Planet Neuroscience

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Addressing the specific roles of histone modifications in transcriptional repression

Nature Communications, Published online: 22 November 2025; doi:10.1038/s41467-025-66426-z

Hedehus et al. show that H3K9me3 and H3K36me3 can only partially compensate for loss of H3K27me3, supporting the concept of a combinatorial histone code.

in Nature Communications on 2025-11-22 00:00:00 UTC.

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Single-cell and spatially resolved omics reveal transcriptional and metabolic signatures of ovarian endometriomas

Nature Communications, Published online: 22 November 2025; doi:10.1038/s41467-025-66706-8

Ovarian endometriomas, with distinct microenvironment and heightened hormonal sensitivity, are recognized as precursors of ovarian carcinomas. This study decodes ovarian endometriomas by integrating single-cell and spatial transcriptomics with spatial metabolomics to reveal key markers and altered pathways, offering new avenues for diagnosis and therapy.

in Nature Communications on 2025-11-22 00:00:00 UTC.

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Strong metal-support interaction of Ru-NPs/WCx boosts alkaline hydrogen evolution and oxidation for alkaline fuel cells and electrolyzers

Nature Communications, Published online: 22 November 2025; doi:10.1038/s41467-025-65273-2

High-performance anion exchange membrane fuel cells and electrolyzers relay on Pt based catalysts. Here, the authors design WCx supported Ru nanoparticles as electrocatalyst with strong metal-support interaction for efficient alkaline hydrogen oxidation and evolution.

in Nature Communications on 2025-11-22 00:00:00 UTC.

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A dataset of building surface defects collected by UAVs for machine learning-based detection

Scientific Data, Published online: 22 November 2025; doi:10.1038/s41597-025-06318-5

A dataset of building surface defects collected by UAVs for machine learning-based detection

in Nature scientific data on 2025-11-22 00:00:00 UTC.

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Developing a Systemic Framework to Reduce the Bullwhip Effect in the Construction Industry: Empirical Insights and Practical Implications [version 1; peer review: awaiting peer review]

Background The construction industry faces systemic inefficiencies and cost overrun. Many of these issues result from demand amplification, known as the Bullwhip Effect (BWE), within supply chains. Aim To investigate the root causes and impacts of the Bullwhip Effect during construction. Establish a foundation for mitigation strategies using a conceptual framework. This framework was validated using a real-world case study to support effective mitigation. Methods This study systematically identified and analyzed twenty-one underlying causes of the Bullwhip Effect in the supply chain. The effect was calculated for the selected construction materials using data from Mostashar United Company-Kuwait. Results The Bullwhip Effect in the construction industry emerges not from a single cause but from a complex interaction of factors that significantly influence the phenomenon and are deeply embedded within the industry’s structural and operational practices. These causes are grouped into three main dimensions: informational, operational, and behavioral factors. BWE can be quantitatively measured and directly escalates production costs and intensifies over time if mitigating strategies are not implemented. Research has identified several strategies that can effectively prevent the occurrence or reduce the bullwhip effect in the construction industry, such as collaboration and teamwork enhanced strategies between SCM partners, optimizing information exchange and communications among SCM partners, Building SCM Resilience Against Component Shortages, and Strategic Planning for Resource Utilization. Conclusion The causes of Bullwhip Effects and impacts are interconnected rather than segregated or isolated, creating a reinforcing feedback loop where informational opacity sparks behavioral reactions, further intensifying operational instability. A bullwhip mitigation policy should include addressing data transparency, supply chain process coordination, and contractual early incentives, instead of focusing on isolated symptom management, instead of systemic resolution.

in F1000Research on 2025-11-21 17:32:31 UTC.

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Building Entrepreneurship Ecosystem: A Systematic Review [version 2; peer review: 1 approved with reservations, 2 not approved]

The primary objective of this study is to advance research by providing a conceptual framework for entrepreneurship ecosystem building and the growth of entrepreneurship intention among students in higher education institutions. The study conducted a comprehensive literature review, selecting peer-reviewed articles on entrepreneurial ecosystem building and entrepreneurial intention growth. A systematic review (SR) method was used to achieve he stated objectives. The PRISMA protocol, searching approach, inclusion and exclusion criteria, and data analysis technique were successfully applied. The research finding shows that developing a robust entrepreneurial ecosystem within universities can stimulate entrepreneurial activities, enhance self-efficacy, and cultivate an entrepreneurial culture. The findings also underscore the importance of creating environments that not only provide knowledge and skills but also practical experiences and support networks essential for nurturing future entrepreneurs. Finally, both empirical and practical implication was identified and a future research direction was suggested for future researchers.

in F1000Research on 2025-11-21 17:30:02 UTC.

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Study Protocol: Intrafamily Communication on Mental Disorders (IFACOM) [version 1; peer review: awaiting peer review]

Our study deals with intra-family communication on mental disorders. We plan to develop a questionnaire, which can be used to measure the functionality of intra-family communication. Previous studies have shown that certain forms of communication in families affected by mental disorders impact the further course of the disease. Derogatory or taboo communication content are known to be disease-promoting, while open and positive communication has a preventive effect on the occurrence of further mental disorders. The functionality of communication therefore describes the potential of a health-promoting effect of intra-family communication styles. On the other hand, dysfunctional communication styles might be associated with a higher risk of the new emergence or recurrence of mental health problems in other family members. Following a systematic literature search on data containing information on intra-family communication patterns on mental disorders we plan to collect further data suing qualitative interviews (n=10). Interviewees include family members of individuals affected by mental disorders. We then plan to create a questionnaire with approximately 30 factors and items. This questionnaire will be tested in a large cohort of family members of individuals affected by mental disorders (n=300) and consequently validated by a confirmatory factor analysis. With the help of the planned questionnaire, risk factors of patients could be recognized earlier and taken into account for therapeutic interventions.

in F1000Research on 2025-11-21 17:27:44 UTC.

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Barriers and Strategies for Antiretroviral Therapy Appointment Adherence in Rural South Africa: A Narrative Review with a Focus on the Vhembe District [version 1; peer review: awaiting peer review]

Background and Objective Antiretroviral therapy (ART) is the cornerstone of HIV treatment, but its effectiveness depends heavily on consistent patient adherence to scheduled appointments. Rural regions, such as the Vhembe district in South Africa, face persistent structural, economic, and psychosocial challenges that hinder ART adherence and continuity of care. This narrative review synthesizes evidence on the multifaceted barriers affecting ART appointment adherence in rural settings and evaluates intervention strategies that have demonstrated success across sub-Saharan Africa. It emphasizes the relevance of these findings to the Vhembe district context. Methods The review draws on three key evidence sources: a doctoral study evaluating home delivery models for ART, a systematic review on treatment supporter interventions (TSIs), and a meta-analysis on adherence among pregnant women using digital and educational tools. The selected studies were critically examined for their applicability to rural service delivery and adherence outcomes. Results The review identifies major adherence barriers, including poor transport infrastructure, high indirect costs, clinic overcrowding, limited refill durations, stigma, and the impact of public health emergencies. Strategies such as home delivery, multi-month dispensing (MMD), mHealth device reminders, and community-based support programs (TSIs) are shown to mitigate these challenges effectively. Combined socio-structural interventions yield the most substantial improvements in adherence outcomes. Conclusions Improving ART appointment adherence in Vhembe requires an integrated model tailored to local realities. Combining decentralized care, social support structures, mHealth solutions, and financial incentives offers a sustainable path forward. However, research gaps in implementation science, cost-effectiveness, and context-specific interventions must be addressed to scale these solutions effectively.

in F1000Research on 2025-11-21 16:24:36 UTC.

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Urban Noise Pollution through Combined Analysis of Sound Levels [version 1; peer review: awaiting peer review]

Introduction Noise pollution has become one of the most frequent urban environmental problems, with negative effects on public health, social well-being, and quality of life in high population density contexts. Within this framework, the present study was developed with the purpose of characterizing environmental noise levels in the Historic Center of Lima, integrating objective measurements and citizens’ perceptions. Methodology The research adopted a quantitative approach, applied type, with a non-experimental and cross-sectional design. Measurements were carried out at thirteen strategic points along Abancay Avenue using a type I integrating sound level meter, while population perception was collected through a structured survey applied to 392 participants selected by non-probabilistic sampling. Data were processed through descriptive and comparative analysis between instrumental records and population responses. Results The findings showed that equivalent noise levels consistently exceeded environmental quality standards for commercial zones, reaching maximum values above 90 dB(A). Vehicular traffic and informal commercial activity were identified as the main noise sources, and most respondents perceived noise as intense and disturbing, especially during the evening-nighttime period. Conclusion Noise pollution in the studied area constitutes a persistent problem that affects environmental quality and the daily lives of the population. Furthermore, the need to design urban management and acoustic control strategies is recognized, aiming to reduce exposure in heritage and commercial corridors

in F1000Research on 2025-11-21 16:14:20 UTC.

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The Genetic Association of Single Nucleotide Polymorphisms of SERPINE1 (rs6092) and IFNAR2 (rs1051393, rs2229207) Genes Is Related to Post Covid-19 Respiratory Syndrome [version 1; peer review: awaiting peer review]

Background Coronavirus disease 2019 (Covid-19) is a disease of the respiratory system caused by the SARS-CoV-2 virus. The severity of Covid-19 can be affected by the presence of single nucleotide polymorphisms (SNPs) in certain genes, such as IFNAR2 and SERPINE-1. This study aimed to identify and analyze the presence of SNP rs6092 in the SERPINE1 gene and rs1051393 and rs2229207 in the IFNAR2 gene relation in Covid-19 respiratory syndrome in Indonesia. Methods DNA was isolated from saliva samples of all patients, and a TaqMan Genotyping Assay with a real-time PCR instrument was used to run the samples. The output data were analyzed for demographic data, allele frequency, genotype frequency, and the association of all SNPs with the Covid-19 respiratory syndrome (case) and control subjects. We also analyzed blood laboratory results, blood gas analyses, coagulation factors, and inflammatory factors using SPSS. Results This study included 85 subjects comprise with Covid-19 respiratory syndrome and control subjects. Our study found no association between subjects with Covid-19 respiratory syndrome and any of the variants. However, based on the symptoms caused by rs1051393, we found that it had an effect on fever symptoms. In addition, a significant relationship between rs2229207 and chest pain symptoms was observed in patients with case group. Furthermore, our study found significant differences (p < 0.05) in several blood laboratory analyses, such as the level of basophils and eGFR for rs6092 and the potassium level for rs2229207. Furthermore, arterial blood gas analysis showed that pCO2 and pH levels were significantly different for rs2229207. Conclusion Our study found an association between rs1051393 and fever and between rs2229207 and chest pain in patients with post Covid-19 respiratory syndrome.

in F1000Research on 2025-11-21 16:12:21 UTC.

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Are We Truly Preparing Students for Financial Success? Insights from Economic Education Curricula in Indonesia [version 1; peer review: awaiting peer review]

Background Financial literacy is an essential competency for university students, especially those in economics education programs, as it supports effective money management and responsible decision-making. However, higher education curricula in Indonesia still emphasize theoretical aspects over practical financial skills, raising concerns about whether graduates are adequately prepared for financial challenges. Methods This study employed a qualitative content analysis to evaluate the integration of financial literacy within economics education curricula in Indonesia. Data were collected through curriculum document reviews, semi-structured interviews with economics educators, and student surveys. The analysis focused on identifying the extent of financial literacy integration and perceptions of curriculum effectiveness. Results The findings indicate that while fundamental topics such as budgeting and savings are covered, critical elements including investment diversification, risk management, and digital financial tools remain underdeveloped. Students expressed a strong demand for more experiential learning approaches, such as case studies, financial simulations, and collaboration with industry partners. The results highlight a gap between theoretical instruction and the practical competencies required for effective financial decision-making. Conclusions The study concludes that strengthening economics education curricula requires the integration of applied financial literacy training, digital financial education, and industry collaboration to better prepare students for personal and professional financial challenges. While this research provides valuable insights, its qualitative scope presents limitations. Future studies with broader institutional coverage and quantitative approaches are recommended to generate more generalizable findings.

in F1000Research on 2025-11-21 16:09:56 UTC.

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A Systematic Literature Review and Bibliometric Analysis of Workplace Coaching [version 1; peer review: awaiting peer review]

Workplace Coaching has evolved significantly over the last two decades and has become a mainstream global activity in business organizations. The concept has been recognized for its potential in enhancing the well-being and performance of individuals, groups, and leaders, making it a popular intervention in modern organizations. Therefore, this study provides a comprehensive understanding of workplace coaching research from 2000 to 2025 by examining global trends in terms of publications, contributors, keyword co-occurrences, and thematic clusters, utilizing a systematic literature review with bibliometric analysis. The review was conducted to synthesise the available literature on workplace coaching to suggest future trends. The Scopus and Web of Science databases were used to explore and analyze published works using the PRISMA framework and VOSviewer software. A total of 343 published journal articles were considered in the analysis, eliminating duplication and minimizing potential risks during the screening process. The findings reveal a significant growth in academic interest in coaching in workplace research, with four key thematic clusters emerging: Coaching for Workplace Learning and Development, Multifaceted advantages of Executive and Leadership Coaching, Dimensions of Workplace Coaching, and Employee Coaching for Human Resource Management and Development. The study findings serve as a foundation for future studies that explore under-researched areas, such as the application of artificial intelligence in coaching practices, ethical considerations, digital transformation, sustainability in leadership, and employee well-being practices. Moreover, this study reveals the potential of meta-analyses and systematic reviews that incorporate grey literature to provide a more comprehensive understanding of coaching effectiveness. Comparative studies across different sectors, countries, and regions can help consolidate the existing findings and uncover new insights. These limitations and opportunities present avenues for future research, motivating researchers to advance and refine existing literature.

in F1000Research on 2025-11-21 16:08:14 UTC.

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Automated and modular protein binder design with BinderFlow

by Nayim González-Rodríguez, Carlos Chacón-Sánchez, Oscar Llorca, Rafael Fernández-Leiro

Deep learning has revolutionised de novo protein design, with new models achieving unprecedented success in creating novel proteins with specific functions, including artificial protein binders. However, current workflows remain computationally demanding and challenging to operate without dedicated infrastructure and expertise. To overcome these limitations, we present BinderFlow, an open, structured, and parallelised pipeline that automates end-to-end protein binder design. Its batch-based architecture enables live monitoring of design campaigns, seamless coexistence with other GPU-intensive processes, and minimal user intervention. BinderFlow’s modular design facilitates the integration of new tools, allowing rapid adaptation to emerging methods. We demonstrate its utility by running automated design campaigns that rapidly generate diverse, high-confidence candidates suitable for experimental validation. To complement the pipeline, we developed BFmonitor, a web-based dashboard for real-time campaign monitoring, design evaluation, and hit selection. Together, BinderFlow and BFmonitor make generative protein design more accessible, scalable, and reproducible, streamlining both exploratory and production-level research. The software is freely available at https://github.com/cryoEM-CNIO/BinderFlow under the GNU LGPL v3.0 license.

in PLoS Computational Biology on 2025-11-21 14:00:00 UTC.

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Ten simple rules for maximizing summer research experiences for students, mentors, and research groups

by Miriam B. Goodman

Whether hosted by colleges, universities, stand-alone research institutions, federal research labs, or private companies, immersive summer (6–12 weeks) research experiences build students’ confidence in their scientific capabilities and help to refine their professional trajectories. Such internships are an important tool to introduce students to STEM careers and energize participants, each of whom realizes a powerful benefit. The student gains hands-on research experience, insight into the research process, and clarity regarding their educational and career aspirations. The bench mentor, typically an advanced graduate student, postdoctoral researcher, or staff scientist, acquires essential skills in training and mentoring while incorporating fresh perspectives from an inquisitive novice into their research project. The principal investigator (PI) promotes the professional development of the bench mentor, expands interest in STEM careers, while exploring a focused and compact research question. This set of Ten Simple Rules is a guide for PIs, bench mentors, and research groups and seeks to foster excellence in the design of short-term research experiences for students. They emphasize projects co-created by PIs and bench mentors, accessible techniques that can be mastered in a few weeks, and strategies enabling interns to develop their own mental model of the research question and approach. Although tailored primarily to full-time summer internships for individual students in an academic research setting, this advice may be applicable to short-term, mentored research experiences in multiple settings.

in PLoS Computational Biology on 2025-11-21 14:00:00 UTC.

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Nash equilibrium of attack and defense behaviors between predators and prey

by Hiroyuki Ichijo, Yuichiro Kawamura, Tomoya Nakamura

How animals process information, compute, and execute behaviors is a central question in neuroscience and computational biology. Predators attack prey by chasing or ambushing them, while prey respond with escaping or freezing. These behaviors are fundamental for survival. Uncovering functions of such behaviors requires an understanding not only of the implementation of neuronal circuits but also of the underlying algorithms and computation. However, how animals respond to predators or prey depending on whether they can detect them from a distance remains unclear. Here, we modeled and analyzed attack and defense behaviors with game theory. Using encounter probabilities to construct payoff matrices under a sensory–motor algorithm that lacked directional information, we identified the corresponding equilibrium behaviors for the agents (predators and prey). Different detection distances yielded distinct Nash equilibrium behaviors, representing a computational mechanism that can account for diverse attack and defense behaviors. The games based on interactions among multiple predators and prey were, in most cases, non-constant-sum and positive-sum games. Measured payoffs of Nash equilibrium behaviors indicated that the predators were able to increase their payoffs by attacking, and the prey were also able to increase their payoffs even in the presence of predators. These results suggest that each of the agents initiates attack and defense behaviors. Moreover, Nash equilibrium behaviors were also identified under a simpler non-sensory motor algorithm. Despite the similarity, the non-sensory motor algorithm and the sensory–motor algorithm had distinct adaptive significance. The sensory–motor algorithm produced substantially greater prey payoffs. By implementing these algorithms, agents interact in ways that give rise to payoff matrices from which various Nash equilibrium behaviors can be mathematically derived under different conditions. Furthermore, this approach offers an experimental framework for understanding behavioral evolution and suggests a possible difference in evolutionary mechanisms of attack and defense behaviors.

in PLoS Computational Biology on 2025-11-21 14:00:00 UTC.

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Parameterization of cell-free systems with time-series data using KETCHUP

by Mengqi Hu, Syed Bilal Jilani, Daniel G. Olson, Costas D. Maranas

Kinetic models mechanistically link enzyme levels, metabolite concentrations, and allosteric regulation to metabolic reaction fluxes. This coupling allows for the quantitative elucidation of the dynamics of the evolution of metabolite concentrations and metabolic fluxes as a function of time. So far, most large-scale kinetic model parameterizations are carried out using mostly steady-state flux measurements supplemented with metabolomics and/or proteomics data when available. Even though the parameterized kinetic model can trace a temporal evolution of the system, lack of anchoring to temporal data reduces confidence in the dynamics predictions. Notably, the simulation of enzymatic cascade reactions requires a full description of the dynamics of the system as a steady-state is not applicable given that all measured metabolite concentrations vary with time. Here we describe how kinetic parameters fitted to the dynamics of single-enzyme assays remain accurate for the simulation of multi-enzyme cell-free systems. Herein, we demonstrate two extensions for the Kinetic Estimation Tool Capturing Heterogeneous datasets Using Pyomo (KETCHUP) software tool for parameterizing a kinetic model of the cell-free kinetics of formate dehydrogenase (FDH) and 2,3-butanediol dehydrogenase (BDH) through the use of time-course data across various initial conditions. An implemented extension of KETCHUP allowing for the reconciliation of measurement time-lag errors present in datasets was used to parameterize kinetic models using multiple datasets. By combining the kinetic parameters identified by the FDH and BDH assays, accurate simulation of the binary FDH-BDH system was achieved.

in PLoS Computational Biology on 2025-11-21 14:00:00 UTC.

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Universal scale-free representations in human visual cortex

by Raj Magesh Gauthaman, Brice Ménard, Michael F. Bonner

How does the human brain encode complex visual information? While previous research has characterized individual dimensions of visual representation in cortex, we still lack a comprehensive understanding of how visual information is organized across the full range of neural population activity. Here, analyzing fMRI responses to natural scenes across multiple individuals, we discover that neural representations in human visual cortex follow a remarkably consistent scale-free organization—their variance decay is consistent with a power-law distribution, detected across four orders of magnitude of latent dimensions. This scale-free structure appears consistently across multiple visual regions and across individuals, suggesting it reflects a fundamental organizing principle of visual processing. Critically, when we align neural responses across individuals using hyperalignment, we find that these representational dimensions are largely shared between people, revealing a universal high-dimensional spectrum of visual information that emerges despite individual differences in brain anatomy and visual experience. Traditional analysis approaches in cognitive neuroscience have focused primarily on a small number of high-variance dimensions, potentially missing crucial aspects of visual representation. Our results demonstrate that visual information is distributed across the full dimensionality of cortical activity in a systematic way, thus revealing a key property of neural coding in visual cortex. These findings suggest that we need to move beyond low-dimensional characterizations to fully understand how the brain represents the visual world.

in PLoS Computational Biology on 2025-11-21 14:00:00 UTC.

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Protein drift-diffusion in membranes with non-equilibrium fluctuations arising from gradients in concentration or temperature

by Dev Jasuja, Paul J. Atzberger

We investigate proteins within heterogeneous cell membranes where non-equilibrium phenomena arises from spatial variations in concentration and temperature. We develop simulation methods building on non-equilibrium statistical mechanics to obtain stochastic hybrid continuum-discrete descriptions which track individual protein dynamics, spatially varying concentration fluctuations, and thermal exchanges. We investigate biological mechanisms for protein positioning and patterning within membranes and factors in thermal gradient sensing. We also study the kinetics of Brownian motion of particles with temperature variations within energy landscapes arising from heterogeneous microstructures within membranes. The introduced approaches provide self-consistent models for studying biophysical mechanisms involving the drift-diffusion dynamics of individual proteins and energy exchanges and fluctuations between the thermal and mechanical parts of the system. The methods also can be used for studying related non-equilibrium effects in other biological systems and soft materials.

in PLoS Computational Biology on 2025-11-21 14:00:00 UTC.

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Emergence of sparse coding, balance and decorrelation from a biologically-grounded spiking neural network model of learning in the primary visual cortex

by Marko A. Ruslim, Martin J. Spencer, Hinze Hogendoorn, Hamish Meffin, Yanbo Lian, Anthony N. Burkitt

Many experimental and computational studies deal with sparseness, balance, and decorrelation in neural networks and explain the presence of these properties as fulfilling requirements related to optimum energy efficiency, network stability, and information representation. These studies leave the question of how these properties arise in the brain unanswered. The present study attempts to address this question using a model built upon the experimentally observed properties of neural responses, homeostasis, and synaptic plasticity. The experimentally observed properties of sparseness, balance, and decorrelation are then expected to emerge from this substrate. A spiking neural model of the primary visual cortex (V1) was investigated. Populations of both inhibitory and excitatory leaky integrate-and-fire neurons with recurrent connections were provided with spiking input from simulated ON and OFF neurons of the lateral geniculate nucleus. This network was provided with natural image stimuli as input. All synapses underwent learning using spike-timing-dependent plasticity learning rules. A homeostatic rule adjusted the weights and thresholds of each neuron based on target homeostatic spiking rates and mean synaptic input values. These experimentally grounded rules resulted in a number of the expected properties of information representation. The network showed a temporally sparse spike response to inputs and this was associated with a sparse code with Gabor-like receptive fields. The network was balanced at both slow and fast time scales; increased excitatory input was balanced by increased inhibition. This balance was associated with decorrelated firing that was observed as population sparseness. This population sparseness was both the cause and result of the decorrelation of receptive fields. These observed emergent properties (balance, temporal sparseness, population sparseness, and decorrelation) indicate that the network is implementing expected principles of information processing: efficient coding, information maximization (’infomax’), and a lateral or single-layer form of predictive coding. These emergent features of the network were shown to be robust to randomized jitter of the values of key simulation parameters.

in PLoS Computational Biology on 2025-11-21 14:00:00 UTC.

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The efficacy of longevity interventions in Caenorhabditis elegans is determined by the early life activity of RNA splicing factors

by Sneha Dutta, Maria Camila Perez Matos, Caroline Heintz, Ayse Sena Mutlu, Mary Piper, Meeta Mistry, Arpit Sharma, Christopher S. Morrow, Hannah Smith, Porsha Howell, Rohan Sehgal, Anne Lanjuin, Meng C. Wang, William B. Mair

Geroscience aims to target the aging process to extend healthspan. However, even isogenic individuals show heterogeneity in natural aging rate and responsiveness to pro-longevity interventions, limiting translational potential. Using RNAseq analysis of young, isogenic, subpopulations of Caenorhabditis elegans selected solely on the basis of the splicing pattern of an in vivo minigene reporter that is predictive of future life expectancy, we find a strong correlation in young animals between predicted life span and alternative splicing of mRNAs related to lipid metabolism. The activity of two RNA splicing factors, Reversed Polarity-1 (REPO-1) and Splicing Factor 1 (SFA-1), early in life is necessary for C. elegans response to specific longevity interventions and leads to context-specific changes to fat content that is mirrored by knockdown of their direct target POD-2/ACC1. Moreover, POD-2/ACC1 is required for the same longevity interventions as REPO-1/SFA-1. In addition, early inhibition of REPO-1 renders animals refractory to late onset suppression of the TORC1 pathway. Together, we propose that splicing factor activity establishes a cellular landscape early in life that enables responsiveness to specific longevity interventions and may explain variance in efficacy between individuals.

in PLoS Biology on 2025-11-21 14:00:00 UTC.

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Cardiometabolic health and physical robustness map onto distinct patterns of brain structure and neurotransmitter systems

by Eliana Nicolaisen-Sobesky, Somayeh Maleki Balajoo, Mostafa Mahdipour, Agoston Mihalik, Mahnaz Olfati, Felix Hoffstaedter, Janaina Mourao-Miranda, Masoud Tahmasian, Simon B. Eickhoff, Sarah Genon

The link between brain health and risk/protective factors for non-communicable diseases (such as high blood pressure, high body mass index, diet, smoking, physical activity, etc.) is increasingly acknowledged. However, the specific effects that these factors have on brain health are still poorly understood, delaying their implementation in precision brain health. Here, we studied the multivariate relationships between risk factors for non-communicable diseases and brain structure, including cortical thickness (CT) and gray matter volume (GMV). Furthermore, we adopted a systems-level perspective to understand such relationships, by characterizing the cortical patterns (yielded in association to risk factors) with regards to brain morphological and functional features, as well as with neurotransmitter systems. Similarly, we related the pattern of risk/protective factors dimensions with a peripheral marker of inflammation. First, we identified latent dimensions linking a broad set of risk factors for non-communicable diseases to parcel-wise CT and GMV across the whole cortex. Data was obtained from the UK Biobank (n = 7,370, age range = 46–81 years). We used regularized canonical correlation analysis (RCCA) embedded in a machine learning framework. This approach allows us to capture inter-individual variability in a multivariate association and to assess the generalizability of the model. The brain patterns (captured in association with risk/protective factors) were characterized from a multi-level perspective, by performing correlations (spin tests) between them and different brain patterns of structure, function, and neurotransmitter systems. The association between the risk/protective factors pattern and C-reactive protein (CRP, a marker of inflammation) was examined using Spearman correlation. We found two significant and partly replicable latent dimensions. One latent dimension linked cardiometabolic health to brain patterns of CT and GMV and was consistent across sexes. The other latent dimension linked physical robustness (including non-fat mass and strength) to patterns of CT and GMV, with the association to GMV being consistent across sexes and the association to CT appearing only in men. The CT and GMV patterns of both latent dimensions were associated to the binding potentials of several neurotransmitter systems. Finally, the cardiometabolic health dimension was correlated to CRP, while physical robustness was only very weakly associated to it. We observed robust, multi-level and multivariate links between both cardiometabolic health and physical robustness with respect to CT, GMV, and neurotransmitter systems. Interestingly, we found that cardiometabolic health and physical robustness are associated with not only increases in CT or GMV, but also with decreases of CT or GMV in some brain regions. Our results also suggested a role for low-grade chronic inflammation in the association between cardiometabolic health and brain structural health. These findings support the relevance of adopting a holistic perspective in health, by integrating neurocognitive and physical health. Moreover, our findings contribute to the challenge to the classical conceptualization of neuropsychiatric and physical illnesses as categorical entities. In this perspective, future studies should further examine the effects of risk/protective factors on different brain regions in order to deepen our understanding of the clinical significance of such increased and decreased CT and GMV.

in PLoS Biology on 2025-11-21 14:00:00 UTC.

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Nanobody-drug conjugates for targeting specific GPCR pairs

by Xianglin Huang, Bryan L. Roth

Bitopic ligands that engage two distinct binding sites offer exciting opportunities for finely tuned control of G protein-coupled receptor signaling. A recent study in PLOS Biology employed click chemistry to generate novel nanobody-small molecule conjugates and demonstrated their logic-gated activity at co-expressed receptor pairs with improved signaling profiles. Bitopic ligands that engage two distinct binding sites offer exciting opportunities for finely tuned control of G protein-coupled receptor signaling. This Primer explores a recent study in PLOS Biology that reports novel nanobody-small molecule conjugates and demonstrates their logic-gated activity at co-expressed receptor pairs with improved signaling profiles.

in PLoS Biology on 2025-11-21 14:00:00 UTC.

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Effect of Canal Size on Isthmus Cleaning Efficiency and Safety of High-Frequency Sonic Agitation: An In Vitro Study [version 1; peer review: awaiting peer review]

Objective This study aimed to evaluate the effect of root canal preparation size on isthmus cleaning efficiency and periapical extrusion using high-frequency sonic agitation with the EDDY irrigation system. Materials and Methods Thirty custom-made epoxy split models were used to simulate a root canal system with two curved canals merging at the apical 1 mm and an isthmus extending along their length. A periapical lesion was simulated to assess the extrusion tendency. Canals were prepared using the WaveOne Gold system in small, primary, and medium sizes. The isthmuses were filled with bovine dentin debris, while dyed gelatin was used in the periapical lesion to quantify extruded irrigant volume. EDDY irrigation efficiency was evaluated based on the total cleared surface area (mm2) using ImageJ software. Statistical analysis was performed using one-way ANOVA and post hoc multiple comparisons, with a significance level of P ≤ 0.05. Results Isthmus cleaning efficiency remained consistent across all canal sizes, with no significant differences among groups (P > 0.05). However, periapical extrusion increased significantly with larger canal preparation sizes, with medium-sized preparations showing significantly higher extrusion than small (P = 0.001) and primary (P = 0.026) sizes. Conclusion EDDY irrigation was effective in achieving isthmus cleanliness regardless of canal preparation size. However, larger instrumentation increased the risk of apical extrusion, underscoring the need for careful irrigation management in clinical applications.

in F1000Research on 2025-11-21 11:25:21 UTC.

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Association of cancer and outcomes of patients hospitalized for COVID-19 between 2020 and 2023 [version 3; peer review: 1 approved, 2 approved with reservations, 1 not approved]

Background The coronavirus disease 2019 (COVID-19) has caused substantial morbidity and mortality on a global scale. A strong correlation has been found between COVID-19 treatment outcomes and noncommunicable diseases such as cancers. However, there is limited information on the outcomes of cancer patients who were hospitalised for COVID-19. Methods We conducted an analysis on data collected in a large prospective cohort study set-up by the World Health Organisation (WHO) International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC). All patients with laboratory-confirmed or clinically-diagnosed SARS-CoV-2 infection were included. Cancer was defined as having a current solid organ or haematological malignancy. The following outcomes were assessed; The hazard ratio of 30-day in-hospital mortality, intensive care unit (ICU) admission, length of hospitalization and receipt of higher-level care. Results Of the 560,547 hospitalised individuals who were analysed, 27,243 (4.9%) had cancer. Overall, cancer patients were older and had more comorbidities than non-cancer patients. Patients with cancer had a higher hazard ratio of 30-day in-hospital mortality than non-cancer patients (29.1.3% vs 18.0%) and longer hospital stays (median of 12 days vs 8 days). However, patients with cancer were admitted less often to intensive care units than non-cancer patients (12.6% vs 17.1%) and received less invasive mechanical ventilation than non-cancer patients (4.5% vs 7.6%). The hazard ratio of dying from cancer, adjusted for age, sex and country income level was 1.18 (95%CI: 1.15-1.2). Conclusions This study’s findings underscore the heightened vulnerability of hospitalized COVID-19 patients with cancer, revealing a higher mortality rate, longer hospital stays, and an unstructured pattern of care that reflects the complexity of managing severely ill patients during a public health crisis like the COVID-19 pandemic.

in F1000Research on 2025-11-21 10:43:08 UTC.

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The complete chloroplast genome of Phyllanthus acidus (L.) Skeels (Phyllanthaceae) [version 3; peer review: 3 approved with reservations]

Phyllanthus acidus (L.) Skeels (Phyllanthaceae) is a potential medicinal plant recognized for its sour and tart-tasting fruits. In this study, the chloroplast genome of P. acidus was sequenced, assembled, and characterized. The chloroplast genome size was 156,331 bp, and the overall GC content was 36.9%. Additionally, the chloroplast genome had a quadripartite structure consisting of a large single copy (LSC; 85,807 bp in length; GC content: 34.6%), a small single copy (SSC; 19,262 bp in length; GC content: 30.6%), and two inverted repeat regions (IR; 25,631 bp in length; GC content: 43.1%). A total of 113 unique genes were annotated in the chloroplast genome, including 79 protein-coding genes, 30 tRNAs, and four rRNAs. The phylogenetic analysis based on 79 protein-coding genes revealed the paraphyly of the Phyllanthus genus. These findings provided additional genetic information for further research on P. acidus and the cp genome in the Phyllanthaceae family.

in F1000Research on 2025-11-21 10:39:01 UTC.

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Boundary homogenization and numerical modeling of solute transport across the blood-brain barrier

Author(s): Reza Yousofvand, Gregory Handy, and Jeffrey Tithof

Effective clearance of amyloid- $β$ ( $A β$ ) from the brain is essential for preventing neurodegenerative diseases such as Alzheimer's. A significant portion of this clearance occurs through the blood-brain barrier (BBB) via receptor-mediated transport. However, current models fail to capture the complex k…

[Phys. Rev. E 112, 054410] Published Fri Nov 21, 2025

in Physical Review E: Biological physics on 2025-11-21 10:00:00 UTC.

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