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Background Aggregatibacter actinomycetemcomitans and Enterococcus faecalis are pathogenic bacteria of the oral cavity that cause various diseases such as periodontitis and endodontics. These bacteria are easily resistant to antibiotics. Photodynamic inactivation (PDI) is a method of inactivating microorganisms that utilizes light to activate a photosensitizer agent (PS) that produces reactive oxygen species causing cell lysis. Methods This study used the PDI method with a 405 nm diode laser at various energy density with the addition PS curcumin or chlorophyll Alfalfa, as much as 1.6 mg/ml on A. actinomycetemcomitans and E. faecalis bacteria. Results The study on E. faecalis bacteria showed that the energy density diode laser irradiation of 1.59 J/cm² gave the percentage of E. faecalis bacteria death 36.7% without PS, 69.30% with the addition of chlorophyll Medicago sativa L and 89.42% with the addition of curcumin. Meanwhile, the bacteria A. actinomycetemcomitans showed that the energy density diode laser irradiation of 1.59 J/cm² gave the percentage of bacterial death 35.81% without PS, 64.39% with the addition of chlorophyll Medicago sativa L and 89.82% with the addition of curcumin. PS was critical to the success of the PDI. Conclusions The addition of PS curcumin increased the effectiveness of reducing bacteria E. faecalis and A. actinomycetemcomitans compared to chlorophyll Medicago sativa L.
in F1000Research on 2025-04-04 08:09:26 UTC.
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Science, Volume 388, Issue 6742, April 2025.
in Science on 2025-04-04 07:00:00 UTC.
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Science, Volume 388, Issue 6742, April 2025.
in Science on 2025-04-04 07:00:00 UTC.
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Science, Volume 388, Issue 6742, April 2025.
in Science on 2025-04-04 07:00:00 UTC.
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Science, Volume 388, Issue 6742, April 2025.
in Science on 2025-04-04 07:00:00 UTC.
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Science, Volume 388, Issue 6742, April 2025.
in Science on 2025-04-04 07:00:00 UTC.
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Science, Volume 388, Issue 6742, April 2025.
in Science on 2025-04-04 07:00:00 UTC.
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Science, Volume 388, Issue 6742, April 2025.
in Science on 2025-04-04 07:00:00 UTC.
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arXiv:2504.02171v1 Announce Type: cross
Abstract: A fundamental characteristic of excitable systems is their ability to exhibit distinct subthreshold and suprathreshold behaviors. Precisely quantifying this distinction requires a proper definition of the threshold, which has remained elusive in neurodynamics. In this paper, we introduce a novel, energy-based threshold definition for excitable circuits grounded in dissipativity theory, specifically using the classical concept of required supply. According to our definition, the threshold corresponds to a local maximum of the required supply, clearly separating subthreshold passive responses from suprathreshold regenerative spikes. We illustrate and validate the proposed definition through analytical and numerical studies of three canonical systems: a simple RC circuit, the FitzHugh--Nagumo model, and the biophysically detailed Hodgkin--Huxley model.
in arXiv: Quantitative Biology: Neurons and Cognition on 2025-04-04 04:00:00 UTC.
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arXiv:2503.21611v4 Announce Type: replace
Abstract: This paper presents an analysis of the orientation selectivity properties of idealized models of complex cells in terms of affine quasi quadrature measures, which combine the responses of idealized models of simple cells in terms of affine Gaussian derivatives by (i) pointwise squaring, (ii) summation of responses for different orders of spatial derivation and (iii) spatial integration. Specifically, this paper explores the consequences of assuming that the family of spatial receptive fields should be covariant under spatial affine transformations, thereby implying that the receptive fields ought to span a variability over the degree of elongation.
We investigate the theoretical properties of three main ways of defining idealized models of complex cells and compare the predictions from these models to neurophysiologically obtained receptive field histograms over the resultant of biological orientation selectivity curves. It is shown that the extended modelling mechanism lead to more uniform behaviour and a wider span over the values of the resultat that are covered, compared to earlier presented idealized models of complex cells without spatial integration.
More generally, we propose (i) to include a variability over the degree of elongation of the receptive fields in functional models of complex cells, and that (ii) the presented methodology with comparisons to biological orientation selectivity curves and orientation selectivity histograms could be used as a new tool to evaluate other computational models of complex cells in relation to biological measurements.
in arXiv: Quantitative Biology: Neurons and Cognition on 2025-04-04 04:00:00 UTC.
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arXiv:2504.02280v1 Announce Type: new
Abstract: In machine learning, Neural Architecture Search (NAS) requires domain knowledge of model design and a large amount of trial-and-error to achieve promising performance. Meanwhile, evolutionary algorithms have traditionally relied on fixed rules and pre-defined building blocks. The Large Language Model (LLM)-Guided Evolution (GE) framework transformed this approach by incorporating LLMs to directly modify model source code for image classification algorithms on CIFAR data and intelligently guide mutations and crossovers. A key element of LLM-GE is the "Evolution of Thought" (EoT) technique, which establishes feedback loops, allowing LLMs to refine their decisions iteratively based on how previous operations performed. In this study, we perform NAS for object detection by improving LLM-GE to modify the architecture of You Only Look Once (YOLO) models to enhance performance on the KITTI dataset. Our approach intelligently adjusts the design and settings of YOLO to find the optimal algorithms against objective such as detection accuracy and speed. We show that LLM-GE produced variants with significant performance improvements, such as an increase in Mean Average Precision from 92.5% to 94.5%. This result highlights the flexibility and effectiveness of LLM-GE on real-world challenges, offering a novel paradigm for automated machine learning that combines LLM-driven reasoning with evolutionary strategies.
in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-04-04 04:00:00 UTC.
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arXiv:2504.02221v1 Announce Type: cross
Abstract: A novel approach to learning is presented, combining features of on-line and off-line methods to achieve considerable performance in the task of learning a backgammon value function in a process that exploits the processing power of parallel supercomputers. The off-line methods comprise a set of techniques for parallelizing neural network training and $TD(\lambda)$ reinforcement learning; here Monte-Carlo ``Rollouts'' are introduced as a massively parallel on-line policy improvement technique which applies resources to the decision points encountered during the search of the game tree to further augment the learned value function estimate. A level of play roughly as good as, or possibly better than, the current champion human and computer backgammon players has been achieved in a short period of learning.
in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-04-04 04:00:00 UTC.
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arXiv:2504.02654v1 Announce Type: cross
Abstract: We propose a learning architecture that allows symbolic control and guidance in reinforcement learning with deep neural networks. We introduce SymDQN, a novel modular approach that augments the existing Dueling Deep Q-Networks (DuelDQN) architecture with modules based on the neuro-symbolic framework of Logic Tensor Networks (LTNs). The modules guide action policy learning and allow reinforcement learning agents to display behaviour consistent with reasoning about the environment. Our experiment is an ablation study performed on the modules. It is conducted in a reinforcement learning environment of a 5x5 grid navigated by an agent that encounters various shapes, each associated with a given reward. The underlying DuelDQN attempts to learn the optimal behaviour of the agent in this environment, while the modules facilitate shape recognition and reward prediction. We show that our architecture significantly improves learning, both in terms of performance and the precision of the agent. The modularity of SymDQN allows reflecting on the intricacies and complexities of combining neural and symbolic approaches in reinforcement learning.
in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-04-04 04:00:00 UTC.
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arXiv:2504.02781v1 Announce Type: cross
Abstract: Optimization of radio hardware and AI-based network management software yield significant energy savings in radio access networks. The execution of underlying Machine Learning (ML) models, which enable energy savings through recommended actions, may require additional compute and energy, highlighting the opportunity to explore and adopt accurate and energy-efficient ML technologies. This work evaluates the novel use of sparsely structured Neural Circuit Policies (NCPs) in a use case to estimate the energy consumption of base stations. Sparsity in ML models yields reduced memory, computation and energy demand, hence facilitating a low-cost and scalable solution. We also evaluate the generalization capability of NCPs in comparison to traditional and widely used ML models such as Long Short Term Memory (LSTM), via quantifying their sensitivity to varying model hyper-parameters (HPs). NCPs demonstrated a clear reduction in computational overhead and energy consumption. Moreover, results indicated that the NCPs are robust to varying HPs such as number of epochs and neurons in each layer, making them a suitable option to ease model management and to reduce energy consumption in Machine Learning Operations (MLOps) in telecommunications.
in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-04-04 04:00:00 UTC.
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arXiv:2501.02906v3 Announce Type: replace
Abstract: Generalization is the core objective when training optimizers from data. However, limited training instances often constrain the generalization capability of the trained optimizers. Co-evolutionary approaches address this challenge by simultaneously evolving a parallel algorithm portfolio (PAP) and an instance population to eventually obtain PAPs with good generalization. Yet, when applied to a specific problem class, these approaches have a major limitation. They require practitioners to provide instance generators specially tailored to the problem class, which is often non-trivial to design. This work proposes a general-purpose, off-the-shelf PAP construction approach, named domain-agnostic co-evolution of parameterized search (DACE), for binary optimization problems where decision variables take values of 0 or 1. The key novelty of DACE lies in its neural network-based domain-agnostic instance representation and generation mechanism that eliminates the need for domain-specific instance generators. The strong generality of DACE is validated across three real-world binary optimization problems: the complementary influence maximization problem (CIMP), the compiler arguments optimization problem (CAOP), and the contamination control problem (CCP). Given only a small set of training instances from these problem classes, DACE, without requiring domain knowledge, constructs PAPs with even better generalization performance than existing approaches on all three classes, despite their use of domain-specific instance generators.
in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-04-04 04:00:00 UTC.
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Nature Communications, Published online: 04 April 2025; doi:10.1038/s41467-025-58509-8
Nanopore electrical detection has shown potential in sensing subtle protein and peptide conformation changes, and its sensitivity makes it promising for point-of-care applications. In this Review, the authors discuss the capability of nanopore sensing for detecting and quantifying conformational modifications and enantiomers in biomarker proteins and peptides, as well as the practicalities and challenges for this approach to be used for clinical and point-of-care diagnosis.
in Nature Communications on 2025-04-04 00:00:00 UTC.
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Nature Communications, Published online: 04 April 2025; doi:10.1038/s41467-025-58385-2
The porous solid electrolyte (PSE) reactor for hydrogen peroxide (H2O2) electrosynthesis has gained global interest but is challenging to scale up. Here, the authors optimize the reactor design and develop a stacked PSE reactor with a total electrode area of 1200 cm2 for efficient H2O2 production.
in Nature Communications on 2025-04-04 00:00:00 UTC.
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Nature Communications, Published online: 04 April 2025; doi:10.1038/s41467-025-58357-6
Smoking remains a leading cause of preventable death and disease. Here, the authors explore the link between smoking and DNA methylation using arrays and next generation sequencing, and develop mCigarette, an epigenetic biomarker of smoking.
in Nature Communications on 2025-04-04 00:00:00 UTC.
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Nature Communications, Published online: 04 April 2025; doi:10.1038/s41467-025-58421-1
How the motor cortex adapts to the changing environments remains unclear. Here, the authors show that continuous sensorimotor transformations enhance the motor cortex’s resilience to intracortical microstimulation perturbations during preparation for manual interception.
in Nature Communications on 2025-04-04 00:00:00 UTC.
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Characterized by a highly complex branching of their dendrites, Purkinje cells (PCs) have a unique architecture that enables them to receive impressive amounts of sensorimotor information through their parallel fiber (PF) input. They are tasked to encode this information with high accuracy. In this work, we discuss the mechanisms through which PCs encode this information, and we show how they multiplex between linear-rate and burst-pause coding. Particularly, somatic pauses are of utmost importance due to their involvement in learning. Using a novel heterogeneous model, we show that all branches can achieve a burst-pause response in response to branch-specific PF clustered input. We quantify the somatic pauses obtained and propose various mechanisms to alter the pause duration. Firstly, our results show that increasing local SK2 channel conductance density systematically increases pause duration. In four branches somatic pauses occurred only when SK2 conductance was increased. Interestingly, when adding feed-forward inhibition via stellate cells, our results show either an increase or a decrease in somatic pauses, highlighting the important role of branch morphology and branch location within the PC.
in bioRxiv: Neuroscience on 2025-04-04 00:00:00 UTC.
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The calyx of Held, a giant excitatory cup-like axo-somatic synapse, has been historically described exclusively in the auditory brainstem. Here, using PACAP immunohistochemistry combined with confocal and tomographic electron microscopy, we report the discovery of a morphologically similar calyx-like synapse in the extended amygdala of rodents, exhibiting unique neurochemical features. This previously unrecognized structure forms massive axo-somatic terminals with mixed glutamatergic and cholinergic identities, co-expressing VGluT1, VGluT2, VAChT, and the neuropeptides PACAP, CGRP, and neurotensin, along with calretinin in the presynaptic compartment. The postsynaptic targets are a distinct subset of PKC{delta}-expressing neurons that co-express the synaptic adhesion molecule GluD1. Strikingly, GluD1 immunolabeling is concentrated specifically at axo-somatic contact sites apposed to VAChT+ calyceal terminals, but absent at PSD of conventional type I synapse, suggesting a specialized molecular architecture for calyceal synapse. Our findings reveal a previously unknown calyx-like synapse in the forebrain, exhibiting a unique convergence of fast and modulatory transmission with implications for transmission fidelity within emotional-viscerosensory circuits.
in bioRxiv: Neuroscience on 2025-04-04 00:00:00 UTC.
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Background Both term and preterm neonates can develop sepsis, a potentially lethal and life-threatening condition, during the first 28 days of life. Neonatal sepsis accounts for 8% of all neonatal fatalities. This study aimed to evaluate the predictive power of lab-based diagnostic indices for neonatal sepsis in preterm infants. Methods The Systemic Inflammatory Indices of the two groups of preterms – one control group without sepsis and one case group with sepsis–were compared to assess their value in predicting Neonatal Sepsis. Data from 138 preterm neonates were used in the present study. Systemic Inflammatory Indices were calculated and compared from the collected data in both the case and control groups. Results Platelet count, Pan Immune Inflammation Value (PIV), Platelet to Lymphocyte Ratio (PLR) and Systemic Immune Inflammatory Index (SII) were found to be significant predictors of neonatal sepsis. Platelet count had the highest predictive value, with an AUC value of 0.715 and optimal cut-off value of 219500. It had a sensitivity of 75.4 and specificity of 65.2. Conclusion According to this study, sepsis in preterm infants can be predicted by using systemic inflammatory indices. This will aid in early sepsis diagnosis and management and, in turn, reduce neonatal morbidity and mortality associated with sepsis.
in F1000Research on 2025-04-03 17:07:28 UTC.
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The prevalence of Drug Induce Liver Injury (DILI) in Tuberculosis (TB) patients is a critical concern, as it complicates the treatment regimen. The hepatotoxicity of first-line anti-TB drugs such as isoniazid and rifampicin can lead to significant liver damage, which in turn affects the metabolism of these medications, potentially resulting in treatment failure or increased mortality. Given the limited certainty surrounding the clinical outcomes of tuberculosis-associated drug-induced liver injury (TB-DILI), an in-depth evaluation of existing evidence is essential. This systematic review and meta-analysis aimed to assess the clinical outcomes in patients with TB-DILI. Comprehensive searches were conducted across the Scopus, Embase, and PubMed databases, adhering to inclusion criteria derived from the PICOS framework. Keywords related to "drug-induced liver injury" and "tuberculosis," as well as their synonyms, were employed in the search. The Newcastle-Ottawa Scale (NOS) was utilized to assess the risk of bias in observational studies. Data were independently extracted, and the quality of the included studies was evaluated. Relative risk (RR) and tests for heterogeneity were conducted, and results were visualized through RR estimates and forest plots. A total of five studies, encompassing 5,798 patients, were ultimately included in the analysis. This study indicates that TB DILI has no significant risk on 2 months conversion compared to TB Non – DILI patients with RR: 1.03; 95%CI: 0.97–1.03, p<0.31. However, treatment success (RR: 1.11; 95%CI: 1.05–1.18, p<0.0004) and mortality risk (RR: 2.62; 95%CI: 1.14–6.03, p<0.02) were significant in TB Non – DILI patients.
in F1000Research on 2025-04-03 17:06:10 UTC.
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Background ELIXIR is a pan-European public-funded research infrastructure dedicated to life science data. As such, it must demonstrate public value to its funders and stakeholders. We present methods to inventory research publications linked to ELIXIR that have received funding and support, as well as related citation metrics, used as performance metrics for these audiences. Methods To overcome challenges inherent in ELIXIR’s distributed structure, and the fact that those publishing ELIXIR-supported work are typically working part-time on ELIXIR matters, a semi-automated approach, consisting of text-mining followed by manual curation, is presented. A country-level case study (ELIXIR Italy) refines and expands the methods, notably by introducing more granularity in the curation process (e.g. considering all national-level grants, examining affiliations to report publication per institute) and by additionally looking at the scientific impact of the resources developed and operated by the Italian Node of ELIXIR. Results Overall, the methods described in this article have shown to: (1) be repeatable with acceptable levels of accuracy and consistency (notably across curators); (2) require reasonable effort in terms of curation of monthly ‘harvests’ of publications (obtained by text-mining); and (3) to be well-adapted to ELIXIR’s distributed nature. Conclusions Concrete examples are provided of downstream uses of the inventoried publications and their citations, both for ELIXIR as a whole and for the Italian case study. Limitations of the methods are discussed, particularly the challenges associated with using an ‘Open literature’ database (Europe PMC) for the text-mining, and the constraints related to curation capacity. The methods, along with the valuable lessons learned during their development, are sufficiently generic and pragmatic enough to be readily adapted by other similar research infrastructures.
in F1000Research on 2025-04-03 17:04:18 UTC.
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Background The objective was to summarize the methodology used to develop the international minimum data elements for surveillance and Reporting of Musculoskeletal Injuries in the MILitary (ROMMIL) statement. This is a recommended list of elements to be collected and reported when conducting injury surveillance research in military settings. Methods A Delphi methodology was employed to reach consensus. Preliminary steps included conducting a literature review and surveying a convenience sample of military stakeholders to 1) identify barriers and facilitators of military musculoskeletal injury (MSKI) prevention programs, 2) identify relevant knowledge gaps, and 3) establish future research priorities. A sequential three-round Delphi consensus survey followed, including relevant stakeholders from militaries around the world, using results to conduct an asynchronous knowledge user meeting (mixture of in-person and live video conference and recording) to explore the level of agreement among subject matter experts. Knowledge users, including former and current military service members, civilian practitioners working in military health networks, and international subject matter experts having experience with policy, execution, or clinical investigation of MSKI mitigation programs, MSKI diagnoses, and MSKI risk factors in military settings. For each round, participants scored questions on a Likert scale of 1-5. Scores ranged from No Importance (1) to Strong Importance (5). Results Literature review and surveys helped inform the scope of potential variables. Three rounds were necessary to reach minimum consensus. Ninety-five, 65, and 42 respondents participated in the first, second and third rounds, respectively. Conclusions Achieving consensus across relevant knowledge users representing military organizations globally can be challenging. This paper details the methodology employed to reach consensus for a core minimum data elements checklist for conducting MSKI research in military settings and improve data harmonization and scalability efforts. These methods can be used as a resource to assist in future consensus endeavors of similar nature.
in F1000Research on 2025-04-03 17:02:14 UTC.
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Background: Early studies found that the mental health problems rate was relatively high in university students. We aimed to investigate the prevalence of mental problems and associated factors in university students. Methods: We conducted a cross-sectional descriptive study at Supara mental health service in the Faculty of Medicine Vajira Hospital between February 2020 to June 2021. The primary outcome was the prevalence of psychiatric diagnosis according to the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10). The secondary assessments included the Patient Health Questionnaire-9 (PHQ-9), 8 items from the Mini International Neuropsychiatric Interview (MINI) to assess suicidal risk (8Q), , and the Thai Mental Health Indicator (TMHI-15). The prevalence of mental health problems was presented by frequency and percentage. In addition, multivariable regression analysis was used to identify potential predictors of mental health problems. Results: A total of 184 participants (62% female; mean age = 22.49 years (SD 3.93) were recruited. The depressive disorders, adjustment disorders, and anxiety disorders rates were 57.1%, 15.2% and 13.6%, respectively. Grade point averages (GPAs) below 3.0 (OR=3.09, 95%CI: 1.17-8.14) and a family history of mental disorder (OR=3.40, 95%CI: 1.10-10.48) were significant associated factors of moderate to severe mental health problems. Detecting and screening these factors may help the university to provide early detection and treatment for students. Conclusions: Depressive disorders were the most common mental health disorders. Females, low GPAs and a family history of mental disorder were predictors of moderate to severe mental health problems.
in F1000Research on 2025-04-03 16:59:39 UTC.
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Background Multidrug-resistant tuberculosis (MDR TB) affects the physical, psychosocial and inter-relationship structure and thus quality of life (QoL) of an individual. WHO QOL BREF is presumed to capture the QoL construct. This study investigates the diagnostic accuracy and construct of WHO QOL BREF from a psychometric perspective and complements and converges findings through classical test theory. Methods The instrument validity study was conducted in a district of Central India amongst the microbiologically confirmed MDR TB cohort of year 2017 (n=98). We calculated global and domain-specific Cronbach alpha and Inter-domain Pearson correlations. The dichotomized items were fitted through Rasch model for item endorsement, response pattern and for variation inconsistencies. Item Characteristic Curves and person item maps were also plotted. We performed DIF (Differential Item Functioning) to check the effect of subgroups on underlying traits. This was complimented with an Exploratory Factor Analysis (EFA) using oblique ProMax rotation. The optimum number of factors were identified by Scree plot and parallel analysis approach and the emerging factor structure was compared with the result obtained through the Rasch model. Results The global Cronbach’s alpha was 0.94 (95% CI 0.92-0.96). Social relationship domain had poor correlations with all three domains (r=0.42, r=0.41 r=0.58), higher beta values and less discrimination. DIF showed a differential response by gender. There was a visual clustering and a non-uniform distribution of items across the perceived QoL. A 3-factor model emerged through EFA and was reframed on the notion of self-concept. Items related to pain, medical aid had significant misfit and weak factor loading while items of sexual activity and social support had relatively poor performance in Infit, Wald, DIF on factor loading parameters. Conclusions The study indicates the possible deviation of scale from theorized dimensional construct in Indian MDR TB context more with the items of the social relationship domain.
in F1000Research on 2025-04-03 16:58:30 UTC.
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Background Health technology assessment (HTA) reports are based on comprehensive information retrieval. Current standards discourage the use of search restrictions, such as publication date and language. Given limited resources, it was unclear whether the effort invested in screening and translating studies published in languages other than English provided relevant additional information compared with the inclusion of English-language publications alone. We therefore analysed the impact of non-English publications on the conclusions of HTA reports produced by the German HTA agency, the Institute for Quality and Efficiency in Health Care (IQWiG). Methods We determined whether non-English publications were included in all German HTA reports on non-drug interventions (published by IQWiG between 06/2007 to 08/2018) and on selected drug interventions. If at least one non-English publication was included, we assessed for each endpoint whether or not the exclusion of non-English publications changed the conclusion. If a non-English publication did not contain information relevant to the HTA report, we classified the publication as “not relevant”. Results Of 70 HTA reports, 38 (54%) included 126 non-English publications. In 4 reports (6%) with 50 endpoints investigated in 39 PICO questions, the exclusion of a total of 10 non-English publications led to a change in the conclusions for 13 endpoints (8 PICO questions). This was largely due to the fact that in many cases, non-English publications were the predominant or only literature available, resulting in a lack of analysable data after their exclusion. Conclusions In general, studies only published in non-English languages have little influence on the conclusions of German HTA reports. For the vast majority of topics, a language restriction to English seems justified. Studies published in non-English languages may be useful in exceptional cases, for example when an intervention is only available in certain countries.
in F1000Research on 2025-04-03 16:55:15 UTC.
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Background It is widely reported that the most prominent emotion following abortions is relief. This claim primarily rests on two studies of abortion clinic patients which had methodological and self-censure bias. Other studies have indicated that negative emotions are more common than positive emotions. The objective of this study is to obtain self-assessed data on the intensity of emotional responses to abortion and pregnancy loss in a random national sample. Methods Using visual analog scales, a random sample of 1,925 women aged 41 to 45 completed a survey in which respondents rated the degree to which they experienced emotional responses to their first abortion or natural pregnancy loss. The emotions assessed included relief, grief, depression, anxiety, guilt, emptiness, anger, regret, shame, unforgiveness of self, uncontrollable weeping, frequent thoughts of the child they could have had, and difficulty completing the grief process. Women were categorized into five groups based on pregnancy outcomes, and four abortion decision types: Wanted, Inconsistent, Unwanted, or Coerced. Results Among women with a history of abortion (n=409), negative emotions were reported more intensely than relief. Relief was the predominant emotion only among the 29.8% of women whose abortions were freely wanted and consistent with their own values and preferences. For all other groups, relief was low and negative emotions were more prominent. Emotions following natural pregnancy losses were similar to those following abortion, but less severe following wanted abortions and more severe following coerced abortions. Conclusions Relief is only common after freely wanted abortions. Most abortions are inconsistent or contrary to women’s own values. In these cases, strong negative emotions are far more dominant than relief. These results should inform pre-abortion screening, counseling supportive of women’s own values and preferences, and mental health support post-abortion.
in F1000Research on 2025-04-03 16:52:54 UTC.
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Background Deaf individuals are considered a high-risk population for health disparities. During the covid-19 epidemic, deaf and hearing loss persons also suffer from psychological issues, post-traumatic stress disorder, and seropositive HIV. Objective This study aims to examine the effectiveness of an mobile health educational program to increase mental health and HIV prevention among deaf community Methods This study employs a quasi-experimental design with a non-randomized controlled trial, involving single-blinded participants and a parallel group assignment, purpose for health service research, study phase 2-3. pronounced to escalate the sample size to 40 deaf per group, which is 80 total participants. Results The analysis of the data will be conducted utilizing the generalized estimation equation, with a confidence interval set at 95%. Significant differences, both between and within groups, will be identified at a threshold of P<.05. The findings of this study highlight the efficacy of a mobile educational program in enhancing mental health and preventing HIV within the deaf community. Furthermore, the outcomes of this research will augment existing knowledge regarding psychological distress, HIV prevention practices, and coping self-efficacy among individuals who are deaf. Conclusion The intervention group is expected to demonstrate significantly lower scores in psychological distress during both the immediate evaluation and the assessment conducted three months post-intervention, compared to the wait-list group. Additionally, the intervention group is anticipated to exhibit enhanced levels of HIV prevention practices and coping self-efficacy, resulting in a greater degree of adjustment. Clinical trial SLCTR/2024/039, 25 November 2024, https://slctr.lk/trials/slctr-2024-039
in F1000Research on 2025-04-03 16:51:27 UTC.
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Background Polyetheretherketone (PEEK) is widely used in the biomedical field due to its outstanding biological and mechanical properties. Originally employed as a temporary abutment in implantology, recent research has expanded its indications for more definitive applications, such as frameworks and dental post and core. However, PEEK’s inert nature and low surface energy pose challenges for adhesion, necessitating surface modifications. Various physical and chemical modification techniques, including acid etching (e.g., 98% sulfuric acid), sandblasting with alumina oxide (Al₂O₃), plasma treatment, laser irradiation, silanization, and air abrasion with silica-coated particles, have been proposed to enhance PEEK’s bonding performance. Despite numerous clinical investigations, standardized protocols for surface treatment remain lacking. This systematic review aims to assess the impact of surface treatments on the bonding performance of PEEK posts. Methods A detailed search of the literature will be conducted across several databases including PubMed, Scopus and clinical trial registries. Additional databases such as Cochrane Central, EMBASE, Web of Science and EBSCO will also be included. The search strategy will target controlled randomized studies and non-randomized clinical trials evaluating the impact of surface treatments on PEEK post adhesion strength. The Newcastle-Ottawa Scale (NOS) will be used to assess bias in non-randomized studies, while the Cochrane Risk of Bias (ROB II) tool will be employed for evaluating randomized controlled trials. Data extraction will focus on study design, treatment methods, outcomes and results. This systematic review protocol will adhere to the guidelines for systematic reviews outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Discussion The discussion will explore the implications of findings on clinical practice, highlighting the importance of enhancing PEEK’s bioactivity and surface energy to improve bonding efficacy in dental procedures. Moreover, it will suggest areas for future research to advance dental materials science, aiming to optimize the utilization of PEEK in dental applications Systematic review registration PROSPERO: CRD42024529783 (Registered on 08/04/2024).
in F1000Research on 2025-04-03 16:49:48 UTC.
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Background Traditional dietary assessments are often inaccurate and prone to self-reporting biases. Tracking the physiological responses associated with eating and digestion events via wearable technologies may provide an effective approach for continuously monitoring food intake and estimating energy consumption. Eating and digestion are accompanied by a series of changes in the heart rate, skin temperature, blood oxygen saturation, and blood pressure. These changes can be tracked by wearable devices, such as smartwatches, which have been widely accepted in the market. This systematic review is the first to evaluate the effectiveness of tracking such physiological biomarkers in differentiating between high- and low-calorie meals, potentially paving the way for more accurate dietary monitoring. Methods Following the PRISMA-P guidelines, we will conduct a systematic literature search through MEDLINE, EMBASE, and PubMed for clinical trials that investigated physiological responses following meal intake in healthy subjects. Two independent reviewers will screen and select articles based on pre-defined eligibility criteria, with a third review to resolve any discrepancies. This will be followed by data extraction and quality assessment of the included studies. Statistical analyses, including meta-analyses, will be performed using R Studio software. Our primary outcome will be the comparison of physiological biomarkers before and after meal intake, while secondary outcomes will include comparisons of physiological biomarkers between high- and low-calorie meal consumption and the correlation between the caloric content of consumed meals and postprandial physiological changes. Discussion This systematic review and meta-analysis will identify physiological indicators for eating events and inform the design of wearable sensors that estimate food intake in healthy subjects. Systematic Review Registration PROSPERO Registration ID: CRD42024544353
in F1000Research on 2025-04-03 16:47:32 UTC.
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Background Comparing non-randomized groups, such as COVID-19 vaccinated and unvaccinated, even in the presence of seemingly relevant control variables, is challenging, but in this study, using English data, I show an achievable approach. Methods First, I estimated age-standardized all-cause mortality among vaccinated and unvaccinated ten years and older, covering 26 months from Apr 21 to May 23. Then, I estimated mortality not involving COVID-19, and finally, I differentiated the calculations. Results First, I found that all-cause mortality among unvaccinated was higher than among vaccinated. But, as the pattern was similar concerning mortality not involving COVID-19, the discrepancy is attributed mainly to unvaccinated having inferior health at the outset. There was nonetheless significant protection for vaccinated between July 21 and Jan 22. Absent of control variables as a means to compare non-randomized groups, I reached that finding by differentiating all-cause mortality from mortality not involving COVID-19. However, while mortality not involving COVID-19 decreased among unvaccinated compared to the first observation month, it was high among vaccinated, i.e., a relative increase in mortality among vaccinated. Conclusions An interpretation is that vaccination, despite temporary protection, increased mortality. Strengthening the interpretation was relatively high mortality among vaccinated not involving COVID-19 counterintuitively following periods of excess mortality. Further strengthening the interpretation was relatively high mortality not involving COVID-19 among vaccinated, corresponding with excess mortality during much of the same period. An implication of the study, which particularly has relevance for future pandemics, is that vaccinated may have a limited time window of protection and can even be exposed to detrimental health consequences. The pattern should be followed up over an extended period in future research. Also, future research should examine different age groups, vaccination types, and the number of doses given.
in F1000Research on 2025-04-03 15:12:51 UTC.
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Background Elevated levels of carbon dioxide (CO2) within academic settings can adversely affect the health and academic efficacy of both students and faculty. High concentrations of CO2 are correlated with reduced cognitive functioning, compromised decision-making abilities, diminished academic performance, and various health-related issues. The escalating apprehensions regarding the detrimental health consequences of air pollution have precipitated an increase in research focused on air quality assessment and amelioration. Method The investigation utilized Internet of Things (IoT) devices that were outfitted with sensors to gather data on various environmental parameters, such as temperature, humidity, CO2 concentrations, and light intensity. This data underwent analysis through the application of summary statistics to delineate the dataset and to visualize the distribution of variables via scatter matrix plots. Result The dataset obtained, which encompasses essential air quality and environmental parameters, is now accessible to the public through the Mendeley repository. The analytical findings illuminated significant characteristics of the data concerning CO2 levels and their prospective ramifications on the academic milieu. Conclusion The amalgamation of IoT technology with summary statistical analysis presents a promising methodology for the real-time surveillance of air quality. This approach yields critical insights into the health and academic ramifications of heightened CO2 levels within educational environments, underscoring the necessity for ongoing air quality monitoring to enhance campus conditions.
in F1000Research on 2025-04-03 14:38:30 UTC.
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Background The burden of sexually transmitted infections (STIs) and unintended pregnancy remains a significant public health concern, with young women being disproportionately affected. While both risks can be prevented simultaneously by the same safe sexual practice, such as abstinence or dual protection use, little is known about the patterns and predictors of a range of safer sexual dual protection behaviors among youth based on theoretical models in Ethiopia. This study aimed to examine the effects of information-motivation-behavioral skills (IMB) model in predicting various safer sexual dual protection behaviors, including primary sexual abstinence and dual-protection use among female university students in Ethiopia. Methods A cross-sectional study was conducted among female university students at MattuUniversity. Data were collected using a self-administered questionnaire and analyzed using SPSS version 23. Bivariate and multivariate analyses were conducted using structural equation modeling (SEM) with AMOS 23. Results Of the 1,020 participants, 624 (61.2%) practiced primary sexual abstinence, whereas 396 (38.8%) have ever had sexual intercourse, of whom only 76 (20.5%) used dual protection at their last sexual encounter. Results of the structural equation model analysis indicated that primary sexual abstinence was strongly correlated with motivation (β = 0.34, P < 0.001) and behavioralskills (β = 0.24, P < 0.001) and information (β = 0.11, P < 0.001). Among sexually active participants, dual protection use was strongly correlated with motivation (β = 0.23, P < 0.05) and behavioral skills (β = 0.24, P < 0.001), while it was moderately correlated with information (β = 0.04, P < 0.05). Approximately 28% of the variance in primary sexual abstinence and 27.4% of the variance in dual protection use was explained by the model constructs. Conclusions The findings indicate that the IMB model is useful for identifying powerful predictors of sexual abstinence and dual protection use among female university students, which has potential implications for designing interventions to improve knowledge, motivation, behavioral skills and practice of abstinence and/or dual protection use among youth at risk of both STI/HIV and unwanted pregnancy in settings with high HIV burdens.
in F1000Research on 2025-04-03 14:30:35 UTC.
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by Wenqian Tu, Lihua Zhang
Due to the rapid development of spatial sequencing technologies, large amounts of spatial transcriptomic datasets have been generated across various technological platforms or different biological conditions (e.g., control vs. treatment). Spatial transcriptomics data coming from different platforms usually has different resolutions. Moreover, current methods do not consider the heterogeneity of spatial structures within and across slices when modeling spatial transcriptomics data with graph-based methods. In this study, we propose a community-enhanced graph contrastive learning-based method named Tacos to integrate multiple spatial transcriptomics data. We applied Tacos to several real datasets coming from different platforms under different scenarios. Systematic benchmark analyses demonstrate Tacos’s superior performance in integrating different slices. Furthermore, Tacos can accurately denoise the spatially resolved transcriptomics data.
in PLoS Computational Biology on 2025-04-03 14:00:00 UTC.
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by Khanh N. Dinh, Ignacio Vázquez-García, Andrew Chan, Rhea Malhotra, Adam Weiner, Andrew W. McPherson, Simon Tavaré
Cancer development is characterized by chromosomal instability, manifesting in frequent occurrences of different genomic alteration mechanisms ranging in extent and impact. Mathematical modeling can help evaluate the role of each mutational process during tumor progression, however existing frameworks can only capture certain aspects of chromosomal instability (CIN). We present CINner, a mathematical framework for modeling genomic diversity and selection during tumor evolution. The main advantage of CINner is its flexibility to incorporate many genomic events that directly impact cellular fitness, from driver gene mutations to copy number alterations (CNAs), including focal amplifications and deletions, missegregations and whole-genome duplication (WGD). We apply CINner to find chromosome-arm selection parameters that drive tumorigenesis in the absence of WGD in chromosomally stable cancer types from the Pan-Cancer Analysis of Whole Genomes (PCAWG, n=718 ). We found that the selection parameters predict WGD prevalence among different chromosomally unstable tumors, hinting that the selective advantage of WGD cells hinges on their tolerance for aneuploidy and escape from nullisomy. Analysis of inference results using CINner across cancer types in The Cancer Genome Atlas (n=8207) further reveals that the inferred selection parameters reflect the bias between tumor suppressor genes and oncogenes on specific genomic regions. Direct application of CINner to model the WGD proportion and fraction of genome altered (FGA) in PCAWG uncovers the increase in CNA probabilities associated with WGD in each cancer type. CINner can also be utilized to study chromosomally stable cancer types, by applying a selection model based on driver gene mutations and focal amplifications or deletions (chronic lymphocytic leukemia in PCAWG, n=95). Finally, we used CINner to analyze the impact of CNA probabilities, chromosome selection parameters, tumor growth dynamics and population size on cancer fitness and heterogeneity. We expect that CINner will provide a powerful modeling tool for the oncology community to quantify the impact of newly uncovered genomic alteration mechanisms on shaping tumor progression and adaptation.
in PLoS Computational Biology on 2025-04-03 14:00:00 UTC.
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by Daniel J.B. Clarke, John Erol Evangelista, Zhuorui Xie, Giacomo B. Marino, Anna I. Byrd, Mano R. Maurya, Sumana Srinivasan, Keyang Yu, Varduhi Petrosyan, Matthew E. Roth, Miroslav Milinkov, Charles Hadley King, Jeet Kiran Vora, Jonathon Keeney, Christopher Nemarich, William Khan, Alexander Lachmann, Nasheath Ahmed, Alexandra Agris, Juncheng Pan, Srinivasan Ramachandran, Eoin Fahy, Emmanuel Esquivel, Aleksandar Mihajlovic, Bosko Jevtic, Vuk Milinovic, Sean Kim, Patrick McNeely, Tianyi Wang, Eric Wenger, Miguel A. Brown, Alexander Sickler, Yuankun Zhu, Sherry L. Jenkins, Philip D. Blood, Deanne M. Taylor, Adam C. Resnick, Raja Mazumder, Aleksandar Milosavljevic, Shankar Subramaniam, Avi Ma’ayan
The Playbook Workflow Builder (PWB) is a web-based platform to dynamically construct and execute bioinformatics workflows by utilizing a growing network of input datasets, semantically annotated API endpoints, and data visualization tools contributed by an ecosystem of collaborators. Via a user-friendly user interface, workflows can be constructed from contributed building-blocks without technical expertise. The output of each step of the workflow is added into reports containing textual descriptions, figures, tables, and references. To construct workflows, users can click on cards that represent each step in a workflow, or construct workflows via a chat interface that is assisted by a large language model (LLM). Completed workflows are compatible with Common Workflow Language (CWL) and can be published as research publications, slideshows, and posters. To demonstrate how the PWB generates meaningful hypotheses that draw knowledge from across multiple resources, we present several use cases. For example, one of these use cases prioritizes drug targets for individual cancer patients using data from the NIH Common Fund programs GTEx, LINCS, Metabolomics, GlyGen, and ExRNA. The workflows created with PWB can be repurposed to tackle similar use cases using different inputs. The PWB platform is available from: https://playbook-workflow-builder.cloud/.
in PLoS Computational Biology on 2025-04-03 14:00:00 UTC.
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by Wenwen Min, Donghai Fang, Jinyu Chen, Shihua Zhang
Understanding the spatial locations of cell within tissues is crucial for unraveling the organization of cellular diversity. Recent advancements in spatial resolved transcriptomics (SRT) have enabled the analysis of gene expression while preserving the spatial context within tissues. Spatial domain characterization is a critical first step in SRT data analysis, providing the foundation for subsequent analyses and insights into biological implications. Graph neural networks (GNNs) have emerged as a common tool for addressing this challenge due to the structural nature of SRT data. However, current graph-based deep learning approaches often overlook the instability caused by the high sparsity of SRT data. Masking mechanisms, as an effective self-supervised learning strategy, can enhance the robustness of these models. To this end, we propose SpaMask, dual masking graph autoencoder with contrastive learning for SRT analysis. Unlike previous GNNs, SpaMask masks a portion of spot nodes and spot-to-spot edges to enhance its performance and robustness. SpaMask combines Masked Graph Autoencoders (MGAE) and Masked Graph Contrastive Learning (MGCL) modules, with MGAE using node masking to leverage spatial neighbors for improved clustering accuracy, while MGCL applies edge masking to create a contrastive loss framework that tightens embeddings of adjacent nodes based on spatial proximity and feature similarity. We conducted a comprehensive evaluation of SpaMask on eight datasets from five different platforms. Compared to existing methods, SpaMask achieves superior clustering accuracy and effective batch correction.
in PLoS Computational Biology on 2025-04-03 14:00:00 UTC.
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by Shiwei Fu, Wei Vivian Li
The advent of 5’ single-cell RNA sequencing (scRNA-seq) technologies offers unique opportunities to identify and analyze transcription start sites (TSSs) at a single-cell resolution. These technologies have the potential to uncover the complexities of transcription initiation and alternative TSS usage across different cell types and conditions. Despite the emergence of computational methods designed to analyze 5’ RNA sequencing data, current methods often lack comparative evaluations in single-cell contexts and are predominantly tailored for paired-end data, neglecting the potential of single-end data. This study introduces scTSS, a computational pipeline developed to bridge this gap by accommodating both paired-end and single-end 5’ scRNA-seq data. scTSS enables joint analysis of multiple single-cell samples, starting with TSS cluster prediction and quantification, followed by differential TSS usage analysis. It employs a Binomial generalized linear mixed model to accurately and efficiently detect differential TSS usage. We demonstrate the utility of scTSS through its application in analyzing transcriptional initiation from single-cell data of two distinct diseases. The results illustrate scTSS’s ability to discern alternative TSS usage between different cell types or biological conditions and to identify cell subpopulations characterized by unique TSS-level expression profiles.
in PLoS Computational Biology on 2025-04-03 14:00:00 UTC.
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by Cecilia Fruet, Ella Linxia Müller, Claude Loverdo, Anne-Florence Bitbol
Bacterial populations often have complex spatial structures, which can impact their evolution. Here, we study how spatial structure affects the evolution of antibiotic resistance in a bacterial population. We consider a minimal model of spatially structured populations where all demes (i.e., subpopulations) are identical and connected to each other by identical migration rates. We show that spatial structure can facilitate the survival of a bacterial population to antibiotic treatment, starting from a sensitive inoculum. Specifically, the bacterial population can be rescued if antibiotic resistant mutants appear and are present when drug is added, and spatial structure can impact the fate of these mutants and the probability that they are present. Indeed, the probability of fixation of neutral or deleterious mutations providing drug resistance is increased in smaller populations. This promotes local fixation of resistant mutants in the structured population, which facilitates evolutionary rescue by drug resistance in the rare mutation regime. Once the population is rescued by resistance, migrations allow resistant mutants to spread in all demes. Our main result that spatial structure facilitates evolutionary rescue by antibiotic resistance extends to more complex spatial structures, and to the case where there are resistant mutants in the inoculum.
in PLoS Computational Biology on 2025-04-03 14:00:00 UTC.
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by Daniel T. Blumstein
Can we ever have too much ecological field data? Are data-sharing norms and the environmental costs of travel disincentivizing its collection? Allocating proper funding and resources to the collection of long-term ecological data is essential for studies of behavior and adaptation, which are particularly important in the face of anthropogenic change.
in PLoS Biology on 2025-04-03 14:00:00 UTC.
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by Chaoqiong Ding, Zhenzhong Pan, Xiang Yan, Ran Zhou, Huifang Li, Lu Chen, Yuan Wang, Yan Zhang
Quiescent neural stem cells (qNSCs) in the adult mouse subventricular zone (SVZ) normally have limited capacity to generate glia. Gliogenic domains are present in both dorsal and ventral SVZ, with the ventral region featuring a subpopulation of Gli1+ qNSCs. In dorsal SVZ, however, the molecular identity and developmental origin of oligodendrogenic qNSCs remains elusive. Here, through single-cell analysis and lineage tracing, we identify an undefined subpopulation of Gas1high qNSCs in dorsal SVZ, distinct from Gli1+ qNSCs. These cells originate from embryonic Gas1high dorsal radial glia, and persist into the aged SVZ. Remarkably, they are multipotent and more gliogenic than Gas1low/− qNSCs, continuously generating oligodendrocytes in the adult and aged brain, and can be mobilized for myelin repair upon demyelination. Together, our study uncovers a subpopulation of dorsally derived, multipotent long-term qNSCs in the adult and aged SVZ with enhanced gliogenic potential, shedding light on the heterogeneity and plasticity of NSCs in normal, aging, and disease conditions.
in PLoS Biology on 2025-04-03 14:00:00 UTC.
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Central nervous system disorders impair information transmission by causing synapse loss and dysfunction. Synaptic plasticity, involving the dynamic strengthening or weakening of synapses, enables brain adaptation. Regulating this process can alleviate disease progression and support synaptic recovery, introducing innovative treatment strategies that restore neural connectivity and improve overall brain function.
ABSTRACT
Mild traumatic brain injury (mTBI) is a common condition, particularly pervasive in contact sports environments. A range of symptoms can accompany this type of injury and negatively impact people's lives. As mTBI diagnosis and recovery largely rely on subjective reports, more objective injury markers are needed. The current study compared structural brain MRI-T2 relaxometry between a group of 40 male athletes with mTBI within 14 days of injury and 40 age-matched male controls. Voxel-averaged T2 relaxometry within the gray matter was increased for the mTBI group compared to controls (p < 0.001), with statistically significant increased T2 relaxometry particularly in superior cortical regions. Our findings indicate subtle brain abnormalities can be identified in acute mTBI using MRI-T2 relaxometry. These brain abnormalities may reflect inflammation present in the brain and could constitute an objective injury marker to supplement current subjective methods that dominate clinical decisions regarding diagnosis and prognosis. Future research should validate this potential marker with other data types, such as blood biomarkers or histological samples.
in Journal of Neuroscience Research on 2025-04-03 13:05:56 UTC.
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Journal of Neurophysiology, Volume 133, Issue 4, Page 1205-1207, April 2025.
in Journal of Neurophysiology on 2025-04-03 11:45:26 UTC.
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Journal of Neurophysiology, Volume 133, Issue 4, Page 1176-1190, April 2025.
in Journal of Neurophysiology on 2025-04-03 11:45:25 UTC.
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Journal of Neurophysiology, Volume 133, Issue 4, Page 1148-1149, April 2025.
in Journal of Neurophysiology on 2025-04-03 11:45:22 UTC.
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Journal of Neurophysiology, Volume 133, Issue 4, Page 1191-1204, April 2025.
in Journal of Neurophysiology on 2025-04-03 11:45:21 UTC.
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Journal of Neurophysiology, Volume 133, Issue 4, Page 1222-1233, April 2025.
in Journal of Neurophysiology on 2025-04-03 11:45:20 UTC.
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Journal of Neurophysiology, Volume 133, Issue 4, Page 1159-1175, April 2025.
in Journal of Neurophysiology on 2025-04-03 11:45:19 UTC.
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Journal of Neurophysiology, Volume 133, Issue 4, Page 1208-1215, April 2025.
in Journal of Neurophysiology on 2025-04-03 11:45:18 UTC.
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Journal of Neurophysiology, Volume 133, Issue 4, Page 1216-1221, April 2025.
in Journal of Neurophysiology on 2025-04-03 11:45:18 UTC.
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Journal of Neurophysiology, Volume 133, Issue 4, Page 1150-1158, April 2025.
in Journal of Neurophysiology on 2025-04-03 11:45:17 UTC.
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Journal of Neurophysiology, Volume 133, Issue 4, Page 1146-1147, April 2025.
in Journal of Neurophysiology on 2025-04-03 11:45:15 UTC.
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Science, Volume 388, Issue 6742, April 2025.
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Science, Volume 388, Issue 6742, April 2025.
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Science, Volume 388, Issue 6742, Page 39-39, April 2025.
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Science, Volume 388, Issue 6742, Page 38-38, April 2025.
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Science, Volume 388, Issue 6742, Page 74-81, April 2025.
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Science, Volume 388, Issue 6742, Page 96-104, April 2025.
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Science, Volume 388, Issue 6742, Page 68-74, April 2025.
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Science, Volume 388, Issue 6742, Page 60-68, April 2025.
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Science, Volume 388, Issue 6742, Page 52-59, April 2025.
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Science, Volume 388, Issue 6742, Page 88-95, April 2025.
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Science, Volume 388, Issue 6742, Page 82-88, April 2025.
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Science, Volume 388, Issue 6742, Page 109-115, April 2025.
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Science, Volume 388, Issue 6742, Page 104-108, April 2025.
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Science, Volume 388, Issue 6742, Page 118-118, April 2025.
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Science, Volume 388, Issue 6742, Page 43-44, April 2025.
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Science, Volume 388, Issue 6742, Page 26-27, April 2025.
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Science, Volume 388, Issue 6742, Page 30-31, April 2025.
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Science, Volume 388, Issue 6742, Page 29-30, April 2025.
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Science, Volume 388, Issue 6742, Page 28-29, April 2025.
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Science, Volume 388, Issue 6742, Page 35-37, April 2025.
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Science, Volume 388, Issue 6742, Page 20-24, April 2025.
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Science, Volume 388, Issue 6742, Page 10-11, April 2025.
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Science, Volume 388, Issue 6742, Page 12-13, April 2025.
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Science, Volume 388, Issue 6742, Page 13-14, April 2025.
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Science, Volume 388, Issue 6742, Page 14-15, April 2025.
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Science, Volume 388, Issue 6742, Page 16-16, April 2025.
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Science, Volume 388, Issue 6742, Page 17-17, April 2025.
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Science, Volume 388, Issue 6742, Page 18-18, April 2025.
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Science, Volume 388, Issue 6742, Page 19-19, April 2025.
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Science, Volume 388, Issue 6742, Page 9-9, April 2025.
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Science, Volume 388, Issue 6742, Page 116-116, April 2025.
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Science, Volume 388, Issue 6742, Page 41-41, April 2025.
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Science, Volume 388, Issue 6742, Page 40-41, April 2025.
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Science, Volume 388, Issue 6742, Page 41-41, April 2025.
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Science, Volume 388, Issue 6742, Page 32-34, April 2025.
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Science, Volume 388, Issue 6742, Page 42-44, April 2025.
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Obesity rates are rapidly rising, driven by overeating because of easy access to ultra-processed foods. We discuss the dichotomy of hedonic and homeostatic feeding circuits and how palatable food impacts synaptic plasticity. A roadmap for novel treatment is emerging.
in Neuron: In press on 2025-04-03 00:00:00 UTC.
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Zhong et al. find that tick feeding capacity is determined by mitochondrial fission in midgut cells that regulates muscle fiber assembly through ATP production.
in Cell Reports: Current Issue on 2025-04-03 00:00:00 UTC.
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The human ribosome is highly modified by protein methylation. Here, Hamey et al. discover SMYD5 as the methyltransferase responsible for trimethylating ribosomal protein RPL40 at lysine 22. Systematic analysis of SMYD5 substrate recognition shows that it targets a KXY motif in RPL40, strongly suggesting that it is not a histone methyltransferase.
in Cell Reports: Current Issue on 2025-04-03 00:00:00 UTC.
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Nature, Published online: 03 April 2025; doi:10.1038/s41586-025-08951-x
Strategic atom replacement enables regiocontrol in pyrazole alkylation
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Nature, Published online: 03 April 2025; doi:10.1038/s41586-025-08954-8
Hidden states and dynamics of fractional fillings in twisted MoTe2 bilayers
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Nature, Published online: 03 April 2025; doi:10.1038/d41586-025-00971-x
Lunar soil processed to form ‘moonglass’ allows the creation of efficient, radiation-resistant solar panels.
in Nature on 2025-04-03 00:00:00 UTC.
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Nature, Published online: 03 April 2025; doi:10.1038/d41586-025-01031-0
The new administration is reshaping the research landscape in the United States in profound ways. What do you think of all the changes?
in Nature on 2025-04-03 00:00:00 UTC.
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Nature, Published online: 03 April 2025; doi:10.1038/d41586-025-01021-2
In a world of constant stimulation, the thalamus filters which thoughts we become aware of and which we don’t.
in Nature on 2025-04-03 00:00:00 UTC.
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Nature, Published online: 03 April 2025; doi:10.1038/d41586-025-01029-8
After cancelling nearly all NIH projects studying transgender health, Trump’s team instructs the US biomedical agency to study negative consequences of transitioning.
in Nature on 2025-04-03 00:00:00 UTC.
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Nature, Published online: 03 April 2025; doi:10.1038/d41586-025-01010-5
Dozens of problematic papers remain in the literature, after a publication hit by fraudsters pledged to tackle the issue.
in Nature on 2025-04-03 00:00:00 UTC.
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Nature Neuroscience, Published online: 03 April 2025; doi:10.1038/s41593-025-01907-4
Sun et al. report human lifespan changes in the brain’s functional connectome in 33,250 individuals, which highlights critical growth milestones and distinct maturation patterns and offers a normative reference for development, aging and diseases.
in Nature Neuroscience on 2025-04-03 00:00:00 UTC.
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Nature Photonics, Published online: 03 April 2025; doi:10.1038/s41566-025-01655-8
Breaking down plastics with light
in Nature Photomics on 2025-04-03 00:00:00 UTC.
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Nature Photonics, Published online: 03 April 2025; doi:10.1038/s41566-025-01649-6
A vernier dual frequency comb provides a chip-based highly precise reference between the optical and radio frequency domains.
in Nature Photomics on 2025-04-03 00:00:00 UTC.
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Nature Photonics, Published online: 03 April 2025; doi:10.1038/s41566-025-01656-7
Two-dimensional materials have revolutionized the field of photonics by enabling the manipulation of light at the nanoscale. As their potential continues to grow, we can expect to see more innovative applications emerging in the future.
in Nature Photomics on 2025-04-03 00:00:00 UTC.
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Nature Photonics, Published online: 03 April 2025; doi:10.1038/s41566-025-01647-8
Continuing the diversity conversation
in Nature Photomics on 2025-04-03 00:00:00 UTC.
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Nature Photonics, Published online: 03 April 2025; doi:10.1038/s41566-025-01654-9
Neuromorphic photonic systems mimicking biological neurons promise to boost the efficiency of light-based computing.
in Nature Photomics on 2025-04-03 00:00:00 UTC.
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Nature Photonics, Published online: 03 April 2025; doi:10.1038/s41566-025-01652-x
An angular Fourier optics framework has been established and demonstrated, unlocking unprecedented opportunities for the analysis and manipulation of light waves carrying orbital angular momentum.
in Nature Photomics on 2025-04-03 00:00:00 UTC.
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Nature Photonics, Published online: 03 April 2025; doi:10.1038/s41566-025-01641-0
Intrinsically polarized white-light emission is highly demanded for many applications. It is now possible to realize it via a bimolecular doping strategy of organic semiconductor single crystals, overcoming long-standing limitations in organic emitters.
in Nature Photomics on 2025-04-03 00:00:00 UTC.
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Nature Photonics, Published online: 03 April 2025; doi:10.1038/s41566-025-01650-z
By integrating a moiré photonic structure on-chip with advanced microelectromechanical system (MEMS) technology, an in situ twisted moiré photonic platform that can be tuned is realized, enabling nanometre-scale positioning of two optical nanostructures in either the near- or far-field coupling regime.
in Nature Photomics on 2025-04-03 00:00:00 UTC.
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Nature Methods, Published online: 03 April 2025; doi:10.1038/s41592-025-02637-y
xTrimoPGLM, a protein language model scaled to 100 billion parameters, showcased scaling behavior to excel in various protein-related tasks. This development advances protein understanding and design, and contributes to the evolving landscape of comprehensive models designed to serve as a base for various specialized tasks (foundation models) in protein science.
in Nature Methods on 2025-04-03 00:00:00 UTC.
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Nature Methods, Published online: 03 April 2025; doi:10.1038/s41592-025-02636-z
xTrimo protein general language model (xTrimoPGLM) is a unified pretraining framework and foundation model designed for various protein-related tasks, including protein understanding and generation or design.
in Nature Methods on 2025-04-03 00:00:00 UTC.
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Nature Communications, Published online: 03 April 2025; doi:10.1038/s41467-025-58580-1
Author Correction: The dynamics of plasmon-induced hot carrier creation in colloidal gold
in Nature Communications on 2025-04-03 00:00:00 UTC.
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Nature Communications, Published online: 03 April 2025; doi:10.1038/s41467-025-58564-1
Author Correction: Marine biogenic humic substances control iron biogeochemistry across the Southern Ocean
in Nature Communications on 2025-04-03 00:00:00 UTC.
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Nature Communications, Published online: 03 April 2025; doi:10.1038/s41467-025-58601-z
Author Correction: “Pink power”—the importance of coralline algal beds in the oceanic carbon cycle
in Nature Communications on 2025-04-03 00:00:00 UTC.
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Nature Communications, Published online: 03 April 2025; doi:10.1038/s41467-025-58241-3
Here, the authors describe an N-heterocyclic carbene and chiral phosphoric acid dual-catalytic process for the desymmetrization of 1,3-diols, to achieve macrocyclization and stereoselective control over two chiral elements.
in Nature Communications on 2025-04-03 00:00:00 UTC.
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Nature Physics, Published online: 03 April 2025; doi:10.1038/s41567-025-02831-x
Nodes in a quantum network must be able to interface with photonic qubits as well as perform local quantum computations. The quantum node device presented here is capable of storing quantum information and correcting bit-flip errors.
in Nature Physics on 2025-04-03 00:00:00 UTC.
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Scientific Data, Published online: 03 April 2025; doi:10.1038/s41597-025-04930-z
High-resolution fundus images for ophthalmomics and early cardiovascular disease prediction
in Nature scientific data on 2025-04-03 00:00:00 UTC.
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Scientific Data, Published online: 03 April 2025; doi:10.1038/s41597-025-04827-x
Chromosome-scale genome assembly of Zoysia japonica uncovers cold tolerance candidate genes
in Nature scientific data on 2025-04-03 00:00:00 UTC.
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Scientific Data, Published online: 03 April 2025; doi:10.1038/s41597-025-04782-7
Fast Single-Particle Tracking of Membrane Proteins Combined with Super-Resolution Imaging of Actin Nanodomains
in Nature scientific data on 2025-04-03 00:00:00 UTC.
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Scientific Data, Published online: 03 April 2025; doi:10.1038/s41597-025-04865-5
A Multisensor Dataset of South Asian Post-Graduate Students Working on Mental Rotation Tasks
in Nature scientific data on 2025-04-03 00:00:00 UTC.
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Scientific Data, Published online: 03 April 2025; doi:10.1038/s41597-025-04408-y
Potential tree cover under current and future climate scenarios
in Nature scientific data on 2025-04-03 00:00:00 UTC.
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Scientific Data, Published online: 03 April 2025; doi:10.1038/s41597-025-04900-5
Remote sensing for land cover mapping across Victoria, Australia – a machine learning application
in Nature scientific data on 2025-04-03 00:00:00 UTC.
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Scientific Data, Published online: 03 April 2025; doi:10.1038/s41597-025-04889-x
Genome assemblies of Nuttall’s White-crowned sparrow (Zonotrichia leucophrys nuttalli) and Rufous-collared sparrow (Zonotrichia capensis)
in Nature scientific data on 2025-04-03 00:00:00 UTC.
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Scientific Data, Published online: 03 April 2025; doi:10.1038/s41597-025-04891-3
Chromosome-level genome assembly of the traditional medicinal plant Lindera aggregata
in Nature scientific data on 2025-04-03 00:00:00 UTC.
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Communications Biology, Published online: 03 April 2025; doi:10.1038/s42003-025-07987-z
Mechanistic exploration of paclobutrazol induction reveals the role of the MYB transcription factor SlMYB and its direct regulatory interactions with key genes in the MVA pathway, shedding light on the transcriptional regulation underlying enhanced triterpenoid biosynthesis in Sanghuangporus lonicericola.
in Nature communications biology on 2025-04-03 00:00:00 UTC.
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Communications Biology, Published online: 03 April 2025; doi:10.1038/s42003-025-07778-6
A combinatorial mutagenesis optimization strategy (CoSMOS) generated a tryptophan-substituted peptide with improved inhibitory potency against pools of chemokines present in atherosclerotic plaque, inflamed islets and rheumatoid arthritis synovium.
in Nature communications biology on 2025-04-03 00:00:00 UTC.
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The evolutionarily conserved Hippo (Hpo) pathway has been shown to impact early development and tumorigenesis by governing cell proliferation and apoptosis. However, its post-developmental roles are relatively unexplored. Here, we demonstrate its roles in post-mitotic cells by showing that defective Hpo signaling accelerates age-associated structural and functional decline of neurons in Caenorhabditis elegans. Loss of wts-1/LATS, the core kinase of the Hpo pathway, resulted in premature deformation of touch neurons and impaired touch responses in a yap-1/YAP-dependent manner, the downstream transcriptional co-activator of LATS. Decreased movement as well as microtubule destabilization by treatment with colchicine or disruption of microtubule-stabilizing genes alleviated the neuronal deformation of wts-1 mutants. Colchicine exerted neuroprotective effects even during normal aging. In addition, the deficiency of a microtubule-severing enzyme spas-1 also led to precocious structural deformation. These results consistently suggest that hyper-stabilized microtubules in both wts-1-deficient neurons and normally aged neurons are detrimental to the maintenance of neuronal structural integrity. In summary, Hpo pathway governs the structural and functional maintenance of differentiated neurons by modulating microtubule stability, raising the possibility that the microtubule stability of fully developed neurons could be a promising target to delay neuronal aging. Our study provides potential therapeutic approaches to combat age- or disease-related neurodegeneration.
in eLife on 2025-04-03 00:00:00 UTC.
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Detecting causal relations structures our perception of events in the world. Here, we determined for visual interactions whether generalized (i.e. feature-invariant) or specialized (i.e. feature-selective) visual routines underlie the perception of causality. To this end, we applied a visual adaptation protocol to assess the adaptability of specific features in classical launching events of simple geometric shapes. We asked observers to report whether they observed a launch or a pass in ambiguous test events (i.e. the overlap between two discs varied from trial to trial). After prolonged exposure to causal launch events (the adaptor) defined by a particular set of features (i.e. a particular motion direction, motion speed, or feature conjunction), observers were less likely to see causal launches in subsequent ambiguous test events than before adaptation. Crucially, adaptation was contingent on the causal impression in launches as demonstrated by a lack of adaptation in non-causal control events. We assessed whether this negative aftereffect transfers to test events with a new set of feature values that were not presented during adaptation. Processing in specialized (as opposed to generalized) visual routines predicts that the transfer of visual adaptation depends on the feature similarity of the adaptor and the test event. We show that the negative aftereffects do not transfer to unadapted launch directions but do transfer to launch events of different speeds. Finally, we used colored discs to assign distinct feature-based identities to the launching and the launched stimulus. We found that the adaptation transferred across colors if the test event had the same motion direction as the adaptor. In summary, visual adaptation allowed us to carve out a visual feature space underlying the perception of causality and revealed specialized visual routines that are tuned to a launch’s motion direction.
in eLife on 2025-04-03 00:00:00 UTC.
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in eLife on 2025-04-03 00:00:00 UTC.
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Polyamines are biologically ubiquitous cations that bind to nucleic acids, ribosomes, and phospholipids and, thereby, modulate numerous processes, including surface motility in Escherichia coli. We characterized the metabolic pathways that contribute to polyamine-dependent control of surface motility in the commonly used strain W3110 and the transcriptome of a mutant lacking a putrescine synthetic pathway that was required for surface motility. Genetic analysis showed that surface motility required type 1 pili, the simultaneous presence of two independent putrescine anabolic pathways, and modulation by putrescine transport and catabolism. An immunological assay for FimA—the major pili subunit, reverse transcription quantitative PCR of fimA, and transmission electron microscopy confirmed that pili synthesis required putrescine. Comparative RNAseq analysis of a wild type and ΔspeB mutant which exhibits impaired pili synthesis showed that the latter had fewer transcripts for pili structural genes and for fimB which codes for the phase variation recombinase that orients the fim operon promoter in the ON phase, although loss of speB did not affect the promoter orientation. Results from the RNAseq analysis also suggested (a) changes in transcripts for several transcription factor genes that affect fim operon expression, (b) compensatory mechanisms for low putrescine which implies a putrescine homeostatic network, and (c) decreased transcripts of genes for oxidative energy metabolism and iron transport which a previous genetic analysis suggests may be sufficient to account for the pili defect in putrescine synthesis mutants. We conclude that pili synthesis requires putrescine and putrescine concentration is controlled by a complex homeostatic network that includes the genes of oxidative energy metabolism.
in eLife on 2025-04-03 00:00:00 UTC.
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Synchronous neuronal activity is organized into neuronal oscillations with various frequency and time domains across different brain areas and brain states. For example, hippocampal theta, gamma, and sharp wave oscillations are critical for memory formation and communication between hippocampal subareas and the cortex. In this study, we investigated the neuronal activity of the dentate gyrus (DG) with optical imaging tools during sleep-wake cycles in mice. We found that the activity of major glutamatergic cell populations in the DG is organized into infraslow oscillations (0.01–0.03 Hz) during NREM sleep. Although the DG is considered a sparsely active network during wakefulness, we found that 50% of granule cells and about 25% of mossy cells exhibit increased activity during NREM sleep, compared to that during wakefulness. Further experiments revealed that the infraslow oscillation in the DG was correlated with rhythmic serotonin release during sleep, which oscillates at the same frequency but in an opposite phase. Genetic manipulation of 5-HT receptors revealed that this neuromodulatory regulation is mediated by Htr1a receptors and the knockdown of these receptors leads to memory impairment. Together, our results provide novel mechanistic insights into how the 5-HT system can influence hippocampal activity patterns during sleep.
in eLife on 2025-04-03 00:00:00 UTC.
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The classical diagnosis of Parkinsonism is based on motor symptoms that are the consequence of nigrostriatal pathway dysfunction and reduced dopaminergic output. However, a decade prior to the emergence of motor issues, patients frequently experience non-motor symptoms, such as a reduced sense of smell (hyposmia). The cellular and molecular bases for these early defects remain enigmatic. To explore this, we developed a new collection of five fruit fly models of familial Parkinsonism and conducted single-cell RNA sequencing on young brains of these models. Interestingly, cholinergic projection neurons are the most vulnerable cells, and genes associated with presynaptic function are the most deregulated. Additional single nucleus sequencing of three specific brain regions of Parkinson’s disease patients confirms these findings. Indeed, the disturbances lead to early synaptic dysfunction, notably affecting cholinergic olfactory projection neurons crucial for olfactory function in flies. Correcting these defects specifically in olfactory cholinergic interneurons in flies or inducing cholinergic signaling in Parkinson mutant human induced dopaminergic neurons in vitro using nicotine, both rescue age-dependent dopaminergic neuron decline. Hence, our research uncovers that one of the earliest indicators of disease in five different models of familial Parkinsonism is synaptic dysfunction in higher-order cholinergic projection neurons and this contributes to the development of hyposmia. Furthermore, the shared pathways of synaptic failure in these cholinergic neurons ultimately contribute to dopaminergic dysfunction later in life.
in eLife on 2025-04-03 00:00:00 UTC.
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in eLife on 2025-04-03 00:00:00 UTC.
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Wing dimorphism is a common phenomenon that plays key roles in the environmental adaptation of aphid; however, the signal transduction in response to environmental cues and the regulation mechanism related to this event remain unknown. Adenosine (A) to inosine (I) RNA editing is a post-transcriptional modification that extends transcriptome variety without altering the genome, playing essential roles in numerous biological and physiological processes. Here, we present a chromosome-level genome assembly of the rose-grain aphid Metopolophium dirhodum by using PacBio long HiFi reads and Hi-C technology. The final genome assembly for M. dirhodum is 447.8 Mb, with 98.50% of the assembled sequences anchored to nine chromosomes. The contig and scaffold N50 values are 7.82 and 37.54 Mb, respectively. A total of 18,003 protein-coding genes were predicted, of which 92.05% were functionally annotated. In addition, 11,678 A-to-I RNA-editing sites were systematically identified based on this assembled M. dirhodum genome, and two synonymous A-to-I RNA-editing sites on CYP18A1 were closely associated with transgenerational wing dimorphism induced by crowding. One of these A-to-I RNA-editing sites may prevent the binding of miR-3036-5p to CYP18A1, thus elevating CYP18A1 expression, decreasing 20E titer, and finally regulating the wing dimorphism of offspring. Meanwhile, crowding can also inhibit miR-3036-5p expression and further increase CYP18A1 abundance, resulting in winged offspring. These findings support that A-to-I RNA editing is a dynamic mechanism in the regulation of transgenerational wing dimorphism in aphids and would advance our understanding of the roles of RNA editing in environmental adaptability and phenotypic plasticity.
in eLife on 2025-04-03 00:00:00 UTC.
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Harnessing the regenerative potential of endogenous stem cells to restore lost neurons is a promising strategy for treating neurodegenerative disorders. Müller glia (MG), the primary glial cell type in the retina, exhibit extraordinary regenerative abilities in zebrafish, proliferating and differentiating into neurons post-injury. However, the regenerative potential of mouse MG is limited by their inherent inability to re-enter the cell cycle, constrained by high levels of the cell cycle inhibitor p27Kip1 and low levels of cyclin D1. Here, we report a method to drive robust MG proliferation by adeno-associated virus (AAV)-mediated cyclin D1 overexpression and p27Kip1 knockdown. MG proliferation induced by this dual targeting vector was self-limiting, as MG re-entered cell cycle only once. As shown by single-cell RNA-sequencing, cell cycle reactivation led to suppression of interferon signaling, activation of reactive gliosis, and downregulation of glial genes in MG. Over time, the majority of the MG daughter cells retained the glial fate, resulting in an expanded MG pool. Interestingly, about 1% MG daughter cells expressed markers for retinal interneurons, suggesting latent neurogenic potential in a small MG subset. By establishing a safe, controlled method to promote MG proliferation in vivo while preserving retinal integrity, this work provides a valuable tool for combinatorial therapies integrating neurogenic stimuli to promote neuron regeneration.
in eLife on 2025-04-03 00:00:00 UTC.
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Background: -Synuclein (Syn) can misfold and aggregate to form fibrillar {beta}-sheet-rich aggregates ("strains") that are phosphorylated (p-Syn) and deposited into intracellular inclusions in the brain, the pathological hallmark of synucleinopathies including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Previously, we reported that seed amplification assays such as real-time quaking-induced conversion (RT-QuIC) amplifies and detects Syn strains from the patient skin. However, whether skin-derived Syn strains induce disease-specific pathological features in a biological system is unknown. Methods: We generated a U251 human glioblastoma cell line expressing fluorescently tagged Syn carrying the PD-linked A53T mutation and fluorescence resonance energy transfer (FRET)-based U251 biosensor cells. Using fluorescence microscopy coupled with in situ detergent extraction, FRET-Flow cytometry and high-content confocal imaging, we examined the pathological burden and morphology of p-Syn inclusions seeded by RT-QuIC-amplified patient skin and brain Syn strains in Syn-expressing U251 cells, FRET-based Syn biosensor cells and Syn biosensor cell-derived neurons. Results: U251 cells allow robust and rapid in situ detection of detergent-insoluble intracellular Syn inclusions triggered by exogenous Syn seeds. In U251 FRET-based biosensor cells, PD skin-amplified strains induce a greater pathological burden and distinct p-Syn inclusion morphology from PD brain-amplified and DLB skin-amplified strains. Inclusion morphology of DLB and MSA skin- and brain-amplified strains are comparable. Furthermore, skin-amplified Syn strains induce neuronal inclusions and cause degeneration of induced neurons reprogrammed from the U251 biosensor cells. Finally, biosensor cell-propagated PD skin Syn strains induce higher seeding activity measured by RT-QuIC than PD brain and DLB skin Syn strains, linking intracellular pathological burden to in vitro seeding activity. Conclusions: We report the detection of distinct PD strains derived from patient skin and brain tissues that trigger unique pathological phenotypes in U251 Syn biosensor cells and cause degeneration of reprogrammed neurons from the same cell lineage. Moreover, DLB and MSA skin Syn strains mimic pathological features of their brain Syn strains in these biosensor cells. Therefore, the U251 Syn biosensor cell model is a robust tool to potentially discriminate PD and DLB synucleinopathies and to study Syn tissue- and strain-specific etiology and pathogenesis.
in bioRxiv: Neuroscience on 2025-04-03 00:00:00 UTC.
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The ability to adjust brain resources to manage expected uncertainty is hypothesized to be impaired in autism spectrum disorder (ASD), though the evidence remains limited. To investigate this, we studied 23 neurotypical (NT) and 23 high-functioning adults with ASD performing a probabilistic two-alternative value-based task while undergoing magnetoencephalography (MEG) and pupillometry. The task comprised five sequential blocks with stable reward probabilities (70%:30%), but varying stimulus pairs and reward values, enabling the assessment of behavioral and neural adaptation to expected uncertainty. We analyzed the hit rate of advantageous choices, response times, and computational measures of prior belief strength and precision. To examine cortical activation during decision-making, we used magnetoencephalographic (MEG) source reconstruction to quantify -{beta} oscillation suppression in decision-relevant cortical regions within the pre-decision time window. Linear mixed models were applied to assess trial-by-trial effects. Behaviorally, ASD participants exhibited lower overall belief precision but intact probabilistic rule generalization, showing gradual performance improvement and strengthening of prior beliefs across blocks. However, unlike NT individuals, they did not show a progressive downscaling of neural activation during decision-making or a reduction in neural response to feedback signals as performance improved. Furthermore, on a trial-by-trial basis, increased belief precision in ASD was not associated with reduced cortical activation, a pattern observed in NT individuals. These findings suggest an atypically rigid and enhanced allocation of neural resources to advantageous decisions that individuals with ASD rationally judge as optimal. This pattern may reflect an aversive response to the irreducible uncertainty inherent in probabilistic decision-making.
in bioRxiv: Neuroscience on 2025-04-03 00:00:00 UTC.
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Spatially integrated mechanisms of consciousness are unclear. An approach to manipulate brainwide circuits regulating consciousness via synthetic central nervous system activation may pave the way for more precise transitions in consciousness and reveal underlying mechanisms. Toward this goal, we leverage anesthesia as a tool to probe consciousness at cellular resolution within the intact network. We perform brainwide chemogenetic capture of isoflurane anesthesia-activated circuitry in mice in parallel with electrocorticography, wireless mechano-acoustic recording of peripheral physiology, and behavioral classification, to describe a synthetic state of altered consciousness generated in the absence of an anesthetic agent. We define patterns of activation under isoflurane using intact brain immediate early gene mapping combined with brainwide high density silicon probe recordings. Our data identify subcortical hotspots of neural activity in an unconsciousness network that is globally characterized by increased functional connectivity driven by select nodes. We provide technical resources spanning brainwide single-cell resolution maps and neurophysiologic datasets of the isoflurane-rendered unconscious state, along with an approach to further probe its global cellular-level mechanisms. Together, we present the foundation for future research to refine this viral-genetic brainwide approach to generate synthetic conscious state transitions, such as sleep, stasis, analgesia or anesthesia.
in bioRxiv: Neuroscience on 2025-04-03 00:00:00 UTC.
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Structural similarity has emerged as a promising tool in mapping the network organization of an individual, living human brain. Here, we propose diffusion similarity networks (DSNs), which employ rotationally invariant spherical harmonic features derived from diffusion magnetic resonance imaging (dMRI), to map gray matter structural organization. Compared to prior approaches, DSNs showed clearer laminar, cytoarchitectural, and micro-architectural organization; greater sensitivity to age, cognition, and sex; higher heritability in a large dataset of healthy young adults; and straightforward extension to non-cortical regions. We show DSNs are correlated with functional, structural, and gene expression connectomes and their gradients align with the sensory-fugal and sensorimotor-association axes of the cerebral cortex, including neuronal oscillatory dynamics, metabolism, immunity, and dopaminergic and glutaminergic receptor densities. DSNs can be easily integrated into conventional dMRI analysis, adding information complementary to structural white matter connectivity, and could prove useful in investigating a wide array of neurological and psychiatric conditions.
in bioRxiv: Neuroscience on 2025-04-03 00:00:00 UTC.
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The assembly of tau into amyloid filaments is a defining characteristic of Alzheimer's disease (AD) and other tauopathies. Cryo-electron microscopy (cryo-EM) showed that specific tau folds characterise different diseases, and that in vitro models often yield filaments with folds that do not replicate those that form in disease. Here, we investigated the aggregation of full-length recombinant 0N3R tau, using wild-type, or mutations C322A or C322S and a real-time quaking-induced conversion (RT-QuIC) assay with brain homogenate seeding. The assembly of C322A 0N3R tau resulted in filaments with a structure resembling the AD fold in paired helical filaments (PHFs), but with a more open C-shaped core attributed to the C322A mutation. C322S 0N3R tau formed structurally more distinct filaments with respect to PHFs, with an ordered carboxy-terminal region. Both mutant filaments retained the ability to seed a second round of aggregation. Meanwhile, wild-type 0N3R tau exhibited poor reproducibility and formed predominantly unfolded aggregates. Our findings emphasise the need for optimised assembly conditions to obtain disease-relevant filament folds. Refining these methodologies could enhance our understanding of the molecular origins of tauopathies and facilitate the development of targeted therapeutic strategies for these conditions
in bioRxiv: Neuroscience on 2025-04-03 00:00:00 UTC.
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The results of functional magnetic resonance imaging (fMRI) cannot be interpreted directly at the molecular or genetic level. Our integrative workflow aims to add such a new dimension to the functional interpretation using a publicly available mouse brain gene expression database from the Allen Institute for Brain Science (ABA). From an average of 164 in-house measured mouse thermal pain fMRI datasets, we identified the top and bottom 5% of voxels according to their activation probability (AP) in response to warm and hot hind paw stimulation. Here, we investigated whether high AP voxels differ from low AP voxels in terms of gene expression: Analyzing nine core brain regions of the 'pain'/saliency system, the top (high AP) and bottom (low AP) 5% of voxels showed distinct gene expression profiles. In nearly all regions, only high AP voxels were significantly enriched for gene ontology (GO) terms related to neurotransmitter activity, synaptic structure and neuronal function, while only the dorsal striatum showed GO term enrichment in low AP voxels. Notably, randomly selected voxels showed no significant enrichment, demonstrating the reliability of this approach. These results highlight the potential of gaining knowledge by integrating gene expression and fMRI data. Despite the limitations of using fixed gene expression data from the ABA cohort, this approach may provide new insights into physiological processes and improve the parcellation and interpretation of imaging data.
in bioRxiv: Neuroscience on 2025-04-03 00:00:00 UTC.
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During navigation, the brain builds representations of self-motion and of environmental information for future action. The classic view suggests that these representations consolidate and eventually stabilize. However, there is no data on their fate at extended memory delays. Here, we investigated memory of navigational episodes from a real-world setting across memory delays of up to three decades. We show that memory of navigational episodes does not achieve a stable state, but rather continues to transform for many years. Our data suggest that at any given point in time, memory of navigational episodes is a changing combination of episode-independent schematic information with several interacting spatial representations that directly relate to a navigational episode and that show distinct decay rates. Consistent with recent accounts of memory reorganization, we further show that neither current theories of systems consolidation nor classic models of forgetting fully explain spatial memory performance at extended memory delays.
in bioRxiv: Neuroscience on 2025-04-03 00:00:00 UTC.
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Primary cilia are polymodal sensory organelles which project from the apical side of polarized cells. They are found in all brain hemispheres but are most pronounced in neurons which comprise the granular layers of the hippocampus and cerebellum. Pathogenic variants in genes which encode primary cilia components are responsible for neuronal ciliopathies, a group of central nervous system disorders characterized by neurodevelopmental conditions such as intellectual disability, seizure, ataxia, and sensory deficits. In the hippocampus, neuronal primary cilia form chemical synapses with axons and their membranes are populated with unique sets of ion channels and G protein-coupled receptors (GPCRs). Primary cilia are small and privileged compartments that are challenging organelles to study. In detail, we describe cilia electrophysiology methods and the use of cilia-specific fluorescent sensors to assay neuronal polycystin channel function and serotonergic receptor signaling, respectively. These tools allow researchers to assay calcium, cAMP and channel-related signaling pathways in isolated neurons in real time and in semi-quantitative terms, while enhancing our understanding of this understudied organelle and its dysregulation in ciliopathy disease states.
in bioRxiv: Neuroscience on 2025-04-03 00:00:00 UTC.
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The mode of presynaptic compensatory endocytosis has been controversial for decades. Recently, an ultrastructural study on synaptic membrane retrieval following synaptic vesicle fusion revealed an ultrafast mechanism of endocytosis in mouse hippocampal synapses at physiological temperature. Using live cell imaging of single-vesicle exo- and endocytosis in mouse hippocampal synapses, combined with accelerated optogenetic acidification of synaptic vesicles, we found that compensatory endocytosis occurs mostly through a slow clathrin-dependent and actin-independent mode at both room and physiological temperatures.
in bioRxiv: Neuroscience on 2025-04-03 00:00:00 UTC.
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Here, we present a synthetic biology approach to assess the social behavioral consequences of altered function of the Kruppel-associated box zinc finger protein (KZFP) interacting protein TRIM28 within the prefrontal cortex (PFC) of male and female mice. We reprogrammed natural TRIM28WT by replacing the transcriptionally repressive domain with an enhanced transcriptional activation domain VP64-p65-Rta (TRIM28VPR), or by excising the transcriptional regulatory domain (TRIM28NFD). In vitro validation confirmed that TRIM28WT represses, and TRIM28VPR activates, the expression of a KZFP-regulated luciferase reporter gene. Upon intra-PFC viral-mediated delivery of TRIM28 variants, we observed that inversion of TRIM28 transcriptional control via HSV-TRIM28VPR reduced the salience of novel social interaction for male and female mice while not affecting non-social behaviors. RNA-sequencing revealed HSV-TRIM28VPR promoted transcriptional escape of all classes of TEs, particularly those located within intronic and distal enhancer regions of downregulated immune genes. HSV-TRIM28VPR-driven social deficits were reversible by intra-PFC repletion of interferon cytokines. These novel data point to PFC KZFP-TRIM28 interactions as necessary to stabilize TEs to enable cis-regulation of key immune gene expression and enhance organismal capacity for complex, pro-social behaviors.
in bioRxiv: Neuroscience on 2025-04-03 00:00:00 UTC.
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Mounting evidence implicates inflammation as a key factor in Alzheimer's disease (AD) development. We previously identified pro-inflammatory soluble epoxide hydrolase (sEH) metabolites to be elevated in plasma and CSF of AD patients and to be associated with lower cognition in non-AD subjects. Soluble epoxide hydrolase is a key enzyme converting anti-inflammatory epoxy fatty acids to pro-inflammatory diols, reported to be elevated in multiple cardiometabolic disorders. Here we analyzed over 700 fasting plasma samples from the baseline of Alzheimer's Disease Neuroimaging Initiative (ADNI) 2/GO study. We applied targeted mass spectrometry method to provide absolute quantifications of over 150 metabolites from oxylipin and endocannabinoids pathway, interrogating the role for inflammation/immune dysregulation and the key enzyme soluble epoxide hydrolase in AD. We provide further insights into the regulation of this pathway in different disease stages, APOE genotypes and between sexes. Additionally, we investigated in mild cognitive impaired (MCI) patients, metabolic signatures that inform about resilience to progression and conversion to AD. Key findings include I) confirmed disruption in this key central pathway of inflammation and pointed to dysregulation of sEH in AD with sex and disease stage differences; II) identified markers of disease progression and cognitive resilience using sex and ApoE genotype stratified analysis highlighting an important role for bile acids, lipid peroxidation and stress response hormone cortisol. In conclusion, we provide molecular insights into a central pathway of inflammation and links to cognitive dysfunction, suggesting novel therapeutic approaches that are based on targeting inflammation tailored for subgroups of individuals based on their sex, APOE genotype and their metabolic profile.
in bioRxiv: Neuroscience on 2025-04-03 00:00:00 UTC.
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Coleoid cephalopods such as the common octopus have a complex visual system, with a camera-type eye and a large optic lobe, that evolved independently from its counterpart in vertebrates. However, the molecular and neurochemical basis of signalling in Octopus visual circuits is not well understood. Through heterologous expression of ligand-gated ion channel genes from Octopus vulgaris, we have identified and characterised novel ionotropic receptors for two of the major optic lobe neurotransmitters, dopamine and acetylcholine. One of these, DopC1, defines a new class of dopamine-gated cation channels that is broadly conserved in many invertebrates. Dopamine robustly stimulates neural activity in the optic lobe, particularly in layers where DopC1 is expressed, consistent with a role for this channel in excitatory neurotransmission. A second protein, AChRB1, forms acetylcholine-gated anion channels and is implicated in inhibition of dopaminergic amacrine cells in the outer granular layer (OGL). This combination of inhibitory cholinergic input and excitatory dopaminergic output may allow OGL amacrine cells to carry out lateral inhibition; thus, despite their very different functional and neurochemical properties, Octopus amacrine cells may execute similar computations to amacrine and horizontal cells in the vertebrate retina.
in bioRxiv: Neuroscience on 2025-04-03 00:00:00 UTC.
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Background: Enteric glial cells (EGC) play a crucial role in maintaining gut homeostasis, but their dysregulation in inflammatory bowel diseases (IBD) remains poorly understood. Emerging preclinical data suggests activated EGC have beneficial roles in controlling gut pathophysiology. Objective: Understanding EGC activation and adaptation during experimental and clinical IBD. Design: We provide the first highly integrated approach to identify EGC activation signature in IBD. Profiling 390 samples from IBD patients via bulk and single-nucleus (sn) transcriptomics and replicate the findings on publicly available bulk and single-cell (sc) datasets from 1160 patients and 19,000 single EGC. Preclinical modelling of Th1/Th17 inflammation, reporter-assisted EGC sorting, analysis of regulated cell death, and Casp8 ablation in EGC was performed. Results: We identified novel IBD type and sampling associated EGC activation signature. Specific EGC activation markers were shared in biopsies and resection specimens, and were divergent between Crohns disease and Ulcerative colitis. Preclinical modelling of intestinal inflammation identified combinatorial TNF and IFN-{gamma}-driven activation of EGC, associated with elevated necroptosis, and negatively impacting gut motility. Genetic-reporter-enabled sorting and downstream analyses confirmed TNF and IFN-{gamma}-driven EGC necroptosis, potentiated by Casp8 deficiency. Furthermore, snRNA-Seq from IBD patient samples confirmed elevated cell death signature in activated but not in rare neuroglia progenitor-like cluster. Conclusion: Our findings identify IBD type-associated activated EGC markers involved in immune and epithelial homeoastasis. We uncover necroptosis of activated EGCs as a constituent of intestinal inflammation. Advancing our understanding of activated EGC survival is pivotal in elucidating their complex roles in maintaining gut immune-epithelial homeostasis.
in bioRxiv: Neuroscience on 2025-04-03 00:00:00 UTC.
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A key challenge in correlating neuronal activity with brain function is the limited sampling probability of neuronal activity in real time. It is crucial to increase the sampling probability substantially and in real time. We hypothesized that 3-dimensional (3D) neural probes offer faster and stronger prospects for cell yield than 2D electrode arrays. We simulated a 1000-neuron neuronal network, mimicking the granular layer of the barrel cortical column, recorded signals from inserted 384 electrodes (organized in 3D or 2D), and sorted units using Kilosrt or triangulation localization. We demonstrated that 3D electrode arrays converge more space for triangulation spike sorting than 2D probes do. 3D neural probes, together with triangulation, could isolate up to 80% of the simulated 1000 neurons (as ground truth) and have a cell yield of up to 5, which is, to the best of our knowledge, significantly higher than standard 2D electrodes with Kilosort or triangulation. With a signal-to-noise ratio (SNR) of 10, which is close to the real world, the simulation data suggest that 3D electrode arrays in a face-centric cubic (FCC) arrangement provide a better cell yield. However, larger background noise (e.g. an SNR of 1, which can be improved with lower electrode impedance) has a stronger impact on the triangulation spike sorting. Since only the peak value of spikes are required for triangulation localization, the computing loading is much less than spike waveform-based spike sorting approach. Thus, combining 3D electrode arrays with triangulation localization is ideal for real-time spike sorting. Thus, we demonstrated that adding one more dimension in designing neural probes can dramatically increase cell yield and speed up isolating neuronal unit activity. We, for the first time, provide a tool for utilizing computer simulations to optimize the design of neural electrode arrays before time-consuming probe fabrication.
in bioRxiv: Neuroscience on 2025-04-03 00:00:00 UTC.
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Light affects not only vision but also attention, alertness, and cognition, primarily through intrinsically photosensitive retinal ganglion cells sensitive to blue-wavelength light. While previous research has shown that light influences brain regional activity, its impact on brain connectivity remains unclear. Using 7-Tesla fMRI, this study examined how light modulates thalamo-cortical connectivity during an auditory executive task involving the thalamus, the prefrontal cortex (in supramarginal gyrus : SMG), and parietal cortex (in the inferior frontal junction : IFJ). Fifty-five participants, including young adults (19-30y: scanned in the morning or evening) and adolescents (15-16y: scanned in the evening), were studied. Across all groups, moderate blue-enriched light strengthened SMG-to-IFJ connectivity, while low-illuminance orange light enhanced thalamus-to-SMG connectivity. High-illuminance blue-enriched light strengthened thalamus-to-IFJ connectivity only in the morning for young adults, while moderate blue-enriched light enhanced thalamus-to-SMG connectivity in adolescents in the evening. These findings suggest that the thalamus plays a key role in mediating cognitive effects of light and timing and age influence non-image-forming responses.
in bioRxiv: Neuroscience on 2025-04-03 00:00:00 UTC.
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The primary unit of exocytosis, the synaptic vesicle, is replete with proteins which enable vesicle fusion. For maintaining synaptic transmission the vesicle proteins have to be rapidly cleared from the active zone. The immediate fate of the cargo post-fusion and the precise mechanism of its resorting into a readily retrievable pool (RRetP) for endocytosis remains unclear. To address this, we developed a purely presynaptic preparation, the xenapse, presynaptic boutons formed en face directly onto a glass coverslip enabling optical single vesicle recording by total internal reflection microscopy (TIRFM). Electron microscopy showed xenapses contain a few hundred synaptic vesicles (SVs), of which ~40 SVs are primed (readily releasable pool, RRP), as revealed by single vesicle recordings using the pH-sensitive fluorescent protein pHluorin. Single fusion events synchronous with action potentials could be localized with ~20 nm precision and rapid post-fusion diffusional dispersion of vesicular proteins observed with diffusion constants in the order of 0.1 m2/s. Unroofing of xenapses revealed numerous Clathrin-coated structures, enriched for vesicle cargo and numerically equivalent to about twice the measured RRP size. In this way SV proteins are rapidly cleared from the release site into this RRetP of pre-assembled pits to allow for rapid re-docking and re-priming at vacated release sites in synapses tuned for high-fidelity fast signaling.
in bioRxiv: Neuroscience on 2025-04-03 00:00:00 UTC.
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Head direction cells (HDCs) encode the animal's orientation in space and form a core component of the brain's navigation system. While their dependence on vestibular input is well established, how directional circuits respond to unilateral vestibular loss (UVL) - the most frequent and ecologically relevant form of vestibular imbalance - remains largely unknown. UVL offers a powerful model to investigate how spatial circuits adapt to asymmetric sensory disruption and partial deafferentation. To explore this, we examined the impact of UVL on anterior thalamic nuclei (ATN) activity and spatially tuned neurons in freely moving rats following unilateral vestibular neurectomy (UVN). UVN induced long-lasting alterations in ATN firing dynamics, including reduced theta modulation, diminished burst firing, and selective disruption across functionally defined neuronal classes: head-direction and speed-modulated cells were strongly affected, while angular head velocity and position cells remained largely preserved. Despite initial degradation, HDCs persisted and progressively regained directional tuning. Crucially, spike waveform analysis revealed two distinct HDC subtypes with markedly different vulnerabilities: one subtype showed reduced prevalence and degraded tuning, whereas the other remained resilient and supported the recovery of directional coding. These findings uncover a previously unrecognized heterogeneity within the head direction system and show that compensation following UVL is partial, cell type-specific, and functionally selective. Together, they offer new insight into sensory plasticity within thalamic navigation circuits and provide a framework to understand spatial deficits associated with vestibular imbalance.
in bioRxiv: Neuroscience on 2025-04-03 00:00:00 UTC.
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Cognitive cost plays a crucial role in determining action choices and task engagement. We have proposed that cognitive cost relates to the amount of Bayesian inference required, quantified using relative entropy. In continuous tasks, such as visuomotor tracking, this demand can be estimated using transfer entropy (TE), which accounts for the information transferred from input to output variables. This study aimed to test experimentally the relationship between TE and markers of cognitive cost. We designed a continuous tracking task, manipulating target speed, predictability, and response lag. The effects of task variables on performance, subjective effort and pupil-linked arousal were assessed using Bayesian mixed models. We disentangled the effect of TE from that of other correlated variables (predictability, acceleration, spatial error), by using model comparison and mediation models. Results showed that TE was mostly affected by target predictability and impacted significantly on subjective effort and pupil response. While the variations of pupillary response induced by task conditions were accounted for by TE only, subjective effort was only partially predicted by TE, and depended also on target predictability. These findings suggest that the cognitive demand of motor control tasks can be quantified using TE, which relates to both subjective effort and pupillary response. However, the multifaceted nature of effort in motor tasks and the limitations of subjective measures highlight the need for more nuanced tools to isolate mental and physical effort.
in bioRxiv: Neuroscience on 2025-04-03 00:00:00 UTC.
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The biological mechanisms underlying the spontaneous and recurrent transition to seizures in the epileptic brain are still poorly understood. As a result, seizures remain uncontrolled in a substantial proportion of patients. Brain stimulation is an emerging and promising method to treat various brain disorders, including drug-refractory epilepsy. Selected stimulation protocols previously demonstrated therapeutic efficacy in reducing the seizure rate. The stimulation efficacy critically depends on chosen stimulation parameters, such as the time point, amplitude, and frequency of stimulation. This study aims to explore the neurobiological impact of 1Hz stimulation and provide the mechanistic explanation behind its seizure-delaying and seizure-suppressing effects. We study this effect using a computational model, a modified version of the Epileptor-2 model, in close comparison with such stimulation effects on spontaneous seizures recorded in vitro in a high-potassium model of ictogenesis in rat hippocampal slices. In particular, we investigate the mechanisms and dynamics of spontaneous seizure emergence, the seizure-delaying effect of the stimulation, and the optimal stimulation parameters to achieve the maximal anti-seizure effect. We show that the modified Epileptor-2 model replicates key experimental observations, and captures seizure dynamics and the anti-seizure effects of low-frequency electrical stimulation (LFES) observed in hippocampal slices. We identify the critical thresholds in the model for seizure onset and determine the optimal stimulation parameters -- timing, amplitude, and duration -- that exceed specific thresholds to delay seizures without triggering premature seizures. Our study highlights the central role of sodium-potassium pump dynamics in terminating seizures and mediating the LFES effect.
in bioRxiv: Neuroscience on 2025-04-03 00:00:00 UTC.
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Research indicates that significant damage to primates' medial frontal cortex (MFC) can impede action initiation when anticipating rewards. However, the specific roles within the MFC related to self-generated action preparation remain debated. Here, while two macaques were engaged in an oculomotor task, they occasionally paused and self-resumed the task after varying amounts of time. We utilized the high signal-to-noise ratio from spatial changes in cerebrovascular blood volume (CBV) recorded with ultrafast ultrasound imaging (fUSi) to determine whether the intervals of breaks or the resumption of task-related CBV signals could predict the execution of an ongoing single action. We show that self-initiated eye movements activate the Supplementary eye field (SEF) and the midcingulate cortex (MCC) up to 5.5 seconds before movement execution. Importantly, our results show that a concurrent activity in the SEF and MCC predicts how these two regions might simultaneously exert opposing influences on the voluntary pause and resume of tasks on a single trial basis. The quantification of this dynamic interaction is a novel step for understanding voluntary action in primates and its ability to initiate one's movement based on internal motivations rather than driven instructed behavior.
in bioRxiv: Neuroscience on 2025-04-03 00:00:00 UTC.
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Metaplasticity dynamically adjusts how synaptic e[ffi]cacy and connectivity change, helping neural circuits adapt to experience. However, the interaction between changes in synaptic weight(W) and connection probability (P) remains poorly understood. We explored their interaction using a biologically-inspired, multi layer spiking neural network. We found that while W controls network excitability, P exerts layer-specific and time-dependent control, crucial for network stability. Simultaneous changes in W and P, i.e. metaplasticity, revealed complex, non-additive interactions, shaping response timing and neural recruitment, resulting in the emergence of functionally distinct neuronal subtypes: input-invariant neurons maintaining responsiveness and variant neurons enabling adaptation, based on di[ff]erential E-I dynamics. This interaction allows the network to achieve functional homeostasis in the inputlayer while preserving flexibility in superficial layers. We provide a novel framework for understanding how metaplasticity balances the competing demands of stability and adaptability in cortical circuits, with significant implications for learning, memory, and neural coding.
in bioRxiv: Neuroscience on 2025-04-03 00:00:00 UTC.
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Neural entrainment to acoustic rhythms underlies intelligibility in speech as well as sensorimotor responses to music. This property of neural dynamics, where cortical oscillations align in phase and frequency with a periodic stimulus, is well-studied in the context of sensory encoding and perception. However, little is known about how affective components in naturalistic music influence neural entrainment. The present study investigates the effect of live versus recorded music on neural entrainment and tracking using phase-based and linear modeling approaches. 21 participants listened to 2 live and 2 recorded performances of fast and slow movements of solo violin while their EEG data were collected with a mobile system. Participants made behavioral ratings of engagement, spontaneity, pleasure, investment, focus, and distraction after each trial. Live performances were rated as more engaging, pleasurable, and spontaneous than recorded performances. Live trials showed significantly higher acoustic-EEG phase-locking than recorded trials in the frequency range associated with the note-rate of the fast excerpts. Furthermore, the effect of liveness on phase-locking was strongest in individuals who reported the greatest increases in pleasure and engagement for live over recorded trials. Finally, forward linear mapping revealed stronger neural tracking of spectral over amplitude-related acoustic features and a sensitivity to tempo in neural tracking. Altogether, results suggest that experiencing music live strengthens cerebro-acoustic relationships by enhancing rhythmically-driven neural entrainment alongside perceived pleasure and engagement.
in bioRxiv: Neuroscience on 2025-04-03 00:00:00 UTC.
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Viewing an object in the external world evokes a rich variety of concepts associated with it in the human mind, such as whether it is animate or not, man-made or not, big or small, and countless other attributes. This concept recognition seems to depend on the human-specific knowledge about these objects. However, studies have shown that neurons in visual areas of non-human primates encode some object concepts, raising questions about the extent to which object concepts are uniquely possessed by humans. Here, we show that macaque monkeys can rapidly learn to classify natural object images according to a surprisingly rich set of rules defined by what humans would call abstract concepts. We tested more than 10 binary classification tasks, including animate versus inanimate, natural versus man-made objects, and mammalian versus non-mammalian animals. The monkeys learned each rule in a few days, generalized the learned rules to new images of objects they had probably never seen before and made error patterns consistent with human judgments. Visual deep neural networks (DNNs) could also perform the tasks that monkeys could learn, whereas both DNNs and monkeys failed to classify some less common abstract concepts. Thus, the monkeys' successful classification likely depended on whether concepts were embedded in natural images as visual features that could be extracted by high-level visual processing. The observed capacity of primate brains may subserve the formation of rich abstract concepts that the human mind possesses.
in bioRxiv: Neuroscience on 2025-04-03 00:00:00 UTC.
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INTRODUCTION: Genome-wide association studies (GWAS) have identified Bridging Integrator 1 (BIN1) as the second-most significant genetic risk factor for Alzheimer's disease (AD). We performed GWAS by proxy (GWAX) using UKBiobank and replicated this finding. However, the mechanism by which BIN1 impacts AD risk is largely unknown. METHODS: To address this, we first measured the expression of BIN1 isoforms in a human induced pluripotent stem cells (hiPSC) model and further evaluated whether the BIN1 risk loci associated with the expression of BIN1 isoforms in a Phase 2 AD clinical trial. RESULTS: Our data indicated BIN1 isoform expression patterns associated with the differentiation of hiPSC into neurons or microglia and found the variant rs35103166 impacts the expression of the BIN1 microglia-specific isoforms. DISCUSSION: Given the strong association with susceptibility to AD, exploring the mechanisms of BIN1 genetic variants and their impacts on cell-type specific expression could serve as a valuable resource for novel drug discovery.
in bioRxiv: Neuroscience on 2025-04-03 00:00:00 UTC.
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Animals can learn and seamlessly perform a great number of behaviors. However, it is unclear how neural activity can accommodate new behaviors without interfering with those an animal has already acquired. Recent studies in monkeys performing motor and brain-computer interface (BCI) learning tasks have identified neural signatures - so-called "memory traces" and "uniform shifts" - that appear in the neural activity of a familiar task after learning a new task. Here we asked when these signatures arise and how they are related to continual learning. By modeling a BCI learning paradigm, we show that both signatures emerge naturally as a consequence of learning, without requiring a specific mechanism. In general, memory traces and uniform shifts reflected savings by capturing how information from different tasks coexisted in the same neural activity patterns. Yet, although the properties of these two different signatures were both indicative of savings, they were uncorrelated with each other. When we added contextual inputs that separated the activity for the different tasks, these signatures decreased even when savings were maintained, demonstrating the challenges of defining a clear relationship between neural activity changes and continual learning.
in bioRxiv: Neuroscience on 2025-04-03 00:00:00 UTC.
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BACKGROUND. Transcranial magnetic stimulation (TMS) is a widely used non-invasive brain stimulation technique in neuroscience research and clinical applications. TMS-based motor hotspot hunting, the process of identifying the optimal scalp location to elicit robust and reliable motor responses, is critical to ensure reproducibility and efficiency, as well as to determine safe and precise stimulation intensities in both healthy participants and patients. Typically, this process targets motor responses in contralateral short hand muscles. However, hotspot hunting remains challenging due to the vast parameter space and time constraints. OBJECTIVE. To address this, we present an approach that concurrently optimizes both spatial and angular TMS parameters for hotspot hunting using Gaussian processes and Bayesian optimization. METHODS. We systematically evaluated five state-of-the-art acquisition functions on electromyographic TMS data from eight healthy individuals enhanced by simulated data from generative models. RESULTS. Our results consistently demonstrate that optimizing spatial and angular TMS parameters simultaneously enhances the efficacy and spatial precision of hotspot hunting. Furthermore, we provide mechanistic insights into the acquisition function behavior and the impact of coil rotation constraints, revealing critical limitations in current hotspot-hunting strategies. Specifically, we show that arbitrary constraints on coil rotation angle are suboptimal, as they reduce flexibility and fail to account for individual variability. We further demonstrate that acquisition functions differ in sampling strategies and performance. Functions overly emphasizing exploitation tend to converge prematurely to local optima, whereas those balancing exploration and exploitation-particularly Thompson sampling-achieve superior performance. CONCLUSION. These findings highlight the importance of acquisition function selection and the necessity of removing restrictive coil rotation constraints for effective hotspot hunting. Our work advances TMS-based hotspot identification, potentially reducing participant burden and improving safety in both research and clinical applications beyond the motor cortex.
in bioRxiv: Neuroscience on 2025-04-03 00:00:00 UTC.
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Mutations in Myo7a cause Usher syndrome type 1B and non-syndromic deafness, but the precise function of MYO7A in sensory hair cells remains unclear. We identify and characterize a novel isoform, MYO7A-N, expressed in auditory hair cells alongside the canonical MYO7A-C. Isoform-specific knock-in mice reveal that inner hair cells primarily express MYO7A-C, while outer hair cells express both isoforms in opposing tonotopic gradients. Both localize to the upper tip-link insertion site, consistent with a role in the tip link for mechanotransduction. Loss of MYO7A-N leads to outer hair cell degeneration and progressive hearing loss. Cryo-EM structures reveal isoform-specific differences at actomyosin interfaces, correlating with distinct ATPase activities. These findings reveal an unexpected layer of molecular diversity within the mechanotransduction machinery. We propose that MYO7A isoform specialization enables fine-tuning of tip-link tension, thus hearing sensitivity, and contributes to the frequency-resolving power of the cochlea.
in bioRxiv: Neuroscience on 2025-04-03 00:00:00 UTC.
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Significance: Accurate modeling of light diffusion in the human brain is crucial for applications in optogenetics and spectroscopy diagnostic techniques. White matter tissue is composed of myelinated axon bundles, suggesting the occurrence of enhanced light diffusion along their local orientation direction, which however has never been characterized experimentally. Existing diffuse optics models assume isotropic properties, limiting their accuracy. Aim: We aim to characterize the anisotropic scattering properties of human white matter tissue by directly measuring its tensor scattering components along different directions, and to correlate them with the local axon fiber orientation. Approach: Using a time- and space-resolved setup, we image the transverse propagation of diffusely reflected light across two perpendicular directions in a ex vivo human brain sample. Local fiber orientation is independently determined using light sheet fluorescence microscopy (LSFM). Results: The directional dependence of light propagation in organized myelinated axon bundles is characterized via Monte Carlo (MC) simulations accounting for a tensor scattering coefficient, revealing a lower scattering rate parallel to the fiber orientation. The effects of white matter anisotropy are further assessed by simulating a typical time-domain near-infrared spectroscopy measurement in a four-layer human head model. Conclusions: This study provides a first characterization of the anisotropic scattering properties in ex vivo human white matter, highlighting its direct correlation with axon fiber orientation, and opening to the realization of quantitatively accurate anisotropy-aware human head 3D meshes for diffuse optics applications.
in bioRxiv: Neuroscience on 2025-04-03 00:00:00 UTC.
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in Journal of Neuroscience on 2025-04-02 16:30:29 UTC.
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in Journal of Neuroscience on 2025-04-02 16:30:29 UTC.
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Chronic excessive alcohol (ethanol) consumption induces neuroadaptations in the brain's reward system, including biochemical and structural abnormalities in white matter that are implicated in addiction phenotypes. Here, we demonstrate that long-term (12 week) voluntary ethanol consumption enhances myelination in the nucleus accumbens (NAc) of female and male adult mice, as evidenced by molecular, ultrastructural, and cellular alterations. Specifically, transmission electron microscopy analysis showed increased myelin thickness in the NAc following long-term ethanol consumption, while axon diameter remained unaffected. These changes were paralleled by increased mRNA transcript levels of key transcription factors essential for oligodendrocyte (OL) differentiation, along with elevated expression of critical myelination-related genes. In addition, diffusion tensor imaging revealed increased connectivity between the NAc and the prefrontal cortex, reflected by a higher number of tracts connecting these regions. We also observed ethanol-induced effects on OL lineage cells, with a reduction in the number of mature OLs after 3 weeks of ethanol consumption, followed by an increase after 6 weeks. These findings suggest that ethanol alters OL development prior to increasing myelination in the NAc. Finally, chronic administration of the promyelination drug clemastine to mice with a history of heavy ethanol consumption further elevated ethanol intake and preference, suggesting that increased myelination may contribute to escalated drinking behavior. Together, these findings suggest that heavy ethanol consumption disrupts OL development, induces enhanced myelination in the NAc, and may drive further ethanol intake, reinforcing addictive behaviors.
in Journal of Neuroscience on 2025-04-02 16:30:29 UTC.
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Despite the prevalence of attention-deficit hyperactivity disorder (ADHD), efforts to develop a detailed understanding of the neuropsychology of this neurodevelopmental condition are complicated by the diversity of interindividual presentations and the inability of current clinical tests to distinguish between its sensory, attentional, arousal, or motoric contributions. Identifying objective methods that can explain the diverse performance profiles across individuals diagnosed with ADHD has been a long-held goal. Achieving this could significantly advance our understanding of etiological processes and potentially inform the development of personalized treatment approaches. Here, we examine key neuropsychological components of ADHD within an electrophysiological (EEG) perceptual decision-making paradigm that is capable of isolating distinct neural signals of several key information processing stages necessary for sensory-guided actions from attentional selection to motor responses. Using a perceptual decision-making task (random dot motion), we evaluated the performance of 79 children (aged 8–17 years) and found slower and less accurate responses, along with a reduced rate of evidence accumulation (drift rate parameter of drift diffusion model), in children with ADHD (n = 37; 13 female) compared with typically developing peers (n = 42; 18 female). This was driven by the atypical dynamics of discrete electrophysiological signatures of attentional selection, the accumulation of sensory evidence, and strategic adjustments reflecting urgency of response. These findings offer an integrated account of decision-making in ADHD and establish discrete neural signals that might be used to understand the wide range of neuropsychological performance variations in individuals with ADHD.
in Journal of Neuroscience on 2025-04-02 16:30:29 UTC.
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Numerous studies have shown that neuronal representations in sensory pathways are far from static but are instead strongly shaped by the complex properties of the sensory inputs they receive. Adaptation dynamically shapes the neural signaling that underlies our perception of the world yet remains poorly understood. We investigated rapid adaptation across timescales from hundreds of milliseconds to seconds through simultaneous multielectrode recordings from the ventro-posteromedial nucleus of the thalamus (VPm) and layer 4 of the primary somatosensory cortex (S1) in male and female anesthetized mice in response to controlled, persistent whisker stimulation. Observations in VPm and S1 reveal a degree of adaptation that progresses through the pathway. Under these experimental conditions, signatures of two distinct timescales of rapid adaptation in the firing rates of both thalamic and cortical neuronal populations were revealed, also reflected in the synchrony of the thalamic population and in the thalamocortical synaptic efficacy that was measured in putatively monosynaptically connected thalamocortical pairs. Controlled optogenetic activation of VPm further demonstrated that the longer timescale adaptation observed in S1 is likely inherited from slow decreases in thalamic firing rate and synchrony. Despite the degraded sensory responses, adaptation induced by the controlled repetitive stimulation presented here resulted in a shift in coding strategy that favors theoretical discrimination over detection across the observed timescales of adaptation. Overall, although multiple mechanisms contribute to rapid adaptation at distinct timescales, they support a unifying framework on the role of adaptation in sensory processing.
in Journal of Neuroscience on 2025-04-02 16:30:29 UTC.
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Zebra finches sing individually unique songs and recognize conspecific songs and individual identities in songs. Their songs comprise several syllables/elements that share acoustic features within the species, with unique sequential arrangements. However, the neuronal mechanisms underlying the detection of individual differences and species specificity have yet to be elucidated. Herein, we examined the neuronal auditory responsiveness of neurons in the higher auditory area, the caudal nidopallium (NCM), to songs and their elements in male zebra finches to understand the mechanism for detecting species and individual identities in zebra finch songs. We found that various adult male zebra finch songs share acoustically similar song elements but differ in their sequential arrangement between individuals. The broader spiking (BS) neurons in the NCM detected only a small subset of zebra finch songs, whereas NCM BS neurons, as a neuronal ensemble, responded to all zebra finch songs. Notably, distinct combinations of BS neurons responded to each of the 18 presented songs in one bird. Subsets of NCM BS neurons were sensitive to sequential arrangements of species-specific elements, which dramatically increasing the capacity for song variation with a limited number of species-specific elements. The naive Bayes decoder analysis further showed that the response of sequence-sensitive BS neurons increased the accuracy of song stimulus predictions based on the response strength of neuronal ensembles. Our results suggest the neuronal mechanisms that NCM neurons as an ensemble decode the individual identities of songs, while each neuron detects a small subset of song elements and their sequential arrangement.
in Journal of Neuroscience on 2025-04-02 16:30:29 UTC.
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Opioids initiate dynamic maladaptation in brain reward and affect circuits that occur throughout chronic exposure and withdrawal that persist beyond cessation. Protracted abstinence is characterized by negative affective behaviors such as heightened anxiety, irritability, dysphoria, and anhedonia, which pose a significant risk factor for relapse. While the ventral tegmental area (VTA) and μ-opioid receptors (MORs) are critical for opioid reinforcement, the specific contributions of VTAMOR neurons in mediating protracted abstinence-induced negative affect is not fully understood. In our study, we elucidate the role of VTAMOR neurons in mediating negative affect and altered brain-wide neuronal activities following forced opioid exposure and abstinence in male and female mice. Utilizing a chronic oral morphine administration model, we observe increased social deficit, anxiety-related, and despair-like behaviors during protracted forced abstinence. VTAMOR neurons show heightened neuronal FOS activation at the onset of withdrawal and connect to an array of brain regions that mediate reward and affective processes. Viral re-expression of MORs selectively within the VTA of MOR knock-out mice demonstrates that the disrupted social interaction observed during protracted abstinence is facilitated by this neural population, without affecting other protracted abstinence behaviors. Lastly, VTAMORs contribute to heightened neuronal FOS activation in the anterior cingulate cortex (ACC) in response to an acute morphine challenge, suggesting their unique role in modulating ACC-specific neuronal activity. These findings identify VTAMOR neurons as critical modulators of low sociability during protracted abstinence and highlight their potential as a mechanistic target to alleviate negative affective behaviors associated with opioid abstinence.
in Journal of Neuroscience on 2025-04-02 16:30:29 UTC.
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Providing nutrition or health labels on product packaging can be an effective strategy to promote a conscious and healthier diet. However, such labels also have the potential to be counterproductive by creating obstructive expectations about the flavor of the food and influencing odor perception. Conversely, olfaction could significantly influence label perception, whereby negative expectations could be mitigated by pleasant odors. This study explored the neural processing of the interplay between odors and nutrition labels using fMRI in 63 participants of either sex, to whom we presented beverage labels with different nutrition-related statements either with or without a congruent odor. On a behavioral level, the products for which the label was presented together with the odor were in general perceived as more positive than the same labels without an odor. Neuroimaging results revealed that added odors significantly altered activity in brain regions associated with flavor and label processing as well as decision-making, with higher activations in the right amygdala/piriform cortex (Amy/pirC) and orbitofrontal cortex. The presentation of odors induced pattern-based encoding in the right dorsolateral prefrontal cortex, the left ventral striatum/nucleus accumbens, and the right Amy/pirC when accounting for behavioral differences. This suggests that odors influence the effects of labels both on a neural and behavioral level and may offer the possibility of compensating for obstructive associations. The detailed mechanisms of odor and statement interactions within the relevant brain areas should be further investigated, especially for labels that evoke negative expectations.
in Journal of Neuroscience on 2025-04-02 16:30:29 UTC.
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A growing body of evidence suggests that the link between the cardiac autonomic nervous system (ANS) and the central nervous system (CNS) is crucial to the onset and development of major depressive disorder (MDD), affecting perception, cognition, and emotional processing. The bottom-up heart–brain communication pathway plays a significant role in this process. Previous studies have shown that slow-frequency oscillations of peripheral signals (e.g., respiration, stomach) can influence faster neural activities in the CNS via phase–amplitude coupling (PAC). However, the understanding of heart–brain coupling remains limited. Additionally, while MDD patients exhibit altered brain activity patterns, little is known about how heart rate variability (HRV) affects brain oscillations. Therefore, we used PAC to investigate heart–brain coupling and its association with depression. We recorded MEG and ECG data from 55 MDD patients (35 females) and 52 healthy subjects (28 females) at rest and evaluated heart–brain PAC at a broadband level. The results showed that the low-frequency component of HRV (HRV-LF) significantly modulated MEG alpha power (10 Hz) in humans. Compared with the healthy group, the MDD group exhibited more extensive heart–brain coupling cortical networks, including the pars triangularis. LF-alpha coupling was observed in the bilateral insula in both groups. Notably, results revealed a significantly increased sympathetic-dominated HRV-LF modulation effect on left insula alpha oscillations, along with increased depressive severity. These findings suggest that MDD patients may attempt to regulate their internal state through enhanced heart–brain modulation, striving to restore normal physiological and psychological balance.
in Journal of Neuroscience on 2025-04-02 16:30:29 UTC.
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Understanding the intricate mechanisms underlying slow-wave sleep (SWS) is crucial for deciphering the brain's role in memory consolidation and cognitive functions. It is well established that cortical delta oscillations (0.5–4 Hz) coordinate communications among cortical, hippocampal, and thalamic regions during SWS. These delta oscillations feature periods of Up and Down states, with the latter previously thought to represent complete cortical silence; however, new evidence suggests that Down states serve important functions for information exchange during memory consolidation. The retrosplenial cortex (RSC) is pivotal for memory consolidation due to its extensive connectivity with memory-associated regions, although it remains unclear how RSC neurons engage in delta-associated consolidation processes. Here, we employed multichannel in vivo electrophysiology to study RSC neuronal activity in ad libitum behaving male mice during natural SWS. We discovered a discrete assembly of putative excitatory RSC neurons (~20%) that initiated firing at SWS Down states and reached maximal firing at the Down-to-Up transitions. Therefore, we termed these RSC neurons the Down-to-Up transition assembly (DUA) and the remaining RSC excitatory neurons as non-DUA. Compared with non-DUA, DUA neurons appear to exhibit higher firing rates and larger cell body size and lack monosynaptic connectivity with nearby RSC neurons. Furthermore, optogenetics combined with electrophysiology revealed differential innervation of RSC excitatory neurons by memory-associated inputs. Collectively, these findings provide insight into the distinct activity patterns of RSC neuronal subpopulations during sleep and their potential role in memory processes.
in Journal of Neuroscience on 2025-04-02 16:30:29 UTC.
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Our eyes are never still. Even when we attempt to fixate, the visual gaze is never motionless, as we continuously perform miniature oculomotor movements termed as fixational eye movements. The fastest eye movements during the fixation epochs are termed microsaccades (MSs) that are leading to continual motion of the visual input, affecting mainly neurons in the fovea. Yet our vision appears to be stable. To explain this gap, previous studies suggested the existence of an extraretinal input (ERI) into the visual cortex that can account for the motion and produce visual stability. Here, we investigated the existence of an ERI to V1 fovea in macaque monkeys (male) while they performed spontaneous MSs, during fixation. We used voltage-sensitive dye imaging (VSDI) to measure and characterize at high spatiotemporal resolution the influence of MSs on neural population activity, in the foveal region of the primary visual cortex (V1). Microsaccades, performed over a blank screen, induced a two-phase response modulation: an early suppression followed by an enhancement. A correlation analysis revealed a widespread foveal increase in neural synchronization, peaking around ~100 ms after MS onset. Next, we investigated the MS effects in the presence of a small visual stimulus and found that this modulation was different from the blank condition yet both modulations coexisted in the fovea. Finally, the VSD response to an external motion of the fixation point could not explain the MS modulation. These results support an ERI that may be involved in visual stabilization already at the level of V1.
in Journal of Neuroscience on 2025-04-02 16:30:29 UTC.
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Alpha-synuclein (αsyn) is the key pathogenic protein implicated in synucleinopathies including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). In these diseases, αsyn is thought to spread between cells where it accumulates and induces pathology; however, mechanisms that drive its propagation or aggregation are poorly understood. We have previously reported that the small GTPase Rab27b is elevated in human PD and DLB and that it can mediate the autophagic clearance and toxicity of αsyn in a paracrine αsyn cell culture model. Here, we expanded our previous work and characterized the role of Rab27b in neuronal lysosomal processing and αsyn clearance. We found that Rab27b KD in this αsyn-inducible neuronal model resulted in lysosomal dysfunction and increased αsyn levels in lysosomes. Similar lysosomal proteolytic defects and enzymatic dysfunction were observed in both primary neuronal cultures and brain lysates from male and female Rab27b knock-out (KO) mice. αSyn aggregation was exacerbated in Rab27b KO neurons upon treatment with αsyn preformed fibrils. We found no changes in lysosomal counts or lysosomal pH in either model, but we did identify changes in acidic vesicle trafficking and in lysosomal enzyme maturation and localization, which may drive lysosomal dysfunction and promote αsyn aggregation. Rab27b OE enhanced lysosomal activity and reduced insoluble αsyn accumulation. Finally we found elevated Rab27b levels in human postmortem incidental Lewy body disease subjects relative to healthy controls. These data suggest the role of Rab27b in neuronal lysosomal activity and identify it as a potential therapeutic target in synucleinopathies.
in Journal of Neuroscience on 2025-04-02 16:30:29 UTC.
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Because of the important roles of both serotonin (5-HT) and the cerebellum in regulating anxiety, we asked whether 5-HT signaling within the cerebellum is involved in anxiety behavior. Physiological 5-HT levels were measured in vivo by expressing a fluorescent sensor for 5-HT in lobule VII of the cerebellum, while using fiber photometry to measure sensor fluorescence during anxiety behavior on the elevated zero maze. Serotonin increased in lobule VII when male mice were less anxious and decreased when mice were more anxious. To establish a causal role for this serotonergic input in anxiety behavior, we photostimulated or photoinhibited serotonergic terminals in lobule VII while mice were in an elevated zero maze. Photostimulating these terminals reduced anxiety behavior in mice, while photoinhibiting them enhanced anxiety behavior. Our findings add to evidence that cerebellar lobule VII is a topographical locus for anxiety behavior and establish that 5-HT input into this lobule is necessary and sufficient to bidirectionally influence anxiety behavior. These results represent progress toward understanding how the cerebellum regulates anxiety behavior and provide new evidence for a functional connection between the cerebellum and the serotonin system within the anxiety circuit.
in Journal of Neuroscience on 2025-04-02 16:30:29 UTC.
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Dopaminergic (DA) neurons of the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) play a crucial role in controlling animals’ orienting and approach behaviors toward relevant environmental stimuli. The ventral midbrain receives sensory input from the superior colliculus (SC), a tectal region that processes information from contralateral receptive fields of various modalities. Given the significant influence of dopamine release imbalance in the left and right striatum on animals’ movement direction, our study aimed to investigate the lateralization of the connection between the lateral SC and the midbrain DA system in male rats. We explored the circuit's anatomy using transsynaptic viral tract-tracing and its physiology using in vivo single-unit and ex vivo multi-electrode array recordings of SNc and VTA neuronal activity combined with optogenetic stimulation of either the ipsilateral or contralateral SC or its terminals. During the experiments, DA neurons were identified optogenetically (in vivo recordings) or pharmacologically (ex vivo recordings). Anatomical findings revealed a bilateral innervation pattern of the lateral SC to the ventral midbrain, with a significantly stronger ipsilateral connection, particularly evident in the SNc, involving both DA and non-DA neurons. This anatomical asymmetry was also expressed during in vivo and ex vivo recordings, which showed a predominance of ipsilateral connections, especially within the SNc. Ex vivo recordings also confirmed that this lateralized pathway is direct. The described features of the SC->VTA/SNc neuronal circuit, particularly its anatomical and physiological asymmetry, suggest its involvement in orienting and approach behaviors guided by the direction of incoming sensory stimuli.
in Journal of Neuroscience on 2025-04-02 16:30:29 UTC.
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Stimulus-driven attention allows us to react to relevant stimuli (and imminent danger!) outside our current focus of attention. But irrelevant stimuli can also disrupt attention, for example, during listening to speech. The degree to which sound captures attention is called salience, which can be estimated by existing, behaviorally validated, computational models (Huang and Elhilali, 2017). Here we examined whether neurophysiological responses to task-irrelevant sounds indicate the degree of distraction during a sustained-listening task and how much this depends on individual hearing thresholds. Forty-seven Danish-speaking adults (28/19 female/male; mean age, 60.1; SD, 15.9 years) with heterogenous hearing thresholds (PTA; mean, 25.5; SD, 18.0 db HL) listened to continuous speech while 1-s-long, task-irrelevant natural sounds (distractors) of varying computed salience were presented at unpredictable times and locations. Eye tracking and electroencephalography were used to estimate pupil response and neural tracking, respectively. The task-irrelevant sounds evoked a consistent pupil response (PR), distractor-tracking (DT), and a drop of target-tracking (TT), and statistical modeling of these three measures within subjects showed that all three are enhanced for sounds with higher computed salience. Participants with larger PR showed a stronger drop in target tracking (TT) and performed worse in target speech comprehension. We conclude that distraction can be inferred from neurophysiological responses to task-irrelevant stimuli. These results are a first step toward neurophysiological assessment of attention dynamics during continuous listening, with potential applications in hearing care diagnostics.
in Journal of Neuroscience on 2025-04-02 16:30:29 UTC.
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Adaptation affects neuronal responsivity and selectivity throughout the visual hierarchy. However, because most prior studies have tailored stimuli to a single brain area of interest, we have a poor understanding of how exposure to a particular image alters responsivity and tuning at different stages of visual processing. Here we assess how adaptation with naturalistic textures alters neuronal responsivity and selectivity in primary visual cortex (V1) and area V2 of macaque monkeys. Neurons in both areas respond to textures, but V2 neurons are sensitive to higher-order image statistics which do not strongly modulate V1 responsivity. We tested the specificity of adaptation in each area with textures and spectrally matched "noise" stimuli. Adaptation reduced responsivity in both V1 and V2, but only in V2 was the reduction dependent on the presence of higher-order texture statistics. Despite this specificity, the texture information provided by single neurons and populations was reduced after adaptation, in both V1 and V2. Our results suggest that adaptation effects for a given feature are induced at the stage of processing that tuning for that feature first arises and that stimulus-specific adaptation effects need not result in improved sensory encoding.
in Journal of Neuroscience on 2025-04-02 16:30:29 UTC.
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Emotionally arousing events are typically vividly remembered, which is generally adaptive but may contribute to mental disorders such as post-traumatic stress disorder. Previous research on emotional memory focused primarily on events that were experienced only once, leaving the memory mechanisms underlying repeatedly encountered emotional events largely unexplored. Here, we aimed to elucidate the brain mechanisms associated with memory for recurring emotional events. Specifically, we sought to determine whether the memory enhancement for recurring emotional events is linked to more variable neural representations, as predicted by the encoding-variability hypothesis, or to more stable representations across repetitions, as suggested by a memory reinstatement account. To investigate this, we repeatedly presented healthy men and women with images of emotionally negative or neutral scenes during three consecutive runs in an MRI scanner. Subsequent free recall was, as expected, enhanced for emotional compared with neutral images. Neural data showed that this emotional enhancement of memory was linked to (1) activation of the amygdala and anterior hippocampus during the initial encounter of the emotional event and (2) increased neural pattern similarity in frontoparietal cortices across event repetitions. Most importantly, a multilevel-moderated mediation analysis revealed that the impact of neocortical pattern stability across repetitions on emotional memory enhancement was moderated by amygdala activity during the initial exposure to the emotional event. Together, our findings show that the amygdala response during the initial encounter of an emotional event boosts subsequent remembering through a more precise reinstatement of the event representation during subsequent encounters of the same event.
in Journal of Neuroscience on 2025-04-02 16:30:29 UTC.
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Background The Ichu River serves as the primary water source for urban and agricultural use and industrial operations, but anthropogenic pollution has a serious negative impact on its water quality. Methods The investigation measured water quality and health-related risks by analyzing physicochemical parameters, heavy metals, and microbial pollutants at eight sampling points, site 1 (S1) through (S8). Results The research data showed that water quality worsened progressively from upstream to downstream locations such as turbidity, TDS, conductivity, and BOD levels increased. Oil pollution and oxygen depletion arose from a reduction in dissolved oxygen from 6.3 to 4.5 mg/L at the different sampling sites (S1 to S8). Heavy metals (As, Pb, Cd, and Cr) in the samples exceeded the standards established by the World Health Organization (WHO) established standards because of mining and industrial wastewater and local wastewater discharge. The presence of excessive Escherichia coli (E. coli) and total coliforms in microbial tests proved that the water was severely contaminated by fecal matter. Principal Component Analysis showed that heavy metals exist with microbial pollution and organic load as the main sources of water quality decline, and pollution indicators were found to establish powerful relationships with depleted oxygen levels. Conclusion The severe contamination risks found in this study justify immediate pollution control measures, wastewater treatment enforcement, and sustainable watershed management practices. Urgent action is necessary because vital parameters surpass the standards set by the WHO and (United States Environmental Protection Agency (USEPA) to avoid enduring environmental damage and health problems. This research demonstrates the value of continuing water quality assessments while enforcing policies and raising public awareness to improve the water quality of the Ichu River.
in F1000Research on 2025-04-02 15:54:30 UTC.
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Dental implants provide a reliable treatment option for completely or partially edentulous patients. In case of a membrane perforation, the gap can be closed using a piece of resorbable collagen membrane or by suturing the Schneiderian membrane using a resorbable suture. The present study shows a new development in this technique, which involves modifying the design of the absorbable membrane and using bins to fix the membrane. This study concluded that the novel design of the collagen membrane and its fixation with the bins led to greater stability of the bone graft and led to subsequent bone gain that enables dental implantation. Still, this technique requires a histological study to determine the nature of the bone formed.
in F1000Research on 2025-04-02 15:44:51 UTC.
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Background Cervical cancer poses a significant health threat, especially for women living with HIV, who are at increased risk of developing premalignant cervical lesions. Large Loop Excision of the Transformation Zone (LLETZ) is a standard treatment for cervical intraepithelial neoplasia (CIN) to prevent progression to malignancy. This study explores the experiences of HIV-positive women who underwent LLETZ in Vhembe District, South Africa, where access to such specialized treatments remains limited. Methods Using a qualitative, phenomenological approach, this study engaged seven HIV-positive women who underwent LLETZ, capturing their lived experiences through in-depth, unstructured interviews. Thematic analysis identified key themes and subthemes to elucidate their psychological, physical, and social encounters related to the procedure. Results Analysis revealed eight central themes: psychological and physical experiences, psychosocial and financial support, misconceptions, education, recommendations, and time-related factors. Participants reported anxiety, fear, and initial stress about the procedure, coupled with resilience and acceptance over time. Physical effects such as pain and bleeding were common, though recovery experiences varied. Social support from family and community played a critical role in coping, while financial constraints impacted access to and continuity of care. Misunderstandings about the LLETZ procedure underscored the need for enhanced patient education. Participants emphasized timely screening and support systems to improve treatment outcomes and reduce psychological distress. Conclusions The study highlights the multifaceted impact of LLETZ on HIV-positive women, including the psychological and financial burdens and the importance of clear communication and patient education. Improved support structures, timely result communication, and access to follow-up care are essential to enhance patient outcomes. Recommendations advocate for health system improvements, partner involvement, and proactive counselling to address the specific needs of HIV-positive women undergoing cervical cancer prevention treatments.
in F1000Research on 2025-04-02 15:41:49 UTC.
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by Suzana de Siqueira Santos, Haixuan Yang, Aldo Galeano, Alberto Paccanaro
Computational approaches for drug repurposing for viral diseases have mainly focused on a small number of antivirals that directly target pathogens (virus centric therapies). In this work, we combine ideas from collaborative filtering and network medicine for making predictions on a much larger set of drugs that could be repurposed for host centric therapies, that are aimed at interfering with host cell factors required by a pathogen. Our idea is to create matrices quantifying the perturbation that drugs and viruses induce on human protein interaction networks. Then, we decompose these matrices to learn embeddings of drugs, viruses, and proteins in a low dimensional space. Predictions of host-centric antivirals are obtained by taking the dot product between the corresponding drug and virus representations. Our approach is general and can be applied systematically to any compound with known targets and any virus whose host proteins are known. We show that our predictions have high accuracy and that the embeddings contain meaningful biological information that may provide insights into the underlying biology of viral infections. Our approach can integrate different types of information, does not rely on known drug-virus associations and can be applied to new viral diseases and drugs.
in PLoS Computational Biology on 2025-04-02 14:00:00 UTC.
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by Kaustuv Sanyal, Aswathy Narayanan
The rapid growth in antimicrobial resistance is of great medical concern. A new study in PLOS Biology unveils the link between ploidy plasticity and the emergence of antifungal resistance in Candida tropicalis.
The rapid growth in antimicrobial resistance is of great medical concern. This Primer highlights a new study in PLOS Biology that unveils the link between ploidy plasticity and the emergence of antifungal resistance in Candida tropicalis.
in PLoS Biology on 2025-04-02 14:00:00 UTC.
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by Andreas Sichert
An alga that abandoned photosynthesis? This Primer explores a PLOS Biology study showing that a single horizontal gene transfer event allowed the diatom Nitzschia sing1 to evolve a complete enzymatic machinery to break down alginate from brown algae, unlocking a new ecological niche.
in PLoS Biology on 2025-04-02 14:00:00 UTC.
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by Md. Hashim Reza, Rashi Aggarwal, Jigyasa Verma, Nitesh Kumar Podh, Ratul Chowdhury, Gunjan Mehta, Ravi Manjithaya, Kaustuv Sanyal
Emerging studies hint at the roles of autophagy-related proteins in various cellular processes. To understand if autophagy-related proteins influence genome stability, we sought to examine a cohort of 35 autophagy mutants in Saccharomyces cerevisiae. We observe cells lacking Atg11 show poor mitotic stability of minichromosomes. Single-molecule tracking assays and live cell microscopy reveal that Atg11 molecules dynamically localize to the spindle pole bodies (SPBs) in a microtubule (MT)-dependent manner. Loss of Atg11 leads to a delayed cell cycle progression. Such cells accumulate at metaphase at an elevated temperature that is relieved when the spindle assembly checkpoint (SAC) is inactivated. Indeed, atg11∆ cells have stabilized securin levels, that prevent anaphase onset. Ipl1-mediated activation of SAC also confirms that atg11∆ mutants are defective in chromosome biorientation. Atg11 functions in the Kar9-dependent spindle positioning pathway. Stabilized Clb4 levels in atg11∆ cells suggest that Atg11 maintains Kar9 asymmetry by facilitating proper dynamic instability of astral microtubules (aMTs). Loss of Spc72 asymmetry contributes to non-random SPB inheritance in atg11∆ cells. Overall, this study uncovers an essential non-canonical role of Atg11 in the MT-mediated process of chromosome segregation.
in PLoS Biology on 2025-04-02 14:00:00 UTC.
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by Marta Rodríguez Aramendía, Mariachiara Esposito, Raphael Kaplan
Mounting evidence suggests the human hippocampal formation (HF) maps how different people’s attributes relate to each other. Yet, it’s unclear if hippocampal map-like knowledge representations of other people are shaped by self-knowledge. Here, we test if a prominent heuristic involving an implicit reliance on self-knowledge when rating others, egocentric anchoring-and-adjustment, is present in the HF when relational information about different social entities is retrieved. Participants first provided likelihood ratings of partaking in everyday activities for themselves, fictitious individuals, and familiar social groups. During a neuroimaging task that doesn’t require using self-knowledge, participants then learned a stranger’s preference for an activity relative to one of the fictitious individuals and inferred how the stranger’s preference related to the groups’ preferences. Isolating the neural representation of egocentric anchoring when retrieving relational social knowledge, the HF and dorsomedial prefrontal cortex (dmPFC) represented group entities’ preferences relative to the self. Furthermore, the HF selectively represented group identity over other learned entities, confirming the HF was primarily engaged by social comparisons in the more ample map-like reference frame. Taken together, these results imply that self-knowledge implicitly influences how the HF learns about others.
in PLoS Biology on 2025-04-02 14:00:00 UTC.
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Objective
This study aimed to evaluate the association between computed tomography perfusion (CTP) parameters and outcomes in basilar artery occlusion (BAO), and to select patients with BAO who may benefit from thrombectomy.
Methods
We performed a post-hoc analysis of patients from the ATTENTION trial with available admission CTP data. CTP parameters evaluated included time to maximum (T
max) >6 s/8 s/10 s, relative cerebral blood flow (rCBF) <20%/30%/34%/38%/50%, Critical Area Perfusion Score (CAPS), and CTP-posterior circulation acute stroke prognosis early computed tomography score (CTP-pc-ASPECTS), pons-midbrain-thalamus (PMT) hypoperfusion. Multivariable Firth logistic regression was used to analyze associations between CTP parameters and outcomes and to explore treatment interactions. The primary outcome was favorable outcome, defined as modified Rankin Scale score of 0–3, at 90 days.
Results
The study included 109 patients (70 thrombectomy, 39 control). Multivariable analysis showed that lower CAPS, smaller rCBF <34% volume, and higher CTP-pc-ASPECTS were associated with favorable outcome. Patients who underwent thrombectomy had a higher likelihood of favorable outcome with increasing CAPS (T
max > 6 s) compared to control (P
interaction = 0.048 for continuous variable). When CAPS (T
max > 6 s) was treated as a categorical variable, the interaction remained significant (P
interaction = 0.03). Similarly, the treatment effect was also modified by PMT hypoperfusion (T
max >6 s) (P
interaction = 0.03). In patients with CAPS (T
max >6 s) >3 or with PMT hypoperfusion (T
max >6 s), thrombectomy was associated with favorable outcome.
Interpretation
Higher CAPS correlated with a decrease in the rate of favorable outcomes. However, patients with higher CAPS were more likely to benefit from thrombectomy compared to medical management alone, suggesting that severe hypoperfusion should not preclude endovascular treatment. ANN NEUROL 2025
in Annals of Neurology on 2025-04-02 12:04:55 UTC.
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The medial amygdala and BSTM are part of the social behavior network and include a subpopulation of glutamatergic neurons that express the transcription factor Otp. We show that the vast majority of these neurons express mRNA of gonadal hormone receptors (Ar, Esr1, and Esr2), and at least part of them are sexually dimorphic.
ABSTRACT
The medial extended amygdala (EAme) is part of the social behavior network and its subdivisions show expression of sex-steroid receptors, which participate in the regulation of sexually dimorphic behaviors. However, EAme subdivisions are highly heterogeneous in terms of neuron subtypes, with different subpopulations being involved in regulation of different aspects of social and non-social behaviors. To further understand the role of the different EAme neurons and their contribution to sexual differences, here we studied one of its major subtypes of glutamatergic neurons, those derived from the telencephalon-opto-hypothalamic domain that coexpress Otp and Foxg1 genes during development. Our results showed that the vast majority of the Otp glutamatergic neurons of the medial amygdala and medial bed nucleus of the stria terminalis (BSTM) in both sexes express Ar, Esr1 (ERα), and Esr2 (ERβ) mRNA. Moreover, the high percentage of receptors expression in the Otp neurons (between 93% and 100%) indicates that probably the majority of the Otp neurons of EAme are coexpressing the three receptors. In addition, Otp neurons of the posterodorsal medial amygdala have a larger soma and occupy more space in males than in females. These and other features of the Otp neurons regarding their expression of sex-steroid receptors likely contribute to some of the sexually dimorphic behaviors regulated by EAme.
in Journal of Comparative Neurology on 2025-04-02 12:04:42 UTC.
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Central nervous system disorders impair information transmission by causing synapse loss and dysfunction. Synaptic plasticity, involving the dynamic strengthening or weakening of synapses, enables brain adaptation. Regulating this process can alleviate disease progression and support synaptic recovery, introducing innovative treatment strategies that restore neural connectivity and improve overall brain function.
ABSTRACT
Central nervous system (CNS) disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and migraines, rank among the most prevalent and concerning conditions worldwide. Despite ongoing research, the pathophysiology of these disorders remains incompletely understood, primarily due to their complex etiology. Current pharmacological treatments mainly focus on alleviating symptoms rather than addressing the underlying causes of these diseases. CNS disorders are marked by impairments in neurocognitive and neuromuscular functions, and cognitive processes like learning and memory. This deterioration not only impacts the quality of life of affected individuals but also places a significant burden on their families. Neuroplasticity is a key property of the nervous system that enables brain repair and functional recovery. However, in CNS disorders, neuroplasticity is often compromised. Neuroplasticity, which is regulated by gene expression, is also modulated by environmental factors and epigenetic mechanisms, thereby reshaping neuronal networks in response to various biological and environmental stimuli and brain function. Importantly, neuroplasticity plays a critical role in repairing the brain, especially in the context of neurodegenerative diseases, where damaged neurons can reorganize and re-establish lost functions. Targeting neuroplasticity mechanisms holds significant potential for developing therapeutic interventions to improve treatment outcomes and prevent CNS disorders. A deeper understanding of neuroplasticity in neurological diseases could open new avenues for enhancing patient quality of life. This review aims to provide a comprehensive overview of synaptic function and the neuroplasticity mechanisms that are disrupted in neurological disorders.
in Journal of Neuroscience Research on 2025-04-02 12:04:40 UTC.
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Author(s): Alice Longhena, Martin Guillemaud, Fabrizio De Vico Fallani, Raffaella Migliaccio, and Mario Chavez
Alzheimer’s disease disrupts the brain’s connectivity structure, through processes such as progressive neuronal loss and brain atrophy. In this study, the authors propose a method based on a hyperbolic representation of brain networks to characterize brain regions with connectivity anomalies. They show that the method successfully identifies regions affected by neurodegeneration, opening the door to use it as a biomarker for disease progression.
#BiophysicsSpotlight #Interdisciplinary

[Phys. Rev. E 111, 044402] Published Wed Apr 02, 2025
in Physical Review E: Biological physics on 2025-04-02 10:00:00 UTC.
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Proceedings of the National Academy of Sciences, Volume 122, Issue 14, April 2025.
SignificanceHomeostatic synaptic plasticity mechanisms evolved to keep neuronal firing rates within a physiological range in response to alterations in neural network activity. Similar mechanisms take place during slow wave sleep, a non-rapid-eye-movement ...
in PNAS on 2025-04-02 07:00:00 UTC.
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Science Advances, Volume 11, Issue 14, April 2025.
in Science Advances on 2025-04-02 07:00:00 UTC.
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Science Advances, Volume 11, Issue 14, April 2025.
in Science Advances on 2025-04-02 07:00:00 UTC.
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- Wallabag.it! - Save to Instapaper - Save to Pocket -
Science Advances, Volume 11, Issue 14, April 2025.
in Science Advances on 2025-04-02 07:00:00 UTC.
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- Wallabag.it! - Save to Instapaper - Save to Pocket -
Science Advances, Volume 11, Issue 14, April 2025.
in Science Advances on 2025-04-02 07:00:00 UTC.
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- Wallabag.it! - Save to Instapaper - Save to Pocket -
Science Advances, Volume 11, Issue 14, April 2025.
in Science Advances on 2025-04-02 07:00:00 UTC.
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- Wallabag.it! - Save to Instapaper - Save to Pocket -
Science Advances, Volume 11, Issue 14, April 2025.
in Science Advances on 2025-04-02 07:00:00 UTC.
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- Wallabag.it! - Save to Instapaper - Save to Pocket -
Science Advances, Volume 11, Issue 14, April 2025.
in Science Advances on 2025-04-02 07:00:00 UTC.