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Nature Communications, Published online: 17 January 2026; doi:10.1038/s41467-026-68454-9
Chromatin profiling methods are often limited by a lack of suitable antibodies. Here, authors present Af-CUT&Tag, a chromatin profiling strategy based on CRISPR-integrated peptide tags which enables sensitive bulk and single-cell mapping of transcriptional regulators.
in Nature Communications on 2026-01-17 00:00:00 UTC.
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Nature Communications, Published online: 17 January 2026; doi:10.1038/s41467-026-68480-7
Changing fire regimes, leading to higher likelihood of high severity fire, are having unknown impacts on biodiversity. This study identifies regions of high avian biodiversity and individual bird species predicted to be highly exposed to future high severity.
in Nature Communications on 2026-01-17 00:00:00 UTC.
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Nature Communications, Published online: 17 January 2026; doi:10.1038/s41467-025-67999-5
Smc5/6 association with DNA junctions can support genomic functions. Here, the authors show that Smc5/6 junction polarity preferences, targeting, and dwell times are determined by its structural modules as well as the RPA and PCNA genomic factors.
in Nature Communications on 2026-01-17 00:00:00 UTC.
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Nature Communications, Published online: 17 January 2026; doi:10.1038/s41467-025-66627-6
Inspired by nature, this study reports a dual-gradient aerogel via freeze-casting. It blends flexibility with rigidity, offers high sensitivity and wide range, withstands extreme heat and cold, with promise for integration in spacesuits.
in Nature Communications on 2026-01-17 00:00:00 UTC.
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Nature Communications, Published online: 17 January 2026; doi:10.1038/s41467-026-68597-9
Ma et al. report an organic cation engineering strategy to improve the luminescent properties and charge transport in organic-inorganic antimony halide films, enabling red LEDs with efficiency up to 19.4% and half-lifetime of 10,190 min. Large-area (12.15 cm2) LEDs show efficiency of 14.2%.
in Nature Communications on 2026-01-17 00:00:00 UTC.
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Nature Communications, Published online: 17 January 2026; doi:10.1038/s41467-026-68416-1
Asexual-to-sexual switching underpins malaria transmission. Prajapati et al. identify an AP2-G loss-of function mutation and use it as a genetic tool to show that GDV1 is essential for initial ap2-g activation and sexual commitment initiation.
in Nature Communications on 2026-01-17 00:00:00 UTC.
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Nature Communications, Published online: 17 January 2026; doi:10.1038/s41467-026-68464-7
Untargeted metabolomics faces challenges in metabolite origin inference and metabolite annotation. Here, the authors present TidyMass2, a user-friendly computational framework with metabolite origin inference and feature-based functional module analysis to enhance biological interpretation.
in Nature Communications on 2026-01-17 00:00:00 UTC.
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Communications Biology, Published online: 17 January 2026; doi:10.1038/s42003-026-09526-w
Multi-modal integration of spatial transcriptomes and metabolomes via haCCA reveals metabolic heterogeneity and NETs-mediated Scd1 upregulation driving fatty acid metabolism in intrahepatic cholangiocarcinoma.
in Nature communications biology on 2026-01-17 00:00:00 UTC.
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Communications Biology, Published online: 17 January 2026; doi:10.1038/s42003-026-09521-1
Acetaldehyde treatment and whole genome sequencing of human cells reveal no increased base substitution mutagenesis but an induction of structural genomic alterations mirrored by the association of similar events with alcohol consumption in cancer.
in Nature communications biology on 2026-01-17 00:00:00 UTC.
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Aim To examine the determinants influencing cultural reproduction, comprehend the fundamental concepts of cultural reproduction, and evaluate the model of cultural reproduction as a manifestation of socio-cultural resilience. Materials and Methods The research employed the Systematic Literature Review (SLR) methodology, utilizing the PRISMA protocol and the PICO framework. Data were sourced from Scopus, Web of Science, ProQuest, and Google Scholar, chosen based on inclusion criteria (2015–2025, empirical articles, pertinent to socio-cultural resilience). Out of the 688 initial articles, 143 studies satisfied the criteria. The Mixed Methods Appraisal Tool (MMAT) was used to assess quality, and NVivo 14 was used for thematic synthesis to find patterns of direct relationships, mediation, and moderation between factors. Results and discussions The analysis identified eight principal factors: education, politics, family, economy, media, technology, religion, and community. Politics (15.3%) and education (17.6%) were the most important factors. Cultural reproduction operates through micro–macro interactions involving direct relationships (family, religion, community), mediation (education, media, politics, technology), and moderation (economics, technology). The resulting integrative model elucidates the way this amalgamation of factors enhances socio-cultural resilience via conservation and value adaptation. Conclusions Cultural reproduction serves both as a means of value preservation and as an adaptive mechanism that enhances social resilience. This research enhances Bourdieu’s theory by incorporating digital and participatory dimensions, providing a conceptual foundation for sustainable cultural policy.
in F1000Research on 2026-01-16 12:29:53 UTC.
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Background This study aims to detect the efficiency of two Artificial Intelligence (AI) translation models, ChatGPT and DeepSeek, in the translation of Yemeni San’ani Arabic (YSA) dialectical terms into English. As dialectal Arabic presents significant linguistic variability and cultural specificity, accurate translation remains a major challenge for the current ChatGPT and DeepSeek (and perhaps other AI models). Methods Fifty San’ani Arabic terms were involved in the translation process, assessing the ability of both models to capture their semantic fidelity, cultural relevance, and contextual accuracy. Results The study findings reveal that, while both models demonstrate a foundational understanding of Standard Arabic (SA), their performance diminishes considerably when faced with the nuances and idiomatic expressions of the San’ani Arabic dialect. ChatGPT displays a relatively better performance in certain cases, particularly when translating terms with dialectical connotations. However, both models exhibit limitations, such as literal translation, misinterpretation, or complete ignorance of the intended meaning. Conclusions The study concludes by highlighting the critical need for dialect-aware AI development and provides recommendations for improving the dialectical accuracy and cultural sensitivity of AI model translation.
in F1000Research on 2026-01-16 12:25:26 UTC.
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The proposed design of neural network in this article is based on new accurate approach for training by unconstrained optimization, especially update quasi-Newton methods are perhaps the most popular general-purpose algorithms. A limited memory BFGS algorithm is presented for solving large-scale symmetric nonlinear equations, where a line search technique without derivative information is used. On each iteration, the updated approximations of Hessian matrix satisfy the quasi-Newton form, which traditionally served as the basis for quasi-Newton methods. On the basis of the quadratic model used in this article, we add a new update of quasi-Newton form. One innovative features of this form's is its ability to estimate the energy function's or performance function with high order precision with second-order curvature while employ the given function value data and gradient. The global convergence of the proposed algorithm is established under some suitable conditions. Under some hypothesis the approach is established to be globally convergent. The updated approaches can be numerical and more efficient than the existing comparable traditional methods, as illustrated by numerical trials. Numerical results show that the given method is competitive to those of the normal BFGS methods. We show that solving a partial differential equation can be formulated as a multi-objective optimization problem, and use this formulation to propose several modifications to existing methods. Also the proposed algorithm is used to approximate the optimal scaling parameter, which can be used to eliminate the need to optimize this parameter. Our proposed update is tested on a variety of partial differential equations and compared to existing methods. These partial differential equations include the fourth order three dimensions nonlinear equation, which we solve in up to four dimensions, the convection-diffusion equation, all of which show that our proposed update lead to enhanced accuracy.
in F1000Research on 2026-01-16 12:20:41 UTC.
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Abstract* Background Social media marketing dynamics have been reshaped with the rise of micro-influencers, with the offering of community-driven and authentic brand engagement that goes beyond traditional celebrity endorsements and advertising. This study aims to systematically examine the micro-influencer research published between 2020 and 2025, focusing on identifying themes, research gaps, methodological characteristics, and providing future directions. Methods This paper focuses on providing a thorough systematic literature review (SLR) incorporating the PRISMA protocol on micro-influencers, while identifying interdependencies and relationships. 68 research papers that were derived from the Scopus database were analysed through bibliometric and content analysis. Bibliometric analysis was conducted using a combination of VOSviewer and Biblioshiny packages. Results were analysed through thematic clusters, co-occurrence, and bibliographic coupling analysis. Results The analysis depicts a steady growth in publications accelerated with digitalisation and post-COVID consumer shift that placed a commercial value on small-scale influencers. Research is fragmented across authenticity, trust, engagement, sponsorship disclosure, and niche-domains for micro-influencers. The literature is geographically skewed towards the West and high-income Asian countries. Less longitudinal evidence with strong methodological homogeneity was present. Algorithmic visibility, emerging platform comparisons, influencer labour, and non-commercial uses of micro-influencers were underexplored themes. Five research areas were identified from clustering. Conclusion Despite the rapid expansions, micro-influencer literature remains theoretically fragmented and unevenly distributed. This review provides a comprehensive analysis of the literature on micro-influencers and provides implications and future research directions. Most studies focused on analysing a single platform with cross-sectional designs. This study highlights the need for thorough theoretical integration with methodological diversification, considering emerging platforms to better understand how micro influencers shape digital communication.
in F1000Research on 2026-01-16 12:14:45 UTC.
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Background Natural resources and their pharmaceutical products play an important role in disease management because of their potential for new drug discovery and historical traditional use in healthcare. This study aimed to investigate the effects of hesperidin and its derivatives on MCF-7 human breast cancer cells and leishmaniosis. Methods The colorimetric cell viability MTT assay was used to measure the efficacy of these compounds in inhibiting MCF-7 cell growth and the promastigote forms of Leishmania tropica. Cells treated with different concentrations (3.125, 6.25, 12.5, 25, 50, 100, and 200 μg/ml) of hesperidin and their derivative, derv.1(5-amino-1,3,4-thiadiazole-2-thiol), and derv. 2 (5-(methylthio)-1,3,4-thiadiazol-2-thiol) after 24 h exposure. Results The Results showed that hesperidin was the most effective in inhibiting MCF-7 cells, with a 58.3% inhibition rate at a concentration of 100 μg/ml, whereas the derivative (derv.2) exhibited the highest antileishmanial activity, with a 50.2% inhibition rate at the same concentration. The anticancer and antileishmanial effects were concentration-dependent, with inhibition rates decreasing at lower concentrations. Conclusions These findings indicate the potential role of hesperidin and its derivatives as anti-cancer and antileishmanial agents, suggesting new ways for further research into their medical applications.
in F1000Research on 2026-01-16 12:06:37 UTC.
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Background Pancreatic cancer has a poor prognosis and is highly aggressive and deadly. Most pancreatic cancer diagnoses are adenocarcinomas, which account for more than 90 % of all cases. Developing effective therapeutic strategies requires an understanding of the molecular mechanisms associated with pancreatic cancer progression. Small nucleolar RNA 64 (SNORA64) was presented as a predictive marker for pancreatic cancer stages in our previous study. SNORA64 showed a gradual loss of its expression throughout the carcinogenesis process, and it inhibited metastasis by interfering with epithelial to mesenchymal transition (EMT). In this study, we investigated the role of SNORA64 on an intrinsic apoptotic pathway in pancreatic cancers by using human pancreatic cell line derived from adenocarcinoma PK-8 with SNORA64 knockdown and the scramble to compare with. Methods QPCR techniques used to measure the gene expression level of apoptosis related genes and cell viability analyzer are implanted in this study as investigational methods. Results Pk-8 with low expression of SNORA64 shows significantly high expression of anti-apoptotic genes B-cell leukemia/lymphoma-2 (BCl2) and B-cell lymphoma-extra-large (BCL-Xl) in contrast to the scramble control cell line. Conversely, the pro-apoptotic genes BH3 interacting domain death agonist (BID), BCL2 Associated X (BAX), and BCL2 homologous antagonist/killer (BAK) show significantly low expression compared to the scramble control. However, there is no change in the expression of BAD and BIM in Pk-8 with SNORA64 knockdown compared to the scrambled control cell line. Furthermore, the Pk-8 with low expression of SNORA64 shows a significant high proliferation rate and viability percentage compared to the scramble control cell line. Conclusion The downregulation of SNORA64 affects apoptosis pathways by manipulating pro- and anti-apoptotic gene regulators. The SNORA64 interactions with apoptotic inhibitor molecules and downregulation of pro-apoptotic molecules significantly sustain cellular viability. Therefore; SNORA64 can be used to increase the cell sensitivity to death during treatment.
in F1000Research on 2026-01-16 11:57:26 UTC.
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Background Beta-hemolytic streptococci (BHS) constitute a significant etiology of tonsillitis and rheumatic heart disease (RHD), affecting approximately 55 million individuals and causing 360,000 deaths annually worldwide. In the Middle East and North Africa region, RHD prevalence reaches 389 per 100,000 population, though diagnostic inadequacies may obscure the true disease burden. This investigation compared polymerase chain reaction (PCR)-based detection with conventional culture-based methods for BHS identification in Iraqi tonsillitis patients and assessed associated clinical, immunological, and systemic dissemination parameters. Methods A prospective cross-sectional study included 250 tonsillitis patients at Ramadi General Hospital, Iraq (April 2020–January 2025) and 25 healthy controls. Diagnostics comprised throat culture with Lancefield serogrouping, bacitracin testing, and PCR targeting the spy1258 gene. Blood specimens underwent PCR for systemic bacterial detection. Statistical analyses included chi-square testing, logistic regression, and diagnostic accuracy calculations. Results PCR detected Group A Streptococcus (GAS) in 52 of 83 (62.7%) culture-positive specimens, whereas Lancefield serogrouping identified only 19 (22.9%), representing a statistically significant threefold detection disparity (p < 0.001). PCR demonstrated 100% sensitivity and 100% specificity. Groups C and F streptococci comprised the majority of isolates. Elevated anti-streptolysin O (ASO) titers (≥200 IU/mL) were observed in 42.2% of non-GAS infections. Among severe cases, 45.7% demonstrated positive blood PCR for GAS DNA, indicating systemic dissemination. The highest disease burden occurred in the 6–15 years age cohort (54.2% of all isolates). DNA extraction optimization achieved an estimated efficiency of 90.4% compared to negligible efficiency with standard methodologies. Conclusion PCR-based diagnostics detected threefold more GAS cases than serological methods, revealing significant underdiagnosis. Non-Group A streptococci showed pathogenic potential and may cause post-infectious complications, warranting revised diagnostic paradigms.
in F1000Research on 2026-01-16 11:37:44 UTC.
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Protein–protein interactions play a central role in cellular signaling, immune recognition, and therapeutic development, yet they are often characterized by weak affinities, transient binding, and pronounced conformational flexibility. These features present significant challenges for conventional structural biology techniques. Biophysical approaches, particularly nuclear magnetic resonance (NMR) spectroscopy, and isothermal titration calorimetry (ITC) have emerged as powerful tools for elucidating peptide interactions under near-physiological conditions. NMR offers residue-level information on interaction interfaces, conformational changes, and protein dynamics in solution, making it uniquely suited for the analysis of weak and transient interactions. In contrast, ITC provides a direct and label-free measurement of binding thermodynamics, yielding quantitative parameters such as affinity, stoichiometry, and the enthalpic and entropic contributions to binding. This review highlights the principles, applications, and limitations of NMR and ITC in protein–protein interaction research, emphasizing how their combined use enables an integrated understanding of structure, dynamics, and energetics. Representative examples from the literature are discussed, including viral peptide–host protein interactions such as those involving Epstein–Barr virus latent membrane protein 1 (LMP1). Together, these studies illustrate the unique ability of NMR and ITC to capture structural and dynamic features of peptide recognition that are critical for understanding biological function and guiding peptide-based therapeutic design.
in F1000Research on 2026-01-16 11:32:11 UTC.
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Background With the aim of making it easier for researchers to produce policy-relevant research, the UK Government now requires all departments and arms-length bodies to publish annually-updated statements of their evidence needs, called ‘Areas of Research Interest’ (ARIs). We describe how ARIs are produced, and how they are used to support this aim. Aims and objectives In this paper we offer a description of ARIs and their development by UK governmental departments, and an assessment of how different stakeholders, including academia and funders, have responded to or otherwise used the ARIs. Key conclusions ARIs are a mechanism for organisations to share their research interests with external audiences in the form of a published document. In addition to this primary aim, they also have a much broader set of uses, including connecting departments with each other and helping intermediaries shape engagement plans. All groups would benefit from more robust evidence to choose effective engagement mechanisms, and more can be done to make the ARIs discoverable and useable. Overall, the ARIs are a useful tool to illuminate, and begin to connect different parts of the research-policy system.
in F1000Research on 2026-01-16 11:28:18 UTC.
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Streptomyces sp. BTA 1-131 was isolated from the marine sponge Melophlus sarasinorum collected in Indonesia. The crude extracts of this strain displayed antibacterial and cytotoxic activity, and therefore, to further investigate the bioactive potential of the strain, whole genome sequencing was performed in this study. The whole genome sequencing of Streptomyces sp. BTA 1-131 was conducted using both Illumina NextSeq and Oxford Nanopore platforms with a de novo hybrid assembly approach. The high-quality genome obtained is 10.23 Mbp with a GC content of 71.57%. It is organised into a single chromosomal contig, two linear plasmids, and one circular plasmid. Interestingly, a long-terminal inverted repeat (L-TIR) sequence of 1.5 Mbp has been confirmed in the strain genome. Phylogenomic analysis suggested that the strain BTA 1-131 likely represents a new species within the genus Streptomyces. To the best of our knowledge, the genome data described here would be the first report on the hybrid genome sequence of Streptomyces associated with the rarely reported sponge Melophlus sarasinorum from Indonesia, with a unique feature of L-TIR. The complete genome data generated here will provide compelling information for further analysis of the biosynthetic potential of the strain BTA 1-131 to produce new bioactive compounds.
in F1000Research on 2026-01-16 10:14:14 UTC.
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In cases where vaginal delivery is not feasible and the mother’s or the child’s health is in danger, a Caesarean section (CS) is medically warranted. The World Health Organization (WHO) projects that between 10% and 15% of all births will have medically justifiable CS rates. Globally, WHO estimates that 6.2 million CSs are performed each year without medical justification. The determination to proceed with or forgo a CS can be understood as the result of weighing three key categories of influence: demand-side factors, supply-side factors, and clinical factors. Each of these categories contributes uniquely to the ultimate decision of whether to perform a CS, highlighting the multifaceted nature of this healthcare challenge. Within each input, there is also, often, a complex interplay. For example, there is a local narrative of mothers seeking an elective CS being “too posh to push”, inextricably linking household socioeconomic factors and maternal preferences. On the supply side there are issues of the policy within the healthcare facility (private hospitals prefer CSs) and an interplay with time management and maximizing the efficiency of the facility. Bangladesh’s CS has been on the rise; according to the most recent survey, it was 45%, far higher than the WHO recommendation. The private sector interacts with the high rates of CS in Bangladesh; MOH Bangladesh has little control over this sector. To optimize the CS rate, the nation must first recognize that needless CS is an issue and take all necessary action to address it.
in F1000Research on 2026-01-16 10:09:20 UTC.
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Background This study investigates the mediating role of comfort (CMT), convenience (CNV), and aesthetics (AST) in the relationship between the enablers of an age-friendly built environment for walkability and outcomes such as increased physical activity level (IPL), increased socialization (ISL), and improved quality of life (IQL) in older adults. The research emphasizes the importance of creating age-friendly environments to support the well-being and quality of life of older adults, with implications for urban planners and policymakers to promote sustainable and inclusive design. Methods The research follows a positivist paradigm using a quantitative approach and survey strategy with a cross-sectional design. A sample of 333 older adults was selected using the convenience sampling technique, and data were gathered through a self-administered questionnaire. Results Findings from hypothesis testing indicate that, among the enablers, age-friendly urban design policies are the most significant construct, positively impacting all three mediating variables. Aesthetics was found to have a significant positive effect on increased physical activity level and increased socialization, while comfort and convenience significantly influenced increased physical activity level and improved quality of life, respectively. Conclusion These results suggest implications for urban planners and policymakers to enhance the contribution of built environment for walkability toward increased physical activity level, increased socialization, and improved quality of life for older adults. The research offers valuable insights for academics and practitioners, emphasizing the importance of sustainable design while ensuring inclusivity to promote the well-being and quality of life of older adults.
in F1000Research on 2026-01-16 10:02:14 UTC.
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In a district of the Lambayeque province, considerable levels of political disaffection are evident, manifesting not only in the alienation from power but also in a significant gap between citizens and government institutions. Although efforts have been made to continue the participatory trend in democratic institutions, innovative proposals for social intervention in political processes and decision-making are still needed. The study aimed to propose a model of conventional participation to mitigate political disaffection in Lambayeque, Peru. The research was quantitative, with a non-experimental, descriptive-propositional design. It employed a survey technique applied to a randomly selected sample of 506 citizens from a total universe of 19,342 voters. The results indicate that the implementation of a conventional participatory practice, tailored to the sociocultural peculiarities of the district, positively impacts the political perception of the population. The findings reveal that a large portion of the Lambayeque population has disconnected from politics in everyday life, registering a general malaise that may reflect in future elections, as interest that does not translate into action is meaningless. General distrust in institutions, particularly the sentiment of corruption, has fostered this detachment; moreover, the results reflect a rejection of the political system. Despite many being informed about politics, the feeling of participation remains impotent.
in F1000Research on 2026-01-16 09:14:41 UTC.
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Background Cardiac hydatid cysts are uncommon presentation of heart disease that most often affects the left ventricle of the heart. The clinical picture may be quite different and may include arrhythmias and myocarditis up to a potentially life-threatening embolism of the cystic contents in cases of rupture into a cardiac chamber. Early and proper diagnosis is very important to avoid serious complications, such as infection and rupture of cysts. Even though medical treatment can bring certain control, surgery is the preferred type of treatment, which has good results and a low possibility of recurrence in cases where it is performed early. Methodology This retrospective case-series study examined five patients diagnosed with cardiac hydatid cysts between January 2018 and July 2024. All cases were handled by a qualified cardiac surgeon at Al-Anbar Governorate in Iraq. The effectiveness and safety of surgical management were evaluated based on clinical information, radiographic findings, surgical procedures, and post-operative experiences. Results All five patients successfully underwent successful excision of the cardiac hydatid cysts. In all cases, the post-operative course was uneventful, except for one patient who developed significant post-operatve bleeding requiring re-exploration. There were no deaths, and high-quality clinical recovery was achieved. No incidence of cyst rupture, secondary infection, or cyst reccurrence was reported during the follow-up period. Conclusions Although uncommon, cardiac hydatid cysts should be included in the diagnosis of cardiac masses, particularly in endemic areas. Echocardiography and high-tech imaging should be used to diagnose heart disease early to prevent severe complications. Surgery has been the pillar of treatment as it offers high success rates with low risk in case it is performed in a timely and careful manner. The positive results in this series prove the necessity of timely surgical referral and multidisciplinary treatment.
in F1000Research on 2026-01-16 09:09:21 UTC.
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Background The anabolic-androgenic steroid boldenone is widely abused and is strongly linked to nephrotoxicity, primarily mediated through oxidative stress and inflammation. Curcumin, a natural polyphenol, is renowned for its potent antioxidant and anti-inflammatory properties, but its protective role against boldenone-induced renal injury is not fully elucidated. This study aimed to investigate the potential nephroprotective effects of curcumin against boldenone-induced kidney damage in a rat model, focusing on biochemical parameters, oxidative stress markers, inflammatory response, and histological changes. Methods Thirty-two male Wistar rats were divided into four groups (n=8): control, curcumin-only (300 mg/kg/day), boldenone-only (5 mg/kg/week), and boldenone + curcumin. Over the experimental period, body weight, kidney weight, food/water intake, and serum renal function markers (urea, creatinine, electrolytes) were monitored. Renal tissue was analyzed for oxidative stress markers (MDA, GSH, CAT, SOD), the inflammatory cytokine TNF-α, and histological alterations. Results Boldenone administration significantly increased body and kidney weights, serum urea, creatinine, potassium, and chloride, while decreasing sodium and calcium. It induced marked oxidative stress (elevated MDA, depleted GSH, CAT, SOD) and inflammation (elevated TNF-α), resulting in significant tubular necrosis and hypertrophy. Co-treatment with curcumin substantially mitigated these abnormalities, normalizing serum markers, restoring antioxidant defenses and electrolyte balance, reducing TNF-α expression, and ameliorating histological damage. Conclusion Curcumin exerts significant nephroprotection against boldenone-induced toxicity through its antioxidant, anti-inflammatory, and cytoprotective mechanisms. These findings justify its exploration as a potential adjunct therapy to prevent steroid-associated kidney injury. Future studies should focus on elucidating the precise molecular signaling pathways involved and validating these effects in clinical scenarios of AAS abuse.
in F1000Research on 2026-01-16 09:04:16 UTC.
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Introduction Tuberculous pleural effusion (TPE) is the second most frequent manifestation of extrapulmonary tuberculosis (TB), predominantly characterised by mononuclear (MN) cells in pleural fluid. However, approximately 6.7% of cases show polymorphonuclear (PMN) cell predominance in pleural fluid, often causing delayed diagnosis and treatment, as these cases may not be initially recognised as tuberculosis. This study aimed to compare the clinical characteristics of PMN- and MN-predominant TPE. Methods This cross-sectional analytical study included 60 patients with bacteriologically confirmed TB with pleural effusion at Wahidin Sudirohusodo Hospital, Makassar, Indonesia. Primary data were collected from patient interviews, physical examinations, and pleural fluid analysis of thoracentesis samples. The diagnosis of pleural effusion was confirmed by radiological imaging and thoracentesis. Patients were classified as PMN-predominant (≥50% PMN) or MN-predominant (≥50% MN) based on pleural fluid cell counts. Results Among the patients, 24 (40%) had PMN-predominant and 36 (60%) had MN-predominant pleural effusion. Significant differences were found between cell predominance and clinical features, including weight loss (p < 0.001), symptom duration (p = 0.034), clinical severity (p = 0.033), pleural fluid leukocyte and lactate dehydrogenase (LDH) levels (p < 0.001). PMN predominance was associated with severe clinical presentation and higher pleural leukocyte and LDH levels in pleural fluid than MN predominance. Conclusions PMN-predominant TPE reflects an early, more severe inflammatory phase characterised by severe clinical manifestations and elevated leukocyte and LDH levels. While MN predominance suggests a more chronic disease phase with longer symptoms and mild to moderate clinical
in F1000Research on 2026-01-16 08:58:22 UTC.
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Science Advances, Volume 12, Issue 3, January 2026.
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Science Advances, Volume 12, Issue 3, January 2026.
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Science Advances, Volume 12, Issue 3, January 2026.
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Science Advances, Volume 12, Issue 3, January 2026.
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Science Advances, Volume 12, Issue 3, January 2026.
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Science Advances, Volume 12, Issue 3, January 2026.
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Science Advances, Volume 12, Issue 3, January 2026.
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Science Advances, Volume 12, Issue 3, January 2026.
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Science Advances, Volume 12, Issue 3, January 2026.
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Science Advances, Volume 12, Issue 3, January 2026.
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Science Advances, Volume 12, Issue 3, January 2026.
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Science Advances, Volume 12, Issue 3, January 2026.
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Science Advances, Volume 12, Issue 3, January 2026.
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Science Advances, Volume 12, Issue 3, January 2026.
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Science Advances, Volume 12, Issue 3, January 2026.
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Science Advances, Volume 12, Issue 3, January 2026.
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Science Advances, Volume 12, Issue 3, January 2026.
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Science Advances, Volume 12, Issue 3, January 2026.
in Science Advances on 2026-01-16 08:00:00 UTC.
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Science Advances, Volume 12, Issue 3, January 2026.
in Science Advances on 2026-01-16 08:00:00 UTC.
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Science Advances, Volume 12, Issue 3, January 2026.
in Science Advances on 2026-01-16 08:00:00 UTC.
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Science Advances, Volume 12, Issue 3, January 2026.
in Science Advances on 2026-01-16 08:00:00 UTC.
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Science Advances, Volume 12, Issue 3, January 2026.
in Science Advances on 2026-01-16 08:00:00 UTC.
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Background The objective of this systematic review was to analyze the effects of physical activity (PA) intervention as an adjuvant strategy to pharmacological treatment in people with treatment-resistant depression (TRD) and non-remitted depression (NRD). Methods A search strategy was conducted from five databases: PubMed, Cochrane Central Register of Controlled Trials, Scopus, SPORTDiscus, and Web of Science. The Physiotherapy Evidence Database and Oxford’s Evidence Levels were used to classify the quality appraisal. Results Of the 10777 records, 11 randomized controlled studies met the inclusion criteria. The main outcome for this analysis was the effect of physical activity (PA) or exercise on depressive symptoms in people with TRD and NRD diagnosis. According to the FITT (Frequency, Intensity, Time, and Type) principle, there was some variability in the PA intervention. However, except for one article, all were classified as excellent in terms of quality description. Conclusions This review highlights the potential of PA intervention as an adjuvant program to improve various traits in TRD and NRD. The remission of depression seems to be higher after PA intervention, showing improvements in quality of life, sleep quality, executive function, and vitality.
in F1000Research on 2026-01-16 07:26:52 UTC.
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Background Osteoporotic vertebral compression fractures (OVCFs) are frequent reasons behind painful, spinal deformity, and low-quality of life among the aged. Percutaneous balloon kyphoplasty (KP) is a minimally invasive procedure aimed at stabilizing fractured vertebrae, regaining vertebral height, and correcting kyphotic deformity. The purpose of this study was to compare the radiological and functional outcome of unilateral percutaneous kyphoplasty in patients with OVCFs that are not responding to conservative therapy. Methods This retrospective case study was conducted on 32 adult patients with vertebral compression fracture as a result of osteoporosis who received percutaneous kyphoplasty in the Department of Neurosurgery, Hatay Mustafa Kemal University, Turkey, between 2022 and 2024. Radiological evaluation was conducted before surgery, in the 24 hours after surgery and 1 month after surgery. The heights of anterior, middle, and posterior vertebral bodies and kyphosis angles were measured on the lateral radiographs using Cobb method. The Visual Analogue Scale (VAS) of pain was used as a measure of functional outcomes. Paired statistical tests were conducted to statistically compare pre and postoperative values and the significance was set at p < 0.05. Results The sample population was a group of 24 females (75% of the total population) and 8 males (25% of the total population) with the mean age of the sample population equal to 63.09 years. The number of kyphoplasties carried out was 36. The mean VAS pain scores reduced significantly by the 8.56 at preoperative stage to 5.83 in the early postoperative stage and further to 0.63 at 1 month postoperative, which is a 92.64% pain reduction. Anterior and middle height of vertebral bodies was significantly better after operation and there was no significant change of the height of the posterior walls. Mean kyphosis angle dropped to 10.73 owing to surgery as compared to 18.44 owing to surgery, and was maintained at 1 month. No significant complications such as cement leakage, pulmonary embolism or neurological deficit were observed. Conclusions Percutaneous balloon kyphoplasty is safe and effective, minimally invasive therapy of osteoporotic compression fracture of the vertebra. The surgery offers quick and lasting analgesia, considerable recovery of vertebral stature, and lasting remedy of kyphotic deformity at a low complication rate. These results justify using kyphoplasty as a useful treatment measure to patients with symptomatic OVCFs.
in F1000Research on 2026-01-16 07:09:59 UTC.
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Journal of Neurophysiology, Ahead of Print.
in Journal of Neurophysiology on 2026-01-16 02:51:47 UTC.
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Jia et al. show that the antiseizure effects of Bacteroides fragilis are mediated by enhanced cholinergic signaling along the gut-vagus-brain axis and reinforced by the gut colonization of Lactobacillus. These findings reveal a microbiota-neural circuit interaction with translational implications for pediatric refractory epilepsy.
in Neuron: In press on 2026-01-16 00:00:00 UTC.
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Nature, Published online: 16 January 2026; doi:10.1038/d41586-026-00128-4
A drop in precancerous growths in women who hadn’t received the jab suggests the existence of a ‘herd effect’ against the virus.
in Nature on 2026-01-16 00:00:00 UTC.
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Nature, Published online: 16 January 2026; doi:10.1038/d41586-026-00194-8
Nature staff discuss some of the week’s top science news.
in Nature on 2026-01-16 00:00:00 UTC.
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Nature, Published online: 16 January 2026; doi:10.1038/d41586-026-00129-3
Better understanding of multi-year global weather cycles could help airlines to reduce fuel consumption and cost.
in Nature on 2026-01-16 00:00:00 UTC.
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Nature, Published online: 16 January 2026; doi:10.1038/d41586-026-00112-y
Particularly talented canines have sociolinguistic skills akin to those of young toddlers.
in Nature on 2026-01-16 00:00:00 UTC.
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Nature, Published online: 16 January 2026; doi:10.1038/d41586-025-04125-x
A safety engineer feels abandoned by their principal investigator. How should they find support?
in Nature on 2026-01-16 00:00:00 UTC.
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Nature, Published online: 16 January 2026; doi:10.1038/d41586-026-00146-2
As Robert F. Kennedy Jr slashes the US childhood vaccine roster, Japan is racing to make up for lost ground after decades of setbacks.
in Nature on 2026-01-16 00:00:00 UTC.
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Nature, Published online: 16 January 2026; doi:10.1038/d41586-026-00164-0
Chinese factories have embraced the machines, but many activities still require human operators.
in Nature on 2026-01-16 00:00:00 UTC.
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Nature Reviews Neuroscience, Published online: 16 January 2026; doi:10.1038/s41583-026-01022-8
In this Journal Club, Arjen Boender describes a 2017 study that showed that diffusible peptidergic signals coordinate behaviour in Trichoplax adhaerens, a tiny marine animal that lacks a nervous system.
in Nature Reviews on 2026-01-16 00:00:00 UTC.
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Nature Communications, Published online: 16 January 2026; doi:10.1038/s41467-026-68591-1
Here the authors show a general method to make alkoxide-based network-forming glasses with tunable properties by combining titanium, zirconium and boron-based nodes, multi-dentate alcohol linkers and mono-dentate alcohol modulators.
in Nature Communications on 2026-01-16 00:00:00 UTC.
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Nature Physics, Published online: 16 January 2026; doi:10.1038/s41567-025-03159-2
Suspensions of colloidal hard spheres are excellent model systems for studying glass dynamics. Adding tracer particles enables a hydrodynamic approach for probing the glass transition.
in Nature Physics on 2026-01-16 00:00:00 UTC.
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Nature Physics, Published online: 16 January 2026; doi:10.1038/s41567-025-03146-7
The properties of electronic transport through edge states of three-dimensional quantum Hall-like states are not yet resolved. Now, increasing the surface area of the edges is shown to produce increased conductance, suggesting that chiral surface states are present.
in Nature Physics on 2026-01-16 00:00:00 UTC.
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Nature Physics, Published online: 16 January 2026; doi:10.1038/s41567-025-03140-z
Colloidal suspensions are known to display a glass transition. Now, insights into this transition, via its effect on the solvent, are gained by probing the correlated motion of tracer particles in such systems.
in Nature Physics on 2026-01-16 00:00:00 UTC.
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Scientific Data, Published online: 16 January 2026; doi:10.1038/s41597-026-06612-w
Global deep-sea hydrothermal deposit metagenomes and metagenome-assembled genomes over time and space
in Nature scientific data on 2026-01-16 00:00:00 UTC.
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Scientific Data, Published online: 16 January 2026; doi:10.1038/s41597-026-06561-4
Haplotype-resolved chromosome-level genome assembly of creeping bentgrass, Agrostis stolonifera
in Nature scientific data on 2026-01-16 00:00:00 UTC.
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Scientific Data, Published online: 16 January 2026; doi:10.1038/s41597-026-06601-z
Brain/MINDS Marmoset Brain Atlas 2.0: Population Cortical Parcellation With Multi-Modal Templates
in Nature scientific data on 2026-01-16 00:00:00 UTC.
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Scientific Data, Published online: 16 January 2026; doi:10.1038/s41597-026-06606-8
Temporal multiomics gene expression data across human embryonic stem cell-derived polyhormonal cell differentiation
in Nature scientific data on 2026-01-16 00:00:00 UTC.
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Scientific Data, Published online: 16 January 2026; doi:10.1038/s41597-026-06578-9
GlobalBuildingMap — Unveiling the mystery of global buildings
in Nature scientific data on 2026-01-16 00:00:00 UTC.
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Scientific Data, Published online: 16 January 2026; doi:10.1038/s41597-025-06519-y
A Global High-Resolution Comprehensive Heat Indices Dataset from 1950 to 2024
in Nature scientific data on 2026-01-16 00:00:00 UTC.
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Scientific Data, Published online: 16 January 2026; doi:10.1038/s41597-025-06526-z
ImitateCholec: A Multimodal Dataset for Long-Horizon Imitation Learning in Robotic Cholecystectomy
in Nature scientific data on 2026-01-16 00:00:00 UTC.
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Scientific Data, Published online: 16 January 2026; doi:10.1038/s41597-026-06595-8
High-resolution gridded dataset of sectoral water pollution discharges in China from 2007 to 2022
in Nature scientific data on 2026-01-16 00:00:00 UTC.
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Communications Biology, Published online: 16 January 2026; doi:10.1038/s42003-026-09536-8
Brain folds emerge in the womb and deepen throughout the first year of infant life. Early folds are deeper at birth but deepen slowly post-birth. Deepening is complex: folds widen, thicken, become more concave, and get denser with tissue after birth.
in Nature communications biology on 2026-01-16 00:00:00 UTC.
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Communications Biology, Published online: 16 January 2026; doi:10.1038/s42003-026-09534-w
Rats and mice have a thermoneutral point below which metabolic rate rises and above which body temperature rises and heat stress occurs, with rats overheating more easily; housing temperatures of 28–29 °C best minimize both cold stress and overheating
in Nature communications biology on 2026-01-16 00:00:00 UTC.
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Communications Biology, Published online: 16 January 2026; doi:10.1038/s42003-026-09549-3
Multiscale and multiway brain network interactions during the first six months of life reveal rapid developmental changes. High-order triadic interactions provide insights beyond pairwise functional network connectivity by capturing nonlinear dynamics and yielding more reliable biomarkers of developmental trajectories.
in Nature communications biology on 2026-01-16 00:00:00 UTC.
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Communications Biology, Published online: 16 January 2026; doi:10.1038/s42003-026-09568-0
A GRK-isoform immunoassay was used to quantify GPCR phosphorylation and evaluate the potency of GRK inhibitors in a controlled cellular system.
in Nature communications biology on 2026-01-16 00:00:00 UTC.
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Communications Biology, Published online: 16 January 2026; doi:10.1038/s42003-025-09471-0
New genome-wide data sheds light on the complex demographic histories of isolation, expansion, and contact among Mainland Southeast Asian Austroasiatic speakers, and also illuminate historical gene flow from East and South Asia into Mainland Southeast Asia.
in Nature communications biology on 2026-01-16 00:00:00 UTC.
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Communications Biology, Published online: 16 January 2026; doi:10.1038/s42003-026-09519-9
The oldest sepioid in the Cretaceous shows intermediate morphologies between cuttlefish and bobtail squids, revealing their early evolution. This discovery was facilitated by Digital fossil-mining method incorporating a zero-shot learning AI model.
in Nature communications biology on 2026-01-16 00:00:00 UTC.
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Interleukin-7 (IL-7) plays a central role in maintaining T cell development and immune homeostasis, and enhancing the cytokine’s immune-stimulatory functionality has broad therapeutic implications against various oncological malignancies. Herein, we show a computationally designed IL7 superkine, Neo-7, which exhibits enhanced folding efficiency and superior binding affinity to its cognate receptors. To streamline the protein candidate prediction and validation process, the loop region of IL7 was strategically targeted for redesign while most of the receptor-interacting regions were preserved. Leveraging advanced computational tools such as AlphaFold2, we show loop remodeling to rectify structural irregularities that allow for iterative stabilization of protein backbone and lead to identification of beneficial mutations conducive to receptor engagement. Neo-7 superkine shows improved thermostability and production yield, and it exhibits heightened immune-stimulatory and anticancer effect in C57BL/6 J mice. Neo-7 addresses intrinsic developability limitations of IL-7, including inefficient folding, aggregation propensity, and suboptimal receptor engagement, while in vivo pharmacokinetic limitations of wild-type IL-7 were addressed separately through Fc fusion. These findings underscore the utility of a targeted computational approach for de novo cytokine development.
in eLife on 2026-01-16 00:00:00 UTC.
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Living with COVID-19 requires continued vigilance against the spread and emergence of variants of concern (VOCs). Rapid and accurate saliva diagnostic testing, alongside basic public health responses, is a viable option contributing to effective transmission control. Nevertheless, our knowledge regarding the dynamics of SARS-CoV-2 infection in saliva is not as advanced as our understanding of the respiratory tract. Here, we analyzed longitudinal viral load data of SARS-CoV-2 in saliva samples from 144 patients with mild COVID-19 (a combination of our collected data and published data). Using a mathematical model, we quantified individual-level viral dynamics and stratified them into three groups using a clustering approach. Notably, the three groups exhibited distinct differences in viral RNA detection durations: 11.5 days (95% CI: 10.6–12.4), 17.4 days (16.6–18.2), and 30.0 days (28.1–31.8), respectively. Surprisingly, this stratified grouping remained unexplained despite our analysis of 47 types of clinical data, including basic demographic information, clinical symptoms, results of blood tests, and vital signs. Additionally, we quantified the expression levels of 92 micro-RNAs in a subset of saliva samples, but these also failed to explain the observed stratification, although the mir-1846 level may have been weakly correlated with peak viral load. Our study provides insights into SARS-CoV-2 infection dynamics in saliva, highlighting the challenges in predicting the duration of viral RNA detection without indicators that directly reflect an individual’s immune response, such as antibody induction. Given the significant individual heterogeneity in the kinetics of saliva viral shedding, identifying biomarker(s) for viral shedding patterns will be crucial for improving public health interventions in the era of living with COVID-19.
in eLife on 2026-01-16 00:00:00 UTC.
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The formation of blood–brain barrier and vascular integrity depends on the coordinated development of different cell types in the brain. Previous studies have shown that zebrafish bubblehead (bbh) mutant, which has mutation in the betaPix locus, develops spontaneous intracerebral hemorrhage during early development. However, it remains unclear in which brain cells betaPix may function. Here, we established a highly efficient conditional knockout method in zebrafish by using homology-directed repair-mediated knockin and knockout technology and generated betaPix conditional trap (betaPixct) allele in zebrafish. We found that betaPix in glia, but neither neurons, endothelial cells, nor pericytes was critical for glial and vascular development and integrity, thus contributing to the formation of blood–brain barrier. Single-cell transcriptome profiling revealed that microtubule aggregation signaling stathmins and pro-angiogenic transcription factors Zfhx3/4 were downregulated in glial and neuronal progenitors, and further genetic analysis suggested that betaPix may act upstream on the PAK1-Stathmin and Zfhx3/4-Vegfaa signaling to regulate glia migration and angiogenesis. Therefore, this work reveals that glial betaPix plays an important role in brain vascular development in zebrafish embryos and possibly human cells.
in eLife on 2026-01-16 00:00:00 UTC.
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A recurrent neural network fitted to large electrophysiological datasets may help us understand the chain of cortical information transmission. In particular, successful network reconstruction methods should enable a model to predict the response to optogenetic perturbations. We test recurrent neural networks (RNNs) fitted to electrophysiological datasets on unseen optogenetic interventions and measure that generic RNNs used predominantly in the field generalize poorly on these perturbations. Our alternative RNN model adds biologically informed inductive biases like structured connectivity of excitatory and inhibitory neurons and spiking neuron dynamics. We measure that some biological inductive biases improve the model prediction on perturbed trials in a simulated dataset and a dataset recorded in mice in vivo. Furthermore, we show in theory and simulations that gradients of the fitted RNN can be used to target micro-perturbations in the recorded circuits and discuss the potential utility to bias an animal’s behavior and study cortical circuit mechanisms.
in eLife on 2026-01-16 00:00:00 UTC.
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Precise, dynamic control of metabolic fuel usage in response to environmental challenges such as altered food availability or temperature change is essential for animal survival. In mammals, metabolic flexibility -- the capacity to shift cellular metabolism between carbohydrate and fatty acid oxidation -- is understood to be largely regulated by circulating hormones such as insulin and glucagon. However, the role of the central nervous system in coordinating fuel selection and tissue metabolic tuning remains underexplored. Here, we investigated the mechanisms that mediate metabolic reprogramming following the acute activation of torpor-associated glutamatergic Adcyap1+ torpor-regulating neurons in the anteroventral preoptic area (avPOAVglut2/PACAP). The activation of these neurons rapidly shifts whole-body fuel use from glucose to fatty acids, irrespective of fuel/food availability. This shift is associated with reduced glucose utilization stemming from the transient induction of selective insulin resistance in skeletal muscle. We find that this reduction in skeletal muscle glucose metabolism does not require direct muscle innervation but is rather mediated via adrenal hormones. In contrast to their activation, avPOAVglut2/PACAP neuronal silencing results in improved glucose tolerance, demonstrating powerful bidirectional control of tissue-specific glucose metabolism, whole-body glucose levels, and fuel usage. Together, our findings uncover a novel POA-adrenal-skeletal muscle pathway that dynamically controls glucose utilization and metabolic flexibility.
in bioRxiv: Neuroscience on 2026-01-16 00:00:00 UTC.
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Precision mapping of individual differences in human brain spontaneous activity is critical for characterizing brain function and guiding clinical translation. Multi-echo resting-state functional MRI (ME-rfMRI) has the potential to provide more reliable mapping of inter-individual differences in intrinsic brain function than conventional single-echo rfMRI (SE-rfMRI). However, the psychometric benefits of ME-rfMRI for mapping individual differences in spontaneous brain activity (SBA) have not been systematically investigated, which is fundamental for understanding the human brain in health and disease. To quantify the psychometric performance of ME-rfMRI in precisely mapping inter-individual variations in SBA, we employed a psychometric design. We scanned 27 healthy adults with both ME-rfMRI and SE-rfMRI to assess short-term (minutes) test-retest reliability, as well as validity across eyes-open (EO) and eyes-closed (EC) resting states. Our results demonstrate that ME-rfMRI improves reliability relative to SE-rfMRI by 10.8% for amplitude of low-frequency fluctuation (ALFF), 4.4% for regional homogeneity (ReHo), and 8.0% for voxel-mirrored homotopic connectivity (VMHC) in cortical regions, and by 12.5% for ALFF, 8.3% for ReHo, and 4.0% for VMHC in subcortical regions. This enhancement is achieved by increasing inter-individual variability while reducing intra-individual variability. Notably, ME-rfMRI accentuates inter-individual variability in the unimodal cortex and clearly delineates two parallel systems with distinct variability patterns within the motor cortex. Concurrently, ME-rfMRI increases effect sizes (4%-8%) for detecting individual differences between EO and EC resting states. Interestingly, ME-rfMRI reveals differential effects of eye closure on two intertwined systems in the primary motor and sensory cortices, extending previous findings. Computational simulations indicate that, compared to SE-rfMRI, ME-rfMRI facilitates experimental designs with reduced costs (i.e., 4%-11% smaller sample sizes) for precise mapping of individual differences. These findings establish, for the first time, the psychometric performance of ME-rfMRI measurements, supporting its potential utility in personalized neuroscience applications, including neurodevelopment and brain disorders.
in bioRxiv: Neuroscience on 2026-01-16 00:00:00 UTC.
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Microglia play essential roles in maintaining energy homeostasis, and their dysfunction contributes to metabolic disease. Although high-fat diet (HFD) exposure induces microglial activation, the underlying mechanisms remain poorly defined. Here, we identified a previously unrecognized role for THIK-1 channel in mediating glucose sensing of microglia in arcuate nucleus of the hypothalamus (ARH), during HFD-induced obesity. Pharmacological inhibition of THIK-1 channel with tetrapentylammonium (TPA) suppresses feeding and attenuates body-weight gain in diet induced obese mice. Mechanistically, inhibition of agouti-related peptide (AgRP) neurons is indispensable for TPA-induced hypophagia. Moreover, THIK-1 inhibition promotes microglial phagocytosis of perineuronal nets (PNNs), leading to reduced AgRP neuronal activity and feeding suppression. Together, these findings establish THIK-1 as a critical glucose sensor in hypothalamic microglia and uncover a microglia-dependent pathway through which overnutrition modulates AgRP neuronal activity via PNN remodeling to regulate energy balance, highlighting THIK-1 as a potential therapeutic target for treatment of diet-induced obesity.
in bioRxiv: Neuroscience on 2026-01-16 00:00:00 UTC.
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Athletes often regulate their breathing to optimize motor performance, suggesting a close link between respiration and movement control. Previous studies have shown that respiration modulates neuronal oscillations and influences behavior. However, how respiratory control directly affects motor behavior remains unclear. Here, we demonstrate that breath holding during the preparatory period facilitates voluntary movement. We examined respiratory patterns while participants performed two types of eye movement tasks: pro-saccade and anti-saccade tasks. In the anti-saccade task, participants were required to suppress a reflexive saccade toward a visual target and instead generate a voluntary saccade in the opposite direction. To assess whether motivation modulates respiratory control, the tasks were conducted under two motivational conditions. Most participants suppressed their breath during the anticipatory period preceding saccade initiation, regardless of task type, and this tendency was more pronounced under high motivation. In the anti-saccade task, stronger respiratory adjustments were associated with shorter reaction times, whereas no such relationship was observed in the pro-saccade task. Moreover, intentional breath holding during the preparatory period selectively reduced reaction times in the anti-saccade task. These findings indicate that individuals spontaneously hold their breath to facilitate voluntary actions in highly motivated situations, and that this effect can be reproduced through intentional breath holding. We propose that anticipatory breath holding may play a functional role in proactively modulating neural processes underlying voluntary movement control.
in bioRxiv: Neuroscience on 2026-01-16 00:00:00 UTC.
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Innately aversive experiences produce emotional states which control behavior as well as long term associative memories1-3. Brainstem regions engage innate defensive reactions1,3-7, but it is unclear how the nervous system transduces external aversive experiences into higher order, emotional representations in the forebrain to instruct learning and modulate behavior. The prevailing view is that the sensory properties of aversive experiences activate forebrain emotional processing1,3,8-10, but classical theories proposed that internal bodily reactions to unpleasant events produce feeling states11,12. Here we identify a brainstem cuneiform (CnF) circuit which conveys information about both the external sensory causes and internal motor reactions related to aversive events to the lateral/basal nuclei of the amygdala (LA/B), a brain region which stores emotional memories, to enhance ongoing defensive behaviors and regulate associative memory formation. Glutamatergic CnF neurons project directly to LA/B and receive afferent inputs from aversive-sensory and aversive-motor brain regions. Notably, LA/B neurons encode a sensorimotor state in response to noxious stimuli, with both sensory and motor features transmitted through the CnF-to-LA/B pathway. Finally, optogenetic perturbation experiments showed that during aversive experiences, the CnF-LA/B circuit instructs emotional memory formation and enhances the intensity of ongoing defensive behaviors. These findings reveal how the nervous system constructs an aversive sensorimotor state in the amygdala used for regulating the strength of emotional behaviors and producing memory formation. This demonstrates a clinically relevant brain mechanism for the regulation of emotional processing by both external traumatic events and the accompanying bodily reactions.
in bioRxiv: Neuroscience on 2026-01-16 00:00:00 UTC.
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Complex ecological systems obey universal scaling laws such as the Taylor law, which links population variance to the sample mean. A natural question is whether other complex systems with integrated and segregated functional networks, such as the human brain, follow analogous scaling laws, and how these laws behave under synchronized activity. Addressing this is challenging because neural signals at all measurement scales contain both positive and negative values, whereas the Taylor law was developed for non-negative ecological data. To overcome this limitation, we replace the sample mean with the root mean square (RMS) of detrended neural activity and formulate a generalized spatial scaling law applicable to signed data. This framework extends spatial scaling obeying the Taylor law to neural systems and other complex systems across disciplines and allows examination of how coordinated, synchronized activity shapes these laws. Synchrony is quantified using a dedicated metric of functional coordination. Analytical derivations and numerical simulations using multivariate Poisson, binomial, uniform, and gamma distributions demonstrate that the scaling exponent is inversely related to synchrony. Applying this framework to human fMRI data from three large lifespan cohorts (N=840, ages 18 to 88) reveals distinct age-associated trajectories of the scaling exponent. Healthy aging is characterized by a substantial synchrony-induced reduction in the exponent. The synchrony and scaling relationship is stable during resting-state activity but progressively shifts during naturalistic tasks across the lifespan. Limbic, subcortical, and cerebellar regions show particularly strong synchrony and scaling coupling, indicating preservation at subnetwork levels. Finally, individuals with ADHD exhibit disrupted synchrony and scaling relationships, underscoring the potential clinical utility of this novel metric.
in bioRxiv: Neuroscience on 2026-01-16 00:00:00 UTC.
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Cerebrospinal fluid (CSF) circulation is tightly coupled to cerebral blood flow under the fixed-volume constraint of the cranial vault, with cardiac pulsations and respiration acting as dominant physiological drivers. Disruption of these flow dynamics has been implicated in various neurological disorders, motivating the need for imaging methods that capture CSF and vascular flow simultaneously and in real time. Conventional phase contrast MRI (PC-MRI) provides quantitative CSF velocity measurements but relies on cardiac gating and velocity encoding, which limit temporal resolution, dynamic range, and sensitivity to non-cardiac fluctuations. Here, we introduce self-gated ultrafast real-time flow-weighted echo-planar imaging (SURF-EPI), an inflow-weighted approach in which signal intensity reflects the replacement of saturated spins by freshly inflowing, unsaturated water molecules, yielding higher signal with higher flow. This allows simultaneous assessment of arterial inflow, venous outflow, and CSF motion at high temporal resolution. SURF-EPI was acquired at the C2-C3 spinal level, enabling real-time imaging of CSF flow dynamics in the cervical spinal canal alongside arterial and venous blood flow in major cervical vessels (frame-rate: 21.7 Hz). In addition to frequency-domain analyses, we leveraged intrinsic arterial signal fluctuations as a timing reference to reconstruct cardiac-resolved CSF dynamics for individual cardiac cycles without external physiological recordings. Frequency-domain analysis revealed distinct spectral signatures in CSF flow compared with neurovascular flow, including broadened cardiac peaks and enhanced respiratory modulation, particularly within the ventral spinal canal. In contrast, dorsal CSF showed increased power within the cardiac frequency band, higher coherence with cervical vasculature at the cardiac frequency, and reduced non-cardiac contributions. Time-domain analysis showed strong correlation between CSF flow waveforms derived from SURF-EPI and PC-MRI. Beyond ensemble-averaged waveforms, SURF-EPI enabled beat-to-beat analysis, revealing substantial cycle-to-cycle variability in CSF flow that is not captured by time-averaged gated approaches. Together, these findings establish SURF-EPI as a rapid, complementary framework to PC-MRI, enabling real-time neurofluid imaging with integrated time- and frequency-domain characterization of CSF and neurovascular flow dynamics.
in bioRxiv: Neuroscience on 2026-01-16 00:00:00 UTC.
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TAR DNA binding protein 43 (TDP-43) is the core pathogenic protein across a spectrum of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) cases, but its pathological deposition shows regional selectivity, with abundant TDP-43 positive aggregates in the frontal cortex and spinal cord, and a much lower burden in the cerebellum. In health, TDP-43 expression in the cerebellum is higher than in cortex, hence what underpins this differential vulnerability to TDP-43 aggregation is unclear. Here we demonstrate that in healthy C57Bl/6J mice not only is TDP-43 expression higher in the cerebellum than the cortex, but that this expression difference is driven primarily by differences in cytoplasmic load. Mass spectrometry analysis of TDP-43 pull downs from the cortex and cerebellum of healthy mice identified TDP-43 interactors across a number of core functional pathways, with numerous differences between the two brain regions. Data are available via ProteomeXchange with identifier PXD062532. Notably, there were more interactors identified in both nuclear and cytoplasmic fractions within the cortex than the cerebellum. Putative interactions with four core paraspeckle proteins; SFPQ, NONO, FUS and PSPC1 were confirmed using immunoprecipitation and western blot analysis. Follow up validation using proximity ligation assay showed abundant perinuclear cytoplasmic interactions between TDP-43 and all four paraspeckle proteins in both large motor cortex neurons and purkinje cells, with significantly reduced nuclear interactions detected in the motor cortex for SFPQ, FUS and PSPC1. These findings suggest that TDP-43-protein interactions markedly differ between the TDP-43 pathogenesis vulnerable cortex and relatively resistant cerebellum and exploring these differences may yield new insight into disease mechanisms within ALS/FTD.
in bioRxiv: Neuroscience on 2026-01-16 00:00:00 UTC.
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Humans frequently interact with robots that approach from different directions; however, how the approach direction systematically biases the perceived speed remains unclear. Here, we demonstrate a robust direction-dependent bias in the perceived approach speed, whereby objects approaching from behind are consistently perceived as moving faster than those approaching from the front are. Across five experiments using both physical robots and immersive virtual reality, this bias manifests as a systematic shift in the point of subjective equality without corresponding changes in discrimination sensitivity, indicating a perceptual bias rather than altered precision. We further show that this effect can be explained by body-induced differences in interocular velocity that arise when observers orient themselves toward stimuli approaching from behind. This bias persists in virtual environments and for nonrobotic objects, suggesting that it is driven primarily by visual factors rather than multisensory cues or robot-specific appearance. Together, these findings provide a perceptual foundation for incorporating approach direction into the design and evaluation of the motion behavior of robots in human-centered environments.
in bioRxiv: Neuroscience on 2026-01-16 00:00:00 UTC.
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Relaxin family peptide receptor-3 (RXFP3) is a ligand-activated G-protein coupled receptor and the cognate receptor for the conserved neuropeptide relaxin-3. We recently demonstrated that chemogenetically activating an RXFP3-expressing population in the lateral hypothalamus and zona incerta (LH/ZIRXFP3) induced escape-like jumping behaviour following fear conditioning, but only in a subset of mice. Given the diverse hodology of the LH and ZI, we hypothesised that LH/ZIRXFP3 cells may consist of discrete subpopulations with unique connectivity patterns that govern different aspects of defensive behaviour. To explore this possibility, we unilaterally injected small volumes of a Cre-dependent anterograde viral tracer into four distinct sites of the LH/ZI in RXFP3-Cre mice and analysed their brain-wide efferent connectivity patterns. Each injection site group produced unique projection patterns, particularly to nuclei involved in threat and defensive behaviour. Of note were strong projections from the rostral ZI and anterior LH to the lateral habenula, and projections from the intermediate and caudal ZI to the ventrolateral periaqueductal gray. By combining retrograde tracing and RNAscope fluorescent in situ hybridisation, we identified that most LH/ZIRXFP3 projections to the lateral habenula arose from a subset of vGlut2-expressing lateral hypothalamus neurons, while most projections to the ventrolateral periaqueductal gray arose from a subset of GAD1-expressing zona incerta neurons. Taken together, our results strongly suggest that LH/ZIRXFP3 cells exhibit distinct efferent projection patterns throughout the brain depending on their topographical location within these nuclei, likely reflecting the functional diversity of these neurons.
in bioRxiv: Neuroscience on 2026-01-16 00:00:00 UTC.
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Diabetic peripheral neuropathy (DPN) is a common complication of diabetes with no disease modifying treatments. Despite the prevalence, the molecular mechanisms of DPN are not fully characterized. Among the various molecular regulators, microRNAs (miRNAs) control protein synthesis and are essential for normal development and homeostasis, with dysregulation implicated in cancer and neurodegenerative diseases. In this study, we performed small RNA-sequencing to profile the miRNA landscape of human sural nerves from individuals with and without DPN. Our analysis revealed that nearly 10% of all miRNAs detected are dysregulated and among those 74% are significantly downregulated in DPN. Target gene enrichment analysis of the differentially expressed miRNAs yielded pathways significantly associated with nerve regeneration, metabolic dysfunction, and immune cell activity. In particular, miR-21-5p is significantly upregulated in DPN, showed a positive association with axonal loss severity, and localizes to Schwann cells, consistent with its broader role as an injury- and inflammation-responsive miRNA that shifts from early pro-regenerative functions to maladaptive, inflammation-amplifying effects that impair Schwann cell mediated nerve repair. These results suggest that miRNAs may contribute to peripheral nerve degeneration by promoting inflammation, apoptosis, oxidative stress, and impaired nerve regeneration, while also opening potential avenues for biomarker discovery and therapeutic intervention.
in bioRxiv: Neuroscience on 2026-01-16 00:00:00 UTC.
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Large-scale lifespan neuroimaging studies increasingly integrate data across distinct cohorts to characterize trajectories of brain development and aging. However, systematic differences in acquisition protocols and hardware across cohorts can alter signal characteristics in ways that bias downstream analyses. Here we examine three cohorts from the Human Connectome Project (HCP), spanning development (HCP-D), young adulthood (HCP-YA) and aging samples (HCP-A), to illustrate this issue and evaluate existing strategies to mitigate it. HCP has set standards for open, deeply phenotyped, high-resolution human neuroimaging, which are frequently used as high-quality reference datasets in tool validation, replication studies, and cross-cohort meta-analyses. Because of HCP's widespread usage, even modest protocol differences between cohorts-and their downstream effects-can have outsized impacts on the field of neuroscience research. Our analysis reveals that the HCP-YA cohort exhibits systematically weaker temporal signal-to-noise-ratio (tSNR) relative to HCP-D/A. These signal quality discrepancies propagate to downstream analyses, leading to differences in overall resting-state functional correlations, and whole-brain and node-level measures of resting-state network organization (e.g., system segregation, modularity, participation coefficient). Consistent with protocol-driven signal differences, resting-state network measures derived from HCP-YA depart from expected lifespan trajectories, as confirmed by examination of two other lifespan datasets. Harmonization approaches accounting for protocol and scanner-model differences alleviate some of the artifactual differences in brain network measurement. Our findings underscore that signal differences do not merely introduce noise, but can qualitatively alter estimated lifespan trajectories of functional network organization, including partially inverting expected lifespan patterns. Without appropriate harmonization, analyses that combine HCP cohorts can therefore result in biologically misleading inferences about development and aging. We demonstrate how small acquisition differences bias resting-state-derived network metrics, and how these effects can be mitigated. This work advances best practices for valid inferences in multi-cohort lifespan neuroscience research.
in bioRxiv: Neuroscience on 2026-01-16 00:00:00 UTC.
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Background: Advancing age, the APOEe4 allele, and female sex are the top nonmodifiable risk factors for Alzheimers disease (AD). Female-specific experiences, such as parity and hormone therapy (HT) affect aging biomarkers such as metabolism and immune signaling and may even affect AD risk. Estradiol (E2), a common component of many HTs, affects cognition and brain health in aging females although this may vary depending on parity, genotype, and metabolic status. We hypothesized that prior parity influences brain and metabolic health, including response to E2, depending on APOE genotype. Methods: Middle-aged female (10 month) wildtype (WT) or humanized (h) APOEe3 or e4 expressing rats, with different reproductive experience (nulliparous or primiparous) were fed a Western (WD) or standard diet (SD) for 2 months. In the second month, rats were given E2 or vehicle (oil) injections daily. Fear associative learning, plasma metabolic hormones, hippocampal inflammatory signalling, and neuroplasticity (neurogenesis, synaptic protein) were assessed. Results: Females fed a WD gained weight and displayed metabolic dysregulation, regardless of genotype. E2 treatment reduced WD-induced weight gain and reduced metabolic hormones, with stronger effects in WT rats. E2 treatment increased dorsal hippocampal inflammatory signalling selectively in primiparous hAPOEe4 females fed a WD. Previous parity increased neurogenesis and reduced certain cytokines in the hippocampus of middle-aged WT rats under a SD. Both E2 treatment and previous parity decreased dorsal neurogenesis in hippocampus of hAPOEe4 rats. In hAPOEe4 females, higher weight was associated with reduced contextual fear memory, an effect driven by primiparous females. In the cued fear conditioning task, hAPOEe4 females displayed better cued fear memory than WT, however, WD exposure reduced cued fear memory in this group. Together, this indicates that diet and weight gain may be more detrimental to associative memory in hAPOEe4 females and that E2 treatment has more favourable outcomes in WT rats. Conclusions: Previous parity alters how females respond to E2 and metabolic stress in midlife. Primiparous hAPOEe4 females were especially vulnerable to the effects of WD and E2, exhibiting more inflammation, impaired memory, and reduced weight-loss. These findings highlight the importance of considering parity and genotype when evaluating midlife metabolic and cognitive risk.
in bioRxiv: Neuroscience on 2026-01-16 00:00:00 UTC.
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Age-related cerebrovascular dysfunction is increasingly recognized as a critical contributor to cognitive decline and Alzheimers disease (AD) progression, yet the extent to which lifestyle interventions preserve microvascular oxygen delivery remains poorly defined. Physical activity (PA) improves vascular health and cognition in humans, but its impact on capillary-level oxygenation and functional hyperemia during aging and amyloid pathology is unknown. Here, we longitudinally quantified microvascular oxygen tension and stimulus-evoked oxygen dynamics in awake APP/PS1 mice and wild-type littermates using two-photon phosphorescence lifetime microscopy. Chronic aerobic PA initiated in early adulthood preserved basal arteriolar, capillary, and venular oxygenation, prevented age-dependent increases in microvascular heterogeneity, and mitigated excessive oxygen extraction in preclinical AD mice. While amyloid pathology impaired stimulus-evoked oxygen responses across vascular compartments, PA selectively enhanced capillary dilation and accelerated hyperemic kinetics without altering vascular density or architecture. Notably, sedentary AD mice developed widespread capillary hypoxia and bimodal oxygen distributions, hallmarks of malignant microvascular dysfunction, which were largely absent in physically active animals. These findings demonstrate that routine aerobic PA preserves microvascular oxygen homeostasis and functional responsiveness during aging and amyloid accumulation, supporting a capillary-centric mechanism through which exercise confers neurovascular resilience in preclinical AD.
in bioRxiv: Neuroscience on 2026-01-16 00:00:00 UTC.
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Zone-like states, defined as high objective performance with low subjective workload, are sought in esports and other demanding digital activities, yet subjective flow does not consistently index efficient performance. We hypothesized that zone-like high performance is supported by regulated arousal dynamics rather than strongly elevated arousal responses, and that such episodes can be detected from the combined dynamics of heart rate and pupil diameter. Fourteen healthy young adult men completed repeated sessions of a one-versus-one fighting game under three contexts: passive watching, play against a computer-controlled opponent, and competition against a human opponent. Heart rate and pupil diameter were recorded continuously, and subjective flow (Sports Flow Scale), subjective workload (NASA Task Load Index), and in-game performance metrics were assessed. Two-dimensional k-means clustering of heart rate and pupil changes relative to the watching condition revealed three arousal-reactivity profiles. Sessions with larger physiological deviations showed higher flow and higher workload but poorer performance. Sessions with smaller deviations showed higher performance with lower workload despite only moderate flow. Nonlinear analyses indicated inverted-U relationships between physiological deviations and performance, with peak performance occurring when heart rate and pupil responses remained close to the watching baseline during active play. These findings indicate that combined heart rate and pupillometry measures provide a useful multimodal physiological marker for identifying efficient high-performance states and for informing strategies to support performance while managing workload in cognitively demanding digital activities.
in bioRxiv: Neuroscience on 2026-01-16 00:00:00 UTC.
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Neuropathic pain arises from complex peripheral and central mechanisms and induces long-lasting maladaptive changes in the brain. To investigate the temporal dynamics of these changes, we examined resting-state functional connectivity (FC) in a mouse model of neuropathic pain across its initiation and maintenance phases. Using functional ultrasound imaging to capture whole-brain FC over disease progression, we conducted two complementary studies: a longitudinal assessment in anesthetized animals and an analysis of awake cohorts at distinct disease stages. Both exploratory and literature-guided analyses revealed that FC across most large-scale networks remained remarkably stable during pain maintenance. In contrast, pain onset was marked by enhanced FC between key regions involved in sensory, emotional, and motivational processing, including the motor cortex and nucleus accumbens, the prelimbic and insular cortices, and the infralimbic cortex and hypothalamus. As pain persisted, we observed reduced FC within the somatomotor network, reflecting functional disconnection. Additionally, postsurgical pain alone produced enduring FC changes within the prefrontal cortex, hippocampus, and insula, indicating long-term central plasticity independent of neuropathic injury. Together, these findings reveal dynamic, network-specific adaptations that distinguish the onset and maintenance phases of neuropathic pain and surgery-related plasticity.
in bioRxiv: Neuroscience on 2026-01-16 00:00:00 UTC.
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Polyglutamine diseases are incurable genetic neurodegenerative disorders characterized by the accumulation of mutant proteins with extended polyglutamine fragments, which are prone to the formation of poorly soluble aggregates. The establishment of adequate cellular models is crucial in uncovering the pathological mechanisms responsible for neurotoxicity in HD, screening for therapeutic molecules and elucidation of the molecular mechanisms impacted by particular compound. In the present study, genetic constructs based on the Sleeping Beauty system were created for the stable inducible expression of full-length normal and mutant huntingtin in eukaryotic cells. These constructs were then employed to develop model neuronal cells using Neuro-2a cell line. The expression of huntingtin as well as the accumulation of Htt-immunopositive intracellular aggregates (most characteristic features of HD) was demonstrated, and these aggregates mostly colocalized with the proteasome. The activation of the proteasome, as well as changes in the expression of proteasome regulators, components of the autophagy system, and the protease cathepsin D, reflect the versatility of cellular responses to the destructive mutant Htt pathological forms.
in bioRxiv: Neuroscience on 2026-01-16 00:00:00 UTC.
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Small extracellular vesicles (sEVs) including exosomes play an important role in intercellular communication and can exert immunomodulatory effects in recipient cells. We have shown that a single prophylactic intrathecal injection of sEVs from RAW 264.7 macrophages two weeks prior, promotes faster resolution of mechanical and thermal hypersensitivity in the complete Freund's adjuvant (CFA) mouse model of inflammatory pain. How this long-term memory develops, and how sEVs regulate immune responses are unknown. Recent studies have shown that priming microglia with inflammatory stimuli can enhance or suppress responses to a delayed secondary insult via epigenetic modifications. We hypothesized that prophylactic intrathecal administration of macrophage-derived sEVs confers accelerated resolution of inflammatory pain by reprogramming epigenetic memory in spinal microglia in recipient CFA model mice. To determine whether prophylactic sEVs could attenuate pain in the absence of microglia when administering sEVs, we ablated microglia using a colony-stimulating factor 1 receptor (CSF1R) inhibitor, PLX5622. sEV-induced pain prophylaxis was completely abolished in PLX5622-fed mice, indicating that microglia are required to be present during sEV administration to confer early resolution of inflammatory pain hypersensitivity. ChIP-seq analysis in spinal microglia 14 days after sEV administration (prior to CFA) revealed an increased number of gene loci enriched for H3K4me1, a hallmark of innate immune memory. Furthermore, inhibiting the H3K4 mono-methyltransferase SETD7 abolished sEV-induced pain attenuation. Our findings indicate that both microglia and its epigenetic reprogramming contribute to pain prophylaxis induced by macrophage-derived sEVs, providing novel insights into the development of non-addictive preventive analgesia.
in bioRxiv: Neuroscience on 2026-01-16 00:00:00 UTC.
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Many genes are implicated in autism spectrum disorder (ASD) as a result of sequencing the genomes of individuals with ASD, however in most cases it remains unclear which genes are playing causative roles. ALDH5A1, which encodes the enzyme succinate semialdehyde dehydrogenase (SSADH), an important regulator of GABA metabolism, is causative in the syndrome SSADH deficiency and is also implicated in ASD. However, it is unknown how variants found in ASD affect SSADH function. We developed a yeast growth assay that models SSADH deficiency to quantify the functional impact of seven ALDH5A1 variants found in ASD. In this assay, expression of human ALDH5A1 partially complemented the growth defect caused by deletion of the ALDH5A1 ortholog UGA2. Using growth rate measurements, we calculated functional scores for 27 variants divided into calibration and ASD test variant groups. Functional scores for benign and pathogenic calibration variants segregated accordingly, validating the assay, while ASD variants displayed a range of activities from complete loss to normal function. Comparisons with published enzymatic assays and computational predictions showed broad agreement, while also identifying some limitations of these approaches.
in bioRxiv: Neuroscience on 2026-01-16 00:00:00 UTC.
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When observers lack sufficient information to support a confident response, they often guess. Guessing plays a pervasive role in visual cognition and working memory, yet the mechanisms that govern how observers generate guesses remain poorly understood. Standard models traditionally assume that responses produced in the absence of information are either uniformly distributed over feature space or are perhaps weighted towards prevailing environmental statistics. In contrast, here we consider an intriguing alternative: that guesses incorporate observers' knowledge of their own perceptual capacities. We empirically measured guessing by eliciting responses under extreme target uncertainty (Experiment 1) as well as a novel '0ms presentation' approach in which no stimulus appeared but subjects believed one had (Experiment 2). We evaluated three accounts of guesses under these conditions: unsystematic (lapse) responding, biases toward environmental statistics, and a self-representational account in which guesses reflect observers' knowledge of their own feature-dependent precision (e.g., preferring to guess feature values they believe they would be likely to miss). Guess responses were non-uniform and systematically biased toward feature values typically encoded with the least precision (e.g., oblique orientations) - a counterintuitive bias away from high-frequency, high-fidelity feature values (e.g., cardinal orientations). This complementary relationship between guessing and perceptual fidelity held within individuals and across paradigms, and was recoverable via an empirical-guess mixture model that replaced the standard uniform assumption with empirically measured guess distributions. Our findings challenge prevailing views that guesses reflect random noise, and suggest instead that guessing behavior reflects metacognitive knowledge of internal precision. Rather than defaulting to environmental priors, observers appear to model their own sensory limitations and leverage these representations to inform decisions in the absence of evidence. These results reframe guessing as a theoretically informative behavior that expresses observers' own beliefs about their perceptual capacities.
in bioRxiv: Neuroscience on 2026-01-16 00:00:00 UTC.
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Stroking touch has been shown to be most pleasant at intermediate velocities of 1-10 cm.s-1, which relates well to activity of C-low threshold mechanoreceptors (C-LTMRs), also called C-tactile afferents in humans, that have been implicated in encoding positive affective touch. This well-established finding has been demonstrated at gentle stroking forces (typically 0.4 N peak normal force), yet few studies have investigated the effect of force on the perception of stroking touch or on the activity of C-LTMRs. Presently, we investigated the perceptual pleasantness and intensity of stroking touch (0.3, 1, 3, 10, 30 cm.s-1) at different forces (0.2, 0.4, 0.8, 1.2, 1.6, 2.0 N) on hairy forearm skin and compared this to responses from C-LTMRs during stroking touch at the same velocities, but over fewer forces (0.05, 0.4, 1.5 N). We found significant effects of stroking velocity and force for both tactile pleasantness and intensity ratings. Pleasantness showed the typical inverted-U shaped relationship over stroking velocities, but this was modified by force: higher forces significantly decreased pleasantness at faster velocities. Conversely, tactile intensity increased linearly with both increasing velocity and force. Recordings from five C-LTMRs showed that their firing frequency changed with stroking velocity, but that they were strongly modulated by force. Overall, we demonstrate the profound effect that force has on the perception of stroking touch, where tactile pleasantness and intensity appear to be a multi-faceted construct that are related to C-LTMR and A{beta}-LTMR activity, respectively, but that the firing in individual mechanoreceptor populations cannot fully account for percepts.
in bioRxiv: Neuroscience on 2026-01-16 00:00:00 UTC.
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Variants in the X-linked gene CASK are associated with neurodevelopmental defects. Animal model studies have demonstrated that conditions such as cerebellar hypoplasia, microcephaly, and optic nerve hypoplasia (ONH) are related to loss-of-function (LOF) in the CASK gene. CASK variants are associated with multiple ocular conditions spanning both anterior and posterior segments of the eye including retinopathies. Both Cask heterozygous knockout (+/-) mice and Cask knock-in (KI) mice with reduced Cask expression have been shown to display ONH. Cask (+/-) mice displayed no defects in retinal structure or function. Here, we have systematically examined the Cask (KI) mice. Our results demonstrate that the anterior segment of the eye in Cask (KI) mice does not display any obvious phenotype. Cask (KI) mice however show a reduced visual acuity in optomotor response. The retina of Cask (KI) mice does not exhibit any major changes in their structure, vasculature, or gene expression pattern. We, however, uncovered a specific dysfunction of the cone receptor in Cask (KI) mice using electroretinogram (ERG). Mechanistically this dysfunction arises due to lowered levels of cone-specific opsin (opsin1mw) in Cask (KI) mice. To the best of our knowledge, this is the first description of retinal dysfunction in an animal model with CASK gene suppression. We infer that like ONH and cerebellar hypoplasia, retinopathy also may represent CASK LOF.
in bioRxiv: Neuroscience on 2026-01-16 00:00:00 UTC.
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Abstract
There has been considerable interest in the neuroanatomical homologue of Broca’s region in nonhuman primates, particularly in our phylogenetically closest relative the chimpanzee (Pan troglodytes), to further our understanding of the evolution of language in hominins. The inferior frontal sulcus (ifs) is a critical landmark below which lie language production areas in the language-dominant hemisphere of the human brain, and its homologue is found in the chimpanzee brain. The present study examined the variability in the morphology of the ifs in 73 chimpanzee brains (ie 146 hemispheres). Examination was carried out on surface reconstructions derived from in vivo 3 T magnetic resonance imaging scans, which permitted detailed intra-sulcal assessment. Based on the connections formed by the ifs and adjacent sulci, two frequent and three less frequent morphological types were identified. The average location and spatial variability of the ifs were quantified in the form of spatial surface probability maps. Relationships were also established between specific morphological features of the ifs in the left hemisphere and oro-facial communication abilities, as measured by attention-getting sound production. These findings refine our knowledge of prefrontal sulcal organization in hominids and offer valuable insights into the structural blueprints that supported the emergence of speech in humans.
in Cerebral Cortex on 2026-01-16 00:00:00 UTC.
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The nigrostriatal and mesoaccumbal dopamine systems are thought to contribute to changes in behavior and learning during adolescence, yet it is unclear how the rise in gonadal hormones at puberty impacts the function of these systems. We studied the impact of prepubertal gonadectomy (GDX) on later evoked dopamine release in male Mus spicilegus, a mouse whose adolescent life history has been carefully characterized in the wild and laboratory. To examine how puberty impacts dopamine neuron function in M. spicilegus males, we removed the gonads prepubertally at postnatal day (P)25 and then examined evoked dopamine release in the dorsomedial, dorsolateral (DLS), and nucleus accumbens core regions of striatal slices at P60–70 (late adolescence/early adulthood). To measure dopamine release, we used near-infrared catecholamine nanosensors which enable study of spatial distribution of dopamine release. We found that prepubertal GDX led to a significantly reduced density of dopamine release sites and reduced dopamine release at each site in the DLS nigrostriatal system compared with sham controls. In contrast, mesoaccumbal dopamine release was comparable between sham and gonadectomized groups. Our data suggest that during adolescence, the development of the nigrostriatal dopamine system is significantly affected by the rise in gonadal hormones in males, while the mesoaccumbal system shows no detectable sensitivity at this time point. These data are consistent with molecular studies in rodents that suggest nigrostriatal neurons are sensitive to androgens at puberty and extend our understanding of how gonadal hormones could impact the spatial distribution and release potential of dopamine terminals in the striatum.
in eNeuro on 2026-01-15 17:30:22 UTC.
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Abstract* The global environmental crisis exposes the flaws of current approaches and highlights the importance of spiritual and locally based ecological ethics. This research examines how Islamic values and Javanese traditional culture are incorporated into environmental rituals at the community level in Selorejo, Malang, Indonesia, as a local response to environmental issues. The primary aim is to illustrate how the incorporation of Islamic values and Javanese traditions constitutes dynamic ecological rituals that foster environmental conservation from both global and local points of view. Using a qualitative ethnographic method, data were collected through three primary techniques: participant observation of community ecological rituals, in-depth interviews with traditional leaders, local community, and local residents involved in conservation efforts. Thematic analysis was applied, utilizing frameworks of acculturation and ecophy. Results reveal that Selorejo’s ecological rituals include six rites: Merti Wono (Selametan Alas), Selametan Sumber, Jogo Wono Performing Arts (Wong Ireng), Jagong Alas, Boundary Marking and Reforestation, and Eco-friendly Agriculture. The rites of Selametan Alas and Sumber demonstrate the fusion of Islamic principles with Javanese traditions, viewing nature as a sacred reflection of God. This combination enhances ecological awareness and establishes a spiritual model of conservation rooted in ecosophy. Such a model presents a relevant global ecological citizenship alternative and supports the achievement of SDGs. This study confirms that spiritually based local ecological rituals can contribute to global ecological citizenship and provide an alternative approach to environmental crises.
in F1000Research on 2026-01-15 15:40:39 UTC.
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Proceedings of the National Academy of Sciences, Volume 123, Issue 3, January 2026.
SignificanceThe vasculature in the brain forms a multiscale network that actively regulates blood flow to support brain health. To determine how brain angioarchitecture defines physiological limits on the control of cerebral microcirculation, we ...
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Science, Volume 391, Issue 6782, January 2026.
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Science, Volume 391, Issue 6782, January 2026.
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Science, Volume 391, Issue 6782, January 2026.
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Science, Volume 391, Issue 6782, January 2026.
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Science, Volume 391, Issue 6782, January 2026.
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Science, Volume 391, Issue 6782, January 2026.
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Science, Volume 391, Issue 6782, Page 245-245, January 2026.
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Science, Volume 391, Issue 6782, Page 246-246, January 2026.
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Science, Volume 391, Issue 6782, Page 280-284, January 2026.
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Science, Volume 391, Issue 6782, Page 275-279, January 2026.
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Science, Volume 391, Issue 6782, Page 306-313, January 2026.
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Science, Volume 391, Issue 6782, Page 294-299, January 2026.
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Science, Volume 391, Issue 6782, Page 267-274, January 2026.
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Science, Volume 391, Issue 6782, Page 285-289, January 2026.
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Science, Volume 391, Issue 6782, Page 314-319, January 2026.
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Science, Volume 391, Issue 6782, Page 249-258, January 2026.
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Science, Volume 391, Issue 6782, Page 322-322, January 2026.
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Science, Volume 391, Issue 6782, Page 260-261, January 2026.
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Science, Volume 391, Issue 6782, Page 237-238, January 2026.
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Science, Volume 391, Issue 6782, Page 238-239, January 2026.
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Science, Volume 391, Issue 6782, Page 234-235, January 2026.
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Science, Volume 391, Issue 6782, Page 235-236, January 2026.
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Science, Volume 391, Issue 6782, Page 240-240, January 2026.
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Science, Volume 391, Issue 6782, Page 247-248, January 2026.
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Science, Volume 391, Issue 6782, Page 248-248, January 2026.
in Science on 2026-01-15 07:00:10 UTC.
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Science, Volume 391, Issue 6782, Page 247-247, January 2026.
in Science on 2026-01-15 07:00:10 UTC.
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Science, Volume 391, Issue 6782, Page 228-232, January 2026.
in Science on 2026-01-15 07:00:10 UTC.
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Science, Volume 391, Issue 6782, Page 220-221, January 2026.
in Science on 2026-01-15 07:00:10 UTC.
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Science, Volume 391, Issue 6782, Page 222-223, January 2026.
in Science on 2026-01-15 07:00:10 UTC.
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Science, Volume 391, Issue 6782, Page 224-225, January 2026.
in Science on 2026-01-15 07:00:10 UTC.
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Science, Volume 391, Issue 6782, Page 225-226, January 2026.
in Science on 2026-01-15 07:00:10 UTC.
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Science, Volume 391, Issue 6782, Page 226-227, January 2026.
in Science on 2026-01-15 07:00:10 UTC.
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Science, Volume 391, Issue 6782, Page 219-219, January 2026.
in Science on 2026-01-15 07:00:10 UTC.
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Science, Volume 391, Issue 6782, Page 241-244, January 2026.
in Science on 2026-01-15 07:00:10 UTC.
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Science, Volume 391, Issue 6782, Page 259-261, January 2026.
in Science on 2026-01-15 07:00:10 UTC.
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Power et al. identify TGF-β as the injury microenvironment signal required for neurofibroma formation, enabling the expansion of Nf1-KO SCs outside of a repairing nerve by blocking axonal interactions and re-differentiation. “Normalization” using TGF-β inhibitors blocks neurofibroma formation, providing a new therapeutic approach for patients who develop tumors throughout life.
in Cell Reports: Current Issue on 2026-01-15 00:00:00 UTC.
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Guo et al. investigate IL-1 signaling in pancreatic ductal adenocarcinoma (PDAC) by analyzing multi-omic single-cell data. Cancer-associated fibroblasts (CAFs) respond to IL-1 signals from myeloid cells and activate an inflammatory signature, mediated by transcription factor NFATC2. Inhibiting NFAT leads to decreased tumor weight, highlighting its potential as a therapeutic target.
in Cell Reports: Current Issue on 2026-01-15 00:00:00 UTC.
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Ge and Kan et al. develop and benchmark a human organoid tumor transplantation (HOTT) system to uncover how microenvironmental cues influence glioblastoma states. They identify a non-catalytic role for microenvironmental PTPRZ1 in driving mesenchymal programs and extending tumor microtubes in patient tumor cells.
in Cell Reports: Current Issue on 2026-01-15 00:00:00 UTC.
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Milovanović et al. uncover a mechanism by which KZFPs restrict the activity of transposon-derived cis-regulatory elements to safeguard cardiomyocyte functionality. This work extends the classical TE-KZFP paradigm, showing that developmental gene expression programs are shaped by the restriction of CRE active in other tissues.
in Cell Reports: Current Issue on 2026-01-15 00:00:00 UTC.
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Alternative polyadenylation generates transcript diversity during human urothelial differentiation. Le et al. combine single-cell sequencing, spatial in situ assays, and functional reporter analyses to reveal isoform-specific regulation of protein expression and identify primate-specific sequence motifs, highlighting an underappreciated layer of post-transcriptional control in tissue biology.
in Cell Reports: Current Issue on 2026-01-15 00:00:00 UTC.
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Sun et al. reveal the origin and maintenance of genomic divergence at a finer scale and explore the sex-determination mechanism in Welwitschia mirabilis through whole-genome re-sequencing of 130 individuals. This study provides insights into the evolutionary forces shaping genomic differentiation and the genetic basis of sex determination in gymnosperms.
in Cell Reports: Current Issue on 2026-01-15 00:00:00 UTC.
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Dunn et al. show that individuals with Down syndrome display widespread evidence of altered hepatic function in the plasma proteome and metabolome, typified by elevated plasma bile acids. Using a mouse model of Down syndrome, they show that these alterations are driven, in part, by diet.
in Cell Reports: Current Issue on 2026-01-15 00:00:00 UTC.
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Chanvillard et al. reveal that NNMT drives tubular senescence and fibrosis in early CKD. Through human data, spatial transcriptomics, and mouse, cell, and organoid models, they show that NNMT inhibition restores methylation balance and reverses senescence and fibrosis, therefore identifying NNMT as a promising therapeutic target for early CKD intervention.
in Cell Reports: Current Issue on 2026-01-15 00:00:00 UTC.
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Chaperone-mediated secretion of substrates through the Legionella Dot/Icm type IVB secretion system is vital for the bacterium’s intracellular survival. Vijayrajratnam et al. investigate the stoichiometry and structural interactions between the T4CP-coupling protein DotL and the chaperones IcmS and IcmW, revealing a new mechanism for the chaperones in substrate secretion.
in Cell Reports: Current Issue on 2026-01-15 00:00:00 UTC.
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Li et al. demonstrate that lactylation drives the nuclear function of RIG-I to suppress DNA damage repair by inhibiting PARP activity. This finding provides a rational basis for the potential co-administration of the MCT1/4 inhibitor syrosingopine and PARPi in the treatment of lung adenocarcinoma.
in Cell Reports: Current Issue on 2026-01-15 00:00:00 UTC.
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In orofacial inflammatory pain, mitochondrial transfer from glial cells to neurons was poorly understood. Li et al. demonstrate that glia-to-neuron mitochondrial transfer attenuates inflammatory hyperexcitability and pain by restoring mitophagy and calcium homeostasis through an ATL1-dependent mechanism, revealing promising therapeutic targets.
in Cell Reports: Current Issue on 2026-01-15 00:00:00 UTC.
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Desiderio et al. show that the Neurog1/2 proneural paralogs are largely interchangeable in controlling DRG neurogenesis and fate specification, indicating that their complementary roles primarily reflect distinct spatiotemporal expression. They also provide evidence that somatosensory precursor commitment toward specific neuronal lineages is rapidly biased but critically relies on differentiation timing.
in Cell Reports: Current Issue on 2026-01-15 00:00:00 UTC.
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Appleby et al. investigate how motion in the receptive-field surround influences the responses of two primate retinal ganglion cell types. They find that broad thorny cells exhibit object-motion sensitivity, while On smooth monostratified cells display motion-dependent facilitation—diverging from classical models and echoing surround modulation seen in visual cortex.
in Cell Reports: Current Issue on 2026-01-15 00:00:00 UTC.
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Honnuraiah et al. find asymmetric interhemispheric communication in binocular visual cortex. Callosal receiving neurons do not project to the opposite hemisphere and are primarily binocular. In contrast, callosal projecting neurons do not receive projections from the opposite hemisphere and are primarily monocular. Furthermore, they show that binocularity and excitability scale with callosal input.
in Cell Reports: Current Issue on 2026-01-15 00:00:00 UTC.
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Cruz-Sanchez et al. show that the maturation trajectory of ventral and intermediate hippocampus-medial prefrontal cortex connectivity displays distinct anatomical and synaptic developmental signatures in mice. Critically, the timing of this maturation guides a sex- and pathway-specific sensitive period during early life, upon which pathway inhibition bidirectionally modulates adult cognitive flexibility.
in Cell Reports: Current Issue on 2026-01-15 00:00:00 UTC.
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Zheng et al. reveal that prenatal dexamethasone exposure (PDE) induces social memory deficiency and increased repetitive behavior in offspring, accompanied by immaturation of MRC1+ microglia and specific upregulation of F13a1 in this cluster. Early postnatal inhibition of F13A1 restores microglial maturation and ameliorates behavioral abnormalities.
in Cell Reports: Current Issue on 2026-01-15 00:00:00 UTC.
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Dakhel et al. present a form of actively migrating astrocyte vehicles named zombosomes. Zombosomes contain a compact core of filamentous vimentin and carry a wide range of cellular organelles. Notably, zombosomes can also transfer α-synuclein aggregates to surrounding cells and thereby contribute to seeding and propagation of the pathology.
in Cell Reports: Current Issue on 2026-01-15 00:00:00 UTC.
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After making macaque and marmoset inter-areal connectomes directly comparable through consensus mapping, Magrou, Theodoni, et al. modeled both species using a large-scale model of working memory, which differed only by the two species' anatomy. The model’s sensitivity to distraction captures real-life behavioral differences between the two species of primates.
in Cell Reports: Current Issue on 2026-01-15 00:00:00 UTC.
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Xu et al. find that GABAergic interneuron subtypes in mouse V1 differentially regulate noise correlations. PV+/SOM+ suppression increases correlations and impairs visual discrimination, while VIP+ suppression decreases correlations and enhances performance. A predictive model demonstrates noise correlations as critical determinants of perceptual abilities, offering insights into sensory-processing disorders.
in Cell Reports: Current Issue on 2026-01-15 00:00:00 UTC.
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Huang et al. show that the brain optimizes working memory by compressing information when environmental regularities exist. MEG reveals distinct neural systems for abstract structure and item details, highlighting how structural compression enhances efficiency, especially in individuals with limited memory capacity.
in Cell Reports: Current Issue on 2026-01-15 00:00:00 UTC.
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Nature, Published online: 15 January 2026; doi:10.1038/d41586-026-00035-8
A study in Australia supports genetic screening in young adults before symptoms show, but the generalizability and cost–benefit ratios need to be examined in other settings.
in Nature on 2026-01-15 00:00:00 UTC.
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Nature, Published online: 15 January 2026; doi:10.1038/d41586-026-00181-z
A mitochondria-induced metabolic pathway helps cancer cells lay low in lymph nodes. Plus, why this year’s flu season is so bad and tips on how to overcome ‘the fear of the blank page’.
in Nature on 2026-01-15 00:00:00 UTC.
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Nature, Published online: 15 January 2026; doi:10.1038/d41586-025-03342-8
Small acts of change have helped me to reset and give myself a break.
in Nature on 2026-01-15 00:00:00 UTC.
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Nature, Published online: 15 January 2026; doi:10.1038/d41586-026-00073-2
Nature Health, the newest journal in the Nature Portfolio, aims to bridge the ‘implementation gap’ from research to policy and practice.
in Nature on 2026-01-15 00:00:00 UTC.
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Nature, Published online: 15 January 2026; doi:10.1038/d41586-026-00160-4
Learned risk-taking behaviours can persist for years after leaving the lab — and even after taking on a new research topic.
in Nature on 2026-01-15 00:00:00 UTC.
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Nature, Published online: 15 January 2026; doi:10.1038/d41586-026-00116-8
Scientists have transformed enigmatic cell structures, called vaults, into storage units for messenger-RNA molecules made in the past.
in Nature on 2026-01-15 00:00:00 UTC.
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Nature, Published online: 15 January 2026; doi:10.1038/d41586-026-00152-4
Scientists who join protest movements often find themselves at the centre of a media and political firestorm, causing tensions with some employers.
in Nature on 2026-01-15 00:00:00 UTC.
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Nature Neuroscience, Published online: 15 January 2026; doi:10.1038/s41593-026-02203-5
Author Correction: Choroid plexus apocrine secretion shapes CSF proteome during mouse brain development
in Nature Neuroscience on 2026-01-15 00:00:00 UTC.
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Nature Neuroscience, Published online: 15 January 2026; doi:10.1038/s41593-025-02196-7
The lesion network mapping method links diverse brain lesions to similar functional brain networks, reflecting general brain organization rather than disorder-specific circuits.
in Nature Neuroscience on 2026-01-15 00:00:00 UTC.
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Nature Methods, Published online: 15 January 2026; doi:10.1038/s41592-025-02948-0
DBiTplus represents an integrated experimental and computational workflow that unifies sequencing-based and imaging-based spatial omics, demonstrated by combining transcriptomic profiling and multiplexed protein imaging on the same tissue section.
in Nature Methods on 2026-01-15 00:00:00 UTC.
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Nature Methods, Published online: 15 January 2026; doi:10.1038/s41592-025-02923-9
MaAsLin 3 is a comprehensive and flexible framework for microbiome association studies with expanded toolsets of statistical models, tests and types of inference.
in Nature Methods on 2026-01-15 00:00:00 UTC.
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Nature Physics, Published online: 15 January 2026; doi:10.1038/s41567-025-03162-7
Preferential play
in Nature Physics on 2026-01-15 00:00:00 UTC.
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Nature Physics, Published online: 15 January 2026; doi:10.1038/s41567-025-03152-9
As our metrology column turns ten years, there is no better way to celebrate than to look at the definitions of a year, finds Stefanie Reichert.
in Nature Physics on 2026-01-15 00:00:00 UTC.
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Nature Physics, Published online: 15 January 2026; doi:10.1038/s41567-025-03149-4
A recently proposed class of magnets, so-called altermagnets, combine features of ferromagnets and antiferromagnets. We discuss the scientific appeal of altermagnets, current controversies and challenges for their practical use.
in Nature Physics on 2026-01-15 00:00:00 UTC.
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Nature Physics, Published online: 15 January 2026; doi:10.1038/s41567-025-03151-w
A star of contradictions
in Nature Physics on 2026-01-15 00:00:00 UTC.
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Nature Physics, Published online: 15 January 2026; doi:10.1038/s41567-025-03130-1
How proteins — sequences of amino acids — fold determines their function. We discuss efforts towards the establishment of metrics traceable to the International System of Units that link the sequence of a protein to its structure and function.
in Nature Physics on 2026-01-15 00:00:00 UTC.
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Calcium binding to BK channels lowers BK activation threshold, substantiating functional coupling with calcium-permeable channels. This coupling requires close proximity between different channel types, and the formation of BK-CaV1.3 hetero-clusters at nanometer distances exemplifies this unique organization. To investigate the structural basis of this interaction, we tested the hypothesis that BK and CaV1.3 channels assemble before their insertion into the plasma membrane. Our approach incorporated four strategies: (1) detecting interactions between BK and CaV1.3 proteins inside the cell, (2) identifying membrane compartments where intracellular hetero-clusters reside, (3) measuring the proximity of their mRNAs, and (4) assessing protein interactions at the plasma membrane during early translation. These analyses revealed that a subset of BK and CaV1.3 transcripts are spatially close in micro-translational complexes, and their newly synthesized proteins associate within the endoplasmic reticulum (ER) and Golgi. Comparisons with other proteins, transcripts, and randomized localization models support the conclusion that BK and CaV1.3 hetero-clusters form before their insertion at the plasma membrane.
in eLife on 2026-01-15 00:00:00 UTC.
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Trained immunity, the long-term reprogramming of innate immune cells to elicit an enhanced response upon subsequent challenges, has become a key concept in understanding a wide range of pathologies, including both acute and chronic inflammatory disorders. Recent evidence suggests that trained immunity also plays a significant role in the development and progression of various neurological disorders and related comorbidities, in which brain pathology can lead to trained immunity. This review summarizes the current understanding of trained immunity within both brain-resident immune cells and myeloid-derived innate immune cells, focusing on their roles in neurological disorders, such as ischemic brain injury, Parkinson’s disease, and Alzheimer’s disease. Additionally, we explore the heterogeneity of trained immunity across different conditions and its potential applications in clinical neurology.
in eLife on 2026-01-15 00:00:00 UTC.
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An agreement between universities, research institutes and funders to support the career development of researchers in the UK has led to improvements in research culture since 2019, but there is still more to do.
in eLife on 2026-01-15 00:00:00 UTC.
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Transcriptional pause-release critically regulates cellular RNA biogenesis, yet how dysregulation of this process impacts embryonic development is not fully understood. Rtf1 is a multifunctional transcription regulatory protein involved in modulating promoter-proximal pausing of RNA Polymerase II (RNA Pol II). Using zebrafish and mouse as model systems, we show that Rtf1 activity is essential for the differentiation of the myocardial lineage from mesoderm. Ablation of rtf1 impairs the formation of nkx2.5+/tbx5a+ cardiac progenitor cells, resulting in the development of embryos without cardiomyocytes. Structure-function analysis demonstrates that Rtf1’s cardiogenic activity requires its Plus3 domain, which confers interaction with the pausing/elongation factor Spt5. In Rtf1-deficient embryos, the occupancy of RNA Pol II at transcription start sites was reduced relative to downstream occupancy, suggesting a reduction in transcriptional pausing. Intriguingly, attenuating pause release by pharmacological inhibition or morpholino targeting of CDK9 improved RNA Pol II occupancy at the transcription start sites of key cardiac genes and restored cardiomyocytes in Rtf1-deficient embryos. Thus, our findings demonstrate the crucial role that Rtf1-mediated transcriptional pausing plays in controlling the precise spatiotemporal transcription programs that govern early heart development.
in eLife on 2026-01-15 00:00:00 UTC.
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in eLife on 2026-01-15 00:00:00 UTC.
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ZC4H2 is an X-linked zinc finger transcription factor essential for early neurodevelopment. Pathogenic variants in ZC4H2 are associated with both central and peripheral nervous system pathologies. The molecular and cellular mechanisms driving these phenotypes remain poorly understood, particularly in human female models that have undergone X chromosome inactivation. Neuronal models were differentiated from a human female cell line with a de novo Xq11.2 deletion causing ZC4H2 loss of function, associated with arthrogryposis multiplex congenita and cognitive impairment. Using iPSC-derived neural stem cells and cortical organoids, we identified premature neuronal differentiation, reduced BMP-SMAD signaling, and decreased SMAD1/5 phosphorylation. In cortical organoids, ZC4H2 deficiency altered neurogenesis timing, retaining proliferative progenitors while prematurely activating neuronal programs, leading to enlarged organoids with persistent dysregulation of gene programs required for complete neuronal maturation. We identified ZC4H2 target genes likely to mediate these phenotypes and tested a codon-optimized transgene showing both the restoration of SMAD1/5 phosphorylation, BMPR2 gene expression, and improved neuronal complexity. These results demonstrate effective ZC4H2 restoration in complex human models and highlight therapeutic potential for ZC4H2-linked neurodevelopmental disorders.
in bioRxiv: Neuroscience on 2026-01-15 00:00:00 UTC.
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Hippocampal function relies on structured patterns of population activity that reflect the intrinsic organization of the circuit. Although experience is known to influence synaptic properties and local activity features, whether prolonged experience reshapes the large-scale organization of population dynamics across hippocampal subfields in the intact brain has remained unclear. Progress on this question has been limited by the lack of measurements that capture circuit-wide activity simultaneously while preserving spatial circuit structure. Here, we combined prolonged environmental experience with large-scale, simultaneous multi-shank recordings spanning CA1, CA3, and dentate gyrus in the mouse hippocampus to examine experience-dependent changes in circuit dynamics. We find that long-term experience reorganizes the basal operating state of the hippocampus, altering the statistical structure of field potentials, population spiking, and sharp-wave ripple activity in a coordinated manner across subfields. These changes are not confined to specific regions but instead reflect a circuit-wide reconfiguration of functional interactions that extends over larger spatial scales. At the population level, experience shifts hippocampal dynamics into a more coordinated dynamical regime, characterized by shared low-dimensional structure across hippocampal subfields. Together, these findings demonstrate that long-term experience reorganizes coordinated population dynamics across hippocampal circuits, establishing an intrinsic activity organization that reflects the experiential history of a memory network.
in bioRxiv: Neuroscience on 2026-01-15 00:00:00 UTC.
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Hierarchical Phase-Contrast Tomography (HiP-CT) was recently developed to enable the ex-vivo imaging of human organs at multiple scales from whole organ down to cellular level. Using whole adult human brain imaging as a case study, this manuscript shows the evolution of this technique from its initial development at the BM05 beamline to its transition and current status at BM18. Thanks to the higher coherence, larger beam size, higher energies and larger propagation distances available at BM18 and due to the European Synchrotron's Extremely Brilliant Source upgrade (ESRF-EBS), this transition resulted in significantly improved data quality, resolution, sensitivity and speed. More recently, the implementation of a new generation of larger sCMOS cameras, helical scanning (including dedicated reconstruction algorithm developments), binning at the chip and projections levels, and the design of high-efficiency optics allowed to progressively improve the trade-off between dose and image quality, while simultaneously reducing scanning times. All these acquisition schemes present the current status of full organ imaging using HiP-CT and represent the constant efforts for the improvement of the technique towards the investigation of human organs in health, disease and aging.
in bioRxiv: Neuroscience on 2026-01-15 00:00:00 UTC.
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An Event-Related Desynchronization (ERD) of the 13-30 Hz sensorimotor (SM1) beta oscillations is commonly observed during movement preparation and execution. Human electrophysiological measurements suggest that such a beta ERD has a wide topographical distribution along the SM1, however, no accessible means of quantifying the degree of its focality exist. Therefore, we investigated how the movement-induced beta ERD in one somatotopic SM1 area affects beta oscillations in a neighbouring SM1 area. Thirty-six participants performed right brachium movements while holding a submaximal isometric contraction with their right first dorsal interosseous (FDI) muscle. Beta ERD in the left SM1 brachium area was assessed with electroencephalography (EEG). The effect of that ERD on beta activity in the neighbouring SM1 FDI area was assessed through the corticomuscular coherence (CMC) between SM1 EEG signals and the electromyographic and force signals recorded from the contracted right FDI muscle. Our results showed that the strong movement-induced beta ERD in the SM1 brachium area spreads to the neighbouring SM1 FDI area and suppresses beta oscillations therein, as evidenced by significantly attenuated CMC with both FDI signals. These findings confirm that beta ERD is not a strictly focal phenomenon as it spreads to a neighbouring SM1 area. Importantly, we introduced a novel approach that combines a dual motor task paradigm with CMC to assess beta propagatory effects. This approach could allow for investigating the topographical properties of beta oscillations and their role for motor control in healthy and clinical populations.
in bioRxiv: Neuroscience on 2026-01-15 00:00:00 UTC.
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Music listening is one of the most compelling and rewarding activities humans engage in spontaneously. But what exactly catches people's attention when listening to music remains unclear. Musicologists have argued that tension-release dynamics in music constitute crucial features of the listening experience. They arise from the intertwining of different low-level and high-level features and sit at the core of music enjoyment by engaging listeners dynamically. This study aims to characterize the relationship between tension dynamics and engagement during naturalistic music listening. Using canonical correlation analysis, we decoded the music envelope from EEG and ECoG responses and found that musical tension patterns, as reported by listeners, were predictive of fluctuations in the coupling between the music and the neural response. Importantly, tension dynamics were significantly correlated with neural measures of envelope tracking even after controlling for loudness and musical expectations, confirming the specific and crucial role of musical tension in engaging listeners. These results shed new light on how musical structure gives rise to internal response modulations that, in turn, dynamically reflect musical engagement. This interplay may underlie the pervasive and emotionally rewarding nature of music.
in bioRxiv: Neuroscience on 2026-01-15 00:00:00 UTC.
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Distributed sensorimotor interactions facilitate the coordination of multilegged locomotion in insects without centralized control, yet the mechanisms that allow coordinated locomotion to re-emerge following limb loss remain poorly understood. Here, we systematically evaluate the effects of leg amputation and the integration of prosthetic legs on walking coordination in crickets (Gryllus bimaculatus). Spherical treadmill experiments revealed that leg amputation disrupts inter-leg phase coupling, decreases locomotor speed, and alters spatial foot placement in a state-dependent manner, indicating impaired load-mediated coordination. Prosthetic legs did not merely restore intact kinematics; instead, they selectively reinstated coherent temporal coordination and axis-specific spatial organization. This structured recovery illustrates that re-introducing mechanically relevant sensory constraints is sufficient to re-engage distributed coordination networks, even in the absence of anatomical integrity. Our findings elucidate an embodied principle through which sensory-mechanical feedback facilitates the self-organization of resilient multi-legged locomotion in the context of morphological interventions.
in bioRxiv: Neuroscience on 2026-01-15 00:00:00 UTC.
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Synaptic depression is often interpreted as reflecting depletion of the readily releasable pool (RRP) following exocytosis. Such a mechanism predicts little or no depression at low stimulation frequency, as RRP replenishment should then offset the loss of vesicles by exocytosis. Nevertheless, in several types of mammalian central synapses, repetitive presynaptic stimulation at low frequency (< 5 Hz) elicits synaptic depression (low frequency depression, or LFD). In the present work we count the number of synaptic vesicles released at individual active zones to study the RRP and its replenishment during LFD. Contrary to depletion models of synaptic depression, we find that LFD does not depend on previous SV consumption. We find that LFD displays a long recovery time course (tens of seconds) when challenged by isolated stimulations but is immediately reversed by a high frequency train. We suggest that LFD results from undocking, a shift between two classes of synaptic vesicles organized sequentially inside the RRP (replacement vs. docked vesicles) in favor of the upstream (replacement) state. While undocking is apparent hundreds of milliseconds after a stimulation, calcium dependent docking takes only a couple of milliseconds, explaining the fast LFD recovery when stimulating at high frequency. Consistent with the undocking model, we find that double presynaptic stimulations alleviate LFD as they favor vesicular docking and RRP replenishment. Finally, we expand our model to explain how stimulation frequency shapes short-term synaptic depression, changing from depression at low frequency to a facilitation-depression sequence at medium or high frequency trains.
in bioRxiv: Neuroscience on 2026-01-15 00:00:00 UTC.
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Transmembrane proteins perform essential roles in cellular transport, signalling, and communication. The function and dynamics of these proteins are precisely regulated by interactions on both sides of the plasma membrane; thus, mapping the composition of these interactomes is a fundamental challenge in molecular biology. Proximity labelling methods are powerful tools for this purpose; however, existing approaches that rely on membrane-impermeable reactive species are limited by the ability to detect only one side, either the extracellular or the intracellular region, of transmembrane proteins. Here, we capitalized on the cell permeability of singlet oxygen to carry out proximity labelling of the cytoplasmic side of transmembrane proteins using an extracellularly anchored photosensitizer. We applied this method, termed transmembrane PhoxID (tmPhoxID), to several receptors (GRID2, GABAAR, and GRM1) in the living mouse brain and successfully determined their specific intracellular interactomes. Notably, network analysis of the identified proteins revealed that this method can characterize the native components of transsynaptic nanocolumns formed at parallel fibre-Purkinje cell synapses. Furthermore, our study revealed a previously uncharacterized GABAAR-CAMKV interaction in mice and human brains. Our results provide a proof of concept for transmembrane and transcellular proximity labelling, providing a powerful platform for analysing the interactome of transmembrane proteins.
in bioRxiv: Neuroscience on 2026-01-15 00:00:00 UTC.
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Speech in everyday life is often masked by background noise, making comprehension effortful. Characterizing brain activity patterns when individuals listen to masked speech can help clarify the mechanisms underlying such effort. In the current study, we used functional magnetic resonance imaging (fMRI) in humans of either sex to investigate how neural signatures of story listening change in the presence of masking noise. We show that, as speech masking increases, spatial and temporal activation patterns in auditory regions become more idiosyncratic to each listener. In contrast, spatial activity patterns in brain networks linked to effort (e.g., cingulo-opercular network) are more similar across listeners when speech is highly masked and less intelligible, suggesting shared neural processes. Moreover, at times during stories when one meaningful event ended and another began, neural activation increased in frontal, parietal, and medial cortices. This event-boundary response appeared little affected by background noise, suggesting that listeners process meaningful units and, in turn, the gist of naturalistic, continuous speech even when it is masked somewhat by background noise. The current data may indicate that people stay engaged and cognitive processes associated with naturalistic speech processing remain intact under moderate levels of noise, whereas auditory processing becomes more idiosyncratic to each listener.
in eNeuro on 2026-01-14 17:30:37 UTC.
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The chemokine CXCL12 plays critical roles in the development of the hippocampus dentate gyrus during both embryogenesis and adulthood. While multiple cell types in the hippocampus express Cxcl12, their individual contributions to the dentate gyrus development and function remain unclear. Here, using Cxcl12 reporter mice of both sexes, we characterize Cxcl12 expression in Cajal–Retzius (CR) cells—neurons that guide dentate gyrus morphogenesis and influence hippocampal circuitry. We show that CR cells prominently express Cxcl12 during early postnatal development, although both the number and proportion of Cxcl12-expressing CR cells decline significantly in adulthood. Notably, partial deletion of Cxcl12 from hippocampal CR cells in male and female mice does not result in detectable changes in dentate gyrus architecture, adult neurogenesis, or specific behaviors. These findings suggest that CR cell-derived CXCL12 may be less critical for dentate gyrus development than previously assumed and underscore the complexity and potential redundancy of CXCL12 signaling in the hippocampus.
in eNeuro on 2026-01-14 17:30:32 UTC.
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Plastic waste accumulation is a global environmental issue. Current methods (recycling, incineration, landfilling, etc.) are not a sustainable long-term solution and so far they cannot prevent continuous accumulation of plastic waste worldwide. This article introduces the concept of deep geological disposal (DGD) of plastic waste as an alternative strategy. The concept principally differs from the traditional landfilling. In the latter, plastic waste is affected by chemical, physical, and microbial factors that cause plastic fragmentation and environmental leakage. On the contrary, DGD isolates plastic waste in abandoned mines, quarries and caves, ensuring safe long-term containment of the waste and the possibility of its reuse as a raw material in the future. Another advantage of DGD is that these geological structures usually have transport infrastructure and storage facilities, and, as a result, they offer a more controlled environment with reduced risk of leachate, microplastic dispersion, and surface pollution. The paper discusses the practical, economic, and environmental aspects of the concept of DGD of plastic waste. The proposal does not offer to replace other available mechanisms of plastic waste management, it presents DGD as a complementary and potentially effective method for addressing non-recyclable and mismanaged plastic waste worldwide.
in F1000Research on 2026-01-14 10:29:48 UTC.
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Background Morbidity and mortality due to tobacco smoking is a public health crisis predicted to rise in coming years with the growing global population. Smoking cessation programs are an important tool to support service users to quit smoking. Understanding how programs are implemented to support the uptake of smoking cessation services may help enhance service design and delivery, service user engagement, and cessation outcomes. Objectives The objective of this review is to evaluate the implementation of smoking cessation programs for adult smokers aged 18 years or older. Rationale Whilst the effectiveness of smoking cessation programs have been previously investigated, there is limited research examining the implementation of programs in practice. This scoping review will provide novel information by evaluating the implementation of smoking cessation programs, including smoking cessation interventions; implementation strategies; and implementation theories, models, and frameworks. Inclusion criteria This review will include the implementation of smoking cessation programs for adults aged 18 years or older, who are daily smokers of tobacco-based cigarettes, accessing a community-based service for smoking cessation support. Methods A search of research databases Medline, CENTRAL, Embase, and Web of Science will be undertaken, in addition to searching for grey literature and hand searches for potential articles for inclusion. Data will be extracted into a spreadsheet and ordered into predetermined categories based on the inclusion criteria; intervention; implementation strategies; and implementation theories, models and/or frameworks. Conclusions This scoping review will evaluate the implementation of smoking cessation services to adults in the community. An evidence map highlighting current knowledge will be developed, contributing to the body of literature on community-based smoking cessation programs. Evidence gaps will be identified, providing direction for future research and service delivery internationally.
in F1000Research on 2026-01-14 09:38:25 UTC.
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Background The aim of this study is to evaluate the long-term psychological impact of the COVID-19 pandemic on students and technical personnel at healthcare institutions, with a focus on levels of depression, anxiety, and stress. Methods A total of 250 participants were included, comprising 130 students from health sciences and 120 individuals from technical fields. In total, 164 participants were females, and 192 participants were aged ≤20 years. A cross-sectional study was conducted using a self-administered electronic questionnaire. The Depression, Anxiety, and Stress Scale (DASS-21), followed by the Impact of Event Scale-Revised (IES-R), was used to retrospectively assess psychological distress linked to the pandemic. The data were analysed via the chi-square test. Results DASS severity ratings revealed that 41.3% of participants aged ≤20 years experienced severe or extremely severe anxiety, which was statistically significant (p = 0.013). The stress scores were also significantly higher in this age group (p = 0.004). Binary logistic regression analysis indicated that younger age and female sex were significantly associated with increased odds of depression and stress. Males had comparatively lower odds of experiencing psychological distress. Participants from technical fields demonstrated higher odds of anxiety and stress, although not of depression. Conclusion The long-term psychological impact of the COVID-19 pandemic appears to be more pronounced among younger individuals, females, and technical staff in healthcare institutions. Although students may have greater awareness about the disease, this awareness may contribute to heightened psychological distress.
in F1000Research on 2026-01-14 09:33:05 UTC.
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Innate immune cells can acquire a form of memory through epigenetic and metabolic reprogramming following exposure to pathogen-associated molecular patterns (PAMPs), resulting in an enhanced, heterologous inflammatory response upon subsequent stimulation, a phenomenon termed trained immunity. This emerging concept challenges the traditional view that immunological memory is restricted to the adaptive immune system and is reshaping current understanding of host defense. Trained immunity is driven by long-lasting functional reprogramming of innate immune cells, particularly monocytes, macrophages, natural killer (NK) cells, dendritic cells, and their progenitors, leading to heightened responsiveness to secondary, often unrelated, stimuli. Comparable forms of innate immune memory have been documented across diverse biological systems, including systemic acquired resistance in plants, immune priming in insects, and trained immunity in mammals, highlighting its evolutionary conservation. The capacity of trained immunity to enhance immune responses provides a mechanistic basis for improved protection against reinfection and strengthened tumor surveillance. However, its dysregulated or excessive activation may also contribute to the development of autoinflammatory and autoimmune diseases, underscoring its dual and context-dependent nature. Consequently, trained immunity holds significant relevance for a wide range of clinical and translational applications, including infectious disease control, cancer immunotherapy, inflammatory disorders, and vaccine development. Harnessing trained immunity in vaccine design offers promising opportunities to achieve broader protective coverage, prolonged immune durability, and improved vaccine efficacy. Despite these advances, key challenges remain, including elucidating the precise molecular mechanisms underlying trained immunity, understanding its crosstalk with adaptive immune responses, and identifying optimal inducers and adjuvants capable of safely modulating trained immune pathways. Addressing these knowledge gaps will be essential for translating the concept of trained immunity into effective and safe therapeutic and vaccine strategies for human health.
in F1000Research on 2026-01-14 09:27:38 UTC.
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Background The fast-paced acceptance of artificial intelligence (AI) technologies in various sectors of society, such as health, the judiciary, and education, has had several socio-ethical, legal, and human rights consequences. While AI technologies allow for more efficiency and specialization in decision-making processes, the use of such technologies in very sensitive spheres of social life brings with it great potential dangers, such as bias, discrimination, and violation of privacy. Methods The analysis was performed using Biblioshiny, which is the web interface of the Bibliometric R-package and VOSviewer, to ascertain trends in publication rates, citation impact, keyword development, concentration of journals, institutional affiliations, and inter-country contributions. A co-word and cluster analysis was also performed to show the current dominant and emerging themes of the literature and the thematic evolution from 2018 to 2025. The (theo–context–characteristics–methodology TCCM () framework was applied to analyze the theoretical, contextual, characteristic, and methodological gaps in the literature. Results Most of the heavier hits and influential research are found in only a small number of journals and institutions, mainly located in the United States, United Kingdom, and Australia. There is a predominance of the themes of AI ethics, governance, and data protection. New themes, such as AI governance and algorithmic accountability, have become apparent in recent years. Conclusions This study contributes to the research in the area in that it provides a comprehensive overview of the developments in AI ethics and human rights and also notes the major gaps in this area. A future agenda for research using the TCCM framework is presented, whereby a call is made for the integration of formal ethical theories into the sphere, a move to empirical methodologies, and enhancement of the geographic and sectoral spread of research.
in F1000Research on 2026-01-14 09:23:18 UTC.
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Abstract* Background Prostate cancer is one of the most prevalent cancers among men in South Africa, particularly affecting those in rural and underserved communities. Despite growing awareness, late presentation and poor health-seeking behaviour remain significant challenges. Understanding the sociocultural factors that shape men’s experiences and decision-making regarding prostate cancer is essential for improving early detection and care. Objective This study explores the perspectives of prostate cancer survivors and men in the general population on prostate cancer, its prevention, treatment and related health-seeking behaviour in rural South African context. Methods This study adopts a qualitative design. Semi-structured interviews conducted with two purposefully sampled groups: prostate cancer survivors (n=15) and men from the general population with no known diagnosis (n=15), in the OR Tambo District OF THE eastern Cape Province, South Africa. Interviews will be conducted in isiXhosa (the local language), audio recorded, transcribes and translated into English. Data will be analysed thematically using NVivo software. Ethical approval has been obtained from the Walter Sisulu University Human Research Ethics Committee (014/2025), with additional permissions granted by the Eastern Cape Provincial Department of health and Nelson Mandela Academic hospital. Conclusion the findings will contribute to a deeper understanding of individual and community-level factors influencing prostate cancer health-seeking behaviour. This study will generate context-specific qualitative evidence to guide public health policy and prostate cancer awareness campaigns in rural African settings, male-friendly community interventions to promote early detection in rural areas, with broader implications for addressing health inequities in non-communicable disease care.
in F1000Research on 2026-01-14 09:15:01 UTC.
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Background This study evaluated the effects of Curcuma longa on histomorphometric parameters and reticular fiber expression in the testes of methamphetamine-exposed Wistar rats. Methods Twenty-five adult male rats were divided into five groups: Group 1 (Normal Control) received distilled water; Group 2 (Methamphetamine-Only) was administered 5 mg/kg b.w. methamphetamine; Group 3 received methamphetamine alongside a low dose of Curcuma longa extract (100 mg/kg b.w.); Group 4 was given methamphetamine with a medium dose of Curcuma longa extract (200 mg/kg b.w.); and Group 5 received methamphetamine and a high dose of Curcuma longa extract (400 mg/kg b.w.), all treatments were administered for 28 days. Histomorphometric analysis (seminiferous tubular diameter, germinal epithelial height) was conducted using ImageJ software, while reticular fibers were visualized via Gomori’s methenamine silver staining. Results Methamphetamine exposure significantly increased reticular fiber density around seminiferous tubules and dilated tubular diameter compared to other groups (p < 0.05). Curcuma longa treatment dose-dependently reversed these alterations, with the High Dose Curcuma longa treated Group (400 mg/kg) showing reduced reticular fiber expression and restored tubular diameter (247.35 ± 4.40 μm), comparable to the normal control group. Germinal epithelial heights remained statistically unchanged across groups, suggesting shorter intervention periods may limit observable epithelial recovery. Tissue anti-oxidant analysis revealed a significant increase (p < 0.05) in superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and glutathione peroxidase (GPx) levels in the methamphetamine group compared to the control, whereas treatment groups showed significant reductions (p< 0.05) compared to the methamphetamine group. The ameliorative effects of Curcuma longa are attributed to curcumin’s antioxidant and anti-apoptotic properties, which mitigate oxidative stress and extracellular matrix remodeling induced by methamphetamine. Conclusions Curcuma longa attenuates methamphetamine-induced testicular damage, highlighting its potential as a therapeutic adjunct for drug-associated male infertility. Further clinical studies are warranted to validate these findings in human populations.
in F1000Research on 2026-01-14 08:23:55 UTC.