requiring rapid gene expression changes. Examining microRNA (miRNA)-mediated control of structural synaptic plasticity, we identified miR-219 and six other conserved miRNAs regulating activity-induced morphogenesis at Drosophila glutamatergic synapses. Among miRNA targets downregulated by acute stimulation, the Ral-activating factor RalGPS is necessary for presynaptic morphogenesis and sufficient to block plasticity. Stimulation elevates miR-219 loading into Argonaute complexes without altering mature miR-219 levels, revealing a post-transcriptional regulatory mechanism. We conclude that activity-induced miRNA loading modulates Ral signaling via RalGPS to enable presynaptic remodeling and growth, establishing a novel link between neuronal activity and synaptic structural plasticity.in bioRxiv: Neuroscience on 2025-11-07 00:00:00 UTC.
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Phase-Specific Hippocampal and Cortical Medial Temporal Lobe Involvement in Allocentric Working Memory
The hippocampus and cortices of the medial temporal lobe (MTL) regions are increasingly implicated in working memory, but their precise contributions--particularly during delay maintenance--remain debated. Using functional magnetic resonance imaging (fMRI), we investigated the involvement of hippocampal and cortical MTL in a demanding allocentric working memory task requiring relational binding. A total of 128 healthy human adults (92 females) aged 20-83 (mean 39) years performed an allocentric working memory task during fMRI, in which object-location bindings had to be learned, maintained, and manipulated across an 8 second delay. The design included a staircase procedure to balance task difficulty across participants and a passive viewing condition to control for perceptual and attentional demands. Across the full sample, anterior and mid hippocampal subregions and cortical MTL areas were engaged in all phases, showing study-related activation, widespread delay-phase deactivation with region-specific sustained responses, and posterior hippocampal and cortical MTL reactivation during test. Contrary to predictions, hippocampal and cortical MTL activation did not vary with performance among younger adults. Instead, differences emerged in a left temporoparietal cluster, potentially reflecting verbal encoding strategies. Older adults, relative to younger adults with the most comparable performance levels, showed lower anterior hippocampal activation and smaller correct-passive viewing differences in perirhinal and parahippocampal cortices. Taken together, these findings accord with hippocampal subregions and cortical MTL involvement across the temporal unfolding of allocentric working memory, but with distinct phase-specific roles.in bioRxiv: Neuroscience on 2025-11-07 00:00:00 UTC.
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Motor Imagery Affects both Cortical and Spinal Circuitry: A Transcranial and Transspinal Magnetic Stimulation Study.
Motor imagery (MI), the mental rehearsal of movement without physical execution, is a key technique in brain-computer interfaces (BCIs) for voluntarily eliciting cortical modulations. Beyond cortical effects, MI could also modulate spinal cord processing, which offers additional potential for neurorehabilitation in conditions like spinal cord injury (SCI) and stroke, where BCIs are used for therapy. To investigate the interactions of MI with both the cortex and the spinal cord, we employed both transcranial magnetic stimulation (TMS) and trans-spinal magnetic stimulation (TSMS). With proper coil orientation, TSMS elicited short- and long-latency motor evoked potentials (MEPs) in forearm muscles and lateralized evoked potentials in the cortex. MI modulated both TMS-induced and TSMS-induced cortical responses and MEPs. This demonstration of MI affecting both cortical and spinal circuitry underscores its potential as a powerful strategy for BCI-driven neurorehabilitation, including pairing MI with magnetic stimulation.in bioRxiv: Neuroscience on 2025-11-07 00:00:00 UTC.
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Adaptation to transient and local electrical muscle stimulation elicits persistent and global changes in walking kinematics
It is generally assumed that motor commands altered by adaptation to a novel environment revert to their original state once the environment returns to baseline. However, this assumption, based mainly on simple movements such as reaching, may not hold for complex actions. In redundant systems, de-adaptation can cause motor commands and resulting kinematics to settle into states distinct from the original. Here, we examined adaptation and de-adaptation in treadmill walking while modulating lower-limb dynamics using closed-loop neuromuscular electrical stimulation (NMES) applied bilaterally to the tibialis anterior. Adaptation to a localized ankle perturbation induced global kinematic changes across the ankle, knee, and hip joints. After perturbation removal, joint kinematics did not fully return to baseline; instead, features of the adapted gait persisted for eight minutes. These findings highlight the distinctive nature of motor adaptation in redundant systems and demonstrate the potential of NMES-based perturbations for inducing implicit modifications in movement patterns.in bioRxiv: Neuroscience on 2025-11-07 00:00:00 UTC.
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A Pilot Study on Assessing Auditory Masking Using Auditory Steady-State Responses
Auditory masking is important in the characterization of human hearing and hearing impairment. Traditionally, masking is assessed through behavioral methods, witch requires active participant engagement. This study investigates the potential of using Auditory Steady-State Response (ASSR) to assess auditory masking, enabling masking assessment without requiring active participation. ASSRs were measured in response to a 40-Hz amplitude-modulated probe signal with and without the presence of a masker. The probe signals were 1/3-octave bandwidth Gaussian noise centered at 891 and 1414 Hz (center frequency, CF) and presented at 10, 20, 30, and 40 dB above individual behavioral masking thresholds (MT). The masker was lowpass Gaussian noise (cut-off 707 Hz) presented at 65 and 85 dB SPL (masker level, ML). The ASSR amplitude increased with presentation level (PL) and decreased in the presence of a masker, confirming a masking effect on ASSR. At 65 dB ML, ASSRs did not differ between center frequencies when probe signals were presented relative to MT, suggesting a simple relationship between MT and ASSR. At 85 dB ML, an effect of CF was observed, suggesting that the relationship between MT and ASSR is more complex than initially anticipated, and involving all the experimental parameters (CF, PL, and ML).in bioRxiv: Neuroscience on 2025-11-07 00:00:00 UTC.
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Spinal interneuronal populations encode static hindlimb posture in the cat
Proprioceptive signals from primary afferents reflect changes in single-joint angles, whereas neuronal population in the cerebral cortex represent whole-limb postures. Where and how this transformation emerges along the somatosensory axis from peripheral proprioceptive receptors remains unclear. We simultaneously recorded many lumbosacral spinal neurons in two decerebrate, immobilized cats while a robotic device held the hindlimb at 16 static endpoint positions spanning hip-knee configurations. Using high-density multielectrode recordings, we asked how spinal populations encode static limb state. At the single-neuronal level, activities in a majority of neurons covaried with a single joint's angle (hip or knee), a smaller subset showed combined modulation by both joints, and a distinct subset ('single-endpoint'neurons) fired selectively at one unique hip-knee configuration near the sampled joint-range limits and was quiescent in adjacent postures. Population analyses revealed a low-dimensional structure: the first two principal components tracked knee and hip angles, respectively, whereas a third component isolated a boundary-aligned, posture-specific pattern, with loadings peaking at the same extreme configurations preferred by single-endpoint neurons. Decoders trained on ensemble activity reconstructed both joint angles and the limb's endpoint position in body-centered coordinates, indicating that the recorded spinal-interneuron populations contain sufficient information to reconstruct whole-limb kinematics. Together, these findings are consistent with a hierarchical organization whereby joint-based representations within spinal-interneuron populations could contribute to the emergence of limb-centered representations in the ascending proprioceptive pathways. The boundary preference of single-endpoint neurons supports a possible categorical coding scheme at workspace limits that may provide spinal ''landmarks'' for switching control modes, enhancing stability near kinematic extremes, and supporting recalibration of proprioceptive population codes.in bioRxiv: Neuroscience on 2025-11-07 00:00:00 UTC.
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Parkinsonian striatal acetylcholine dynamics are refractory to L-DOPA treatment
Background: Fluctuations in striatal dopamine (DA) are interdependent with fluctuations in acetylcholine (ACh), both of which are thought to be important for motor function and dysfunction in Parkinson's disease (PD). Objectives: Determine how ACh dynamics are altered by dopamine under normal and parkinsonian conditions following acute and chronic L-DOPA treatment. Methods: We used fiber photometry to record fluorescent DA and ACh sensors in the dorsomedial striatum (DMS) of normal mice treated with vehicle or amphetamine and in the dorsolateral striatum (DLS) of mice with unilateral substantia nigra (SNc) DA neuron lesions (using 6-OHDA) subjected to an L-DOPA-induced dyskinesia (LID) protocol. Results: Under normal conditions, ACh exhibited transient increases followed by pauses and fluctuated at ~1-Hz frequency in an anti-correlated manner to DA. Amphetamine treatment reduced the frequency of ACh fluctuations and amplitude of ACh transients while prolonging after-transient pauses. In 6-OHDA-lesioned mice, ACh dynamics oscillated at a higher frequency and ACh events had reduced peaks and pauses. L-DOPA increased DA and, after repeated treatments, also reduced ACh. However, L-DOPA neither restored the anti-correlation between DA and ACh nor normalized the reduced ACh transient and pause amplitudes or the increased frequency of ACh fluctuations. In extended recordings during the transition to the L-DOPA OFF state, ACh remained low as DA diminished, and ACh transient and pause amplitudes remained suppressed and the oscillatory frequency elevated. Conclusions: Dopamine depletion transforms striatal ACh dynamics and L-DOPA fails to normalize these dynamics. Because these dynamics are unresponsive to treatment, new therapies targeting them may offer symptomatic improvements for PD and LID.in bioRxiv: Neuroscience on 2025-11-07 00:00:00 UTC.
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An EEG-based Multi-Scale Hybrid Attention and Squeeze Network for objective taste assessment
Taste perception is central to flavor experiences. Electroencephalography (EEG) signals carry rich information about taste perception. Because these neural data are independent of verbal reports and bypassing conscious filtering, EEG holds promise as a neural-sensing platform for objective taste representation. However, taste-evoked EEG signals exhibit complex spatiotemporal and spectral dynamics that require advanced computational approaches to decode effectively. This study developed an EEG-based Multi-Scale Hybrid Attention and Squeeze Network (MHASNet) for taste evaluation. EEG signals evoked by distinct taste stimuli were recorded, a dedicated taste-EEG dataset was compiled, and a novel deep learning architecture, MHASNet, was designed to classify these signals. MHASNet synergistically integrates multi-scale convolutions to capture temporal dynamics across different time scales, dual-attention mechanisms to localize discriminative brain regions and electrode positions, and a squeeze-and-excitation module to optimize frequency-band contributions-collectively enabling precise extraction of taste-specific neural signatures. Results showed that the proposed model achieved superior performance across five taste categories (sweet, sour, salty, bitter, and tasteless), with 94.33% accuracy, 91.37% F1-score, 91.89% precision, and 92.07% recall. These results surpass benchmark models while maintaining millisecond-level inference latency suitable for real-time applications. By complementing subjective evaluations and instrumental analyses, the model offers an objective, neurophysiology-based solution for taste evaluation.in bioRxiv: Neuroscience on 2025-11-07 00:00:00 UTC.
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Luminance Matching in Cognitive Pupillometry Is Not Enough: The Curious Case of Orientation
Abrupt onsets reflexively shift covert spatial attention. Recent work demonstrated that trial-to-trial information about the probability of a peripheral onset modulated the magnitude of the attentional cueing effect (low probability > high probability). Although onsets were physically identical, pupil responses could have been modulated by information about the probability of the onset's appearance. Specifically, anticipatory constrictions may have preceded high-probability onsets. Here, we tested this hypothesis using centrally presented, luminance-matched onset-probability signals. For half the participants, vertical signaled high probability (0.8) of onset appearance, while horizontal signaled low probability (0.2). Contingencies were reversed for the other half. Participants fixated the onset-probability signal for 2,000 ms before the onset was briefly presented or omitted, in line with the signaled probability. To maintain engagement, participants completed a simple localization task. Preliminary evidence for an anticipatory reduction in the pupil area was obtained in Experiment 1. However, this effect disappeared in Experiment 2 with a larger replication sample. Exploratory analyses uncovered a violation of a fundamental methodological assumption: despite being task-irrelevant and perfectly luminance-matched, vertical onset-probability signals consistently generated smaller pupil areas, relative to horizontal signals in both Experiments 1 and 2. Interestingly, this "orientation effect" was stronger in the second half of the experimental session, and in a third experiment, we significantly reduced its magnitude by changing the locations of the task-relevant stimuli. In short, across three experiments (self-reported gender, 52 females, 26 males, 1 nonbinary), we show that even with perfect luminance matching, unforeseen changes in cognitive state can modulate pupillometric measurements.
in eNeuro on 2025-11-06 17:30:15 UTC.
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Variation in the Involvement of Hippocampal Pyramidal Cell Subtypes in Spatial Learning Tasks
Hippocampal pyramidal cells are involved in spatial coding and memory formation. Recent evidence shows that they can be classified according to the origin of their axon, either emerging from the soma (non-AcD for "nonaxon-carrying dendrite") or from a proximal basal dendrite (AcD). We have shown that AcD neurons account for ~50% of CA1 pyramidal neurons and that they integrate excitatory inputs differently. They are less susceptible to perisomatic inhibition and more strongly recruited during memory-related network oscillations with strong inhibitory activity. Here, we tested whether AcD and non-AcD neurons are differentially engaged during distinct stages of spatial learning. We trained mice of either sex on a spatial memory task (m-maze) and quantified c-Fos expression in CA1 pyramidal neurons at different training stages. AcD and non-AcD cells were distinguished by staining the axon initial segment. Across learning stages, dorsal and medioventral hippocampus showed distinct activation patterns. In dorsal CA1, c-Fos expression shifted from a predominant presence in non-AcD cells at early stages to the increased presence in AcD cells at later stages. In medioventral CA1, AcD neurons showed a transient c-Fos expression peak at intermediate stages of the training, accompanied by a progressive reduction of the percentage of AcD cells over time. This reduction was not observable in the dorsal hippocampus. This suggests region- and cell type-dependent recruitment patterns of CA1 pyramidal cells during learning and indicates that the site of axon origin may undergo structural plasticity. In addition, the findings support functional and structural differentiation along the dorsoventral axis of CA1.
in eNeuro on 2025-11-06 17:30:15 UTC.
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Connected But Distant: The Phenomenon of Phubbing among Families and Its Effects on Coexistence [version 1; peer review: awaiting peer review]
Background The increasing integration of mobile technology into everyday life has transformed interpersonal relationships, particularly within families. Phubbing—the act of ignoring one’s immediate social environment by focusing on a mobile device—has emerged as a pervasive and disruptive behavior, yet its effects on family coexistence remain understudied. This study addresses a critical gap by examining how phubbing manifests within family dynamics and how it influences emotional connection, communication patterns, and coexistence strategies among Colombian families with school-aged children. Method A qualitative, descriptive research design was employed to capture parental and adolescent perceptions of phubbing. Data were collected from 25 Colombian families through semi-structured interviews and surveys. Participants were selected via non-probabilistic convenience sampling. A categorical matrix guided thematic analysis, focusing on technology use in daily life, its impact on family relationships, usage regulation, and strategies to counteract phubbing. Results Findings revealed that families experience tension between the necessity and overuse of digital devices. Parents and children alike reported both reliance on and frustration with mobile technology. The ubiquity of screen time contributed to decreased face-to-face communication, emotional disconnection, and psychosocial concerns. Nevertheless, families also reported adaptive behaviors—such as rule-based regulation, digital detox practices, and collaborative agreements—to mitigate negative impacts. The study identified a need for structured tools and shared routines to balance connectivity and relational presence. Conclusions Phubbing poses significant challenges to modern family life by weakening relational quality and coexistence. However, families are actively developing preventive and pedagogical strategies to foster digital awareness and restore interpersonal engagement. These findings underscore the necessity of educational interventions and technological literacy programs that promote balanced device use and reinforce human connection within familial settings.in F1000Research on 2025-11-06 15:09:12 UTC.
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Enhancing Mothers’ Preparedness for Home Safety and Emergency Response: The Effect of Simulation-Based First Aid Training among Mothers of Under-Five Children [version 1; peer review: awaiting peer review]
Background Unintentional home injuries are a leading cause of morbidity and mortality among children under five. Mothers, as primary caregivers, often lack the necessary knowledge, practical skills, and confidence to respond effectively to emergencies. Simulation-based training (SBT) is an evidence-based method that enhances learning, skill acquisition, and self-efficacy. Aim This study evaluated the effect of simulation-based first aid training on mothers’ preparedness for home safety and emergency response in households with children. Methods A quasi-experimental one-group pre- and post-test design was conducted with 144 mothers attending three Primary Health Care Centers. Data were collected using validated and reliable structured questionnaires on socio-demographics, first aid knowledge, and home safety practices, along with a post-simulation self-confidence scale. The intervention consisted of six scenario-based simulation sessions covering common home accidents. Paired comparisons, effect sizes (η2), and correlation analyses were performed. Results Post-training mothers’ first aid knowledge and home safety practices significantly improved (knowledge: pre 36.9 ± 24.0, post 86.4 ± 18.2, η2 ≈ 0.789; safety practices: pre 29.9 ± 12.9, post 91.6 ± 16.4, η2 ≈ 0.902). Most participants reported high satisfaction, found the content relevant, and expressed strong confidence in their ability to master the skills. Significant positive correlations were found between knowledge, home safety practices, and emergency response confidence (r = 0.698–0.791; p < 0.001). Conclusion Simulation-based first aid training effectively enhances mothers’ knowledge, safety practices, and confidence in managing home emergencies. Incorporating such training into maternal and child health programs can strengthen household preparedness and promote child safety.in F1000Research on 2025-11-06 15:07:04 UTC.
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Effects of transcutaneous electrical stimulation on peripheral nerve regeneration after digital neurorrhaphy: A randomized clinical trial. [version 1; peer review: awaiting peer review]
Background Sensory recovery following digital nerve neurorrhaphy is often incomplete, and strategies to enhance regeneration remain under investigation. Low-frequency transcutaneous electrical stimulation has been proposed as a potential adjunctive therapy, but its efficacy in clinical settings is uncertain. Methods In this randomized controlled trial, 32 patients with isolated traumatic digital nerve injuries underwent surgical neurorrhaphy at a tertiary care hospital. Participants were randomly allocated to an intervention group (n = 16) or sham group (n = 16). The intervention consisted of a single postoperative session of square-pulsed, biphasic transcutaneous electrical stimulation at 20 Hz for 1 hour. The sham group received identical conditions without active stimulation. After stimulation, patients underwent physiotherapy sessions for three months. Sensory recovery was assessed using Semmes-Weinstein monofilament testing and two-point discrimination at baseline, 1 week, 1 month, and 3 months postoperatively. Results Both groups showed progressive sensory improvement throughout follow-up, approaching normal values at 3 months. No statistically significant differences were observed between groups in any outcome measure. Confidence intervals for group comparisons overlapped, and no clinically meaningful differences were detected. No adverse effects were reported. Conclusions A single postoperative session of low-frequency transcutaneous electrical stimulation did not significantly enhance sensory recovery after digital nerve repair. Further research with varied stimulation protocols, repeated sessions, or extended follow-up may be warranted to clarify its potential role in peripheral nerve regeneration. Level of Evidence Therapeutic Level I.in F1000Research on 2025-11-06 14:56:22 UTC.
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Factors influencing the purchase of regrooved tyres: An exploratory study on consumer behaviour in South Africa [version 1; peer review: awaiting peer review]
The influx of re-grooved tyres, often of poor quality, has increased in South Africa, driven by affordability and lack of regulation. Despite their popularity among cost-conscious consumers, these tyres raise serious safety concerns. This study aims to investigate the behavioural factors influencing consumers’ decisions to purchase re-grooved tyres, particularly within low-income communities. A qualitative, exploratory design was employed, utilising semi-structured interviews with 21 consumers from three townships in KwaZulu-Natal, South Africa. Participants were selected based on their experience of purchasing re-grooved passenger tyres. The data were thematically analysed using NVivo 12 software to identify recurring patterns and themes in consumer behaviour. The findings indicate that unplanned purchases driven by financial constraints are the primary motivators behind the acquisition of re-grooved tyres. Convenience, proximity to vendors, and word-of-mouth referrals significantly influence decision-making. Most consumers exhibited limited awareness of safety risks and were often misled by persuasive vendor strategies that highlighted low prices and a visible tread life. Quality, lifespan, and warranty considerations were secondary to affordability, and consumers often perceived value solely in terms of low costs. Consumer decisions to purchase re-grooved tyres are influenced by a combination of financial, social, and contextual factors, often at the expense of safety. There is a critical need for targeted educational campaigns and regulatory interventions to raise awareness of the hazards associated with re-grooved tyres. Simultaneously, marketers and policymakers must promote tyre options that balance affordability and safety to ensure informed consumer choices and improve road safety outcomes.in F1000Research on 2025-11-06 14:54:45 UTC.
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TXSelect: A multi-task learning model to identify secretory effectors
by Jing Li, Qing Liu, Quan Zou, Chao Zhan
Secretory effectors from pathogenic microorganisms significantly influence pathogen survival and pathogenicity by manipulating host signalling, immune responses, and metabolic processes. However, because of sequence and structural heterogeneity among bacterial effectors, accurately classifying multiple types simultaneously remains challenging. Therefore, we developed TXSelect, a multi-task learning framework that simultaneously classifies TXSE (types I, II, III, IV and VI secretory effectors) using a shared backbone network with task-specific heads. TXSelect integrates the protein embedding features of evolutionary scale modelling (ESM), particularly the N-terminal mean, with classical descriptors to effectively capture complementary information. These descriptors include distance-based residue (DR) and split amino acid composition general (SC-PseAAC-General). Rigorous evaluation identified ESM N-terminal mean + DR + SC-PseAAC as the optimal feature combination, achieving high accuracy (validation F1 = 0.867, test F1 = 0.8645) and robust generalization. Comprehensive assessments and visualization with Uniform Manifold Approximation and Projection further validated the discriminative capability and interpretability of the model. TXSelect provides an efficient computational tool for accurately classifying bacterial effectors, supporting deeper biological understanding and potential therapeutic development.in PLoS Computational Biology on 2025-11-06 14:00:00 UTC.
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APDCA: An accurate and effective method for predicting associations between RBPs and AS-events during epithelial-mesenchymal transition
by Yangsong He, Zheng-Jian Bai, Wai-Ki Ching, Quan Zou, Yushan Qiu
Motivation: Epithelial-mesenchymal transition (EMT) plays a key role in cancer metastasis by promoting changes in adhesion and motility. RNA-binding proteins (RBPs) regulate alternative splicing (AS) during EMT, enabling a single gene to produce multiple protein isoforms that affect tumor progression. Disruption of RBP-AS interactions may disrupt the progress of diseases like cancer. Despite the importance of RBP-AS relationships in EMT, few computational methods predict these associations. Existing models struggle in sparse settings with limited known associations. To improve performance, we incorporate both sparsity constraints and heterogeneous biological data to infer RBP–AS associations. Result: We propose a new method based on Accelerated Proximal DC Algorithm (APDCA) for predicting RBP–AS associations. In particular, APDCA combines sparse low-rank matrix factorization with a Difference-of-Convex (DC) optimization framework and uses extrapolation to improve convergence. A key feature of APDCA is the use of a sparsity constraint, which filters out noise and highlights key associations. In addition, integrating multiple related data sources with direct or indirect relationships can help in reaching a more comprehensive view of RBPs and AS events and to reduce the impact of false positives associated with individual data sources. we prove that our proposed algorithm is convergent under some conditions and the experimental results have illustrated that APDCA outperforms six baseline methods in both AUC and AUPR. A case study on the RBP QKI shows that the top predictions are verified by the OncoSplicing database. Thus, APDCA provides a fast, interpretable, and scalable tool for discovering post-transcriptional regulatory interactions.in PLoS Computational Biology on 2025-11-06 14:00:00 UTC.
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Cortical state contributions to neuronal response variability in the early visual cortex: A system identification approach
by Jinani Sooriyaarachchi, Chang’an A. Zhan, Curtis L. Baker Jr
Neurons in the early visual cortex respond selectively to multiple features of visual stimuli, but they respond inconsistently to repeated presentation of the same visual stimulus. Such trial-to-trial response variabilities are often treated as random noise and addressed by simple trial-averaging to obtain the stimulus-driven response. However, response variability may primarily be caused by non-sensory factors, particularly by variations in cortical state. Here we recorded and analyzed neuronal spiking activity in response to natural images from areas 17 and 18 of cats, along with local population neuronal signals, i.e., local field potentials (LFPs) and multi-unit activity (MUA). Single neurons showed highly varying degrees of trial-to-trial response variability, even when recorded simultaneously. We used a variability ratio (VR) measure to quantify the trial-wise differences in neural responses, and two cortical state indicative measures, a global fluctuation index (GFI) calculated using MUA, and a synchrony index (SI) calculated from LFP signals. We propose a compact convolutional neural network model with parallel pathways, to capture the stimulus-driven activity and the cortical state-driven response variabilities. The stimulus-driven pathway is comprised of a spatiotemporal filter, a parametric rectifier and a Gaussian map, and the cortical state-driven pathway contains temporal filters for MUA and LFPs. The model parameters are fit to best predict each neuron’s spiking activity. We further evaluated the improvements in estimated receptive fields of neurons when incorporating cortical state related information in our system identification model. The fitted model performed with a significantly higher accuracy in predicting neural responses as well as qualitative improvements in the estimated receptive fields compared to a basic model with a stimulus-driven pathway alone. The neurons with higher response variability benefited more from the cortical state-driven pathway compared to less variable neurons. These results show that different neurons may differ greatly in their variability and in the degree of their relationship to indicators of cortical state fluctuations.in PLoS Computational Biology on 2025-11-06 14:00:00 UTC.
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Ten simple rules for making biomedical data resources accessible
by Thomas C. Smits, Lawrence Weru, Nils Gehlenborg, Sehi L’Yi
in PLoS Computational Biology on 2025-11-06 14:00:00 UTC.
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Data-driven identification of biological systems using multi-scale analysis
by Ismaila Muhammed, Dimitris M. Manias, Dimitris A. Goussis, Haralampos Hatzikirou
Biological systems inherently exhibit multi-scale dynamics, making accurate system identification particularly challenging due to the complexity of capturing a wide time scale spectrum. Traditional methods capable of addressing this issue rely on explicit equations, limiting their applicability in cases where only observational data are available. To overcome this limitation, we propose a data-driven framework that integrates the Sparse Identification of Nonlinear Dynamics (SINDy) method, the multi scale analysis algorithm Computational Singular Perturbation (CSP) and neural networks (NNs). This framework allows the partition of the available dataset in subsets characterized by similar dynamics, so that system identification can proceed within these subsets without facing a wide time scale spectrum. Accordingly, when the full dataset does not allow SINDy to identify the proper model, CSP is employed for the generation of subsets of similar dynamics, which are then fed into SINDy. CSP requires the availability of the gradient of the vector field, which is estimated by the NNs. The framework is tested on the Michaelis-Menten model, for which various reduced models in analytic form exist at different parts of the phase space. It is demonstrated that the CSP-based data subsets allow SINDy to identify the proper reduced model in cases where the full dataset does not. In addition, it is demonstrated that the framework succeeds even in the cases where the available data set originates from stochastic versions of the Michaelis-Menten model. This framework is algorithmic, so system identification is not hindered by the dimensions of the dataset.in PLoS Computational Biology on 2025-11-06 14:00:00 UTC.
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Role of connectivity anisotropies in the dynamics of cultured neuronal networks
by Akke Mats Houben, Jordi Garcia-Ojalvo, Jordi Soriano
An inherent challenge in designing laboratory-grown, engineered living neuronal networks lies in predicting the dynamic repertoire of the resulting network and its sensitivity to experimental variables. To fill this gap, and inspired by recent experimental studies, we present a numerical model designed to replicate the anisotropies in connectivity introduced through engineering, characterize the emergent collective behavior of the neuronal network, and make predictions. The numerical model is developed to replicate experimental data, and subsequently used to quantify network dynamics in relation to tunable structural and dynamical parameters. These include the strength of imprinted anisotropies, synaptic noise, and average axon lengths. We show that the model successfully captures the behavior of engineered neuronal cultures, revealing a rich repertoire of activity patterns that are highly sensitive to connectivity architecture and noise levels. Specifically, the imprinted anisotropies promote modularity and high clustering coefficients, substantially reducing the pathological-like bursting of standard neuronal cultures, whereas noise and axonal length influence the variability in dynamical states and activity propagation velocities. Moreover, connectivity anisotropies significantly enhance the ability to reconstruct structural connectivity from activity data, an aspect that is important to understand the structure-function relationship in neuronal networks. Our work provides a robust in silico framework to assist experimentalists in the design of in vitro neuronal systems and in anticipating their outcomes. This predictive capability is particularly valuable in developing reliable brain-on-a-chip platforms and in exploring fundamental aspects of neural computation, including input-output relationships and information coding.in PLoS Computational Biology on 2025-11-06 14:00:00 UTC.
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Prevalence of Asymptomatic Bacteriuria Among People Living Imo State, Nigeria [version 1; peer review: awaiting peer review]
Background Asymptomatic bacteriuria (ASB) is an under-recognized clinical condition, particularly in low-resource settings, with significant implications for antimicrobial resistance and public health. This study investigated the prevalence, microbial profile, and antibiotic susceptibility patterns of ASB among individuals residing in public housing in Obinze, Imo State, Nigeria. Methods A descriptive cross-sectional study was conducted with 150 randomly selected asymptomatic individuals. Structured questionnaires were used to collect sociodemographic data, assess hygiene practices, and evaluate ASB awareness. Midstream urine samples were collected and subjected to standard microbiological analyses, including culture, gram staining, and biochemical tests. The isolates were tested for antibiotic susceptibility using the Kirby-Bauer disc diffusion method. The data were analyzed using SPSS version 28. Results A total of 75 bacterial isolates were recovered. Escherichia coli was the most prevalent organism (56%), followed by Staphylococcus aureus (28%), Enterococcus spp., Pseudomonas aeruginosa (6.7% each), and Klebsiella spp. (2.6%). Most participants exhibited poor awareness of ASB, with only 2% accurately identifying its diagnostic threshold. Hygiene practices varied, with a high proportion reporting inappropriate genital cleaning methods and urination in public spaces due to a lack of sanitation facilities. Antibiotic resistance was observed among the isolates, highlighting the potential threat of community-based reservoirs for resistant strains. Conclusion This study revealed a high burden of ASB and identified critical gaps in public awareness, hygiene practices, and sanitation infrastructure. These findings underscore the urgent need for targeted health education, routine ASB screening, improved sanitation, and antibiotic stewardship programs to mitigate public health risks in similar settings.in F1000Research on 2025-11-06 11:32:40 UTC.
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Identifying Adaptable Varieties of Sorghum (Sorghum bicolor L) in Tidal Swamplands and Sandy Soils by MGIDI and GGE Biplots [version 2; peer review: 1 approved with reservations]
Background Sorghum has potential as a source of material for food, bioenergy, and animal feed, making it a worthy candidate for promotion. This cereal thrives in regions characterized by low moisture and dry conditions. To address the diminishing availability of arable dry land, it may be necessary to explore the cultivation of sorghum in tidal swamplands and sandy soils. Methods Twelve sorghum varieties were evaluated in tidal swamplands during the rainy and dry seasons, as well as in sandy soil during the dry season, using two levels of organic fertilizers to create six test environments. The experiments were arranged in a completely randomized block design with three replications. To choose sorghum varieties with features that closely resemble an idealized sorghum variety, the Multi-trait Genotype-Ideotype Distance Index (MGIDI) was utilized. Simultaneously, genotype plus genotype-environment interaction (GGE) biplots were employed to determine the best circumstances for choosing broadly adaptable varieties that exhibit desirable features, as well as to find varieties that thrive environmental contexts. Results Based on the MGIDI ranking on the average across environment, two varieties, i.e., Numbu and Kawali were selected. However selected varieties in each environment were differed due to significant variety-environment interaction. In terms of grain weight, the Soper 7 Agritan variety exhibits adaptability across diverse environments, while the Numbu variety likewise demonstrates versatility in various environmental conditions. When evaluating forage yield, several adaptable varieties have emerged. Tidal swamplands treated with a high application of organic fertilizer, as well as sandy soils, provide optimal environments for selecting broadly adaptable varieties that focus on both grain and forage yields. Conclusion Adaptable varieties differ for various groups of environments and different traits under consideration. Optimal environments for identifying broadly adaptable varieties varied by trait. The MGIDI proves to be a valuable tool for selecting varieties based on multiple traits. In parallel, the GGE biplots effectively identifies adaptable varieties based on individual traits.in F1000Research on 2025-11-06 11:28:28 UTC.
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Optimization of Bolus-Tracking Thresholds levels in Cerebral CT Angiography: Influence of Patient Characteristics on contrast enhancement dynamics and radiation dose metrics [version 1; peer review: awaiting peer review]
Background Cerebral computed tomography angiography (CTA) is widely used to assess neurovascular disorders, but venous contamination often obscures arteries. Optimizing bolus-tracking thresholds is crucial, yet patient factors influencing contrast dynamics and the value of radiation dose indices in head CTA remain unclear. Objectives To optimize bolus-tracking thresholds in cerebral CTA by examining patient-related influences on enhancement and radiation metrics. Methods 126 adults undergoing cerebral CTA were evaluated in this prospective study. Demographics, physiologic parameters, peak enhancement time (PET), peak enhancement attenuation (PEA), and dose indices (CTDIvol, SSDE) were recorded. Linear regression identified predictors of enhancement. Two blinded radiologists graded venous contamination. ROC analysis, including age subgroups, determined the optimal HU threshold. Results Median age was 55.5 years; 70% were male. PET rose with age (+0.086 s/year, p < 0.001) and was shorter in females (–2.39 s, p = 0.003). PEA increased with threshold (+1.03 HU/unit, p < 0.001). Arterial enhancement was higher in females (+40.7 HU, p < 0.001) and patients ≥60 years (+70 HU, p < 0.001). Venous enhancement correlated with PET (p = 0.023) and systolic pressure (p = 0.002). ROC analysis showed an optimal threshold of 105 ± 5 HU (AUC = 0.634; sensitivity 88.4%, specificity 77.1%). CTDIvol, but not SSDE, correlated with weight (p = 0.015). Conclusion Intrinsic (age, gender) and extrinsic (threshold) factors shape CTA enhancement. A 105 ± 5 HU threshold reduces venous contamination, especially in younger patients. CTDIvol remains the preferred dose index. Findings support individualized, resource-efficient CTA protocols aligned with UN SDGs 3, 9, and 12.in F1000Research on 2025-11-06 11:25:14 UTC.
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Comparison of different techniques of nasogastric tube insertion in anaesthetized, intubated patients in terms of rate of success, time taken and complications: An Observational Study [version 1; peer review: awaiting peer review]
Aims and background Insertion of a nasogastric tube (NGT) is crucial during surgery for decompressing the stomach and improve abdominal organ visibility. Traditional method of inserting NGT in the intubated, anesthetized patients is challenging and can cause complications like coiling or mucosal bleeding after several attempts. Thus, various modifications to the conventional method have been developed. The aim of this study was to observe and compare the various modified NGT insertion techniques to the standard approach in terms of first attempt success rate, number of attempts, procedure time, and adverse events. Materials and Methods A total of 239 patients scheduled for surgeries under general anaesthesia requiring NGT insertion were enrolled in the study to observe and compare the various modified techniques of NGT insertion in a tertiary care hospital. The total number of attempts for inserting successful NGT, total time taken and adverse events were observed. Results We observed five different modified techniques of NGT insertion which showed greater success rate, decreased complications and the time taken was also less in comparison to the conventional method. Conclusion NGT insertion technique varies from person to person, but has to be tailored as per the individual’s requirement. Patients who are obese with BMI >30 and Mallampati classification 3 and 4 may require more than one attempt or a different technique while inserting the Nasogastric tube. Studying various NGT insertion methods in intubated and anesthetized patients enhances clinical practice and literature. Knowledge of techniques with high success rates and fewer complications can help clinicians perform them more routinely.in F1000Research on 2025-11-06 11:21:32 UTC.
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Determinants of Quality of Life Among Elderly in a Social Care Center: Emphasis on Sleep [version 1; peer review: awaiting peer review]
Background The aging population worldwide has led to increased attention toward ensuring a good quality of life (QoL) among the elderly, particularly those residing in long-term care facilities. This study aims to identify the determinants of quality of life among elderly residents in a social care center in West Jakarta. Method This quantitative study employed a descriptive cross-sectional design involving 288 elderly residents from a social care center. Data were collected using structured questionnaires measuring sleep behavior, medication adherence, nutritional intake, infection prevention, physical activity, and QoL. Results The results indicated that sleep behavior was significantly associated with QoL (p = 0.002), whereas no statistically significant associations were found between QoL and other variables, including medication adherence, nutritional intake, infection prevention, and physical activity. Conclusion Sleep quality is a significant determinant of QoL among institutionalized elderly individuals. These findings suggest that sleep behavior should be prioritized in care strategies to improve the quality of life of elderly residents in long-term care.in F1000Research on 2025-11-06 11:19:34 UTC.
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Real‐World Effectiveness of Switching to Oral or Infusion Versus Injectable Disease‐Modifying Therapy in Pediatric Multiple Sclerosis
Objective
To assess real-world effectiveness of switching disease-modifying therapy (DMT) in pediatric multiple sclerosis (MS) and clinically isolated syndrome (CIS) initially treated with platform injectables on disease activity.
Methods
Of 2615 pediatric-onset demyelinating disease patients at 12 clinics in the United States (US) Network of Pediatric MS Centers, those with MS/CIS on initial therapy with a platform injectable who switched to another class of platform injectable, oral or infusion DMT were analyzed. Relapse rate was modeled with negative binomial regression, adjusted for preidentified confounders.
Results
A total of 212 children switched DMT before age 18 (67% female, 95% MS). Ninety-three switched from injectable to injectable, 76 injectable to oral, and 43 injectable to infusion. Switchers to oral or infusion were older at onset (injectable 12.3 years, oral 13.5 years, and infusion 14.2 years) and switch (injectable 14.6 years, oral 16.0 years, and infusion 15.7 years). Switchers to infusion DMT were more likely to have enhancing lesions (injectable 45%, oral 28%, and infusion 67%). Compared to injectable (annualized relapse rate [ARR] = 0.88, 95% confidence interval [CI] = 0.52–1.48), relapse rates were lower for injectable to oral (ARR = 0.34, 95% CI = 0.20–0.57; rate ratio: 0.38, 95% CI = 0.21–0.69) and injectable to infusion (ARR = 0.18, 95% CI = 0.09–0.37; rate ratio: 0.21, 95% CI = 0.10–0.44) (p < 0.001). Adjusted number needed to treat in person-years to prevent 1 relapse with oral over injectable was 1.84 (95% CI = 1.03–8.69) and infusion over injectable 1.43 (95% CI = 1.00–3.88).
Interpretation
Switching from platform injectable to oral or infusion compared to other platform injectable DMT led to better disease control in pediatric MS. Long-term safety data are required. ANN NEUROL 2025
in Annals of Neurology on 2025-11-06 11:19:05 UTC.
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Exploring the Potential of Peptides Derived from the Coelomic Fluid of Echinometra lucunter Targeting Inflammatory Cytokines in Placental Syndromes: In Silico Study [version 2; peer review: 1 approved with reservations]
Background Placental syndromes—encompassing pregnancy loss, preterm birth, gestational diabetes mellitus, and preeclampsia—have been strongly linked to dysregulated inflammatory responses at the maternal–fetal interface. This study aims to explore the potential of peptides derived from the coelomic fluid of Echinometra lucunter targeting the inflammatory cytokines involved in placental syndromes using in silico approaches. Methods The 3D molecular structure of peptides was modeled using the UCSF Chimera application. The absorption, distribution, metabolism, and excretion (ADMET) properties were analysed using SwissADME and the ProTox web server. The PerMM web server was used to estimate membrane permeability. Crystal structures of target proteins—including c-Met, Interleukin-1β (IL-1β), Interleukin-10 (IL-10), Macrophage Migration Inhibitory Factor (MIF), Platelet-Derived Growth Factor (PDGF), and TNF-Related Apoptosis-Inducing Ligand (TRAIL)—were obtained from the Protein Data Bank Japan (PDBj). Molecular docking and structural visualization were conducted using Molecular Operating Environment (MOE) software, while molecular dynamics simulations were subsequently performed using the YASARA Dynamics software to assess the stability and conformational behavior of the ligand-receptor complexes. Results Peptide A was selected based on favorable ADMET properties. Molecular docking results revealed that Peptide A exhibits low binding affinities toward pro-inflammatory mediators, including TRAIL (–10.02 kcal/mol), MIF (–9.32 kcal/mol), IL-1β (–8.29 kcal/mol), and PDGF (–10.44 kcal/mol). Furthermore, Peptide A showed potential agonistic interactions with IL-10 (–10.26 kcal/mol) and c-Met (–9.27 kcal/mol), indicating a possible role in restoring anti-inflammatory and angiogenic signaling. Molecular dynamics simulations supported the stability of the peptide–receptor complexes. Conclusions Peptide A holds promise as a dual-function therapeutic agent in placental syndromes. However, experimental validation is necessary to confirm its biological efficacy and safety.in F1000Research on 2025-11-06 11:11:40 UTC.
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Flagellar dynamics and entanglement of $\mathit{E}.\phantom{\rule{0.16em}{0ex}}coli$ bacteria in polymeric hydrogel
Author(s): Diksha Shrestha, Deborah Okyere, Sam Mortenson, Jingyi Chen, and Yong Wang
The authors investigate how behavior and dynamics of bacterial flagella are affected by complex environments, an area that has been largely unexplored. They visualize dynamics of fluorescently labeled flagellar filaments of . bacteria in a hydrogel and find three distinct types of flagellar motions.
#BiophysicsSpotlight #TheoryExperiment #ElegantVisuals
[Phys. Rev. E 112, 054404] Published Thu Nov 06, 2025
in Physical Review E: Biological physics on 2025-11-06 10:00:00 UTC.
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Effect of stereochemical constraints on the structural properties of folded proteins
Author(s): Jack A. Logan, Jacob Sumner, Alex T. Grigas, Mark D. Shattuck, and Corey S. O'Hern
This study compares a series of coarse-grained protein models of increasing complexity to identify the simplest model that reproduces key structural properties of protein cores. The results show that accurate modeling of protein cores requires capturing the correct size and anisotropic shape of side chains.
#BiophysicsSpotlight #TheoryExperiment #WellStructured
[Phys. Rev. E 112, 054405] Published Thu Nov 06, 2025
in Physical Review E: Biological physics on 2025-11-06 10:00:00 UTC.
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Dynamic changes of dopamine neuron activity and plasticity at different stages of negative reinforcement learning
Proceedings of the National Academy of Sciences, Volume 122, Issue 45, November 2025.
SignificanceThe critical role of midbrain dopaminergic neurons in encoding reward prediction error (RPE) signals during negative reinforcement learning (NRL) remains poorly understood. Here, we reveal how these neurons dynamically adjust their activity in ...in PNAS on 2025-11-06 08:00:00 UTC.
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Neuronal normalization in monkey MT is an intensity-weighted average
Proceedings of the National Academy of Sciences, Volume 122, Issue 45, November 2025.
SignificanceSensory neurons must remain selective for specific features in a scene, even when many stimuli fall within their receptive fields (RFs). In natural vision, this selectivity is preserved by a process called normalization, which adjusts a neuron’...in PNAS on 2025-11-06 08:00:00 UTC.
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Correction for Reva et al., Higher-order interactions in neuronal function: From genes to ionic currents in biophysical models
Proceedings of the National Academy of Sciences, Volume 122, Issue 45, November 2025.
in PNAS on 2025-11-06 08:00:00 UTC.
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Repair of DNA double-strand breaks leaves heritable impairment to genome function
Science, Volume 390, Issue 6773, November 2025.
in Science on 2025-11-06 08:00:00 UTC.
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Adipogenin promotes the development of lipid droplets by binding a dodecameric seipin complex
Science, Volume 390, Issue 6773, November 2025.
in Science on 2025-11-06 08:00:00 UTC.
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Direct targeting and regulation of RNA polymerase II by cell signaling kinases
Science, Volume 390, Issue 6773, November 2025.
in Science on 2025-11-06 08:00:00 UTC.
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The anti-inflammatory activity of IgG is enhanced by co-engagement of type I and II Fc receptors
Science, Volume 390, Issue 6773, November 2025.
in Science on 2025-11-06 08:00:00 UTC.
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Preventing hypocontractility-induced fibroblast expansion alleviates dilated cardiomyopathy
Science, Volume 390, Issue 6773, November 2025.
in Science on 2025-11-06 08:00:00 UTC.
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Deep generative models design mRNA sequences with enhanced translational capacity and stability
Science, Volume 390, Issue 6773, November 2025.
in Science on 2025-11-06 08:00:00 UTC.
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Unlocking the potential of brassinosteroids: A path to precision plant engineering
Science, Volume 390, Issue 6773, November 2025.
in Science on 2025-11-06 08:00:00 UTC.
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The role of organizations in fostering innovation
Science, Volume 390, Issue 6773, November 2025.
in Science on 2025-11-06 08:00:00 UTC.
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Platforms of power
Science, Volume 390, Issue 6773, Page 580-580, November 2025.
in Science on 2025-11-06 07:00:19 UTC.
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Frankenstein and the problem of abandonment
Science, Volume 390, Issue 6773, Page 578-579, November 2025.
in Science on 2025-11-06 07:00:19 UTC.
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Extreme warming of Amazon waters in a changing climate
Science, Volume 390, Issue 6773, Page 606-611, November 2025.
in Science on 2025-11-06 07:00:19 UTC.
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Multi-timescale frequency-phase matching for high-yield nonlinear photonics
Science, Volume 390, Issue 6773, Page 612-616, November 2025.
in Science on 2025-11-06 07:00:19 UTC.
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River metabolism in the contiguous United States: A West of extremes
Science, Volume 390, Issue 6773, Page 622-627, November 2025.
in Science on 2025-11-06 07:00:19 UTC.
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Cosmic dust reveals dynamic shifts in central Arctic sea-ice coverage over the past 30,000 years
Science, Volume 390, Issue 6773, Page 628-632, November 2025.
in Science on 2025-11-06 07:00:19 UTC.
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Shear-induced bubble nucleation in magmas
Science, Volume 390, Issue 6773, Page 633-637, November 2025.
in Science on 2025-11-06 07:00:19 UTC.
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Strengthening Ni alloys with nanoscale interfaces of negative excess energy
Science, Volume 390, Issue 6773, Page 617-621, November 2025.
in Science on 2025-11-06 07:00:19 UTC.
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Probing critical phenomena in open quantum systems using atom arrays
Science, Volume 390, Issue 6773, Page 601-605, November 2025.
in Science on 2025-11-06 07:00:19 UTC.
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Ultrafast inverse chirality-induced spin selectivity observed by THz emission
Science, Volume 390, Issue 6773, Page 595-600, November 2025.
in Science on 2025-11-06 07:00:19 UTC.
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Homogenized chlorine distribution for >27% power conversion efficiency in perovskite solar cells
Science, Volume 390, Issue 6773, Page 638-642, November 2025.
in Science on 2025-11-06 07:00:19 UTC.
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When ‘we’ turns wicked
Science, Volume 390, Issue 6773, Page 646-646, November 2025.
in Science on 2025-11-06 07:00:19 UTC.
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In Other Journals
Science, Volume 390, Issue 6773, Page 587-588, November 2025.
in Science on 2025-11-06 07:00:19 UTC.
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Shrinking interconnects beyond copper
Science, Volume 390, Issue 6773, Page 572-573, November 2025.
in Science on 2025-11-06 07:00:19 UTC.
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Unbiased discovery of neuronal architectures
Science, Volume 390, Issue 6773, Page 566-568, November 2025.
in Science on 2025-11-06 07:00:19 UTC.
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Cell signaling meets gene transcription
Science, Volume 390, Issue 6773, Page 568-569, November 2025.
in Science on 2025-11-06 07:00:19 UTC.
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Seipin-adipogenin controls lipid storage in fat cells
Science, Volume 390, Issue 6773, Page 570-571, November 2025.
in Science on 2025-11-06 07:00:19 UTC.
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Britain must step up on AI policy
Science, Volume 390, Issue 6773, Page 581-582, November 2025.
in Science on 2025-11-06 07:00:19 UTC.
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FDA export restrictions threaten collaboration
Science, Volume 390, Issue 6773, Page 452-452, November 2025.
in Science on 2025-11-06 07:00:19 UTC.
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Protect Iraq’s Mesopotamian Marshes
Science, Volume 390, Issue 6773, Page 581-581, November 2025.
in Science on 2025-11-06 07:00:19 UTC.
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A foundation of trust
Science, Volume 390, Issue 6773, Page 560-565, November 2025.
in Science on 2025-11-06 07:00:19 UTC.
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Biomedical philanthropy promises dramatic expansion and AI focus
Science, Volume 390, Issue 6773, Page 552-553, November 2025.
in Science on 2025-11-06 07:00:19 UTC.
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Tree rings from ancient coffins offer clues to Earth’s past
Science, Volume 390, Issue 6773, Page 554-555, November 2025.
in Science on 2025-11-06 07:00:19 UTC.
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Thinning of DOE advisory bodies dismays researchers
Science, Volume 390, Issue 6773, Page 555-556, November 2025.
in Science on 2025-11-06 07:00:19 UTC.
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Antarctic glacier’s retreat is fastest in modern history
Science, Volume 390, Issue 6773, Page 557-558, November 2025.
in Science on 2025-11-06 07:00:19 UTC.
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AI hallucinates because it’s trained to fake it till it makes it
Science, Volume 390, Issue 6773, Page 558-559, November 2025.
in Science on 2025-11-06 07:00:19 UTC.
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Advancing research on financial stability and climate-related financial risk
Science, Volume 390, Issue 6773, Page 547-547, November 2025.
in Science on 2025-11-06 07:00:19 UTC.
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New Products
Science, Volume 390, Issue 6773, Page 643-643, November 2025.
in Science on 2025-11-06 07:00:19 UTC.
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Understanding nature and nurture: Statistical and AI innovations uncover how genes and environment shape human health
Science, Volume 390, Issue 6773, Page 584-584, November 2025.
in Science on 2025-11-06 07:00:19 UTC.
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The normalization of (almost) everything: Our minds can get used to anything, and even crises start feeling normal
Science, Volume 390, Issue 6773, Page 585-585, November 2025.
in Science on 2025-11-06 07:00:19 UTC.
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The need for a global effort to attend to human neural organoid and assembloid research
Science, Volume 390, Issue 6773, Page 574-577, November 2025.
in Science on 2025-11-06 07:00:19 UTC.
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In Science Journals
Science, Volume 390, Issue 6773, Page 586-588, November 2025.
in Science on 2025-11-06 07:00:19 UTC.
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Changes in Muscle Synergy Structure and Activation Patterns Underlie Force Field Adaptation, Retention, and Generalization
Journal of Neurophysiology, Ahead of Print.
in Journal of Neurophysiology on 2025-11-06 02:49:39 UTC.
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Linking Motor Working Memory to Explicit and Implicit Motor Learning
Journal of Neurophysiology, Ahead of Print.
in Journal of Neurophysiology on 2025-11-06 02:41:33 UTC.
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Rolipram‐Loaded PgP Nanotherapeutics via Intrathecal Administration Reduces Secondary Injury in a Rat Acute Moderate Contusion SCI Model
The biodistribution of DiR-PgP and the therapeutic efficacy of Rm-PgP after intrathecal administration was investigated in a rat moderate thoracic contusion SCI model. Intrathecal administration of DiR-PgP showed CNS-specific retention without peripheral distribution. Intrathecal administration of Rm-PgP enhanced tissue sparing, increased pCREB/CREB ratio, and reduced inflammation and apoptosis, demonstrating PgP's potential for sustained CNS drug delivery and neuroprotection after SCI.
ABSTRACT
Spinal cord injury (SCI) triggers complex secondary injury mechanisms, resulting in long-term impacts on sensory and motor function. Rolipram, a phosphodiesterase-4 inhibitor, has shown promise in preserving/restoring cyclic adenosine monophosphate (cAMP) to reduce secondary injury responses, but its clinical application is hindered by poor solubility and systemic side effects. To overcome these challenges, we developed rolipram-loaded poly(lactide-co-glycolide)-graft-polyethylenimine (PgP) nanoparticles (Rm-PgP) to enable localized and sustained drug delivery. In our previous findings, Rm-PgP administered via intraspinal injection restored cAMP levels at the lesion site, and reduced secondary injury after moderate, contusive SCI. In this study, we investigated the effect of single and repeat administration of Rm-PgP by the clinically relevant intrathecal route immediately after injury. We observed that the hydrophobic dye, DiR-loaded PgP (DiR-PgP) was retained in the CNS over 7 days post-injury (DPI). In addition, we observed that both single and repeat Rm-PgP treatment groups showed higher cAMP levels compared to those in the untreated SCI group and only the single treatment group showed a significant difference compared to the untreated SCI group. Lastly, we observed that cAMP restoration in both single and repeat Rm-PgP treatment groups showed higher levels of activated cAMP-response element-binding protein (pCREB) relative to the untreated control. We also observed that both Rm-PgP treatment groups showed reduced inflammatory response, reduced astrogliosis and apoptosis, and increased neuronal survival and spared tissue volume. These findings highlight the neuroprotective efficacy of Rm-PgP by intrathecal administration in mitigating secondary injury during the critical early phase of recovery after SCI.
in Journal of Neuroscience Research on 2025-11-06 00:25:06 UTC.
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Cracking the complexity of REM sleep
Rapid eye movement (REM) sleep is a unique state classically defined by brain activation and muscle paralysis. It is now recognized as a dynamic process involving coordinated oscillations and phasic behaviors, with substantial variations across development and species. Neural circuit studies have identified ever-expanding brain networks that regulate state generation and individual components of REM sleep. To account for this structured yet flexible nature, we propose a hierarchical circuit framework in which core REM sleep features are generated by brainstem nuclei, and adaptively tuned by hypothalamic, cortical, and neuromodulatory systems. From this component- and circuit-based perspective, we synthesize recent advances showing how theta oscillations and distributed forebrain circuits mediate REM sleep functions in memory, emotion, and cognition. We finally outline future research paths towards a more refined and integrative understanding of REM sleep.in Trends in Neurosciences: In press on 2025-11-06 00:00:00 UTC.
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Sexual dimorphism in pheromone perception across worms, flies, and rodents
Sex-specific chemosensory behaviors arise from differences in how males and females detect and process environmental chemical cues, including pheromones, which drive sex-appropriate behaviors essential for reproduction across many species. This review compares neural circuits in Caenorhabditis elegans, Drosophila, and rodents that generate sexually dimorphic pheromone responses, spanning peripheral detection, relay centers, and central integration. Recent connectomic and circuit-level analyses reveal how internal states modulate these pathways, adding an additional layer of context-dependent, sex-specific modulation. By synthesizing mechanisms across species, we highlight conserved principles and lineage-specific adaptations, offering an integrative framework for understanding how sex differences are embedded in chemosensory neural systems and setting the stage for future work on sexually dimorphic behaviors.in Trends in Neurosciences: In press on 2025-11-06 00:00:00 UTC.
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Rethinking neurodegeneration through a co-proteinopathy lens
Neurodegenerative diseases have long been considered distinct proteinopathies: amyloid-β and tau in Alzheimer’s disease, α-synuclein in Parkinson’s disease, and TDP-43 in amyotrophic lateral sclerosis. This single-protein paradigm has guided therapeutic development for decades; yet clinical outcomes remain modest. Mounting evidence, however, reveals that protein aggregates rarely occur in isolation; instead, they coexist, colocalise, and modulate each other’s pathogenicity. Here, we propose a co-proteinopathy framework that views neurodegeneration as an interactive network of misfolded proteins rather than as isolated disorders. Adopting this framework demands multiplexed quantification of protein aggregates and disease models that better reflect the biological complexity of human neurodegeneration. The co-proteinopathy perspective offers a more realistic foundation for next-generation approaches to neurodegeneration research and treatment.in Trends in Neurosciences: In press on 2025-11-06 00:00:00 UTC.
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When viral infections rewire neural circuits: towards cognitive virology
Viral infections cause a wide range of neurocognitive disorders. However, the molecular mechanisms that give rise to acute and chronic cognitive deficits remain poorly understood. In this opinion article we review current knowledge on the close interactions between viruses and synapses from animal and human-based models, including how viral infections restructure synapses, disrupt synaptic transmission and neuromodulation, and interfere with synaptic plasticity, as well as how synapses contribute to viral dissemination. We further discuss how neuroimmune responses can both contribute to host defense and cause pathological damage to the nervous system that can lead to cognitive deficits. The emerging field of cognitive virology aims for expanded interdisciplinary studies to understand the molecular mechanisms by which viral infections lead to cognitive dysfunction.in Trends in Neurosciences: In press on 2025-11-06 00:00:00 UTC.
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Nuclear-lamin-guided plastic positioning and folding of the human genome
Wang et al. systematically depicted the lamins-guided 3D epigenome in human stem cells and demonstrated that lamins not only serve as key regulators of chromatin-NL tethering and large-scale genome organization but also are essential for the spatial positioning and clustering of nuclear speckle through direct interactions within the nuclear interior.in Cell Reports: Current Issue on 2025-11-06 00:00:00 UTC.
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Monocyte-derived cells promote transient insult-induced brain injury by enhancing CD8+ T cell response
Zuo et al. show monocyte-derived cells as key contributors to transient insult-induced brain injury. These cells infiltrate lesions, exhibit antigen-presenting features, and promote CD8+ T cell response, potentially through co-stimulatory signaling. Depleting them or blocking their interaction with CD8+ T cells alleviates cognitive impairment, suggesting a potential target for therapy.in Cell Reports: Current Issue on 2025-11-06 00:00:00 UTC.
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REM sleep reduces subthreshold depolarization in cortical pyramidal neurons in a region-specific manner
Campelo et al. show that REM sleep induces region-specific changes in cortical excitability, with NMDARs playing a crucial role. Diazepam-induced sleep differs from natural sleep by disrupting normal inhibitory circuits, suggesting that hypnotic drugs may compromise sleep-dependent brain functions.in Cell Reports: Current Issue on 2025-11-06 00:00:00 UTC.
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Ufd1-Npl4 Recruit Cdc48 for Disassembly of Ubiquitylated CMG Helicase at the End of Chromosome Replication
(Cell Reports 18, 3033–3042; March 28, 2017)in Cell Reports: Current Issue on 2025-11-06 00:00:00 UTC.
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Author Correction: The emergence of transcriptional identity in somatosensory neurons
Nature, Published online: 06 November 2025; doi:10.1038/s41586-025-09817-y
Author Correction: The emergence of transcriptional identity in somatosensory neuronsin Nature on 2025-11-06 00:00:00 UTC.
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Author Correction: TNF-mediated inflammatory skin disease in mice with epidermis-specific deletion of IKK2
Nature, Published online: 06 November 2025; doi:10.1038/s41586-025-09789-z
Author Correction: TNF-mediated inflammatory skin disease in mice with epidermis-specific deletion of IKK2in Nature on 2025-11-06 00:00:00 UTC.
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An ATP-gated molecular switch orchestrates human messenger RNA export
Nature, Published online: 06 November 2025; doi:10.1038/s41586-025-09832-z
An ATP-gated molecular switch orchestrates human messenger RNA exportin Nature on 2025-11-06 00:00:00 UTC.
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