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arXiv:2504.00300v1 Announce Type: new
Abstract: Recurrent Neural Network models have elucidated the interplay between structure and dynamics in biological neural networks, particularly the emergence of irregular and rhythmic activities in cortex. However, most studies have focused on networks with random or simple connectivity structures. Experimental observations find that high-order cortical connectivity patterns affect the temporal patterns of network activity, but a theory that relates such complex structure to network dynamics has yet to be developed. Here, we show that third- and higher-order cyclic correlations in synaptic connectivities greatly impact neuronal dynamics. Specifically, strong cyclic correlations in a network suppress chaotic dynamics, and promote oscillatory or fixed activity. The change in dynamics is related to the form of the unstable eigenvalues of the random connectivity matrix. A phase transition from chaotic to fixed or oscillatory activity coincides with the development of a cusp at the leading edge of the eigenvalue support. We also relate the dimensions of activity to the network structure.
in arXiv: Quantitative Biology: Neurons and Cognition on 2025-04-02 04:00:00 UTC.
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arXiv:2411.04634v4 Announce Type: replace
Abstract: Objective: The circadian rhythm synchronizes physiological and behavioural patterns with the 24-hour light-dark cycle. Disruption to the circadian rhythm is linked to various health conditions, though optimal methods to describe these disruptions remain unclear. An emerging approach is to examine the intra-individual variability in measurable properties of the circadian rhythm over extended periods. Epileptic seizures are modulated by circadian rhythms, but the relevance of circadian rhythm disruption in epilepsy remains unexplored. Our study investigates intra-individual circadian variability in epilepsy and its relationship with seizures.
Methods: We retrospectively analyzed over 70,000 hours of wearable smartwatch data (Fitbit) from 143 people with epilepsy (PWE) and 31 healthy controls. Circadian oscillations in heart rate time series were extracted, daily estimates of circadian period, acrophase, and amplitude properties were produced, and estimates of the intra-individual variability of these properties over an entire recording were calculated.
Results: PWE exhibited greater intra-individual variability in period (76 min vs. 57 min, d=0.66, p<0.001) and acrophase (64 min vs. 48 min, d=0.49, p=0.004) compared to controls, but not in amplitude (2 bpm, d=-0.15, p=0.49). Variability in circadian properties showed no correlation with seizure frequency, nor any differences between weeks with and without seizures.
Significance: For the first time, we show that heart rate circadian rhythms are more variable in PWE, detectable via consumer wearable devices. However, no association with seizure frequency or occurrence was found, suggesting that this variability might be underpinned by the epilepsy aetiology rather than being a seizure-driven effect.
in arXiv: Quantitative Biology: Neurons and Cognition on 2025-04-02 04:00:00 UTC.
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arXiv:2503.19823v2 Announce Type: replace
Abstract: Understanding the structural and functional organization of the human brain requires a detailed examination of cortical folding patterns, among which the three-hinge gyrus (3HG) has been identified as a key structural landmark. GyralNet, a network representation of cortical folding, models 3HGs as nodes and gyral crests as edges, highlighting their role as critical hubs in cortico-cortical connectivity. However, existing methods for analyzing 3HGs face significant challenges, including the sub-voxel scale of 3HGs at typical neuroimaging resolutions, the computational complexity of establishing cross-subject correspondences, and the oversimplification of treating 3HGs as independent nodes without considering their community-level relationships. To address these limitations, we propose a fully differentiable subnetwork partitioning framework that employs a spectral modularity maximization optimization strategy to modularize the organization of 3HGs within GyralNet. By incorporating topological structural similarity and DTI-derived connectivity patterns as attribute features, our approach provides a biologically meaningful representation of cortical organization. Extensive experiments on the Human Connectome Project (HCP) dataset demonstrate that our method effectively partitions GyralNet at the individual level while preserving the community-level consistency of 3HGs across subjects, offering a robust foundation for understanding brain connectivity.
in arXiv: Quantitative Biology: Neurons and Cognition on 2025-04-02 04:00:00 UTC.
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arXiv:2503.21611v3 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 that the presented methodology 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 2025-04-02 04:00:00 UTC.
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arXiv:2503.22808v2 Announce Type: replace
Abstract: Setting up a psychedelic study can be a long, arduous, and kafkaesque process. This rapidly-developing field poses several unique challenges for researchers, necessitating a range of considerations that have not yet been standardised. Many of the complexities inherent to psychedelic research also challenge existing assumptions around, for example, approaches to psychiatric prescribing, the conceptual framing of the placebo effect, and definitions of selfhood. This review paper brings together several of the major psychedelic research teams across the United Kingdom to formalise these unique considerations, identify continuing areas of debate, and provide a practical, experience-based guide, with recommendations for policymakers and future researchers intending to set up a psychedelic research study or clinical trial. We approach this such that the paper can either be read end to end, or treated as a manual: readers can dip into relevant sections as needed.
in arXiv: Quantitative Biology: Neurons and Cognition on 2025-04-02 04:00:00 UTC.
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arXiv:2409.06325v2 Announce Type: replace-cross
Abstract: The dynamics of spatially-structured networks of $N$ interacting stochastic neurons can be described by deterministic population equations in the mean-field limit. While this is known, a general question has remained unanswered: does synaptic weight scaling suffices, by itself, to guarantee the convergence of network dynamics to a deterministic population equation, even when networks are not assumed to be homogeneous or spatially structured? In this work, we consider networks of stochastic integrate-and-fire neurons with arbitrary synaptic weights satisfying a $O(1/N)$ scaling condition. Borrowing results from the theory of dense graph limits, or graphons, we prove that, as $N\to\infty$, and up to the extraction of a subsequence, the empirical measure of the neurons' membrane potentials converges to the solution of a spatially-extended mean-field partial differential equation (PDE). Our proof requires analytical techniques that go beyond standard propagation of chaos methods. In particular, we introduce a weak metric that depends on the dense graph limit kernel and we show how the weak convergence of the initial data can be obtained by propagating the regularity of the limit kernel along the dual-backward equation associated with the spatially-extended mean-field PDE. Overall, this result invites us to reinterpret spatially-extended population equations as universal mean-field limits of networks of neurons with $O(1/N)$ synaptic weight scaling.
in arXiv: Quantitative Biology: Neurons and Cognition on 2025-04-02 04:00:00 UTC.
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arXiv:2410.08025v3 Announce Type: replace-cross
Abstract: Many proposed applications of neural networks in machine learning, cognitive/brain science, and society hinge on the feasibility of inner interpretability via circuit discovery. This calls for empirical and theoretical explorations of viable algorithmic options. Despite advances in the design and testing of heuristics, there are concerns about their scalability and faithfulness at a time when we lack understanding of the complexity properties of the problems they are deployed to solve. To address this, we study circuit discovery with classical and parameterized computational complexity theory: (1) we describe a conceptual scaffolding to reason about circuit finding queries in terms of affordances for description, explanation, prediction and control; (2) we formalize a comprehensive set of queries for mechanistic explanation, and propose a formal framework for their analysis; (3) we use it to settle the complexity of many query variants and relaxations of practical interest on multi-layer perceptrons. Our findings reveal a challenging complexity landscape. Many queries are intractable, remain fixed-parameter intractable relative to model/circuit features, and inapproximable under additive, multiplicative, and probabilistic approximation schemes. To navigate this landscape, we prove there exist transformations to tackle some of these hard problems with better-understood heuristics, and prove the tractability or fixed-parameter tractability of more modest queries which retain useful affordances. This framework allows us to understand the scope and limits of interpretability queries, explore viable options, and compare their resource demands on existing and future architectures.
in arXiv: Quantitative Biology: Neurons and Cognition on 2025-04-02 04:00:00 UTC.
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arXiv:2504.00491v1 Announce Type: new
Abstract: Optimization of mixed categorical-continuous variables is prevalent in real-world applications of black-box optimization. Recently, CatCMA has been proposed as a method for optimizing such variables and has demonstrated success in hyper-parameter optimization problems. However, it encounters challenges when optimizing categorical variables in the presence of interaction between continuous and categorical variables in the objective function. In this paper, we focus on optimizing mixed binary-continuous variables as a special case and identify two types of variable interactions that make the problem particularly challenging for CatCMA. To address these difficulties, we propose two algorithmic components: a warm-starting strategy and a hyper-representation technique. We analyze their theoretical impact on test problems exhibiting these interaction properties. Empirical results demonstrate that the proposed components effectively address the identified challenges, and CatCMA enhanced with these components, named ICatCMA, outperforms the original CatCMA.
in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-04-02 04:00:00 UTC.
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arXiv:2504.00717v1 Announce Type: new
Abstract: Multi-modal optimization involves identifying multiple global and local optima of a function, offering valuable insights into diverse optimal solutions within the search space. Evolutionary algorithms (EAs) excel at finding multiple solutions in a single run, providing a distinct advantage over classical optimization techniques that often require multiple restarts without guarantee of obtaining diverse solutions. Among these EAs, differential evolution (DE) stands out as a powerful and versatile optimizer for continuous parameter spaces. DE has shown significant success in multi-modal optimization by utilizing its population-based search to promote the formation of multiple stable subpopulations, each targeting different optima. Recent advancements in DE for multi-modal optimization have focused on niching methods, parameter adaptation, hybridization with other algorithms including machine learning, and applications across various domains. Given these developments, it is an opportune moment to present a critical review of the latest literature and identify key future research directions. This paper offers a comprehensive overview of recent DE advancements in multimodal optimization, including methods for handling multiple optima, hybridization with EAs, and machine learning, and highlights a range of real-world applications. Additionally, the paper outlines a set of compelling open problems and future research issues from multiple perspectives
in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-04-02 04:00:00 UTC.
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arXiv:2504.00719v1 Announce Type: new
Abstract: Spiking neural networks (SNNs) present a promising computing paradigm for neuromorphic processing of event-based sensor data. The resonate-and-fire (RF) neuron, in particular, appeals through its biological plausibility, complex dynamics, yet computational simplicity. Despite theoretically predicted benefits, challenges in parameter initialization and efficient learning inhibited the implementation of RF networks, constraining their use to a single layer. In this paper, we address these shortcomings by deriving the RF neuron as a structured state space model (SSM) from the HiPPO framework. We introduce S5-RF, a new SSM layer comprised of RF neurons based on the S5 model, that features a generic initialization scheme and fast training within a deep architecture. S5-RF scales for the first time a RF network to a deep SNN with up to four layers and achieves with 78.8% a new state-of-the-art result for recurrent SNNs on the Spiking Speech Commands dataset in under three hours of training time. Moreover, compared to the reference SNNs that solve our benchmarking tasks, it achieves similar performance with much fewer spiking operations. Our code is publicly available at https://github.com/ThomasEHuber/s5-rf.
in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-04-02 04:00:00 UTC.
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arXiv:2504.00772v1 Announce Type: new
Abstract: Multi-task neural architecture search (NAS) enables transferring architectural knowledge among different tasks. However, ranking disorder between the source task and the target task degrades the architecture performance on the downstream task. We propose KTNAS, an evolutionary cross-task NAS algorithm, to enhance transfer efficiency. Our data-agnostic method converts neural architectures into graphs and uses architecture embedding vectors for the subsequent architecture performance prediction. The concept of transfer rank, an instance-based classifier, is introduced into KTNAS to address the performance degradation issue. We verify the search efficiency on NASBench-201 and transferability to various vision tasks on Micro TransNAS-Bench-101. The scalability of our method is demonstrated on DARTs search space including CIFAR-10/100, MNIST/Fashion-MNIST, MedMNIST. Experimental results show that KTNAS outperforms peer multi-task NAS algorithms in search efficiency and downstream task performance. Ablation studies demonstrate the vital importance of transfer rank for transfer performance.
in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-04-02 04:00:00 UTC.
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arXiv:2504.00948v1 Announce Type: new
Abstract: Vision Transformer (ViT)-based models have shown state-of-the-art performance (e.g., accuracy) in vision-based AI tasks. However, realizing their capability in resource-constrained embedded AI systems is challenging due to their inherent large memory footprints and complex computations, thereby incurring high power/energy consumption. Recently, Spiking Vision Transformer (SViT)-based models have emerged as alternate low-power ViT networks. However, their large memory footprints still hinder their applicability for resource-constrained embedded AI systems. Therefore, there is a need for a methodology to compress SViT models without degrading the accuracy significantly. To address this, we propose QSViT, a novel design methodology to compress the SViT models through a systematic quantization strategy across different network layers. To do this, our QSViT employs several key steps: (1) investigating the impact of different precision levels in different network layers, (2) identifying the appropriate base quantization settings for guiding bit precision reduction, (3) performing a guided quantization strategy based on the base settings to select the appropriate quantization setting, and (4) developing an efficient quantized network based on the selected quantization setting. The experimental results demonstrate that, our QSViT methodology achieves 22.75% memory saving and 21.33% power saving, while also maintaining high accuracy within 2.1% from that of the original non-quantized SViT model on the ImageNet dataset. These results highlight the potential of QSViT methodology to pave the way toward the efficient SViT deployments on resource-constrained embedded AI systems.
in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-04-02 04:00:00 UTC.
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arXiv:2504.00957v1 Announce Type: new
Abstract: The rising demand for energy-efficient edge AI systems (e.g., mobile agents/robots) has increased the interest in neuromorphic computing, since it offers ultra-low power/energy AI computation through spiking neural network (SNN) algorithms on neuromorphic processors. However, their efficient implementation strategy has not been comprehensively studied, hence limiting SNN deployments for edge AI systems. Toward this, we propose a design methodology to enable efficient SNN processing on commodity neuromorphic processors. To do this, we first study the key characteristics of targeted neuromorphic hardware (e.g., memory and compute budgets), and leverage this information to perform compatibility analysis for network selection. Afterward, we employ a mapping strategy for efficient SNN implementation on the targeted processor. Furthermore, we incorporate an efficient on-chip learning mechanism to update the systems' knowledge for adapting to new input classes and dynamic environments. The experimental results show that the proposed methodology leads the system to achieve low latency of inference (i.e., less than 50ms for image classification, less than 200ms for real-time object detection in video streaming, and less than 1ms in keyword recognition) and low latency of on-chip learning (i.e., less than 2ms for keyword recognition), while incurring less than 250mW of processing power and less than 15mJ of energy consumption across the respective different applications and scenarios. These results show the potential of the proposed methodology in enabling efficient edge AI systems for diverse application use-cases.
in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-04-02 04:00:00 UTC.
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arXiv:2504.00044v1 Announce Type: cross
Abstract: The widespread use of social media platforms results in the generation of vast amounts of user-generated content, which requires efficient methods for categorization and search. Hashtag recommendation systems have emerged as a crucial tool for automatically suggesting relevant hashtags and improving content discoverability. However, existing static models struggle to adapt to the highly dynamic and real-time nature of social media conversations, where new hashtags emerge and existing ones undergo semantic shifts. To address these challenges, this paper presents H-ADAPTS (Hashtag recommendAtion by Detecting and adAPting to Trend Shifts), a BERT-based hashtag recommendation methodology that can detect and adapt to shifts in the main trends and topics underlying social media conversation. Our approach introduces a trend-aware detection mechanism to identify changes in hashtag usage, triggering efficient model adaptation on a (small) set of recent posts. The framework leverages Apache Storm for real-time stream processing, enabling scalable and fault-tolerant analysis of high-velocity social data. Experimental results on two real-world case studies, including the COVID-19 pandemic and the 2020 US presidential election, demonstrate the ability to maintain high recommendation accuracy by adapting to emerging trends. Our methodology significantly outperforms existing solutions, ensuring timely and relevant hashtag recommendations in dynamic environments.
in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-04-02 04:00:00 UTC.
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arXiv:2504.00515v1 Announce Type: cross
Abstract: Accurate measurement of eyelid parameters such as Margin Reflex Distances (MRD1, MRD2) and Levator Function (LF) is critical in oculoplastic diagnostics but remains limited by manual, inconsistent methods. This study evaluates deep learning models: SE-ResNet, EfficientNet, and the vision transformer-based DINOv2 for automating these measurements using smartphone-acquired images. We assess performance across frozen and fine-tuned settings, using MSE, MAE, and R2 metrics. DINOv2, pretrained through self-supervised learning, demonstrates superior scalability and robustness, especially under frozen conditions ideal for mobile deployment. Lightweight regressors such as MLP and Deep Ensemble offer high precision with minimal computational overhead. To address class imbalance and improve generalization, we integrate focal loss, orthogonal regularization, and binary encoding strategies. Our results show that DINOv2 combined with these enhancements delivers consistent, accurate predictions across all tasks, making it a strong candidate for real-world, mobile-friendly clinical applications. This work highlights the potential of foundation models in advancing AI-powered ophthalmic care.
in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-04-02 04:00:00 UTC.
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arXiv:2504.00613v1 Announce Type: cross
Abstract: Finding deletion-correcting codes of maximum size has been an open problem for over 70 years, even for a single deletion. In this paper, we propose a novel approach for constructing deletion-correcting codes. A code is a set of sequences satisfying certain constraints, and we construct it by greedily adding the highest-priority sequence according to a priority function. To find good priority functions, we leverage FunSearch, a large language model (LLM)-guided evolutionary search proposed by Romera et al., 2024. FunSearch iteratively generates, evaluates, and refines priority functions to construct large deletion-correcting codes. For a single deletion, our evolutionary search finds functions that construct codes which match known maximum sizes, reach the size of the largest (conjectured optimal) Varshamov-Tenengolts codes where the maximum is unknown, and independently rediscover them in equivalent form. For two deletions, we find functions that construct codes with new best-known sizes for code lengths \( n = 12, 13 \), and \( 16 \), establishing improved lower bounds. These results demonstrate the potential of LLM-guided search for information theory and code design and represent the first application of such methods for constructing error-correcting codes.
in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-04-02 04:00:00 UTC.
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arXiv:2504.00761v1 Announce Type: cross
Abstract: The efficient management of complex distributed applications in the Cloud-Edge continuum, including their deployment on heterogeneous computing resources and run-time operations, presents significant challenges. Resource management solutions -- also called orchestrators -- play a pivotal role by automating and managing tasks such as resource discovery, optimisation, application deployment, and lifecycle management, whilst ensuring the desired system performance. This paper introduces Swarmchestrate, a decentralised, application-centric orchestration framework inspired by the self-organising principles of Swarms. Swarmchestrate addresses the end-to-end management of distributed applications, from submission to optimal resource allocation across cloud and edge providers, as well as dynamic reconfiguration. Our initial findings include the implementation of the application deployment phase within a Cloud-Edge simulation environment, demonstrating the potential of Swarmchestrate. The results offer valuable insight into the coordination of resource offerings between various providers and optimised resource allocation, providing a foundation for designing scalable and efficient infrastructures.
in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-04-02 04:00:00 UTC.
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arXiv:2408.12407v2 Announce Type: replace
Abstract: Spiking Neural Networks (SNN) exhibit higher energy efficiency compared to Artificial Neural Networks (ANN) due to their unique spike-driven mechanism. Additionally, SNN possess a crucial characteristic, namely the ability to process spatio-temporal information. However, this ability is constrained by both internal and external factors in practical applications, thereby affecting the performance of SNN. Firstly, the internal issue of SNN lies in the inherent limitations of their network structure and neuronal model, which result in the network adopting a unified processing approach for information of different temporal dimensions when processing input data containing complex temporal information. Secondly, the external issue of SNN stems from the direct encoding method commonly adopted by directly trained SNN, which uses the same feature map for input at each time step, failing to fully exploit the spatio-temporal characteristics of SNN. To address these issues, this paper proposes an Unconstrained Leaky Integrate-and-Fire (ULIF) neuronal model that allows for learning different membrane potential parameters at different time steps, thereby enhancing SNN' ability to process information of different temporal dimensions. Additionally, this paper presents a hybrid encoding scheme aimed at solving the problem of direct encoding lacking temporal dimension information. Experimental results demonstrate that the proposed methods effectively improve the overall performance of SNN in object detection and object recognition tasks. related code is available at https://github.com/hhx0320/ASNN.
in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-04-02 04:00:00 UTC.
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Nature, Published online: 02 April 2025; doi:10.1038/d41586-025-00973-9
A single dose of the drug nitisinone could render a person’s blood lethal to mosquitoes for five days, modelling suggests.
in Nature on 2025-04-02 00:00:00 UTC.
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Nature Communications, Published online: 02 April 2025; doi:10.1038/s41467-025-58153-2
Large capacity vanadium-based aqueous zinc batteries present significant challenges at both electrodes. Here, authors propose a bifacial in-situ modification strategy to alleviate both severe vanadium dissolution and zinc dendrite growth, thereby enabling large capacity aqueous zinc metal batteries.
in Nature Communications on 2025-04-02 00:00:00 UTC.
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Nature Communications, Published online: 02 April 2025; doi:10.1038/s41467-025-58298-0
Viruses protect their genome in protein shells called capsids. Here, authors reveal a molecular mechanism that facilitates the evolution of larger genomes without altering the capsid architecture.
in Nature Communications on 2025-04-02 00:00:00 UTC.
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Nature Communications, Published online: 02 April 2025; doi:10.1038/s41467-025-58435-9
Aumolertinib is a third generation EGFR tyrosine kinase inhibitors, approved for use in patients with advanced EGFR-mutant non-small cell lung cancer (NSCLC). Here, the authors report a phase 2 clinical trial investigating neoadjuvant aumolertinib in patients with unresectable stage III EGFR-mutant NSCLC.
in Nature Communications on 2025-04-02 00:00:00 UTC.
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Nature Communications, Published online: 02 April 2025; doi:10.1038/s41467-025-58350-z
LSD1-CoREST-HDAC1/2 complexes are degraded by both the drug UM171 and cancer-associated mutations in the E3 ligase KBTBD4. Here, the authors use cryo-EM to demonstrate how these mutations and UM171 similarly alter KBTBD4 to recruit HDAC1/2, illustrating a natural example of a molecular glue.
in Nature Communications on 2025-04-02 00:00:00 UTC.
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Parkinson's Disease is the second most common neurodegenerative disorder worldwide, with growing numbers and considerable societal and economic concerns. Human cell culture systems are efficient models for neurodegenerative disorders and allow for personalized, non-invasive analysis of cellular and molecular disease mechanisms. Midbrain organoids and assembloids are advanced 3D culture systems that recapitulate the human midbrain, which is highly affected by Parkinson's disease. Here, we used healthy control and patient-specific midbrain assembloids to assess mitochondrial DNA phenotypes and NfL levels alongside neurodegeneration and alpha-synuclein phosphorylation. Importantly, alterations in mitochondrial DNA homeostasis and NfL levels can be assayed in the supernatant and therefore are particularly suitable as biomarkers and for high throughput screening approaches.
in bioRxiv: Neuroscience on 2025-04-02 00:00:00 UTC.
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Abstract
When practicing a new piece of music, what are the neural substrates influenced by short-term training such as listening to recorded sources or reading sheet music? Do those neural mechanisms reflect the effects of long-term training in music? In the present functional magnetic resonance imaging study with intermediate piano players in the middle of acquiring advanced knowledge and skills in music, we compared short-term training of listening to recorded pieces (“Listen”) and reading sheet music (“Read”). Participants were “Multi-” and “Mono-instrumentalist” groups according to whether they played multiple instruments or only the piano. We used an error-detection task with music stimuli including structural errors made by swapping 2 phrases within a composition, thereby focusing on contextual comprehension of musical phrases. Overall performances were significantly better under Listen than under Read, and significantly better in Multi than in Mono. Moreover, we observed left-lateralized frontal activations under Listen for Multi, whereas bilateral temporo-frontal regions were activated under Read for both groups. Focusing on individual differences under Read, we found a positive correlation between the frontal activations and the accuracy rates for Mono. Overall, our results elucidate how the neural substrates of judgments on structures and context in music are influenced by both long-term and short-term training.
in Cerebral Cortex on 2025-04-02 00:00:00 UTC.
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Response preparation is accomplished by gradual accumulation in neural activity until a threshold is reached. In humans, such a preparatory signal, referred to as the lateralized readiness potential (LRP), can be observed in the EEG over sensorimotor cortical areas before execution of a voluntary movement. Although well described for manual movements, less is known about preparatory EEG potentials for saccadic eye movements in humans and nonhuman primates. Hence, we describe a LRP over the frontolateral cortex in macaque monkeys. Homologous to humans, we observed lateralized electrical potentials ramping before the execution of both rewarded and nonrewarded contralateral saccades. This potential parallels the neural spiking of saccadic movement neurons in the frontal eye field (FEF), suggesting that it may offer a noninvasive correlate of intracortical spiking activity. However, unlike neural spiking in the FEF, polarization in frontolateral channels did not distinguish between saccade generation and inhibition. These findings provide new insights into noninvasive electrophysiological signatures of saccadic preparation in nonhuman primates, highlighting the potential of EEG measures to bridge invasive neural recordings and noninvasive studies of eye movement control in humans.
in eNeuro on 2025-04-01 16:30:13 UTC.
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Attention-deficit/hyperactivity disorder (ADHD) adversely affects the learning, social interaction, and daily living of affected children. Atomoxetine (ATX) hydrochloride (HCI) has been widely used in clinical practice. Electroencephalogram (EEG) biofeedback, as a nonpharmacological treatment approach, has also demonstrated potential in improving symptoms in children with ADHD. We aimed to investigate the clinical efficacy of combining ATX HCI with EEG biofeedback in the treatment of ADHD in children. We hypothesized that this combined therapy would be more effective in alleviating symptoms in children with ADHD. Ninety children with ADHD were randomly separated into the control group (receiving ATX HCI treatment for 12 weeks) and study group (receiving ATX HCI treatment for 12 weeks combined with 60 sessions of EEG biofeedback treatment; n = 45). Swanson, Nolan, and Pelham-IV (SNAP-IV) rating scale scores, integrated visual and auditory continuous performance test results, Conners parent symptom questionnaire (PSQ) scores, and adverse reactions were counted. After 12 weeks of treatment, SNAP-IV scores were lower in both groups and were much lower in the study group; full-scale attention quotient and full-scale response control quotient scores were elevated in both groups and were much higher in the study group; PSQ scores were lower in both groups and were much lower in the study group (all p < 0.05). During the treatment period, there was no difference in the incidence of adverse reactions between both groups (p > 0.05). The treatment combination of ATX HCI and EEG biofeedback is effective for children with ADHD, improving their behavioral issues and psychological conditions.
in eNeuro on 2025-04-01 16:30:13 UTC.
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by Andrey N. Shkoporov, Colin Hill
Phages infecting anaerobic bacteria are highly abundant in the mammalian gut, but their biology and ecological impact are poorly understood. A new PLOS Biology study provides a glimpse into the disruptive biology of the Hankyphages, parasites of the ubiquitous Bacteroidaceae.
in PLoS Biology on 2025-04-01 14:00:00 UTC.
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by Tianren Hu, Qiushi Zheng, Chengjun Cao, Shuaihu Li, Yanfeng Huang, Zhangyue Guan, Lingyu Ji, Jian Bing, Han Du, Austin M. Perry, Clarissa J. Nobile, Bing Li, Haiqing Chu, Guanghua Huang
The human fungal pathogen Candida tropicalis is widely distributed in clinical and natural environments. It is known to be an obligate diploid organism with an incomplete and atypical sexual cycle. Azole-resistant C. tropicalis isolates have been observed with increasing prevalence in many countries in recent years. Here, we report that tebuconazole (TBZ), a triazole fungicide widely used in agriculture, can induce ploidy plasticity and the formation of haploid cells in C. tropicalis. The evolved C. tropicalis strains with ploidy variations exhibit a cross-resistance between TBZ and standard azoles used in clinical settings (such as fluconazole and voriconazole). Similar to its diploid cells, these newly discovered C. tropicalis haploid cells are capable of undergoing filamentation, white-opaque switching, and mating. However, compared to its diploid cells, these haploid C. tropicalis cells grow more slowly under in vitro culture conditions and are less virulent in a mouse model of systemic infection. Interestingly, flow cytometry analysis of a clinical strain with extremely low genome heterozygosity indicates the existence of natural C. tropicalis haploids. Discovery of this C. tropicalis haploid state sheds new light into the biology and genetic plasticity of C. tropicalis and could provide the framework for the development of new genetic tools in the field.
in PLoS Biology on 2025-04-01 14:00:00 UTC.
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by Dongdong Zhao, Yuanhui Huo, Naizhen Zheng, Xiang Zhu, Dingting Yang, Yunqiang Zhou, Shengya Wang, Yiru Jiang, Yili Wu, Yun-wu Zhang
Memprin/A5/mu (MAM) domain containing glycosylphosphatidylinositol anchor 2 (MDGA2) is an excitatory synaptic suppressor and its mutations have been associated with autism spectrum disorder (ASD). However, the detailed physiological function of MDGA2 and the mechanism underlying MDGA2 deficiency-caused ASD has yet to be elucidated. Herein, we not only confirm that Mdga2 +/− mice exhibit increased excitatory synapse transmission and ASD-like behaviors, but also identify aberrant brain-derived neurotrophic factor/tyrosine kinase B (BDNF/TrkB) signaling activation in these mice. We demonstrate that MDGA2 interacts with TrkB through its memprin/A5/mu domain, thereby competing the binding of BDNF to TrkB. Both loss of MDGA2 and the ASD-associated MDGA2 V930I mutation promote the BDNF/TrkB signaling activity. Importantly, we demonstrate that inhibiting the BDNF/TrkB signaling by both small molecular compound and MDGA2-derived peptide can attenuate the increase of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor-mediated excitatory synaptic activity and social deficits in MDGA2-deficient mice. These results highlight a novel MDGA2-BDNF/TrkB-dependent mechanism underlying the synaptic function regulation, which may become a therapeutic target for ASD.
in PLoS Biology on 2025-04-01 14:00:00 UTC.
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by Zeng Hao Lim, Peng Zheng, Christopher Quek, Minou Nowrousian, Finn L. Aachmann, Gregory Jedd
A major goal of evolutionary biology is to identify the genetic basis for the emergence of complex adaptive traits. Diatoms are ancestrally photosynthetic microalgae. However, in the genus Nitzschia, loss of photosynthesis led to a group of free-living secondary heterotrophs whose manner of acquiring chemical energy is unclear. Here, we sequence the genome of the non-photosynthetic diatom Nitzschia sing1 and identify the genetic basis for its catabolism of the brown algal cell wall polysaccharide alginate. N. sing1 obtained an endolytic alginate lyase enzyme by horizontal gene transfer (HGT) from a marine bacterium. Subsequent gene duplication through unequal crossing over and transposition led to 91 genes in three distinct gene families. One family retains the ancestral endolytic enzyme function. By contrast, the two others underwent domain duplication, gain, loss, rearrangement, and mutation to encode novel functions that can account for oligosaccharide import through the endomembrane system and the exolytic production of alginate monosaccharides. Together, our results show how a single HGT event followed by substantial gene duplication and neofunctionalization led to alginate catabolism and access to a new ecological niche.
in PLoS Biology on 2025-04-01 14:00:00 UTC.
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by Yirong He, Debin Zeng, Qiongling Li, Lei Chu, Xiaoxi Dong, Xinyuan Liang, Lianglong Sun, Xuhong Liao, Tengda Zhao, Xiaodan Chen, Tianyuan Lei, Weiwei Men, Yanpei Wang, Daoyang Wang, Mingming Hu, Zhiying Pan, Haibo Zhang, Ningyu Liu, Shuping Tan, Jia-Hong Gao, Shaozheng Qin, Sha Tao, Qi Dong, Yong He, Shuyu Li
From childhood to adolescence, the structural organization of the human brain undergoes dynamic and regionally heterogeneous changes across multiple scales, from synapses to macroscale white matter pathways. However, during this period, the developmental process of multiscale structural architecture, its association with cortical morphological changes, and its role in the maturation of functional organization remain largely unknown. Here, using two independent multimodal imaging developmental datasets aged 6–14 years, we investigated developmental process of multiscale cortical organization by constructing an in vivo multiscale structural connectome model incorporating white matter tractography, cortico–cortical proximity, and microstructural similarity. By employing the gradient mapping method, the principal gradient derived from the multiscale structural connectome effectively recapitulated the sensory-association axis. Our findings revealed a continuous expansion of the multiscale structural gradient space during development, characterized by enhanced differentiation between primary sensory and higher-order transmodal regions along the principal gradient. This age-related differentiation paralleled regionally heterogeneous changes in cortical morphology. Furthermore, the developmental changes in coupling between multiscale structural and functional connectivity were correlated with functional specialization refinement, as evidenced by changes in the participation coefficient. Notably, the differentiation of the principal multiscale structural gradient was associated with improved cognitive abilities, such as enhanced working memory and attention performance, and potentially underpinned by synaptic and hormone-related biological processes. These findings advance our understanding of the intricate maturation process of brain structural organization and its implications for cognitive performance.
in PLoS Biology on 2025-04-01 14:00:00 UTC.
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Author(s): Arunava Patra, Joy Das Bairagya, and Sagar Chakraborty
The symbiotic relationship between the frameworks of classical game theory and evolutionary game theory is well established. However, evolutionary game theorists have mostly tapped into the classical game of complete information where players are completely informed of all other players' payoffs. Of…
[Phys. Rev. E 111, 044401] Published Tue Apr 01, 2025
in Physical Review E: Biological physics on 2025-04-01 10:00:00 UTC.
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Introduction Labour exploitation is a social determinant of health, affecting health outcomes and healthcare access. This scoping review aims to identify health outcomes of migrant victims of labour exploitation and barriers to accessing healthcare in the Eastern Mediterranean Region and Türkiye, and identify gaps in evidence for future studies. Inclusion criteria Studies conducted with/among migrants in the Eastern Mediterranean Region and Türkiye who experience labour exploitation and related health issues or barriers to accessing healthcare, regardless of age, nationality, gender, ethnicity, or migration status. Methods This review follows the updated Joanna Briggs Institute (JBI) guidelines for designing scoping reviews. We will include English and Arabic language peer-reviewed publications and grey literature between March 2011 and the present. An initial limited search in PubMed and Google Scholar was undertaken to refine the keywords. A full search of all selected databases and screening of references of previously published reviews will be conducted. We will search Cochrane, PubMed, Web of Science, SCOPUS databases, Google Scholar, and Overton for grey literature. Using COVIDENCE, two independent reviewers will screen the titles, abstracts, and full texts for eligibility and inclusion. Relevant information will be extracted using a tailored extraction data sheet. Analysis Extracted data will be analysed using descriptive statistics and an inductive content analysis approach. This review employs an intersectional framework, as well as a structural, symbolic, and interpersonal violence framework, alongside Tanahashi's health service coverage framework to analyse and synthesise the data. Results This review will illustrate key themes and relationships between labour exploitation, health outcomes, access to healthcare aspects, and influencing factors using appropriate summaries and visual tools. A comprehensive populated labour exploitation continuum framework will be developed. Dissemination This work will be disseminated through publication in a peer-reviewed journal and presentation in relevant fora.
in F1000Research on 2025-04-01 09:44:02 UTC.
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Background There is evidence that patients with COVID-19 have a higher prevalence of mental health problems than the normal population. This study aimed to investigate the prevalence of mental health problems and their associated factors in patients with asymptomatic or mildly symptomatic in the hospitel in Thailand. Methods Mental health problems were evaluated using the Depression, Anxiety, and Stress Scale - 21 items, and Patient Health Questionnaire-9. The prevalence of mental health problems was presented by frequency and percentage. McNemar's test was used to compare the prevalence of mental health problems between day 1 and day 7. Binary logistic regression was used to identify potential predictors of mental health problems. Results A total of 186 participants (68.3% female; mean age = 37.21 years (SD 13.66) were recruited. The depression, anxiety, and stress rate on day 1 of admission was 26.9%, 32.3% and 25.8%, respectively. Having mild COVID-19 symptoms was a significantly associated factor with anxiety (OR=2.69, 95%CI: 1.05-6.89) and stress (OR=4.53, 95%CI: 1.32-15.55). Conclusions There was a high rate of mental health problems in COVID-19 patients. Detecting and managing mental health problems should be considered standard care for COVID-19 patients.
in F1000Research on 2025-04-01 09:42:18 UTC.
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Failure to reject a null-hypothesis may lead to erroneous conclusions regarding the absence of an association or inadequate statistical power. Because an estimate (and its variance) can never be exactly zero, traditional statistical tests cannot conclusively demonstrate the absence of an association. Instead, estimates of accuracy should be used to identify settings in which an association and its variability are sufficiently small to be clinically acceptable, directly providing information on safety and efficacy. Post-hoc power calculations should be avoided, as they offer no additional information beyond statistical tests and p-values. Furthermore, post-hoc power calculations can be misleading because of an inability to distinguish between results based on insufficient sample size and results that reflect clinically irrelevant differences. Most multiple testing procedures unrealistically assume that all positive results are false positives. However, in applied settings, results typically represent a mix of true and false positives. This implies that multiplicity corrections do not effectively differentiate between true and false positives. Instead, considering the distributions of p-values and the proportion of significant results can help to identify bodies of evidence unlikely to be driven by false-positive results. In conclusion, rather than attempting to categorize results as true or false, medical research should embrace established statistical methods that focus on estimation accuracy, replication, and consistency.
in F1000Research on 2025-04-01 09:40:25 UTC.
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Background This study assessed the functional outcomes and complications of open reduction and internal fixation (ORIF) using pre-contoured superior clavicle locking plates for displaced midshaft clavicular fractures. Methods In a prospective two-center study at Al-Thawra Modern General Hospital and Kuwait University Hospital, Sana’a, Yemen, from January 2018 to September 2024, 65 patients (≥18 years) with closed, displaced midshaft clavicular fractures (displacement >2 cm, shortening >2 cm, comminution, or skin tenting) underwent ORIF. Functional outcomes were evaluated six months postoperatively using the University of California, Los Angeles (UCLA) shoulder rating score. Data were analyzed using SPSS version 26. Results The mean patient age was 32.09 years (83.1% male, n=54). Road traffic accidents were the primary mechanism of injury (66.2%, n=43). At 6 months, the mean UCLA score was 32.46 ± 2.54, with 98.5% (n=64) achieving good or excellent outcomes (UCLA score ≥27) and 1.5% (n=1) fair/poor. Complications included hardware irritation (1.5%, n=1), hardware failure (3.1%, n=2), and superficial infections (1.5%, n=1). All patients (100%) reported satisfaction with their outcomes. The UCLA scores varied significantly according to injury mechanism, side, and age, with older patients showing lower scores. Conclusion ORIF with pre-contoured locked plates yielded promising functional outcomes, high patient satisfaction, and low complication rates. However, the observational design, lack of a control group, and 6-month follow-up limit broader conclusions. Larger controlled studies are needed to validate these findings and guide the optimal management of displaced midshaft clavicular fractures.
in F1000Research on 2025-04-01 09:38:43 UTC.
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Osteoarthritis (OA) and rheumatoid arthritis (RA) are prevalent, debilitating conditions causing significant joint pain and functional impairment. OA affects over 30% of the global population, while RA impacts around 1%, with risk factors including age, sex, and smoking. Both disorders are frequently accompanied by psychological issues such as anxiety and depression, which exacerbate physical symptoms and lead to additional health problems. Fibromyalgia, often co-occurring with OA and RA, further complicates these conditions with symptoms like widespread pain and stiffness. This creates a vicious cycle where pain and inflammation contribute to worsening anxiety and depression, further impairing quality of life. The interplay of these conditions results in severe physical, emotional, and social consequences, including restricted mobility and increased economic burden due to healthcare costs and reduced work capacity. Current research highlights significant comorbidity but is limited by small sample sizes and reliance on self-reported data. There is a critical need for larger, more comprehensive studies to explore these interactions and inform integrated treatment strategies. Enhanced awareness and holistic care approaches are essential to improving outcomes for patients with these chronic conditions.
in F1000Research on 2025-04-01 09:34:55 UTC.
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Tracheostomy tube migration is a rare but potentially life-threatening complication. We present the case of a 66-year-old male with chronic obstructive pulmonary disease, dual-chamber pacemaker implantation for chronic ischemic cardiomyopathy, and supraglottic squamous cell carcinoma. The patient developed respiratory distress due to intrabronchial migration of the tracheostomy tube. Initial evaluation revealed significant respiratory effort, inspiratory stridor, and an absent tube at the stoma site. Imaging and bronchoscopy confirmed the tube’s presence in the left main bronchus with associated mucosal inflammation. The patient underwent bronchoscopic-guided tube removal and successful repositioning of a cuffed tracheostomy tube under spontaneous ventilation anaesthesia. Following stabilization, he was discharged with plans for a permanent tracheostomy. Tracheostomy tube migration presents a significant diagnostic and therapeutic challenge, particularly given the scarcity of studies involving adults with this complication. This case highlights the importance of early recognition, prompt imaging—especially bronchoscopy—and tailored management strategies, while emphasizing the active involvement of the patient and family in the care pathway. It also underscores the necessity for vigilant monitoring to prevent severe, potentially fatal, complications.
in F1000Research on 2025-04-01 09:33:24 UTC.
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Proceedings of the National Academy of Sciences, Volume 122, Issue 14, April 2025.
SignificanceThis work advances our understanding of the mechanisms underlying reactivation of memory-associated neurons. While many studies have shown that reactivating neurons involved in an experience can lead to apparent recall, few have investigated ...
in PNAS on 2025-04-01 07:00:00 UTC.
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Proceedings of the National Academy of Sciences, Volume 122, Issue 14, April 2025.
SignificanceWe modeled human LMX1B missense mutations in mice to explore how they disrupt brain serotonin neuron development. Missense heterozygosity selectively impaired postnatal formation of serotonin axon arbors throughout the forebrain, notably in ...
in PNAS on 2025-04-01 07:00:00 UTC.
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Proceedings of the National Academy of Sciences, Volume 122, Issue 14, April 2025.
SignificanceThis research studied how the cochlea, essential for hearing, recovers from excitotoxic damage. While some connections between nerve cells were permanently lost, the compound action potential of the auditory nerve returned to normal, even ...
in PNAS on 2025-04-01 07:00:00 UTC.
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Proceedings of the National Academy of Sciences, Volume 122, Issue 14, April 2025.
SignificanceSensory perception often occurs under challenging conditions, such as a noisy background or a dim environment, yet stimulus sensitivity can remain unaffected. One hypothesis is that cognitive resources are recruited to the task, thereby ...
in PNAS on 2025-04-01 07:00:00 UTC.
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Proceedings of the National Academy of Sciences, Volume 122, Issue 14, April 2025.
in PNAS on 2025-04-01 07:00:00 UTC.
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Proceedings of the National Academy of Sciences, Volume 122, Issue 14, April 2025.
in PNAS on 2025-04-01 07:00:00 UTC.
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Li et al. found that hypoxia-induced PRMT1 methylates HIF2β, enhancing HIF1α/HIF2β activity, glycolysis, and metabolic reprogramming. Notably, PRMT1 inhibition, particularly in combination with HIF1α/P300 disruption, exhibits a synergistic effect in suppressing breast tumor growth, highlighting PRMT1 as a promising therapeutic target.
in Cell Reports: Current Issue on 2025-04-01 00:00:00 UTC.
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Zhang et al. provide eight high-quality Anas genomes and further construct an Anas pan-genome. Based on these genome resources and resequencing data, the authors performed a comprehensive investigation of Anas evolution and duck domestication with emphasis on the potential impact of the LTR RT burst and several SVs in duck domestication.
in Cell Reports: Current Issue on 2025-04-01 00:00:00 UTC.
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Molinos-Albert et al. developed an integrative analysis of SARS-CoV-2 antibody B-cell responses in a cohort of 113 healthcare workers followed since the beginning of the pandemic during a 3-year period. The authors report that despite differential kinetics, COVID-19-recovered and -naive individuals developed comparable and long-lasting immunity.
in Cell Reports: Current Issue on 2025-04-01 00:00:00 UTC.
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Li et al. revealed a cytokine-independent activity of CD4+ T cells in promoting HFD-induced obesity. Mice deficient in the Sostdc1 gene in T cells showed resistance to obesity and insulin resistance. SOSTDC1 directly promotes adipogenesis and downregulates lipolysis through the LRP5/6-β-catenin pathway in adipocytes, therefore promoting obesity.
in Cell Reports: Current Issue on 2025-04-01 00:00:00 UTC.
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Lai et al. demonstrate that BCG-induced trained immunity promotes antiviral activity of the macrophages through upregulation of low-density lipoprotein receptor (LDLR). Cholesterol is thereafter accumulated to exaggerate type I interferon signaling. The engagement of LDLR in BCG-trained antiviral immunity also makes PCSK9 inhibitors an alternative application against virus infection.
in Cell Reports: Current Issue on 2025-04-01 00:00:00 UTC.
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Perugino et al. examined the durability of all class-switched human B cells after vaccination and identified IgD−CXCR5+CD11c−CD27− DN1 B cells as durable B cells, less somatically mutated and more clonally expanded than germinal center-derived IgD−CXCR5+CD11c−CD27+ memory B cells. These extrafollicular B cells exhibit a TP63 linked transcriptional signature.
in Cell Reports: Current Issue on 2025-04-01 00:00:00 UTC.
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Widloski et al. show that the forward-oriented alternating theta sweeps seen in the hippocampal-entorhinal (HPC-EC) region during navigation emerge spontaneously and robustly in a single continuous attractor network with spike frequency adaptation. These findings suggest that the same mechanism that generates theta sweeps also organizes their content across time.
in Cell Reports: Current Issue on 2025-04-01 00:00:00 UTC.
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Li et al. utilized single-cell and bulk multiomics sequencing techniques to capture the trajectory of in vitro ND1-induced neuronal reprogramming and uncover critical regulations at both transcriptomic and chromatin levels.
in Cell Reports: Current Issue on 2025-04-01 00:00:00 UTC.
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Intrinsic enteric neurons (iENs) emerge as crucial regulators of immune responses in the intestine, but the underlying molecular mechanisms remain unclear. Sun et al. show that AHR differentially regulates iEN activation in different intestinal segments and that AHR expression in neurons constrains ILC3 responses and antibacterial immunity in the ileum.
in Cell Reports: Current Issue on 2025-04-01 00:00:00 UTC.
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Yu et al. identify that the effector EtEC81 from Exserohilum turcicum, a fungal pathogen that causes northern corn leaf blight of maize, is associated with its pathogenesis. EtEC81 targets ZmEIP1 to reprogram pre-mRNA splicing in maize, leading to the misregulation of cellular activities, which, in turn, induces host immune responses.
in Cell Reports: Current Issue on 2025-04-01 00:00:00 UTC.
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Nature, Published online: 01 April 2025; doi:10.1038/s41586-025-08934-y
Author Correction: Controlled patterning of crystalline domains by frontal polymerization
in Nature on 2025-04-01 00:00:00 UTC.
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Nature, Published online: 01 April 2025; doi:10.1038/s41586-025-08906-2
Author Correction: Isoprene nitrates drive new particle formation in Amazon’s upper troposphere
in Nature on 2025-04-01 00:00:00 UTC.
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Nature, Published online: 01 April 2025; doi:10.1038/d41586-025-01006-1
Minerals will shape future geopolitical order
in Nature on 2025-04-01 00:00:00 UTC.
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Nature, Published online: 01 April 2025; doi:10.1038/d41586-025-01007-0
China has already taken steps to reduce retractions of papers from its hospitals
in Nature on 2025-04-01 00:00:00 UTC.
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Nature, Published online: 01 April 2025; doi:10.1038/d41586-025-00985-5
The global scientific community must keep studying LGBT+ health
in Nature on 2025-04-01 00:00:00 UTC.
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Nature, Published online: 01 April 2025; doi:10.1038/d41586-025-01005-2
Action needed to mitigate effects of slashing USAID
in Nature on 2025-04-01 00:00:00 UTC.
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Nature, Published online: 01 April 2025; doi:10.1038/d41586-025-00915-5
Why really good trombones sound the way they do, and the peculiar motion of creatures in the ocean, in this week’s dip into Nature’s archive.
in Nature on 2025-04-01 00:00:00 UTC.
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Nature, Published online: 01 April 2025; doi:10.1038/d41586-025-00972-w
Multi-year episodes of the climatic pattern are much more frequent now than they were seven millennia ago.
in Nature on 2025-04-01 00:00:00 UTC.
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Nature, Published online: 01 April 2025; doi:10.1038/d41586-025-00932-4
Regulatory efforts to purge PFASs from drinking water have led to a rush for technologies that can capture and destroy the chemicals.
in Nature on 2025-04-01 00:00:00 UTC.
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Nature, Published online: 01 April 2025; doi:10.1038/d41586-025-01018-x
Long-awaited report explores the practicalities of building a triple-sized version of the LHC.
in Nature on 2025-04-01 00:00:00 UTC.
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Nature, Published online: 01 April 2025; doi:10.1038/d41586-025-01016-z
In shock move, four institute directors at the US biomedical agency are removed from their posts.
in Nature on 2025-04-01 00:00:00 UTC.
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Nature, Published online: 01 April 2025; doi:10.1038/d41586-025-00997-1
‘Supershear’ quake moved fast and far, amplifying the damage and human toll.
in Nature on 2025-04-01 00:00:00 UTC.
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Nature, Published online: 01 April 2025; doi:10.1038/d41586-025-00992-6
Europe is advertising itself as a destination for embattled US scientists. It seems many are considering leaving.
in Nature on 2025-04-01 00:00:00 UTC.
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Nature, Published online: 01 April 2025; doi:10.1038/d41586-025-01002-5
The European Union’s new research chief Ekaterina Zaharieva speaks to Nature about attracting disaffected US scientists and cutting grant bureaucracy.
in Nature on 2025-04-01 00:00:00 UTC.
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Nature, Published online: 01 April 2025; doi:10.1038/d41586-025-00931-5
As governments fight to regulate access to materials important for many technologies, the people mining them are left behind.
in Nature on 2025-04-01 00:00:00 UTC.
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Nature Neuroscience, Published online: 01 April 2025; doi:10.1038/s41593-025-01930-5
Through multiday imaging and acute whole-cell recordings in behaving mice, Qian, Li and Magee provide insight into place field formation in general and specifically how the hippocampus adaptively remaps for flexible goal-directed navigation.
in Nature Neuroscience on 2025-04-01 00:00:00 UTC.
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Nature Communications, Published online: 01 April 2025; doi:10.1038/s41467-025-58332-1
Author Correction: In-situ positive electrode-electrolyte interphase construction enables stable Ah-level Zn-MnO2 batteries
in Nature Communications on 2025-04-01 00:00:00 UTC.
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Nature Communications, Published online: 01 April 2025; doi:10.1038/s41467-025-58331-2
Author Correction: On-surface synthesis of triangulene trimers via dehydration reaction
in Nature Communications on 2025-04-01 00:00:00 UTC.
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Nature Communications, Published online: 01 April 2025; doi:10.1038/s41467-025-58562-3
Author Correction: A combined adjuvant and ferritin nanocage based mucosal vaccine against Streptococcus pneumoniae induces protective immune responses in a murine model
in Nature Communications on 2025-04-01 00:00:00 UTC.
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Nature Communications, Published online: 01 April 2025; doi:10.1038/s41467-025-58278-4
Hypoglycemia is a serious and potentially life-threatening condition for people with insulin dependent diabetes, but preventative hypoglycemia therapies are elusive. Here, the authors report the use of catechol and boronic acid chemistry to design a self-crosslinkable hydrogel-based microneedle patch that delivers Zinc-Glucagon at low glucose levels and prevents insulin-induced hypoglycemia.
in Nature Communications on 2025-04-01 00:00:00 UTC.
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Nature Physics, Published online: 01 April 2025; doi:10.1038/s41567-025-02846-4
Reply to: Re-examining magnetic tuning of Casimir forces
in Nature Physics on 2025-04-01 00:00:00 UTC.
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Nature Physics, Published online: 01 April 2025; doi:10.1038/s41567-025-02845-5
Re-examining magnetic tuning of Casimir forces
in Nature Physics on 2025-04-01 00:00:00 UTC.
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Nature Physics, Published online: 01 April 2025; doi:10.1038/s41567-025-02853-5
In many optical systems with time-reversal symmetry, it is possible to control the output waves by shaping the input fields. Now a scheme is presented that works for multimode fibres that lack time-reversal symmetry due to thermal effects.
in Nature Physics on 2025-04-01 00:00:00 UTC.
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Scientific Data, Published online: 01 April 2025; doi:10.1038/s41597-025-04919-8
Genome-centric metagenomics reveals uncharacterised microbiomes in Angus cattle
in Nature scientific data on 2025-04-01 00:00:00 UTC.
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Scientific Data, Published online: 01 April 2025; doi:10.1038/s41597-025-04851-x
Ultrasonic pulse-echo dataset from numerical modelling for oil and gas well integrity investigations
in Nature scientific data on 2025-04-01 00:00:00 UTC.
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Scientific Data, Published online: 01 April 2025; doi:10.1038/s41597-025-04882-4
Chromosome-level genome assembly of the Adonis ladybird Hippodamia variegata
in Nature scientific data on 2025-04-01 00:00:00 UTC.
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Scientific Data, Published online: 01 April 2025; doi:10.1038/s41597-025-04890-4
A chromosome-level genome assembly and annotation of the Pseudorasbora elongata (Cypriniformes: Cyprinidae)
in Nature scientific data on 2025-04-01 00:00:00 UTC.
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Scientific Data, Published online: 01 April 2025; doi:10.1038/s41597-025-04879-z
Electrooculography Dataset for Objective Spatial Navigation Assessment in Healthy Participants
in Nature scientific data on 2025-04-01 00:00:00 UTC.
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Scientific Data, Published online: 01 April 2025; doi:10.1038/s41597-025-04881-5
Mapping accumulated carbon storage of global mangroves from 2000 to 2020 at a 1 km resolution
in Nature scientific data on 2025-04-01 00:00:00 UTC.
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Scientific Data, Published online: 01 April 2025; doi:10.1038/s41597-025-04877-1
High-Res Acoustic and Environmental Data to Monitor Bombus dahlbomii Amid Invasive Species, Habitat Loss
in Nature scientific data on 2025-04-01 00:00:00 UTC.
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Scientific Data, Published online: 01 April 2025; doi:10.1038/s41597-025-04912-1
A multiomics dataset of paired CT image and plasma cell-free DNA end motif for patients with pulmonary nodules
in Nature scientific data on 2025-04-01 00:00:00 UTC.
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Communications Biology, Published online: 01 April 2025; doi:10.1038/s42003-025-07982-4
Author Correction: Characterization of a second class Ie ribonucleotide reductase
in Nature communications biology on 2025-04-01 00:00:00 UTC.
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Communications Biology, Published online: 01 April 2025; doi:10.1038/s42003-025-07826-1
Reply to: The genomic structure of complex chromosomal rearrangement at the Fm locus in black-bone Silkie chicken
in Nature communications biology on 2025-04-01 00:00:00 UTC.
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Communications Biology, Published online: 01 April 2025; doi:10.1038/s42003-025-07951-x
Publisher Correction: Transcriptional dynamics in type 2 diabetes progression is linked with circadian, thermogenic, and cellular stress in human adipose tissue
in Nature communications biology on 2025-04-01 00:00:00 UTC.
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Communications Biology, Published online: 01 April 2025; doi:10.1038/s42003-025-07825-2
The genomic structure of complex chromosomal rearrangement at the Fm locus in black-bone Silkie chicken
in Nature communications biology on 2025-04-01 00:00:00 UTC.
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Communications Biology, Published online: 01 April 2025; doi:10.1038/s42003-025-07979-z
The protective role of MAIT cells in the HFRS disease and the ER stress related mechanisms behind MAIT cell pyroptosis during HTNV infection.
in Nature communications biology on 2025-04-01 00:00:00 UTC.
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Communications Biology, Published online: 01 April 2025; doi:10.1038/s42003-025-07953-9
The identification of an unusual glycerol-3-phosphate dehydrogenase in Sulfolobus acidocaldarius highlights the evolution and functional diversity of glycerol degrading enzymes across the archaeal domain.
in Nature communications biology on 2025-04-01 00:00:00 UTC.
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Communications Biology, Published online: 01 April 2025; doi:10.1038/s42003-025-07737-1
An sRNA study in Arabidopsis reveals that a tRF drives immunity via DCL1 and AGO2, activating defense genes, suppressing Gypsy retrotransposons, and binding chromatin to coordinate transcriptional reprogramming in a sequence-dependent manner.
in Nature communications biology on 2025-04-01 00:00:00 UTC.
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Communications Biology, Published online: 01 April 2025; doi:10.1038/s42003-025-07869-4
A patient-derived organoid library of esophageal squamous cell carcinoma (ESCC) identifies chemotherapy (chemo)-resistant ESCC organoids (ESCCOs) and reveals the molecular basis, biomarkers, and candidate therapeutics of the chemo-resistant ESCCOs.
in Nature communications biology on 2025-04-01 00:00:00 UTC.
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Vertebrates have evolved great diversity in the number of segments dividing the trunk body, however, the developmental origin of the evolvability of this trait is poorly understood. The number of segments is thought to be determined in embryogenesis as a product of morphogenesis of the pre-somitic mesoderm (PSM) and the periodicity of a molecular oscillator active within the PSM known as the segmentation clock. Here, we explore whether the clock and PSM morphogenesis exhibit developmental modularity, as independent evolution of these two processes may explain the high evolvability of segment number. Using a computational model of the clock and PSM parameterised for zebrafish, we find that the clock is broadly robust to variation in morphogenetic processes such as cell ingression, motility, compaction, and cell division. We show that this robustness is in part determined by the length of the PSM and the strength of phase coupling in the clock. As previous studies report no changes to morphogenesis upon perturbing the clock, we suggest that the clock and morphogenesis of the PSM exhibit developmental modularity.
in eLife on 2025-04-01 00:00:00 UTC.
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The infralimbic cortex (IL) is essential for flexible behavioral responses to threatening environmental events. Reactive behaviors such as freezing or flight are adaptive in some contexts, but in others a strategic avoidance behavior may be more advantageous. IL has been implicated in avoidance, but the contribution of distinct IL neural subtypes with differing molecular identities and wiring patterns is poorly understood. Here, we study IL parvalbumin (PV) interneurons in mice as they engage in active avoidance behavior, a behavior in which mice must suppress freezing in order to move to safety. We find that activity in inhibitory PV neurons increases during movement to avoid the shock in this behavioral paradigm, and that PV activity during movement emerges after mice have experienced a single shock, prior to learning avoidance. PV neural activity does not change during movement toward cued rewards or during general locomotion in the open field, behavioral paradigms where freezing does not need to be suppressed to enable movement. Optogenetic suppression of PV neurons increases the duration of freezing and delays the onset of avoidance behavior, but does not affect movement toward rewards or general locomotion. These data provide evidence that IL PV neurons support strategic avoidance behavior by suppressing freezing.
in eLife on 2025-04-01 00:00:00 UTC.
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A study in mice reveals key interactions between proteins involved in fibroblast growth factor signaling and how they contribute to distinct stages of eye lens development.
in eLife on 2025-04-01 00:00:00 UTC.
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Resistance to anthelmintics, particularly the macrocyclic lactone ivermectin (IVM), presents a substantial global challenge for parasite control. We found that the functional loss of an evolutionarily conserved E3 ubiquitin ligase, UBR-1, leads to IVM resistance in Caenorhabditis elegans. Multiple IVM-inhibiting activities, including viability, body size, pharyngeal pumping, and locomotion, were significantly ameliorated in various ubr-1 mutants. Interestingly, exogenous application of glutamate induces IVM resistance in wild-type animals. The sensitivity of all IVM-affected phenotypes of ubr-1 is restored by eliminating proteins associated with glutamate metabolism or signaling: GOT-1, a transaminase that converts aspartate to glutamate, and EAT-4, a vesicular glutamate transporter. We demonstrated that IVM-targeted GluCls (glutamate-gated chloride channels) are downregulated and that the IVM-mediated inhibition of serotonin-activated pharynx Ca2+ activity is diminished in ubr-1. Additionally, enhancing glutamate uptake in ubr-1 mutants through ceftriaxone completely restored their IVM sensitivity. Therefore, UBR-1 deficiency-mediated aberrant glutamate signaling leads to ivermectin resistance in C. elegans.
in eLife on 2025-04-01 00:00:00 UTC.
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The protein ligase Connectase can be used to fuse proteins to small molecules, solid carriers, or other proteins. Compared to other protein ligases, it offers greater substrate specificity, higher catalytic efficiency, and catalyzes no side reactions. However, its reaction is reversible, resulting in only 50% fusion product from two equally abundant educts. Here, we present a simple method to reliably obtain 100% fusion product in 1:1 conjugation reactions. This method is efficient for protein-protein or protein-peptide fusions at the N- or C-termini. It enables the generation of defined and completely labeled antibody conjugates with one fusion partner on each chain. The reaction requires short incubation times with small amounts of enzyme and is effective even at low substrate concentrations and at low temperatures. With these characteristics, it presents a valuable new tool for bioengineering.
in eLife on 2025-04-01 00:00:00 UTC.
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Millions of Americans suffering from Opioid Use Disorders face a high risk of fatal overdose due to opioid-induced respiratory depression (OIRD). Fentanyl, a powerful synthetic opioid, is a major contributor to the rising rates of overdose deaths. Reversing fentanyl overdoses has proved challenging due to its high potency and the rapid onset of OIRD. We assessed the contributions of central and peripheral mu opioid receptors (MORs) in mediating fentanyl-induced physiological responses. The peripherally restricted MOR antagonist naloxone methiodide (NLXM) both prevented and reversed OIRD to a degree comparable to that of naloxone (NLX), indicating substantial involvement of peripheral MORs to OIRD. Interestingly, NLXM-mediated OIRD reversal did not produce aversive behaviors observed after NLX. We show that neurons in the nucleus of the solitary tract (nTS), the first central synapse of peripheral afferents, exhibit a biphasic activity profile following fentanyl exposure. NLXM pretreatment attenuates this activity, suggesting that these responses are mediated by peripheral MORs. Together, these findings establish a critical role for peripheral MORs, including ascending inputs to the nTS, as sites of dysfunction during OIRD. Furthermore, selective peripheral MOR antagonism could be a promising therapeutic strategy for managing OIRD by sparing CNS-driven acute opioid-associated withdrawal and aversion observed after NLX.
in eLife on 2025-04-01 00:00:00 UTC.
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The Calvin-Benson-Bassham cycle (CBBC) performs carbon fixation in photosynthetic organisms. Among the eleven enzymes that participate in the pathway, sedoheptulose-1,7-bisphosphatase (SBPase) is expressed in photo-autotrophs and catalyzes the hydrolysis of sedoheptulose-1,7-bisphosphate (SBP) to sedoheptulose-7-phosphate (S7P). SBPase, along with nine other enzymes in the CBBC, contributes to the regeneration of ribulose-1,5-bisphosphate, the carbon-fixing co-substrate used by ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco). The metabolic role of SBPase is restricted to the CBBC, and a recent study revealed that the three-dimensional structure of SBPase from the moss Physcomitrium patens was found to be similar to that of fructose-1,6-bisphosphatase (FBPase), an enzyme involved in both CBBC and neoglucogenesis. In this study we report the first structure of an SBPase from a chlorophyte, the model unicellular green microalga Chlamydomonas reinhardtii. By combining experimental and computational structural analyses, we describe the topology, conformations, and quaternary structure of Chlamydomonas reinhardtii SBPase (CrSBPase). We identify active site residues and locate sites of redox- and phospho-post-translational modifications that contribute to enzymatic functions. Finally, we observe that CrSBPase adopts distinct oligomeric states that may dynamically contribute to the control of its activity.
in eLife on 2025-04-01 00:00:00 UTC.
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We analyze information rates associated with top performances in memory competitions and reveal three phenomena. First, in tasks with short memorization time, information processing reaches up to 42 bit/s with most of the time spent on reading, suggesting that mental associations are formed even more rapidly. Second, record performances show a remarkable concordance across time scales: the processing speed depends on memorization time as a power law. Third, despite dramatic improvements in scores and mnemonic strategies over the last decades, the differences in information rates across memorization tasks remain remarkably consistent.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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Cortical microcircuits play a fundamental role in natural intelligence. While they inspired a wide range neural computation models and artificial intelligence algorithms, few attempts have been made to directly emulate them with an electronic computational substrate that uses the same physics of computation. Here we present a heterogeneous canonical microcircuit architecture compatible with analog neuromorphic electronic circuits that faithfully reproduce the properties of real synapses and neurons. The architecture comprises populations of interacting excitatory and inhibitory neurons, disinhibition pathways, and spike-driven multi=compartment dendritic learning mechanisms. By co-designing the computational model with its neuromorphic hardware implementation, we developed a neural processing system that can perform complex signal processing functions, learning, and classification tasks robustly and reliably, despite the inherent variability of the analog circuits, using ultra-low power energy consumption features comparable to those of their biological counterparts. We demonstrate how both the model architecture and its hardware implementation seamlessly capture the hallmarks of neural computation: attractor dynamics, adaptation, winner-take-all behavior, and resilience to variability, within a compact, low-power computing substrate. We validate the model's learning performance both from the algorithmic perspective and with detailed electronic circuit simulation experiments and characterize its robustness to noise. Our results illustrate how local, biologically plausible rules for plasticity and gating can overcome challenges like catastrophic forgetting and parameter variability, enabling effective always-on adaptation. Beyond offering insights into the nature of computation in neural systems, our approach introduces a foundation for ultra-low power, fault-tolerant architectures capable of complex signal processing at the edge. By embracing -rather than mitigating- variability, these neuromorphic circuits exhibit a powerful synergy with emerging memory technologies, suggesting a new paradigm for sophisticated "in-memory" computing. Through such tight integration of neuroscience principles and analog circuit design, we pave the way toward a class of brain-inspired processors that can learn continuously and respond dynamically to real-world inputs.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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Neural excitation/inhibition (E/I) balance is dynamically regulated on multiple timescales. Adaptive changes in E/I balance changes can support healthy development, learning, and cognition, while disordered E/I balance is implicated in neurodevelopmental disorders, neurodegenerative disorders, and states of impaired vigilance. There has been growing interest in inferring E/I balance from efficient and noninvasive measurements such as electroencephalography (EEG), and several algorithms have been proposed to estimate E/I balance from EEG recordings. Despite promising results, there has been a lack of validation studies testing the underlying neurochemical changes leading to increased or decreased EEG-based E/I. Here we assess E/I balance with concurrent EEG and magnetic resonance spectroscopy (MRS) in humans. We estimate a standard measure of E/I balance, glutamate concentration divided by GABA concentration, and assess the correspondence between each candidate EEG-based E/I algorithm to this MRS-based estimate. Due to the methodological interest in both between-subjects research (e.g., comparing disordered to healthy E/I) as well as within-subjects research (e.g., comparing pre-intervention to post-intervention E/I), we quantify the associations between EEG-based E/I and MRS-based E/I separately for between-subjects and within-subjects comparisons. We find that each EEG-based E/I algorithm shows reliable and positive associations with MRS-based E/I. While these associations are evident for between-subjects comparisons, they are quite weak for within-subjects comparisons. Candidate EEG-based E/I algorithms are thus likely to be reflecting, at least in part, relative concentrations of cortical glutamate and GABA, although poor signal quality appears to limit these methods when attempting to increase temporal precision and identify within-subjects variations.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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Understanding the mechanisms of the human brain enabling complex cognition is a major objective of neuroscientific research. Studies employing functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) identified increased activation in specific brain regions during different cognitive states. However, the neural processes during the performance of an intelligence test remains largely unknown. This study considers intelligence as a whole-brain network phenomenon and investigates how the connectedness of specific brain regions contributes to performance on the Raven Progressive Matrices (RAPM), a well-established intelligence test. Connectedness was characterized with graph-theoretical measures based on functional connectivity derived from fMRI BOLD (N=67) and EEG theta-band (N=128) activity. The results reveal that the extent to which specific frontal and parietal regions are connected to other brain systems during intelligence testing relates to individual test performance. These regions may act as controllers, enabling flexible and efficient switches between cognitive states required to excel in intelligence tests.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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The mouse model is by far the most widely used animal model in preclinical neuroscience, but translating findings to humans suffers from the lack of a formal framework establishing the correspondence between the mouse and the human brain. In this study, we build on the concept of common brain space, and on previous work embedding gene expression profiles, to bring the two species into alignment for comparative analysis. Using a variational autoencoder (VAE) combined with a latent classifier, we create a latent space that strikes a balance between abstract features related to reconstruction and features pertaining to regional segregation. This approach demonstrates improved cross-species homology and within-species locality compared to existing comparative models. In addition, we show that brain alterations in mouse disease models can be translated to humans, predicting patterns of brain changes in Alzheimer's and Parkinson's diseases. The flexibility and scalability of this approach offer a promising framework to bridge between more animal models, comparing quantitative imaging modalities, and disease phenotypes. This in turn will help advance our understanding of species similarities and differences, enhancing both fundamental translational neuroscience and disease modelling.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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The current study investigated the influence of testosterone on agonistic behavior and dominance over an opponent before and after adolescence in male Syrian hamsters (Mesocricetus auratus). We hypothesized that testosterone-dependent modulation of agonistic behavior would be greater following adolescent development. To test this hypothesis, prepubertal (14 days of age) and adult subjects (52-62 days of age) were gonadectomized and immediately implanted with testosterone or vehicle pellets. Fourteen days later, agonistic behavior was assessed in a neutral arena with age-matched testosterone-treated opponents. Flank marking was also assessed separately in response to male odors alone. Our hypothesis predicted that testosterone would modulate agonistic behavior and dominance over an opponent in adult but not in prepubertal subjects, however, only flank marking behavior followed the predicted data pattern. During both social interaction and scent tests, testosterone increased flank marking behavior in adults, but failed to increase flank marking in prepubertal subjects. Contrary to our predictions, testosterone treatment increased prepubertal subject attacks, decreased submissive tail-up displays, and facilitated prepubertal subject dominance over opponents. In adults, testosterone increased paws-on investigation and flank marking during social interactions. Taken together, these data indicate that some, but not all aspects of agonistic behavior are sensitive to the activational effects of testosterone prior to adolescence, and that activational effects of testosterone differ substantially between prepubertal and adult males. Our results may have implications for early pubertal timing and increased risk for externalizing symptoms and aggressive behavior in humans.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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Spike sorting is one of the cornerstones of extracellular electrophysiology. By leveraging advanced signal processing and data analysis techniques, spike sorting makes it possible to detect, isolate, and map single neuron spiking activity from both in vivo and in vitro extracellular electrophysiological recordings. A crucial step of any spike sorting pipeline is to reduce the dimensionality of the recorded spike waveform data. Reducing the dimensionality of the processed data is mandatory to apply the clustering algorithms responsible for detecting, isolating, and sorting the recorded putative neurons. In this paper we propose and illustrate on both synthetic and experimental data that employing the nonlinear dimensionality reduction technique Uniform Manifold Approximation and Projection can drastically improve the performance, efficiency, robustness, and scalability of spike sorting pipelines without increasing their computational cost. We show how replacing the linear or expert-defined dimensionality reduction methods commonly used in spike sorting pipelines by unsupervised, mathematically grounded, nonlinear methods increases the number of correctly sorted neurons, makes the identification of quieter, seldom spiking neurons more reliable, enables deeper and more precise explorations and analysis of the neural code, and paves new ways toward more efficient and end-to-end automatable spike sorting pipelines of large-scale extracellular neural recording as those produced by high-density multielectrode arrays.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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Severe coronavirus infections, including SARS-CoV-2, can cause neurological symptoms, but the underlying neurotropic mechanisms are unclear. Experiments with SARS-CoV-2 variants B.1.258.17, B.1.1.7, and BA.5.3.2 (termed wild-type, alpha and omicron, respectively) revealed that human astrocytes, not neurons, support viral proliferation. During the COVID-19 pandemic, new virus variants exhibited milder disease progression. A retrospective study of patients with COVID-19 infected by wild-type or alpha variants was conducted to test whether ketamine, an anaesthetic that inhibits endocytosis, affects COVID-19. At admission, patients infected with the wild-type showed greater disease severity than alpha variant patients, but the disease course was similar. This may be due to distinct ketamine-mediated SARS-CoV-2 variant-dependent effects, revealing stronger ketamine inhibition of the wild-type variant than the alpha variant mediating astrocyte responses involving the expression of ACE2, a viral cell entry site, viral proteins RNA-dependent RNA polymerase and envelope protein-E in infected cells. Overexpression of SARS-CoV-2 protein 3a attenuated astroglial lysosomal traffic, and 3a and nsp6 differentially modulated lipid droplet accumulation and initiation of autophagy, where ketamine predominantly affected vesicle dynamics. In summary, human astrocytes, but not neurons, contribute to SARS-CoV-2 neurotropism, highlighting the potential benefits of ketamine treatment in coronavirus infections.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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Background and Purpose: Hypertension promotes circulatory endothelial inflammation, reduces endothelial progenitor cell (EPC) function, and impairs their therapeutic potential following ischemic stroke. MiR-126 is known to regulate vascular development and angiogenesis. This study investigates the therapeutic potential of miR-126 by overexpressing it in EPCs to enhance their efficacy in hypertensive stroke conditions. Methods: Adult spontaneously hypertensive rats (SHRs, n=118) underwent permanent suture middle cerebral artery occlusion (MCAO) to induce ischemic stroke. One week post-stroke, animals were injected with EPCs overexpressing miR-126 or control EPCs. Treatment effects were evaluated over 35 days, using neurological scoring, infarct volume measurements, behavioral testing, and assessments of neuroinflammation, blood pressure, and angiogenesis. Exosomes from miR-126 overexpressing EPCs were isolated and analyzed for mechanistic studies. Results: In vitro, miR-126 enhanced EPC angiogenic function under stress. In vivo, miR-126 modified EPC treatment improved functional recovery, reduced infarct volume, and promoted angiogenesis compared to controls in SHRs. Furthermore, miR-126 treatment preserved the blood-brain barrier, reduced peripheral immune cell infiltration, and modulated neuroinflammation. Exosomes derived from miR-126 overexpression EPCs also promoted angiogenesis and reduced endothelial activation under stress conditions. Conclusions: EPC overexpressing miR-126 provides neuroprotection by enhancing angiogenesis, reducing ischemic injury, and preserving blood-brain barrier integrity in hypertensive stroke models. This approach modulates neuroinflammation and improves neurological outcomes, suggesting gene-modified EPCs as a promising strategy for ischemic stroke therapy, particularly under hypertensive conditions.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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Background Synapses are essential for learning and memory, and their loss predicts cognitive decline in Alzheimer's disease (AD). Synaptic loss is associated with excitotoxicity, neuroinflammation, amyloid-{beta}, and tau pathology, but the molecular mechanisms remain unclear. There is an urgent need to identify new targets to modify the disease and slow synaptic loss and cognitive decline. This study examines if calcium-dependent phospholipase A2 (cPLA2) is implicated in AD synaptic loss. cPLA2 catalyzes membrane phospholipids to release arachidonic acid, which can be metabolized into inflammatory eicosanoids. Methods cPLA2 levels were examined in synaptosomes isolated from the postmortem frontal cortex of individuals with no cognitive impairment (NCI), mild cognitive impairment (MCI), and AD dementia from the Religious Orders Study (ROS). Eicosanoids in synaptosomes were analyzed using lipidomics. Immunofluorescent staining investigated cPLA2 interactions with synaptic markers. Human iPSCs-derived neurons were used to study cPLA2 overactivation after exposure to amyloid-{beta} 42 oligomers (A{beta}42O), its relationships with synaptic markers, and the effects of cPLA2 inhibitors. Results We observed elevated cPLA2 (cPLA2 and cPLA2{beta}) in AD synaptosomes and positive correlations with postsynaptic density protein 95 (PSD-95) and cognitive dysfunction. Eicosanoids were increased in AD synaptosomes and correlated with cPLA2, indicating cPLA2 activity at synapses/synaptosomes. Phosphorylated cPLA2(p-cPLA2) colocalized with PSD-95 in synaptosomes, and with postsynaptic Ca2+/calmodulin-dependent protein kinase II (CaMKII) and dendritic microtubule-associated protein 2 (MAP2) in NCI and AD brains, where their levels were reduced in AD. P-cPLA2 colocalizes with MAP2 at the neuronal soma associated with neuritic plaques and neurodegeneration in AD. A{beta}42O activates cPLA2 in human iPSCs-derived neurons, leading to p-cPLA2 relocation from the cytosol to synaptic and dendritic sites to colocalize with CaMKII and MAP2, resulting in their reduction. P-cPLA2 also colocalized with PSD-95 in A{beta}42O-exposed neurons, accompanied with increased PSD-95 intensity at soma membrane. These processes were reversed by the cPLA2 inhibitor ASB14780. Conclusions cPLA2 overactivation at synapses, dendrites, and excitatory neuronal somas is associated with synaptic loss, neuritic plaques and neurodegeneration, potentially contributing to cognitive decline in AD. Future research needs to explore the role of cPLA2 as a disease-modifying target for AD.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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Complex regional pain syndrome (CRPS) is a form of chronic post-injury pain affecting the extremities. The mouse tibial fracture-cast model was developed to enable preclinical study of CRPS mechanisms and guide condition-specific drug development. Given the inherent limitations of reflex pain measures in mice, we sought to characterize pain-like behaviors in this model more holistically. We evaluated spontaneous and evoked pain and naturalistic behaviors after tibial fracture-cast injury in male mice in neutral and aversive environments using LabGym. Here, we report a unique ethological signature of pain in injured mice characterized by reflexive allodynia, thermal hyperalgesia, frequent grooming and reduced rearing in neutral and aversive environments, and decreased paw withdrawal and increased paw licking in an aversive environment. As proof-of-concept, we also leveraged this holistic behavioral evaluation for drug screening by characterizing the peripheral versus central effects of targeting alpha-2 receptors (2-AR) in the tibial fracture-cast model. We evaluated the impact of systemic delivery of dexmedetomidine (DEX), a selective 2-AR agonist, with or without antagonists, on holistic behavioral metrics in injured male mice. We found that DEX reduced mechanical allodynia primarily via central 2-ARs. DEX also decreased motion metrics, grooming and rearing in an open field, and distinctly affected the quality and quantity of grooming in an aversive environment, and this effect was not suppressed by systemic 2-AR antagonists. Ultimately, this study holistically captures pain-related behaviors and provides a detailed characterization of the relative contributions of peripheral and central 2-ARs to alpha2-mediated analgesia in male mice after tibial fracture-cast injury.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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Rationale: Epilepsy presents significant sex-based disparities in prevalence and manifestation. Epidemiological studies reveal that epilepsy is more prevalent in males, with lesional types being more common, whereas idiopathic generalized epilepsies are more frequently observed in females. These differences stress the importance of considering sex-specific factors in epilepsy diagnosis, treatment, and mechanistic research using preclinical models. To elucidate potential molecular differences that could explain these disparities and inform personalized treatment strategies, we conducted a proteomic analysis of epileptic brain tissues from both an experimental mouse model of genetic epilepsy and humans with drug-resistant epilepsy (DRE). Methods: We employed mass spectrometry-based proteomic analysis on brain tissues from DRE patients and the Pten knockout (KO) mouse model of genetic epilepsy with focal cortical dysplasia. Mouse samples included hippocampi from adult wild-type (WT) and Pten KO mice (4-5 per group and sex). Human samples included temporal cortex from 12 DRE adult patients (7 males, 5 females) and 5 non-epileptic (NE) controls (2 males, 3 females). Brain biopsies were collected with patients' informed consent under approved IRB protocols (Indiana University Health Biorepository). Proteomic profiles were analyzed using principal component analysis (PCA) along with volcano plots to identify significant changes in protein expression. The enrichment analysis of differentially expressed proteins was conducted by Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway. Results: PCA revealed distinct clustering of brain proteomes between epilepsy and control cases in both human and mice, with 390 proteins showing significant differences in human and 437 proteins in mouse samples. These proteins are primarily associated with ion channels, synaptic processes, and neuronal energy regulation. In the mouse model, males have more pronounced proteomic changes than females, with enrichment in metabolic pathways and VEGF signaling pathway, indicating a more severe vascular permeability impairment in males. In human DRE cases, 118 proteins were significantly changed by comparing epileptic females to males. Pathway analysis revealed changes in metabolic pathways and the HIF-1 signaling pathway, indicating that altered neuronal activity and inflammation may lead to increased oxygen consumption. Conclusion: These findings highlight significant differences between epilepsy and control brain samples in both humans and mice. Sex-specific analysis revealed distinct pathway enrichments between females and males, with males exhibiting a broader range of alterations, suggesting more extensive proteomic alterations. This study offers valuable insights into potential underlying mechanisms of epilepsy and underscores the importance of considering sex as a key factor in epilepsy research and therapeutic development.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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Background: Behavioral pathologies that characterize alcohol use disorder (AUD) are driven by the powerful reinforcing, or rewarding, properties of the drug. We have shown that glutamate AMPA receptor (AMPAR) activity is both necessary and sufficient for alcohol (ethanol) reinforcement. Transmembrane AMPAR regulatory protein (TARP) {gamma}-8 is an essential auxiliary protein that regulates AMPAR expression and activity; however, the role of TARP {gamma}-8 in AUD or other forms of addiction remains largely unexplored. Objectives: This study investigated the mechanistic role of TARP {gamma}-8 in operant ethanol self-administration (model of primary reinforcement) and cue-induced reinstatement of ethanol-seeking behavior (model of conditioned reinforcement) using TARP {gamma}-8 heterozygous null (+/-) mice. To determine if TARP {gamma}-8 signaling is targeted by ethanol use, we evaluated protein expression of TARP {gamma}-8, GluA1, CaMKII, and PSD-95 following ethanol self-administration. Results: A battery of tests evaluating food and water intake, taste reactivity, anxiety-like behavior, and object recognition memory showed no fundamental behavioral deficits in TARP {gamma}-8(+/-) mice, and no differences in response to acute ethanol or home-cage drinking as compared to wild-types. However, TARP {gamma}-8(+/-) mice exhibited significantly reduced acquisition and escalation of operant ethanol self-administration and reduced cue-induced reinstatement of ethanol-seeking behavior, with no differences in parallel sucrose-only controls. In wild-type mice, ethanol self-administration increased TARP {gamma}-8 expression in the amygdala, nucleus accumbens, and hippocampus, and increased GluA1 expression in the amygdala and prefrontal cortex, compared to sucrose controls. Conclusion: These findings highlight the specificity of TARP {gamma}-8 regulation of ethanol reinforcement mechanisms and identify this crucial AMPAR auxiliary protein as a target of ethanol in reward-related brain regions, highlighting its potential for development of novel pharmacotherapies for AUD.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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Day length, or seasonal photoperiod, shapes mood and affective behaviors but the neural mechanisms underlying these effects are still being defined. Serotonin neurons of the dorsal raphe nucleus (DRN) are critical regulators of affective behaviors and photoperiod modulates their excitability and ongoing activity. Here, we investigated the influence of seasonal photoperiod on the function and expression of small conductance calcium activated potassium (SK) channels which mediate the afterhyperpolarizing potential (AHP) in dorsal raphe serotonin neurons. Building on previous work demonstrating that photoperiod modulates serotonergic excitability and behavior, we hypothesized that day length influences SK channel activity, thereby contributing to differences in neuronal excitability observed between Long, Equinox, and Short photoperiod conditions. Using multi electrode array recording of DRN slices we found a significant dose dependent increase in spike rate to the application of the SK channel inhibitor apamin, indicating that SK channels indeed influence the spike rate of dorsal raphe serotonin neurons. In addition, DRN neurons in slices from Long photoperiod mice exhibited less pronounced responses to apamin relative to those from Short photoperiod mice, suggesting reduced function or expression of SK channels in Long photoperiod. Indeed, whole cell recordings demonstrated that SK channel mediated AHP currents were reduced in Long photoperiod mice. However, there were no significant differences in expression levels of the SK3 subunit (Kcnn3) in DRN serotonin neurons across photoperiod conditions as determined by single molecule fluorescence in situ hybridization. Overall, these findings indicate that photoperiod modulates SK channel function in DRN serotonin neurons likely at a post transcriptional level. This study advances our understanding of how seasonal cues influence intrinsic neuronal properties and provides a mechanistic link between photoperiod, serotonergic excitability, and mood-related behaviors. The identification of SK channels as modulators of photoperiodic effects may offer novel therapeutic targets for mood disorders associated with dysregulated serotonin signaling.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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Despite their importance in shaping visual perception, functional connectivity between ocular dominance columns (ODCs), the building blocks of neuronal processing within the human primary visual cortex (V1), remains largely unknown. Using high-resolution functional MRI (fMRI), we localized ODCs and assessed their resting-state functional connectivity (rs-FC) in 11 human adults (3 females). Consistent with anatomical studies in animals, we found stronger rs-FC in the middle compared to deep and superficial cortical depths and selectively stronger rs-FC between ODCs with alike compared to unalike ocular polarity. Beyond what was known from animal models, and consistent with human perceptual biases, we found stronger intra- and interhemispheric rs-FC in peripheral (compared to central) and in dorsal (compared to ventral) V1 subregions. Lastly, we found a significant correlation between rs-FC patterns and ODC maps, supporting the hypothesis that ODC maps can be predicted from rs-FC patterns within V1. These results highlight the heterogeneity in functional connectivity between ODCs across cortical depths and V1 subfields, underscoring their likely association with human perceptual biases.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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The visibility of a briefly presented stimulus is diminished when followed by a mask, a phenomenon known as backward masking (BM). As the interval between the stimulus and the mask (stimulus-to-mask onset asynchrony, SOA) becomes shorter, the stimulus visibility decreases. Yet, the neural mechanisms underlying BM remains poorly understood. To investigate this, monkeys were trained to discriminate oriented targets in pattern BM. Using Voltage-sensitive dye imaging we measured the population responses in the primary visual cortex (V1). The behavioral performance in short SOAs was lower and reaction times were slower. Population response in V1 showed a figure-ground modulation (FGm) with lower FGm values for short SOAs. A classification analysis revealed the differences in temporal dynamics of the model accuracy and spatial reorganization of the informative neural activity in relation to stimulus visibility. These results suggest that the mask interferes with FGm in V1 and possibly leads to diminished stimulus visibility.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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Neuronal migration during embryonic development is a fundamental process. In the developing nose of rodents, neurons that form during early neurogenic waves in the olfactory placode leave this structure to migrate toward or into the developing brain as part of the migratory mass. This mass includes Gonadotropin-releasing hormone-1 (GnRH-1) neurons, pioneer/terminal nerve (TN) neurons, as well as neural crest-derived olfactory glial cells called olfactory ensheathing cells. There have been a limited number of molecular markers available to effectively trace and functionally manipulate the early migratory neurons that originate in the olfactory region. Contactin-2 (Cntn2), also known as transiently expressed axonal surface glycoprotein-1 (TAG-1), has been used to label various developing neuronal populations, including the commissural neurons of the spinal cord, motor neurons, and TN neurons. Previous single-cell RNA sequencing analyses of the developing olfactory system have identified Cntn2 expression in the TN, suggesting that Cntn2 is a suitable molecular marker for studying nasal migratory neurons. To trace Cntn2 expression in the developing olfactory system, we generated an inducible Cntn2CreERT2 mouse line. In this study, we outline how this mouse line can serve as an effective tool for time-controlled chimeric manipulation of specific neuronal populations of interest.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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Age-related vascular changes accompany or precede the development of Alzheimer's disease (AD) pathology. The comorbidity of AD and arterial stiffening may suggest that vascular changes have a pathogenic role. Carotid artery mechanics and hemodynamics have been associated with age-related cognitive decline. However, the impact of hemodynamics and vascular mechanics on regional vulnerability within the brain have not been thoroughly explored. Despite the venous system's role in transport, the impact of age-related alterations of the brain venous circulation on cognitive impairment is much less understood compared to the arterial system. By studying vascular mechanics and the resulting spatially-resolved brain lipids in young and aged AD mice, we can determine the relationship between vascular stiffening and brain function. Young and aged female 3xTg mice and age-matched controls were imaged using a combination of ultrasound and mass spectrometry. Wall shear stress varied across age and AD (p<0.05). The circumferential cyclic strain values for the carotid arteries and the WSS values for the jugular veins between groups were measured but were not statistically significant. Both mean velocity and pulsatility index (PI) varied across and age and AD (p<0.05).Liquid chromatography mass spectrometry (LC-MS) of brain tissue identified several lipids and metabolites with statistically significant quantities (p<0.05). The fold change was computed for young AD vs. young control, aged AD vs. aged control, aged control vs. young control, and aged AD vs. young AD. The abundance of several lipid headgroups changed significantly with respect to age and AD. Phosphatidylcholines (PC), phosphatidylethanolamines (PE), cardiolipins (CL), phosphatidylserines (PS), and lysophosphatidylcholines (LPC) have been shown to decrease with AD in previous studies. However, we observed a statistically significant increase in PC, PE, CL, PS, and LPC in the aged 3xTG mouse model compared to aged controls. Hexosylceramides (HexCer), ceramides (CER) and sphingomyelin (SM), classes of sphingolipids; lysophosphatidylethanolamine (LPE), a class of phospholipids; and onogalactosyl diglycerides (MGDG), a class of glycerolipids, have been shown to increase with AD in previous studies which aligns with the statistically significant increase of LPC, HexCer, CER, SM, LPE, and MDG observed in the aged 3xTg group compared to controls in this work. Combining both ultrasound imaging and mass spectrometry, we were able determine significant differences in the vascular biomechanics and brain biochemistry seen with aging and AD.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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The convoluted network of myelinated fibers that supports behavior, cognition, and sensory processing in the human brain is the source of its extraordinary complexity. Advancements in tissue optical clearing, 3D fluorescence microscopy, and automated image analysis have enabled unprecedented insights into the architecture of these networks. Here, we investigate the multiscale organization of myelinated fibers in human brain tissue from the brainstem, Broca's area, hippocampus, and primary visual cortex by exploiting a specific fiber staining method, light-sheet fluorescence microscopy (LSFM), and an advanced spatial orientation analysis tool. Using an optimized protocol that integrates tissue clearing with the lipophilic DiD probe to achieve uniform and deep myelinated fiber labeling, we generate micrometer-resolution volumetric reconstructions of multiple brain regions through an inverted LSFM. Automated image processing, employing unsupervised 3D multiscale Frangi filters, provides orientation distribution functions and local orientation dispersion maps. This enables precise characterization of the directionality of white matter bundles, linking mesoscopic structural properties to orientation details computed at the native micrometric resolution of the LSFM apparatus. The presented workflow illustrates a robust platform for large-scale, high-resolution brain mapping, which may facilitate the investigation of pathological alterations with unparalleled spatial resolution and, furthermore, the validation of other neuroimaging modalities.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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Gap junctions (GJ) are intercellular channels that mediate electrical signals and the transfer of small molecules. GJs are crucial for the functions of the brain, heart and other organs. While structures of purified homomeric GJs are available, we lack in situ structures. In vivo, GJs can form heteromers with different functionalities, and may associate with other proteins. Here, we analyzed Caenorhabditis elegans GJs by cryo-electron tomography and sub-tomogram averaging. We observed hexagonal arrays of GJs at cellular junctions in primary embryonal cell culture that displayed distinct wide and narrow conformations. Moreover, in about 20% of the observed channels, we found a cap-like, cytosolic protein assembly enclosing the channel pore. We propose that the cap-structure is formed by the stomatin UNC-1, which is known to interact with C. elegans GJs, and strengthen this hypothesis by matching AlphaFold3 models of UNC-1 multimers with our GJ average. Furthermore, expressing UNC-1 and the C. elegans innexin UNC-9 in HEK cells resulted in similar structures at cell-cell contacts. UNC-1/stomatin ring assemblies may affect GJ formation or functions like rectification, that might be evolutionarily conserved.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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Perceptual organization in the human visual system involves neural mechanisms that spatially group and segment image areas based on local feature similarities, such as the temporal correlation of luminance changes. Successful segmentation models in computer vision, including graph-based algorithms and vision transformer, leverage similarity computations across all elements in an image, suggest that effective similarity-based grouping should rely on a global computational process. However, whether human vision employs a similarly global computation remains unclear due to the absence of appropriate methods for manipulating similarity matrices across multiple elements within a stimulus. To investigate how "temporal similarity structures" influence human visual segmentation, we developed a stimulus generation algorithm based on Vision Transformer. This algorithm independently controls within-area and cross-area similarities by adjusting the temporal correlation of luminance, color, and spatial phase attributes. To assess human segmentation performance with these generated texture stimuli, participants completed a temporal two-alternative forced-choice task, identifying which of two intervals contained a segmentable texture. The results showed that segmentation performance is significantly influenced by the configuration of both within- and cross-correlation across the elements, regardless of attribute type. Furthermore, human performance is closely aligned with predictions from a graph-based computational model, suggesting that human texture segmentation can be approximated by a global computational process that optimally integrates pairwise similarities across multiple elements.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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Oculomotor function is a sensitive marker of neurological impairment with smooth pursuit deficiencies investigated in various disorders. However, the oculomotor deficits following traumatic brain injury (TBI) have not been fully characterized. In this study, we employed a novel bedside eye tracking paradigm to assess oculomotor dysfunction in 30 TBI patients and 30 age matched controls. Our paradigm utilized short, repeated linear tracking segments with head free recording, enabling the extraction of multiple oculomotor indices, including saccadic pursuit, tracking deviation under occlusion, initial tracking speed, initial saccade latency, pupil response, and vergence instability. TBI patients exhibited widespread deficits across these indices (AUC: 0.71 to 0.84), which correlated significantly with functional recovery, as measured by the Functional Independence Measure (R: 0.41 to 0.78, p < 0.001) but not with the initial Glasgow Coma Scale scores. These findings suggest that TBI disrupts multiple components of the oculomotor system, extending to predictive tracking, pupil-linked arousal, and binocular coordination. Additionally, preliminary testing in disorders of consciousness (DOC) patients revealed fragmented tracking, suggesting a potential application for assessing perceptual awareness. Our findings support the use of eye tracking as a promising tool for quantifying brain function in TBI, with potential applications in prognosis, rehabilitation monitoring, and broader neurological assessment.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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Hyperscanning has allowed neuroscience to expand investigations into neuronal activation during social interactions. Rather than analyzing how a single brain responds, we can compare interactions and even synchronization between multiple actors in varying situations. This technique is commonly employed using functional near infrared spectroscopy (fNIRS). Specifically, social cooperation and competition have been thoroughly investigated using this approach. While functional magnetic resonance imaging (fMRI)-based hyperscanning is becoming more prevalent, a link to this fNIRS-based foundation is missing. We here use a dual-fMRI-hyperscanning setup and an established task to investigate neuronal coherence during social cooperative and competitive tasks. Wavelet transform coherence (WTC) allows us to explore task-specific frequency bands of interest of non-stationary neuronal activation signals of paired participants (n=60). We show that cooperation, compared to a control task, increases inter-brain neuronal coherence in regions associated with social interaction and the theory of mind (ToM) network. Verbal communication prior to the task expands this coherence to different regions of this network, including middle and superior temporal gyrus. This spatial shift suggests additional implementations of the ToM network depending on the cooperation approach taken by the participants. Our findings both support and expand on results by previous fNIRS-based studies and show that WTC is an effective way to model fMRI-based neuronal synchronization; thereby closing the gap between two popular hyperscanning methodologies.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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Relational memory retrieval involves a dynamic interplay between eye movements and neural activity, yet the timing of these processes remains unclear. This study investigates how theta and alpha EEG activity align with sequential fixations during relational memory retrieval. Participants performed a two-alternative forced-choice associative memory task while their eye movements and EEG were simultaneously recorded. Results reveal a relational eye-movement effect, with correctly remembered target elements disproportionately viewed during later fixations in the retrieval sequence. Time-frequency EEG analyses across the test interval show that successful retrieval was characterized by an early transient increase in theta power and a sustained decrease in alpha power. Fixation-related analyses linked these effects to specific retrieval processes: the theta increase emerged during the first fixation on the target following the cue, reflecting its role in pattern completion critical for retrieval. In contrast, the alpha decrease extended across subsequent fixations, suggesting a broader involvement in memory reactivation. These findings tie the relational eye-movement effect to distinct neural processes: an early theta increase associated with retrieving cue-target associations and a more gradual alpha decrease linked to memory reactivation across fixations. By uncovering the neural activity underpinning the relational eye-movement effect, this study provides novel insights into the temporal dynamics of relational memory retrieval and highlights the importance of sequential eye movements in shaping memory-guided behavior.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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Alzheimer's disease (AD) is characterized by profound disruption of synaptic function, with mounting evidence suggesting that amyloid-{beta} (A{beta}) oligomers disrupt calcium (Ca2+) homeostasis through membrane pore formation. While these pores are known to alter intracellular Ca2+ dynamics, their immediate impact on synaptic transmission and potential interaction with Familial AD (FAD)-associated endoplasmic reticulum (ER) dysfunction remains unclear. Here, we extend our previously developed model of presynaptic Ca2+ dynamics to examine how A{beta} pore activity alters exocytosis and how such disruptions may manifest in the presence of FAD-associated ER dysfunction. Our model reveals that A{beta} pores fundamentally alter both the timing and strength of neurotransmitter release. Unexpectedly, the impact of pores on synaptic function depends critically on their pattern of activity, where continuous pore activity leads to synaptic hyperactivation, while temporally brief periods of intense pore activity trigger lasting hypoactivation at short timescales. These effects manifest most strongly in synapses with low and intermediate release probabilities, highlighting the established selective vulnerability of such synaptic configurations. We find that A{beta} pores and FAD-driven ER Ca2+ dysregulation form an integrated pathological unit through bidirectional coupling of their respective Ca2+ microdomains to create complex patterns of disruptions. This coupling creates feedback loops that produces an additive effect on neurotransmitter release during brief stimulations, but non-additive effects during sustained activity that promotes a shift towards asynchronous release. Surprisingly, our simulations predict that extended pore activity does not worsen indefinitely but only produces a modest additional disruption beyond initial pore formation that is likely determined by the intrinsic properties of the synapse. These findings indicate that early synaptic dysfunction in AD may arise from subtle perturbations in the temporal coordination of release rather than gross Ca2+ dysregulation, providing new mechanistic insights into the progressive nature of A{beta}-driven synaptic failure in AD.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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Inhibition mediated by {gamma}-aminobutyric acid (GABA) is implicated in motor plasticity and learning, with [GABA] in the motor cortex decreasing during motor learning. However, the causal relationship between [GABA] and learning has yet to be determined. Here, we conducted a within-subject, double-blind, placebo-controlled, crossover study to investigate the effect of increased GABAergic inhibition via GABAB-receptor agonist baclofen on motor learning and Magnetic Resonance Spectroscopic Imaging (MRSI) metrics. Increasing GABA-mediated inhibition with baclofen did not change response times, but significantly impaired motor sequence learning. In parallel, we demonstrated a blunting of the expected decrease in [GABA] during motor learning. These results highlight a causal role for GABAergic inhibition in motor learning and may have clinical implications: baclofen is commonly used to treat post brain-injury spasticity, but may impair motor learning during rehabilitation.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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Numerous studies have shown that caffeine facilitates cognition, particularly memory, when consumed before learning and immediately tested. However, most of this evidence relates to its effects during encoding, and the role in memory consolidation remains unclear. A key study demonstrated that caffeine administered after learning can enhance object recognition memory consolidation by improving the discrimination between previously seen targets and similar lures. Here, we investigated the effects of post-encoding caffeine on the consolidation of face recognition memory using a randomized, double-blind design. Participants (N = 104) viewed ten artificially generated faces on Day 1 and then received 200 mg of caffeine or placebo. On Day 2, they completed a recognition task under two conditions: Present condition (original face with five similar distractors) and Absent condition (six similar distractors) adding a -none of the above- option. The results showed that, contrary to our expectation, caffeine consumption did not improve the consolidation of face recognition memory. Instead, it increased False alarm rate in both conditions, reducing the ability to discriminate between previously seen and similar faces. These findings discuss the idea of caffeine as a general cognition enhancer and aligned with studies suggesting it enhances global processing at the expense of detailed discrimination.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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Successful behavioral adaptation requires an ongoing assessment of rewarding outcomes based on one's current state. A frontocentral ERP associated with reward feedback, the reward positivity (RewP), has been linked to reflect information about reward value and motivational states. It is, however, unclear if changes in the RewP are influenced by changes in reward value as a function of motivational state. To examine this, hungry participants (n=31) completed two rounds of a modified Doors Task incorporating Pavlovian conditioning during EEG recordings and obtained feedback associated with sweet and savory food reinforcers equally matched in pleasantness and desirability. Participants underwent reinforcer devaluation, a paradigm designed to isolate inference-based behavior based on decreasing reward value, in between rounds by eating one of the foods to satiety. Prior to devaluation, participants were hungry and rated both food reinforcers equally pleasant. After devaluation, participants were sated and rated the devalued food, but not the non-devalued food, significantly less pleasant, suggesting a sensory-specific change in reward value. Logistic regression of win-stay/lose-switch behavior during the Doors Task shows participants made sensory-specific adjustments in food preferences during post-devaluation. Non-parametric permutation tests based on the tmax statistic performed revealed no significant differences in RewP amplitudes, suggesting the RewP is insensitive to reinforcer devaluation. This could not be explained by differences in perceived pleasantness or desirability. These findings suggest the RewP signals general properties of reward value if assessment involved inference.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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Neural representation refers to the brain activity that stands in for ones cognitive experience, and in cognitive neuroscience, the principal method to studying neural representations is representational similarity analysis (RSA). The classic RSA (cRSA) approach examines the overall quality of representations across numerous items by assessing the correspondence between two representational similarity matrices (RSMs): one based on a theoretical model of stimulus similarity and the other based on similarity in measured neural data. However, because cRSA cannot model representation at the level of individual trials, it is fundamentally limited in its ability to assess subject-, stimulus-, and trial-level variances that all influence representation. Here, we formally introduce trial-level RSA (tRSA), an analytical framework that estimates the strength of neural representation for singular experimental trials and evaluates hypotheses using multi-level models. First, we verified the correspondence between tRSA and cRSA in quantifying the overall representation strength across all trials. Second, we compared the statistical inferences drawn from both approaches using simulated data that reflected a wide range of scenarios. Compared to cRSA, the multi-level framework of tRSA was both more theoretically appropriate and significantly sensitive to true effects. Third, using real fMRI datasets, we further demonstrated several issues with cRSA, to which tRSA was more robust. Finally, we presented some novel findings of neural representations that could only be assessed with tRSA and not cRSA. In summary, tRSA proves to be a robust and versatile analytical approach for cognitive neuroscience and beyond.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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Abstract
Cue validity significantly influences attention guidance, either facilitating or hindering the ability for conflict resolution. Previous studies have demonstrated that the validity effect and conflict resolution are associated with better/worse behavioral performance and specific neural activations; however, the underlying neural mechanism of their interaction remains unclear. We hypothesized that the effect of cue validity might sustain specific sequences of neural activities until target occurrence and throughout the subsequent conflict resolution. In this study, we recorded the scalp electroencephalography during the Attention Network Test paradigm to investigate their interactions in neural dynamics. Specifically, we performed a cluster-level channel–time–frequency analysis to explore significant time–frequency neural activity patterns associated with these interactions, in scalp regions of interest determined by a data-driven strategy. Our results revealed a string of significant neural dynamics in the frontal and parietal regions, including initial broad-band (especially the gamma-band) activations and subsequent complex cognitive processes evoked/effected by the invalid cue, that were firstly elicited. Finally, the resolution of conflict was completed by the frontal behavior-related theta-band power reduction. In summary, our findings advanced the understanding of the temporal and spectral sequences of neural dynamics, with the key regions involved in the resolution of conflict after invalid cueing.
in Cerebral Cortex on 2025-04-01 00:00:00 UTC.
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Background ST-elevation myocardial infarction (STEMI) and chronic limb-threatening ischemia (CLTI) are severe cardiovascular emergencies requiring urgent intervention. Nephrotic syndrome (NS) increases the risk of arterial thromboembolism (ATE), but its exact contribution remains underrecognized. Case illustration We present three cases of young adults with NS who developed ATE. The first patient had anterior STEMI with high thrombus burden but no significant atherosclerosis, suggesting a thromboembolic event. The second patient, diagnosed with CLTI, had extensive thrombotic occlusions from the infrarenal aorta to the bilateral superficial femoral arteries without atherosclerotic plaques, reinforcing a thromboembolic mechanism. He declined revascularization and was treated with medical therapy, achieving symptom relief. The third patient had CLTI with occlusions in the external iliac and superficial femoral arteries, accompanied by prominent plaque calcification, suggesting an atherosclerotic contribution. He underwent percutaneous transluminal angioplasty with favorable outcomes. Conclusion NS predisposes patients to ATE via hypercoagulability and, in some cases, atherosclerosis. Cardiovascular screening should be prioritized in high-risk patients, and preventive measures, including thromboprophylaxis and lipid management, should be considered. Treatment should be individualized based on the predominant mechanism, with deferred stenting in high thrombus burden STEMI and a multidisciplinary approach for CLTI. Long-term follow-up is essential to prevent recurrence.
in F1000Research on 2025-03-31 17:14:27 UTC.
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Background Hybrid nanofluids, consisting of two distinct nanoparticles dispersed in a base fluid, are widely used in industries requiring enhanced heat and mass transfer, such as cooling systems and heat exchangers. These fluids improve thermal conductivity and fluid dynamics, leading to better heat management and energy efficiency. This study investigates the combined effects of non-linear thermal radiation, Cattaneo-Christov heat and mass fluxes, and other factors on the three-dimensional flow, heat, and mass transfer of a Williamson hybrid nanofluid. The flow occurs over a stretching porous sheet subjected to an external magnetic field, Joule heating, chemical reactions, and heat generation. Methods Copper (Cu) and aluminum oxide (Al₂O₃) nanoparticles are suspended in ethylene glycol (C₂C₆O₂) to form the hybrid nanofluid. The governing partial differential equations are transformed into ordinary differential equations using similarity transformations and solved numerically with MATLAB’s bvp4c solver. The study examines various parameters, including stretching ratio, nanoparticle volume fraction, and relaxation times for concentration and thermal effects. Results are validated against existing literature. Results The findings reveal that a higher stretching ratio reduces velocity, temperature, concentration profiles, and local Nusselt and Sherwood numbers, while also lowering skin friction and secondary velocity. Increasing nanoparticle volume fraction decreases velocity and temperature profiles but enhances skin friction, local Nusselt, and Sherwood numbers. Concentration profiles decline with higher concentration relaxation time, while temperature increases with longer thermal relaxation time. Conclusions In conclusion, Cu−Al₂O₃/C₂C₆O₂ hybrid nanofluids demonstrate superior heat and mass transfer capabilities compared to mono-nanofluids. The performance is significantly influenced by parameters such as nanoparticle volume fraction, relaxation times, and the stretching ratio, providing valuable insights for heat and mass transfer applications.
in F1000Research on 2025-03-31 17:07:49 UTC.
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Background Odisha, the state of rich cultural heritage observes many rituals, traditions and festivals. These rituals often depict the connection between humans, their culture and natural environment. The research aims at exploring the selected rituals and traditions of Odisha such as Nuakhai, Bakula Amavasya, Makar Sankranti etc, to establish their connection with nature. The research paper also discusses how these festivals align with the principles of ecocriticism and cultural ecology. Method The information on the origin, practices in the rituals, ways of celebration, significance of the selected rituals and traditions have been drawn from the experiences of the two authors of the paper who were born and brought up in Odisha. The information was further verified by the elderly people in the authors’ families. For further information we have also referred to secondary sources such as articles, research papers, blogs and books. We employed the principles of ecocriticism and cultural ecology as our theoretical background. Findings In the paper, we have discovered the connection of Odisha’s deep rooted cultural traditions with nature. Whether it is Panchuka (five days of abstenance from non-vegetarian food during Kartika Purnima) during Kartika Purnima, Baula Puja (worshipping of the first mango blossoms of the season) during Bakula Amavasya or Balunka (idol made out of mud) during Raja Parba, these traditions help in protecting the environment and natural resources. The research underlines the prime principles of both the theories of ecocriticism and cultural ecology which emphasize on the interconnectedness of humans and their natural surroundings. The rituals and traditions do not merely showcase the cultural identity of the state but it also gives rise to ecological awareness and sustainability for the long run. The research helps highlight the connection between humans, nature and culture. Conclusion This research paves the way towards environmental stewardship and sustenance with the help of day- to- day festivities in most households in Odisha. The significance of this paper lies in the fact that even though the selected traditions and rituals have separate celebrations, they work towards a common goal of sustainability.
in F1000Research on 2025-03-31 17:05:47 UTC.
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South Sudan is one of the least electrified countries in the world, despite having abundant renewable energy resources that could be exploited to generate electricity. The country relies on imported diesel for electricity generation, besides having limited focus on renewable energy development. This policy brief sheds light on the potential of renewable energy as a solution to South Sudan’s ongoing electricity crisis. It examines the key factors hindering the development of renewable energy resources for electricity generation in the country. The brief also provides recommendations to the Government of South Sudan, policymakers, experts, and funding institutions on how to improve electricity access in the country. It is stressing on the importance of prioritising the development of diverse renewable energy resources, such as solar, wind, and small hydropower, as an immediate solution to the electricity access challenges in the country.
in F1000Research on 2025-03-31 17:04:24 UTC.
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Background The goal of this cadaveric cross-sectional study was to analyse the branching pattern of the obturator nerve morphologically and to determine its dimensions in embalmed cadavers. Methods In this cross-sectional study, we examined 50 embalmed adult cadaveric lower limbs. Gender was not taken into consideration in the analysis; however, a side-based comparison was performed. The measurements were performed using a digital Vernier caliper. Results The branching of obturator nerve was observed at the pelvic cavity in 28 specimens (56%) and inside the obturator canal in 12 specimens (24%). The division of obturator nerve wasn’t observed in 10 specimens (20%). The length, width and thickness of the trunk of obturator nerve was 108.26 ± 9.53 mm, 2.84 ± 0.88 mm and 1.11 ± 0.35 mm. The width and thickness of the anterior and posterior divisions of obturator nerve measured 2.19 ± 0.82 mm, 0.9 ± 0.1 mm, 0.99 ± 0.6 mm and 0.71 ± 0.26 mm. The topography of branching of obturator nerve from the superior and inferior border of the obturator foramen was located at 1.48 ± 0.58 mm and 3.07 ± 1.1 mm away. The length of anterior division of the obturator nerve measured 110.88 ± 12.02 mm over the right side and 107.13 ± 7.81 mm over the left side. The width of the main trunk of obturator nerve was 2.87 ± 0.64 mm over the right side and 2.82 ± 0.64 mm over the left side. Conclusions We believe that morphometric data of the obturator nerve will be enlightening to the operating surgeon during its procedures like nerve block, transplantation, and repairs as few of them are conducted laparoscopically, the prior knowledge of morphological dimensions and branching pattern will assist the surgeons in easy access of the obturator nerve. In this context, the dimensions of the obturator nerve observed in the present study can be utilized as a morphological database for our sample population.
in F1000Research on 2025-03-31 17:03:05 UTC.
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Background Insufficient drug reserves in hospitals ready for immediate use pose significant challenges in the management, procurement, and distribution of medications. Therefore, there is a critical need for improved resource management processes, ensuring a balanced and efficient medication reserve system. Lean Management is a systematic approach designed to eliminate waste, thereby reducing costs and enhancing efficiency, making it more effective than other management systems. Value Stream Mapping (VSM) is a crucial tool within the Lean system, specifically designed to support the development of manufacturing strategies. This approach aids in identifying and categorizing activities as value-added (VA), necessary but non-value-added (NNVA), or non-value-added (NVA). In this study, VSM was employed to comprehensively analyze the drug disbursement process within the medical supply warehouse managementsystem. Method This research conducted using action research methodology. This phase primarily focused on the initial step of planning, outlining the conceptual framework for the research. Regarding potential improvements, it is expected that enhancing the satisfaction period concerning the waiting time for those involved will likely increase sufficiency and availability, making work more convenient. Result Phukhieo Chaleomphrakeit Hospital was able to draw a map of the value stream in the future state, adjusting from 7 steps to 6 steps. The total time in the current system is 1,925 minutes. However, when designing and planning the future state of the pharmaceutical inventory management system, it is expected that the total time spent in the system will be reduced to only 435 minutes, with time spent on valuable activities reduced to 395 minutes. The percentage of time spent on valuable activities is 20.52%, which reduces waste in waiting. Conclusion Design of work systems by those involved. This is a tool that helps reduce waste and has been developed collaboratively to make operations run more smoothly.
in F1000Research on 2025-03-31 16:43:50 UTC.
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This article presents two patients who were diagnosed with genuine autoimmune liver disease (autoimmune hepatitis and primary biliary cholangitis overlap syndrome) during anti-tuberculosis therapy, which is a rarely reported occurrence. It highlights the challenges in distinguishing drug-induced liver injury from authentic autoimmune liver disease. It also points out the importance of considering autoimmune liver disease as a potential diagnosis revealed by the setting of drug-induced liver injury.
in F1000Research on 2025-03-31 16:42:08 UTC.
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Introduction Current dietary assessment methods struggle to accurately capture individuals’ dietary habits. The ‘Standardised and Objective Dietary Intake Assessment Tool’ (SODIAT)-1 study aims to assess the effectiveness of three emerging technologies (urine and capillary blood biomarkers, wearable camera technology) and two online self-reporting dietary assessment tools to monitor dietary intake. Methods This randomised controlled crossover trial was conducted at two sites (Hammersmith Hospital and the University of Reading) and aimed to recruit 30 UK participants (aged 18-70 years, BMI 20-30 kg/m2). Exclusion criteria included recent weight change, food allergies/intolerances, restrictive diets, certain health conditions and medication use. Volunteers completed an online screening questionnaire via REDCap and eligible participants attended a pre-study visit. Participants consumed, in a random order, two highly-controlled diets (compliant/non-compliant with UK guidelines) for four consecutive days, separated by at least one-week. Dietary intake was monitored daily using wearable cameras and self-recorded using Intake24 (24HR). Two versions of the online eNutri FFQ were completed: at baseline to assess habitual diet and on day 4 of each test period to record food intake. Urine and capillary blood samples were collected for biomarker analysis. Data analysis will assess dietary reporting accuracy across these methods using Lin’s concordance correlation coefficient. Discussion and ethical considerations The SODIAT project introduced a novel approach to dietary assessment, aiming to address the limitations like misreporting and inclusivity. However, challenges persist, such as variability in biomarker data due to failure to follow sample storage requirements and the practicalities of wearing cameras throughout the day. To protect privacy, participants removed cameras at inappropriate times, and AI removed non-food related images and blurred faces/device screens captured on the images. The accuracy of the tools in a highly-controlled setting will be evaluated in this study. Future studies are planned to validate these tools further in free-living and minority populations.
in F1000Research on 2025-03-31 16:40:18 UTC.
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Background Camptostemon philippinensis, found in mangrove forests in Indonesia and the Philippines, is listed as endangered on the International Union for Conservation of Nature (IUCN) Red List. It is found primarily in isolated mangrove forests in Kalimantan (Indonesian Borneo) and Sulawesi in Indonesia. Despite significant studies on mangrove biodiversity in this region, the occurrence of C. philippinensis in Balikpapan Bay, East Kalimantan, is not extensively recorded. Methods The study was conducted by exploring the mangrove forests along Balikpapan Bay. The first survey of about 200 km was conducted to observe mangrove vegetation and found one C. philippinensis tree. The second survey focused on the area around the first discovered C. philippinensis tree to census and record its growth stage and distribution. Results The study recorded a population of 527 individuals of C. philippinensis in Pantai Lango Village, East Kalimantan, dominated by seedlings. The high number of seedlings indicates good natural regeneration potential, but the low number of trees indicates intense competition for space in a restricted habitat. This species inhabits a small and restricted area in Balikpapan Bay, in the middle area of Balikpapan Bay, and is associated with other mangrove flora, such as Rhizophora apiculata, Rhizophora mucronata, Sonneratia alba, Avicennia alba, Lumnitzera littorea, Osbornia octodonta, Ceriops tagal, and Xylocarpus granatum. Conclusions C. philippinensis is vulnerable to habitat damage from anthropogenic activities, which could lead to local extinction. Its natural habitat in Balikpapan Bay also has the potential to be under pressure due to the development of Indonesia’s new capital city (Ibu Kota Nusantara/IKN). It emphasizes the need to understand the ecological role of this protected flora in the natural habitat of protected fauna (the proboscis monkey). Documenting the population of C. philippinensis is crucial for conservation efforts, including propagation and understanding its ecological role.
in F1000Research on 2025-03-31 16:35:57 UTC.
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Background This study aimed to answer the following major question: Who thinks better, non-native speakers of English or ChatGPT?. It provides evidence from processing and interpreting center-embedding English constructions that the human brain surpasses ChatGPT and that ChatGPT cannot be regarded as a theory of language. Methods Fifteen non-native English speakers were recruited as participants. A center-embedding English sentence was presented to both the study participants and the ChatGPT. The ability of the ChatGPT to predict and remember was also tested. Results The study findings reveal that the human brain is still far ahead of Large Language Models, specifically ChatGPT, even in the case of non-native speakers of L2 English. They also showed ChatGPT’s inability to predict and remember. Conclusions The study concludes that the human brain’s ability to process and interpret natural language data and to predict and remember is unique and that ChatGPT still lags behind this unique human ability.
in F1000Research on 2025-03-31 16:33:43 UTC.
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Background As Thailand’s population ages, promoting senior citizens’ quality of life (QoL) is crucial. In 2017, the Ministry of Social Development and Human Security launched the “elderly school” initiative to foster lifelong learning and enhance the QoL among senior citizens. However, comprehensive evaluations of its impact on QoL remain limited. Methods This cross-sectional survey aimed to assess the policy’s effect on QoL in Phetchabun province, Thailand. Using quota and systematic sampling, 1,374 senior citizens aged 60-80 participated. Propensity score matching (PSM) with a 1:1 match was employed to estimate the average treatment effect (ATE) of attending the elderly school on QoL. Additionally, multiple linear regression was analyzed to assess the association between QoL and its associated factors. Results PSM were matched successfully, the standardized difference was less than 10 percent, and the baseline after matching indicated balances with 687 elderly people in each group. The mean QoL score of the non-attending group was 44.40 (SD = 7.11), and that of the attending group was 57.50 (SD = 7.53). The ATE for elderly people attending school was 10.67 scores (95% CI: 9.67 – 11.67 scores) higher than those unattended. Being female, having monthly income higher than 20,000, having employment, having a caregiver, and attendance at elderly school were positively associated with QoL, and the standardized beta coefficients were 0.078, 0.059, 0.094, 0.066, and 0.550, respectively. Additionally, higher education was positively associated with higher QoL. Conclusion The elderly school policy significantly enhanced the QoL of the attending senior citizens. Findings suggest continued collaboration among stakeholders to sustain and optimize this policy for improved seniors’ QoL, which has the potential to utilize lifelong learning to create an inclusive framework for healthy aging among senior citizens.
in F1000Research on 2025-03-31 15:51:09 UTC.
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by Pramod Shinde, Lisa Willemsen, Michael Anderson, Minori Aoki, Saonli Basu, Julie G. Burel, Peng Cheng, Souradipto Ghosh Dastidar, Aidan Dunleavy, Tal Einav, Jamie Forschmiedt, Slim Fourati, Javier Garcia, William Gibson, Jason A. Greenbaum, Leying Guan, Weikang Guan, Jeremy P. Gygi, Brendan Ha, Joe Hou, Jason Hsiao, Yunda Huang, Rick Jansen, Bhargob Kakoty, Zhiyu Kang, James J. Kobie, Mari Kojima, Anna Konstorum, Jiyeun Lee, Sloan A. Lewis, Aixin Li, Eric F. Lock, Jarjapu Mahita, Marcus Mendes, Hailong Meng, Aidan Neher, Somayeh Nili, Lars Rønn Olsen, Shelby Orfield, James A. Overton, Nidhi Pai, Cokie Parker, Brian Qian, Mikkel Rasmussen, Joaquin Reyna, Eve Richardson, Sandra Safo, Josey Sorenson, Aparna Srinivasan, Nicola Thrupp, Rashmi Tippalagama, Raphael Trevizani, Steffen Ventz, Jiuzhou Wang, Cheng-Chang Wu, Ferhat Ay, Barry Grant, Steven H. Kleinstein, Bjoern Peters
Systems vaccinology studies have been used to build computational models that predict individual vaccine responses and identify the factors contributing to differences in outcome. Comparing such models is challenging due to variability in study designs. To address this, we established a community resource to compare models predicting B. pertussis booster responses and generate experimental data for the explicit purpose of model evaluation. We here describe our second computational prediction challenge using this resource, where we benchmarked 49 algorithms from 53 scientists. We found that the most successful models stood out in their handling of nonlinearities, reducing large feature sets to representative subsets, and advanced data preprocessing. In contrast, we found that models adopted from literature that were developed to predict vaccine antibody responses in other settings performed poorly, reinforcing the need for purpose-built models. Overall, this demonstrates the value of purpose-generated datasets for rigorous and open model evaluations to identify features that improve the reliability and applicability of computational models in vaccine response prediction.
in PLoS Computational Biology on 2025-03-31 14:00:00 UTC.
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by Yang Wu, Ming Chen, Yufang Qin
Individualized prediction of cancer drug sensitivity is of vital importance in precision medicine. While numerous predictive methodologies for cancer drug response have been proposed, the precise prediction of an individual patient’s response to drug and a thorough understanding of differences in drug responses among individuals continue to pose significant challenges. This study introduced a deep learning model PASO, which integrated transformer encoder, multi-scale convolutional networks and attention mechanisms to predict the sensitivity of cell lines to anticancer drugs, based on the omics data of cell lines and the SMILES representations of drug molecules. First, we use statistical methods to compute the differences in gene expression, gene mutation, and gene copy number variations between within and outside biological pathways, and utilized these pathway difference values as cell line features, combined with the drugs’ SMILES chemical structure information as inputs to the model. Then the model integrates various deep learning technologies multi-scale convolutional networks and transformer encoder to extract the properties of drug molecules from different perspectives, while an attention network is devoted to learning complex interactions between the omics features of cell lines and the aforementioned properties of drug molecules. Finally, a multilayer perceptron (MLP) outputs the final predictions of drug response. Our model exhibits higher accuracy in predicting the sensitivity to anticancer drugs comparing with other methods proposed recently. It is found that PARP inhibitors, and Topoisomerase I inhibitors were particularly sensitive to SCLC when analyzing the drug response predictions for lung cancer cell lines. Additionally, the model is capable of highlighting biological pathways related to cancer and accurately capturing critical parts of the drug’s chemical structure. We also validated the model’s clinical utility using clinical data from The Cancer Genome Atlas. In summary, the PASO model suggests potential as a robust support in individualized cancer treatment. Our methods are implemented in Python and are freely available from GitHub (https://github.com/queryang/PASO).
in PLoS Computational Biology on 2025-03-31 14:00:00 UTC.
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by Julian Heidecke, Jonas Wallin, Peter Fransson, Pratik Singh, Henrik Sjödin, Pascale Claire Stiles, Marina Treskova, Joacim Rocklöv
Temperature influences the transmission of mosquito-borne pathogens with significant implications for disease risk under climate change. Mathematical models of mosquito-borne infections rely on functions that capture mosquito-pathogen interactions in response to temperature to accurately estimate transmission dynamics. For deriving these functions, experimental studies provide valuable data on the temperature sensitivity of mosquito life-history traits and pathogen transmission. However, the scarcity of experimental data and inconsistencies in methodologies for analysing temperature responses across mosquito species, pathogens, and experiments present major challenges. Here, we introduce a new approach to address these challenges. We apply this framework to study the thermal biology of West Nile virus (WNV). We reviewed existing experimental studies, obtaining temperature responses for eight mosquito-pathogen traits across 15 mosquito species. Using these data, we employed Bayesian hierarchical models to estimate temperature response functions for each trait and their variation between species and experiments. We incorporated the resulting functions into mathematical models to estimate the temperature sensitivity of WNV transmission, focusing on six mosquito species of the genus Culex. Our study finds a general optimal transmission temperature around 24°C among Culex species with only small species-specific deviations. We demonstrate that differing mechanistic assumptions underlying published mosquito population models result in temperature optima estimates that differ by up to 3°C. Additionally, we find substantial variability between trait temperature responses across experiments on the same species, possibly indicating significant intra-species variation in trait performance. We identify mosquito biting rate, lifespan, and egg viability as priorities for future experiments, as they strongly influence estimates of temperature limits, optima, and overall uncertainty in transmission suitability. Experimental studies on vector competence traits are also essential, because limited data on these currently require model simplifications. These data would enhance the accuracy of our estimates, critical for anticipating future shifts in WNV risk under climate change.
in PLoS Computational Biology on 2025-03-31 14:00:00 UTC.
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by Simonida Zehr, Sebastian Wolf, Thomas Oellerich, Matthias S. Leisegang, Ralf P. Brandes, Marcel H. Schulz, Timothy Warwick
Extraction of meaningful biological insight from gene expression profiling often focuses on the identification of statistically enriched terms or pathways. These methods typically use gene sets as input data, and subsequently return overrepresented terms along with associated statistics describing their enrichment. This approach does not cater to analyses focused on a single gene-of-interest, particularly when the gene lacks prior functional characterization. To address this, we formulated GeneCOCOA, a method which utilizes context-specific gene co-expression and curated functional gene sets, but focuses on a user-supplied gene-of-interest (GOI). The co-expression between the GOI and subsets of genes from functional groups (e.g. pathways, GO terms) is derived using linear regression, and resulting root-mean-square error values are compared against background values obtained from randomly selected genes. The resulting p values provide a statistical ranking of functional gene sets from any collection, along with their associated terms, based on their co-expression with the gene of interest in a manner specific to the context and experiment. GeneCOCOA thereby provides biological insight into both gene function, and putative regulatory mechanisms by which the expression of the GOI is controlled. Despite its relative simplicity, GeneCOCOA outperforms similar methods in the accurate recall of known gene-disease associations. We furthermore include a differential GeneCOCOA mode, thus presenting the first implementation of a gene-focused approach to experiment-specific gene set enrichment analysis. GeneCOCOA is formulated as an R package for ease-of-use, available at https://github.com/si-ze/geneCOCOA.
in PLoS Computational Biology on 2025-03-31 14:00:00 UTC.
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by Meng Wang, Jonathan Patsenker, Henry Li, Yuval Kluger, Steven H. Kleinstein
Antibodies play a crucial role in the adaptive immune response, with their specificity to antigens being a fundamental determinant of immune function. Accurate prediction of antibody-antigen specificity is vital for understanding immune responses, guiding vaccine design, and developing antibody-based therapeutics. In this study, we present a method of supervised fine-tuning for antibody language models, which improves on pre-trained antibody language model embeddings in binding specificity prediction to SARS-CoV-2 spike protein and influenza hemagglutinin. We perform supervised fine-tuning on four pre-trained antibody language models to predict specificity to these antigens and demonstrate that fine-tuned language model classifiers exhibit enhanced predictive accuracy compared to classifiers trained on pre-trained model embeddings. Additionally, we investigate the change of model attention activations after supervised fine-tuning to gain insights into the molecular basis of antigen recognition by antibodies. Furthermore, we apply the supervised fine-tuned models to BCR repertoire data related to influenza and SARS-CoV-2 vaccination, demonstrating their ability to capture changes in repertoire following vaccination. Overall, our study highlights the effect of supervised fine-tuning on pre-trained antibody language models as valuable tools to improve antigen specificity prediction.
in PLoS Computational Biology on 2025-03-31 14:00:00 UTC.
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by Yun Wen Chu, Suma Chinta, Hayagreev V. S. Keri, Shreya Beri, Scott R. Pluta
A fundamental trait of intelligent behavior is the ability to respond selectively to stimuli with higher value. Where along the neural hierarchy does somatosensory processing transition from a map of stimulus location to a map of stimulus value? To address this question, we recorded single-unit activity from populations of neurons in somatosensory cortex (S1) and midbrain superior colliculus (SC) in mice conditioned to respond to a positive-valued stimulus and withhold responses to an adjacent, negative-valued stimulus. The stimulus preference of the S1 population was equally weighted towards either stimulus, in line with a somatotopic map. Surprisingly, we discovered a large population of SC neurons that were disproportionately biased towards the positive stimulus. This disproportionate bias was largely driven by enhanced spike suppression for the negative stimulus. Removing the opportunity for mice to behaviorally select the positive stimulus reduced positive stimulus bias and spontaneous firing rates in SC but not S1, suggesting that neural selectivity was augmented by task readiness. Similarly, the spontaneous firing rates of SC but not S1 neurons predicted reaction times, suggesting that SC neurons played a persistent role in perceptual decision-making. Taken together, these data indicate that the somatotopic map in S1 is transformed into a value-based map in SC that encodes stimulus priority.
in PLoS Biology on 2025-03-31 14:00:00 UTC.
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by Heather Q. Pollington, Chris Q. Doe
Interneuron diversity within the central nervous system (CNS) is essential for proper circuit assembly. Functional interneurons must integrate multiple features, including combinatorial transcription factor (TF) expression, axon/dendrite morphology, and connectivity to properly specify interneuronal identity. Yet, how these different interneuron properties are coordinately regulated remains unclear. Here we used the Drosophila neural progenitor, NB5-2, known to generate late-born interneurons in a proprioceptive circuit, to determine if the early-born temporal transcription factor (TTF), Hunchback (Hb), specifies early-born interneuron identity, including molecular profile, axon/dendrite morphology, presynapse targeting, and behavior. We found that prolonged Hb expression in NB5-2 increases the number of neurons expressing early-born TFs (Nervy, Nkx6, and Dbx) at the expense of late-born TFs (Runt and Zfh2); thus, Hb is sufficient to promote interneuron molecular identity. Hb is also sufficient to transform late-born neuronal morphology to early-born neuronal morphology. Furthermore, prolonged Hb promotes the relocation of late-born neuronal presynapses to early-born neuronal presynapse neuropil locations, consistent with a change in interneuron connectivity. Finally, we found that prolonged Hb expression led to defects in proprioceptive behavior, consistent with a failure to properly specify late-born interneurons in the proprioceptive circuit. We conclude that the Hb TTF is sufficient to specify multiple aspects of early-born interneuron identity, as well as disrupt late-born proprioceptive neuron function.
in PLoS Biology on 2025-03-31 14:00:00 UTC.
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by Sol Vendrell-Fernández, Beatriz Beamud, Yasmina Abou Haydar, Jorge Am de Sousa, Julien Burlaud-Gaillard, Etienne Kornobis, Bertrand Raynal, Joelle Vinh, David Bikard, Jean-Marc Ghigo
Advances in metagenomics have led to the identification of new intestinal temperate bacteriophages. However, their experimental characterization remains challenging due to a limited understanding of their lysogenic-lytic cycle and the common lack of plaque formation in vitro. In this study, we investigated the hankyphage, a widespread transposable phage of prominent Bacteroides symbionts. Hankyphages spontaneously produced virions in laboratory conditions even in the absence of inducer, but virions did not show any evidence of infectivity. To increase virion production and raise the chances of observing infection events, we identified a master repressor of the hankyphage lytic cycle, RepCHP, whose silencing amplified hankyphage gene expression, and enhanced replicative transposition and virion production. However, attempts to infect or lysogenize new host cells with different capsular types remained unsuccessful. Transmission electron microscopy and capsid DNA sequencing revealed an abnormal virion morphology and incomplete DNA packaging of the hankyphage, suggesting that it cannot complete its assembly in laboratory conditions for reasons that are yet to be identified. Still, metavirome and phylogenetic analyses were suggestive of hankyphage horizontal transmission. We could also detect the activity of diversity-generating retroelements (DGRs) that mutagenize the hankyphage tail fiber, and likely contribute to its broad host range. This study sheds light on the life cycle of this abundant intestinal bacteriophage and highlights important gaps in our understanding of the factors required for the completion of its life cycle. Elucidating this puzzle will be critical to gain a better understanding of the hankyphage biology and ecological role.
in PLoS Biology on 2025-03-31 14:00:00 UTC.
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by Tobias Holm Bønnelykke, Marie-Amandine Chabry, Emeline Perthame, Gregor Dombrowsky, Felix Berger, Sven Dittrich, Marc-Phillip Hitz, Audrey Desgrange, Sigolène M. Meilhac
The TGFβ secreted factor NODAL is a major left determinant required for the asymmetric morphogenesis of visceral organs, including the heart. Yet, when this signaling is absent, shape asymmetry, for example of the embryonic heart loop, is not fully abrogated, indicating that there are other factors regulating left–right patterning. Here, we used a tailored transcriptomic approach to screen for genes asymmetrically expressed in the field of heart progenitors. We thus identify Notch3 as a novel left-enriched gene and validate, by quantitative in situ hybridization, its transient asymmetry in the lateral plate mesoderm and node crown, overlapping with Nodal. In mutant embryos, we analyzed the regulatory hierarchy and demonstrate that Nodal in the lateral plate mesoderm amplifies Notch3 asymmetric expression. The function of Notch3 was uncovered in an allelic series of mutants. In single neonate mutants, we observe that Notch3 is required with partial penetrance for ventricle thickness, septation and aortic valve, in addition to its known role in coronary arteries. In compound mutants, we reveal that Notch3 acts as a genetic modifier of heart looping direction and shape defects in Nodal mutants. Whereas Notch3 was previously mainly associated with the CADASIL syndrome, our observations in the mouse and a human cohort support a novel role in congenital heart defects and laterality defects.
in PLoS Biology on 2025-03-31 14:00:00 UTC.
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Nanocellulose (NC) is one of the most prominent green materials for various applications. They have received increasing attention owing to their unique properties. In this review, a brief background on cellulose, its abundance in nature, chemical structure, and properties is described. Subsequently, the structure of nanocellulose, the procedures of its production, and its characteristics are discussed. This was followed by elaborating on the recent use of nanocellulose in medical and dental fields.
in F1000Research on 2025-03-31 08:27:24 UTC.
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This study explores the adoption of mobile payments as a research field to understand the technological, socioeconomic, and cultural factors that influence the understanding of the users’ experience and satisfaction and attract more users. It is vital to examine the research trends in the adoption of mobile payments from a systematic literature review using PRISMA 2020 to select 63 documents from Scopus and WOS. Among the results, the most used models for this analysis are extended TAM and extended UTAUT. The most representative variables in the studies are social influence, security perception, risk perception, trust and perceived usefulness. It is concluded that the future research agenda should focus on topics such as biometric authentication, payment flexibility and contactless payments. In addition, from the business perspective, there is a focus on designing innovative interfaces that are more intuitive for users.
in F1000Research on 2025-03-31 08:26:02 UTC.
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Proceedings of the National Academy of Sciences, Volume 122, Issue 14, April 2025.
SignificanceWhile the striatum is classically thought of for its role in movement and reward, here we demonstrate that it plays a powerful gating role in seizures. We found that striatal neuromodulation bidirectionally impacts both absence-like seizures ...
in PNAS on 2025-03-31 07:00:00 UTC.
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Proceedings of the National Academy of Sciences, Volume 122, Issue 14, April 2025.
in PNAS on 2025-03-31 07:00:00 UTC.
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Journal of Neurophysiology, Volume 133, Issue 4, Page 1138-1145, April 2025.
in Journal of Neurophysiology on 2025-03-31 04:50:33 UTC.
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Understanding how innate predispositions and learned experiences interact to shape behavior is a central question in systems neuroscience. Traditionally, innate behaviors, that is, those present without prior learning and governed by evolutionarily conserved neural circuits, have been studied separately from learned behaviors, which depend on experience and neural plasticity. This division has led to a compartmentalized view of behavior and neural circuit organization. Increasing evidence suggests that innate and learned behaviors are not independent, but rather deeply intertwined, with plasticity evident even in circuits classically considered ‘innate’. In this opinion, we highlight examples across species that illustrate the dynamic interaction between these behavioral domains and discuss the implications for unifying theoretical and empirical frameworks. We argue that a more integrative approach, namely one that acknowledges the reciprocal influences of innate and learned processes, is essential for advancing our understanding of how neuronal activity drives complex behaviors.
in Trends in Neurosciences: In press on 2025-03-31 00:00:00 UTC.
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Using spatial transcriptomic sequencing and single-nucleus RNA-sequencing techniques, Wang et al. mapped hippocampal single-cell spatial transcriptomics in AD, revealing cell and functional changes, Aβ microenvironment, and spatial pathology. In addition, they identified that brain-derived EVs carrying CCK and PMP2 were significantly reduced in AD plasma, highlighting their diagnostic potential.
in Neuron: In press on 2025-03-31 00:00:00 UTC.
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Sakuma et al. reveal that nucleoporin translation and degradation are main mechanisms regulating nuclear pore complex (NPC) assembly and numbers. They also identify a new role for the CCR4-NOT complex negatively regulating NPC assembly by promoting mRNA degradation and decreasing the levels of available nucleoporins.
in Cell Reports: In press on 2025-03-31 00:00:00 UTC.
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Nature, Published online: 31 March 2025; doi:10.1038/d41586-025-00936-0
Marine ecologist Gemma Galbraith builds remotely operated vehicles and uses them to assess how coral reefs are being affected by climate change.
in Nature on 2025-03-31 00:00:00 UTC.
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Nature, Published online: 31 March 2025; doi:10.1038/d41586-025-01001-6
Improvements to brain–computer interfaces are bringing the technology closer to natural conversational speed.
in Nature on 2025-03-31 00:00:00 UTC.
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Nature, Published online: 31 March 2025; doi:10.1038/d41586-025-00935-1
Overcoming these obstacles in carbon markets can speed up decarbonization.
in Nature on 2025-03-31 00:00:00 UTC.
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Nature, Published online: 31 March 2025; doi:10.1038/d41586-025-01004-3
Following the firm’s bankruptcy, researchers hope that they will be able to continue accessing the valuable data set even if it is sold to new owners.
in Nature on 2025-03-31 00:00:00 UTC.
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Nature, Published online: 31 March 2025; doi:10.1038/d41586-025-00969-5
More than 200 federal grants for research related to HIV and AIDS have been abruptly terminated in the past few weeks.
in Nature on 2025-03-31 00:00:00 UTC.
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Nature, Published online: 31 March 2025; doi:10.1038/d41586-025-01012-3
Two experiments show that small payments can speed up peer review, but there might be unintended consequences. Plus, US grant cuts are ending scientific careers and Lyft drivers’ data reveals speeding-ticket racism.
in Nature on 2025-03-31 00:00:00 UTC.
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Nature, Published online: 31 March 2025; doi:10.1038/d41586-025-00934-2
An exploration of weird and wonderful birds across the world sometimes takes theories of sexual selection to the extreme — but entertains throughout.
in Nature on 2025-03-31 00:00:00 UTC.
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Nature, Published online: 31 March 2025; doi:10.1038/d41586-025-00986-4
The month’s sharpest science shots, selected by Nature’s photo team.
in Nature on 2025-03-31 00:00:00 UTC.
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Nature Neuroscience, Published online: 31 March 2025; doi:10.1038/s41593-025-01905-6
Naturalistic communication is an aim for neuroprostheses. Here the authors present a neuroprosthesis that restores the voice of a paralyzed person simultaneously with their speaking attempts, enabling naturalistic communication.
in Nature Neuroscience on 2025-03-31 00:00:00 UTC.
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Nature Neuroscience, Published online: 31 March 2025; doi:10.1038/s41593-025-01922-5
Kim and coworkers describe a technique, EPSILON, to map AMPA receptor exocytosis, a proxy for synaptic plasticity, in mice. The authors demonstrated a correlation between AMPA receptor exocytosis and cFos expression during a fear conditioning experiment.
in Nature Neuroscience on 2025-03-31 00:00:00 UTC.
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Nature Neuroscience, Published online: 31 March 2025; doi:10.1038/s41593-025-01923-4
Researchers developed DELTA, a method for brain-wide measurement of synaptic protein turnover with single-synapse resolution, providing a powerful tool to localize and study mechanisms underlying synaptic plasticity and learning.
in Nature Neuroscience on 2025-03-31 00:00:00 UTC.
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Nature Reviews Neuroscience, Published online: 31 March 2025; doi:10.1038/s41583-025-00922-5
The hypothalamic preoptic area is involved in numerous homeostatic and social behaviours, and the neurons of this area are shown in this study to consist of numerous subtypes that show diverse maturational profiles that correlate with periods of substantial behavioural change such as weaning and puberty.
in Nature Reviews on 2025-03-31 00:00:00 UTC.
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Nature Methods, Published online: 31 March 2025; doi:10.1038/s41592-025-02643-0
This Perspective outlines the datasets, access methods, data standards, infrastructure, governance and community-engagement strategies of the Human Tumor Atlas Network.
in Nature Methods on 2025-03-31 00:00:00 UTC.
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Nature Physics, Published online: 31 March 2025; doi:10.1038/s41567-025-02793-0
The transition from single cells to multicellularity is a key but not well-understood step in animal evolution. A study shows that loosely-organized colonies of attached single-celled organisms can improve feeding through hydrodynamic cooperation.
in Nature Physics on 2025-03-31 00:00:00 UTC.
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Nature Physics, Published online: 31 March 2025; doi:10.1038/s41567-025-02843-7
Assemblies of active particles display a range of dynamical phenomena. Simulations now show that the transition of an assembly of active particles from a jammed to a fluidized state is similar to the process of mechanical yielding seen in amorphous solids.
in Nature Physics on 2025-03-31 00:00:00 UTC.
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Nature Physics, Published online: 31 March 2025; doi:10.1038/s41567-025-02787-y
How unicellular organisms evolved into multicellular ones is an open question. Now, using unicellular Stentor coeruleus as a model system, the transition between isolated individuals and a coordinated colony is shown to benefit all colony members.
in Nature Physics on 2025-03-31 00:00:00 UTC.
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Nature Physics, Published online: 31 March 2025; doi:10.1038/s41567-025-02849-1
It is well known that flat bands exist in magic-angle twisted bilayer graphene. Now thermopower measurements show that the strong correlations between electrons in these bands result in the formation of local moments.
in Nature Physics on 2025-03-31 00:00:00 UTC.
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Nature Physics, Published online: 31 March 2025; doi:10.1038/s41567-025-02859-z
Quasicrystals, which lack translational symmetry but display rotational order, are difficult to make. Now an assembly method for the fabrication of colloidal quasicrystals that offers a high degree of controllability and reversibility is reported.
in Nature Physics on 2025-03-31 00:00:00 UTC.
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Several recent theoretical accounts have posited that interoception, the perception of internal bodily signals, plays a vital role in early human development. Yet, empirical evidence of cardiac interoceptive sensitivity in infants to date has been mixed. Furthermore, existing evidence does not go beyond the perception of cardiac signals and focuses only on the age of 5–7 mo, limiting the generalizability of the results. Here, we used a modified version of the cardiac interoceptive sensitivity paradigm introduced by Maister et al., 2017 in 3-, 9-, and 18-mo-old infants using cross-sectional and longitudinal approaches. Going beyond, we introduce a novel experimental paradigm, namely the iBREATH, to investigate respiratory interoceptive sensitivity in infants. Overall, for cardiac interoceptive sensitivity (total n=135) we find rather stable evidence across ages with infants on average preferring stimuli presented synchronously to their heartbeat. For respiratory interoceptive sensitivity (total n=120) our results show a similar pattern in the first year of life, but not at 18 mo. We did not observe a strong relationship between cardiac and respiratory interoceptive sensitivity at 3 and 9 mo but found some evidence for a relationship at 18 mo. We validated our results using specification curve- and mega-analytic approaches. By examining early cardiac and respiratory interoceptive processing, we provide evidence that infants are sensitive to their interoceptive signals.
in eLife on 2025-03-31 00:00:00 UTC.
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Life-history theory, central to our understanding of diversity in morphology, behaviour, and senescence, describes how traits evolve through the optimisation of trade-offs in investment. Despite considerable study, there is only minimal support for trade-offs within species between the two traits most closely linked to fitness – reproductive effort and survival – questioning the theory’s general validity. We used a meta-analysis to separate the effects of individual quality (positive survival/reproduction correlation) from the costs of reproduction (negative survival/reproduction correlation) using studies of reproductive effort and parental survival in birds. Experimental enlargement of brood size caused reduced parental survival. However, the effect size of brood size manipulation was small and opposite to the effect of phenotypic quality, as we found that individuals that naturally produced larger clutches also survived better. The opposite effects on parental survival in experimental and observational studies of reproductive effort provide the first meta-analytic evidence for theory suggesting that quality differences mask trade-offs. Fitness projections using the overall effect size revealed that reproduction presented negligible costs, except when reproductive effort was forced beyond the maximum level observed within species, to that seen between species. We conclude that there is little support for the most fundamental life-history trade-off, between reproductive effort and survival, operating within a population. We suggest that within species the fitness landscape of the reproduction–survival trade-off is flat until it reaches the boundaries of the between-species fast–slow life-history continuum. Our results provide a quantitative explanation as to why the costs of reproduction are not apparent and why variation in reproductive effort persists within species.
in eLife on 2025-03-31 00:00:00 UTC.
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The members of the Mycobacterium tuberculosis complex (MTBC) causing human tuberculosis comprise 10 phylogenetic lineages that differ in their geographical distribution. The human consequences of this phylogenetic diversity remain poorly understood. Here, we assessed the phenotypic properties at the host-pathogen interface of 14 clinical strains representing five major MTBC lineages. Using a human in vitro granuloma model combined with bacterial load assessment, microscopy, flow cytometry, and multiplexed-bead arrays, we observed considerable intra-lineage diversity. Yet, modern lineages were overall associated with increased growth rate and more pronounced granulomatous responses. MTBC lineages exhibited distinct propensities to accumulate triglyceride lipid droplets—a phenotype associated with dormancy—that was particularly pronounced in lineage 2 and reduced in lineage 3 strains. The most favorable granuloma responses were associated with strong CD4 and CD8 T cell activation as well as inflammatory responses mediated by CXCL9, granzyme B, and TNF. Both of which showed consistent negative correlation with bacterial proliferation across genetically distant MTBC strains of different lineages. Taken together, our data indicate that different virulence strategies and protective immune traits associate with MTBC genetic diversity at lineage and strain level.
in eLife on 2025-03-31 00:00:00 UTC.
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Prey must balance predator avoidance with feeding, a central dilemma in prey refuge theory. Additionally, prey must assess predatory imminence—how close threats are in space and time. Predatory imminence theory classifies defensive behaviors into three defense modes: pre-encounter, post-encounter, and circa-strike, corresponding to increasing levels of threat—–suspecting, detecting, and contacting a predator. Although predatory risk often varies in spatial distribution and imminence, how these factors intersect to influence defensive behaviors is poorly understood. Integrating these factors into a naturalistic environment enables comprehensive analysis of multiple defense modes in consistent conditions. Here, we combine prey refuge and predatory imminence theories to develop a model system of nematode defensive behaviors, with Caenorhabditis elegans as prey and Pristionchus pacificus as predator. In a foraging environment comprised of a food-rich, high-risk patch and a food-poor, low-risk refuge, C. elegans innately exhibits circa-strike behaviors. With experience, it learns post- and pre-encounter behaviors that proactively anticipate threats. These defense modes intensify with predator lethality, with only life-threatening predators capable of eliciting all three modes. SEB-3 receptors and NLP-49 peptides, key stress regulators, vary in their impact and interdependence across defense modes. Overall, our model system reveals fine-grained insights into how stress-related signaling regulates defensive behaviors.
in eLife on 2025-03-31 00:00:00 UTC.
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Macrophages control intracellular pathogens like Salmonella by using two caspase enzymes at different times during infection.
in eLife on 2025-03-31 00:00:00 UTC.
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Glutamine synthetases (GS) are central enzymes essential for the nitrogen metabolism across all domains of life. Consequently, they have been extensively studied for more than half a century. Based on the ATP-dependent ammonium assimilation generating glutamine, GS expression and activity are strictly regulated in all organisms. In the methanogenic archaeon Methanosarcina mazei, it has been shown that the metabolite 2-oxoglutarate (2-OG) directly induces the GS activity. Besides, modulation of the activity by interaction with small proteins (GlnK1 and sP26) has been reported. Here, we show that the strong activation of M. mazei GS (GlnA1) by 2-OG is based on the 2-OG dependent dodecamer assembly of GlnA1 by using mass photometry (MP) and single particle cryo-electron microscopy (cryo-EM) analysis of purified strep-tagged GlnA1. The dodecamer assembly from dimers occurred without any detectable intermediate oligomeric state and was not affected in the presence of GlnK1. The 2.39 Å cryo-EM structure of the dodecameric complex in the presence of 12.5 mM 2-OG demonstrated that 2-OG is binding between two monomers. Thereby, 2-OG appears to induce the dodecameric assembly in a cooperative way. Furthermore, the active site is primed by an allosteric interaction cascade caused by 2-OG-binding towards an adaption of an open active state conformation. In the presence of additional glutamine, strong feedback inhibition of GS activity was observed. Since glutamine dependent disassembly of the dodecamer was excluded by MP, feedback inhibition most likely relies on the binding of glutamine to the catalytic site. Based on our findings, we propose that under nitrogen limitation the induction of M. mazei GS into a catalytically active dodecamer is not affected by GlnK1 and crucially depends on the presence of 2-OG.
in eLife on 2025-03-31 00:00:00 UTC.
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The model Gram-negative plant pathogen Pseudomonas syringae utilises hundreds of transcription factors (TFs) to regulate its functional processes, including virulence and metabolic pathways that control its ability to infect host plants. Although the molecular mechanisms of regulators have been studied for decades, a comprehensive understanding of genome-wide TFs in Psph 1448A remains limited. Here, we investigated the binding characteristics of 170 of 301 annotated TFs through chromatin immunoprecipitation sequencing (ChIP-seq). Fifty-four TFs, 62 TFs, and 147 TFs were identified in top-level, middle-level, and bottom-level, reflecting multiple higher-order network structures and direction of information flow. More than 40,000 TF pairs were classified into 13 three-node submodules which revealed the regulatory diversity of TFs in Psph 1448A regulatory network. We found that bottom-level TFs performed high co-associated scores to their target genes. Functional categories of TFs at three levels encompassed various regulatory pathways. Three and 25 master TFs were identified to involve in virulence and metabolic regulation, respectively. Evolutionary analysis and topological modularity network revealed functional variability and various conservation of TFs in P. syringae (Psph 1448A, Pst DC3000, Pss B728a, and Psa C48). Overall, our findings demonstrated a global transcriptional regulatory network of genome-wide TFs in Psph 1448A. This knowledge can advance the development of effective treatment and prevention strategies for related infectious diseases.
in eLife on 2025-03-31 00:00:00 UTC.
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Maintenance of rod-shape in bacterial cells depends on the actin-like protein MreB. Deletion of mreB from Pseudomonas fluorescens SBW25 results in viable spherical cells of variable volume and reduced fitness. Using a combination of time-resolved microscopy and biochemical assay of peptidoglycan synthesis, we show that reduced fitness is a consequence of perturbed cell size homeostasis that arises primarily from differential growth of daughter cells. A 1000-generation selection experiment resulted in rapid restoration of fitness with derived cells retaining spherical shape. Mutations in the peptidoglycan synthesis protein Pbp1A were identified as the main route for evolutionary rescue with genetic reconstructions demonstrating causality. Compensatory pbp1A mutations that targeted transpeptidase activity enhanced homogeneity of cell wall synthesis on lateral surfaces and restored cell size homeostasis. Mechanistic explanations require enhanced understanding of why deletion of mreB causes heterogeneity in cell wall synthesis. We conclude by presenting two testable hypotheses, one of which posits that heterogeneity stems from non-functional cell wall synthesis machinery, while the second posits that the machinery is functional, albeit stalled. Overall, our data provide support for the second hypothesis and draw attention to the importance of balance between transpeptidase and glycosyltransferase functions of peptidoglycan building enzymes for cell shape determination.
in eLife on 2025-03-31 00:00:00 UTC.
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N 6,2’-O-dimethyladenosine (m6Am) is a modified nucleotide located at the first transcribed position in mRNA and snRNA that is essential for diverse physiological processes. m6Am mapping methods assume each gene uses a single start nucleotide. However, gene transcription usually involves multiple start sites, generating numerous 5’ isoforms. Thus, gene-level annotations cannot capture the diversity of m6Am modification in the transcriptome. Here, we describe CROWN-seq, which simultaneously identifies transcription-start nucleotides and quantifies m6Am stoichiometry for each 5’ isoform that initiates with adenosine. Using CROWN-seq, we map the m6Am landscape in nine human cell lines. Our findings reveal that m6Am is nearly always a high stoichiometry modification, with only a small subset of cellular mRNAs showing lower m6Am stoichiometry. We find that m6Am is associated with increased transcript expression and provide evidence that m6Am may be linked to transcription initiation associated with specific promoter sequences and initiation mechanisms. These data suggest a potential new function for m6Am in influencing transcription.
in eLife on 2025-03-31 00:00:00 UTC.
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African trypanosomes are the causative agents of neglected tropical diseases affecting both humans and livestock. Disease control is highly challenging due to an increasing number of drug treatment failures. African trypanosomes are extracellular, blood-borne parasites that mainly rely on glycolysis for their energy metabolism within the mammalian host. Trypanosomal glycolytic enzymes are therefore of interest for the development of trypanocidal drugs. Here, we report the serendipitous discovery of a camelid single-domain antibody (sdAb aka Nanobody) that selectively inhibits the enzymatic activity of trypanosomatid (but not host) pyruvate kinases through an allosteric mechanism. By combining enzyme kinetics, biophysics, structural biology, and transgenic parasite survival assays, we provide a proof-of-principle that the sdAb-mediated enzyme inhibition negatively impacts parasite fitness and growth.
in eLife on 2025-03-31 00:00:00 UTC.
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Zhou et al. identify the NAMPT-INSR pathway as a key mediator of hepatocyte-HSC crosstalk in HBV-associated liver disease. Targeting this pathway disrupts fibrosis and cancer progression, presenting a promising therapeutic strategy for HBV-induced liver fibrosis and hepatocellular carcinoma.
in Cell Reports: Current Issue on 2025-03-30 00:00:00 UTC.
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ABSTRACT
Early midlife bilateral salpingo-oophorectomy (BSO) is associated with greater Alzheimer's disease risk compared to spontaneous/natural menopause. Previously, we found that participants with BSO had lower volume in the hippocampal dentate gyrus and cornu ammonis 2/3 composite subfield (DG-CA2/3). We sought to extend those hippocampal subfield findings by assessing whether BSO affected volumes along the anteroposterior hippocampal axis, anterolateral entorhinal cortex, and perirhinal cortex subregions (Brodmann area (BA) 35 and 36). We also correlated volumes with key demographic and wellbeing-related factors (age, depressive mood, education), hormone therapy characteristics, and recognition memory performance. Early midlife participants with BSO (with and without 17β-estradiol therapy (ET)) and age-matched control participants with intact ovaries (AMC) completed high-resolution T2-weighted structural magnetic resonance imaging (MRI). Medial temporal lobe volumes and Remember-Know task recognition memory performance were compared between groups—BSO (n = 23), BSO + ET (n = 28), AMC (n = 34) using univariate analyses. Multivariate Partial Least Squares (PLS) analyses were used to examine how volumes related to demographic and wellbeing-related factors, as well as hormone therapy characteristics. Relative to BSO + ET, BSO had lower posterior hippocampal and DG-CA2/3 volumes but greater perirhinal BA 36 volumes. Compared to age, depressive mood, and education, ET was the strongest positive predictor of hippocampal volumes and negative predictor of perirhinal BA 36 volumes. For BSO + ET, hippocampal volumes were negatively related to ET duration and positively related to concurrent progestogen therapy. Relative to AMC, BSO had greater anterolateral entorhinal cortex and perirhinal BA 35 and BA 36 volumes. BSO groups (with and without ET) relied more on familiarity than recollection for successful recognition memory. BSO and ET may have distinct effects on medial temporal lobe volumes, with potential implications for memory processes affected by Alzheimer's disease risk.
in Hippocampus on 2025-03-29 08:30:07 UTC.
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Zhang et al. demonstrate that activation of the NAIP/NLRC4 inflammasome leads to acute lung injury. They identify pyroptosis of pulmonary macrophages and fibroblasts as an important mechanism driving inflammasome-mediated lung damage.
in Cell Reports: Current Issue on 2025-03-29 00:00:00 UTC.
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Koley et al. indicate that fatty acid oxidation occurs concomitantly with fatty acid biosynthesis in multiple plant tissues, including seeds that are thought to stably house storage reserves. This study suggests that some lipid breakdown and fatty acid oxidation is the rule and not the exception in plant metabolism.
in Cell Reports: Current Issue on 2025-03-29 00:00:00 UTC.
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Objectives Infectious diseases present significant challenges to global health security in contemporary, interconnected global environments. This study aimed to evaluate and compare health security performance in Western Asia (WA), with a focus on income group-based disparities and region-specific insights. Methods This study utilized the Global Health Security Index (GHSI) to assess health security across 17 WA countries categorized by income level. Health security indicators for 2019 and 2021 were analyzed using the D-CRITIC method to determine the relative importance of each indicator (Global Health Security Index, 2021): https://ghsindex.org/report-model/). A combined D-CRITIC-CoCoSo framework was employed to rank the countries, followed by K-means clustering for grading. The study also investigated correlations between financial allocation’s indicators and health security outcomes using Spearman’s rank correlation. A comparative analysis elucidated regional disparities across income categories. Results This study highlights WA’s progress in health security by prioritizing foundational health systems, detection/reporting, rapid response, and risk management. From 2019 to 2021, priorities varied by income group, with high-income countries focusing on detection, upper-middle-income countries focusing on risk environments, and low-income countries focusing on prevention. While some nations demonstrated improvement, others, such as Armenia, experienced decline, revealing persistent vulnerabilities. This study revealed significant variability in health security capacity, with both progress and setbacks among countries in different clusters. High- and upper-middle-income countries, such as Qatar and Georgia, leverage investments and international partnerships to improve their rankings, while conflict-affected, low-resource countries, including Iraq, Yemen, and Syria, face stagnation or decline. Strong correlations were observed between financial resource allocation indicators and health performance. Higher investments in countries like Armenia and Georgia led to significantly improved health outcomes, while minimal spending in Syria and Yemen weakened their resilience to health threats. Conclusion Disparities in health resilience persist, underscoring the need for equitable resource allocation and regional cooperation to enhance public health security.
in F1000Research on 2025-03-28 16:15:05 UTC.
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Background The increasing incidence of emerging infectious diseases is posing serious global threats. Therefore, there is a clear need for developing computational methods that can assist and speed up experimental research to better characterize the molecular mechanisms of microbial infections. Methods In this context, we developed mimicINT, an open-source computational workflow for large-scale protein-protein interaction inference between microbe and human by detecting putative molecular mimicry elements mediating the interaction with host proteins: short linear motifs (SLiMs) and host-like globular domains. mimicINT exploits these putative elements to infer the interaction with human proteins by using known templates of domain-domain and SLiM-domain interaction templates. mimicINT also provides (i) robust Monte-Carlo simulations to assess the statistical significance of SLiM detection which suffers from false positives, and (ii) an interaction specificity filter to account for differences between motif-binding domains of the same family. We have also made mimicINT available via a web server. Results In two use cases, mimicINT can identify potential interfaces in experimentally detected interaction between pathogenic Escherichia coli type-3 secreted effectors and human proteins and infer biologically relevant interactions between Marburg virus and human proteins. Conclusions The mimicINT workflow can be instrumental to better understand the molecular details of microbe-host interactions.
in F1000Research on 2025-03-28 15:39:03 UTC.
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Background Predicting the number and distribution of Olympic medals in the future has become a hot topic, but predicting the number of Olympic medals is not easy and requires comprehensive consideration of multiple factors such as historical data, athlete performance, and host country effects. Method This article uses the GA-BP algorithm model, combined with genetic algorithm (GA) and backpropagation neural network (BPNN), to optimize the weights and bias parameters of the BP neural network using the global search capability of genetic algorithm, thereby improving training efficiency and prediction performance. By estimating the number of Olympic gold medals and total medals, verifying the accuracy of the model, and predicting the medal table for the 2028 Los Angeles Olympics. Meanwhile, based on the synthetic control model, Estonia and China were selected as research subjects to construct a virtual control group and two experimental groups for analysis. Result The experimental results showed that Estonia and China won more medals with a head coach than without one. In 1992, Estonia won 1 gold medal and 2 bronze medals under the guidance of excellent coaches, indicating the significant role of head coaches in improving athletes’ performance. Conclusion This study provides valuable insights for the decision-making of the Olympic Committee, revealing key factors in medal distribution, optimizing the allocation of national strategic resources, and predicting the performance of countries at future Olympic Games.
in F1000Research on 2025-03-28 15:31:59 UTC.
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Background The study investigates the impact of Managerial Ability (MA) on Working Capital Management Efficiency (WCME), focusing on how skilled management influences working capital practices. It also explores the variation in this relationship across firms with different characteristics such as profitability and market valuations within India’s economic landscape. Methods Using a balanced panel dataset of 150 listed companies from the National Stock Exchange (NSE) of India for the period 2014–2023, the study employs Data Envelopment Analysis (DEA). WCME is assessed as a multidimensional efficiency metric incorporating inventory, accounts receivable, accounts payable, cost of goods sold , net revenue, and net income. MA is estimated using a two-step DEA-based approach, separating managerial ability from firm-specific characteristics. Generalized Estimating Equations (GEE) regression models are applied to examine the individual and interactive effects of MA and Tobin’s Q (TBQ) on WCME along with other important variables. Results The results demonstrate that MA significantly enhances WCME, particularly in firms with lower TBQ. The analysis also reveals that skilled managerial characteristics amplifies the efficiency of working capital management, aligning with the Upper Echelon Theory's (UET) claim that managerial attributes play a critical role in organizational efficiency. Conclusion The study demonstrates managerial ability has a strong influence on corporate working capital policies. This advocates prevalence of certain fundamental concepts such as viz. Upper Echelon Theory (UET), Resource-Based View (RBV), and Agency Theory (AT). From managerial point of view, it is suggested to adopt strategic approaches in practicing WCME that will enhance firm’s competitive advantage and long-term sustainability.
in F1000Research on 2025-03-28 15:28:05 UTC.
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Background Neuroinflammation plays a critical role in the progression of neurological disorders such as Alzheimer’s and Parkinson’s diseases, as well as chronic pain. It is characterized by elevated production of pro-inflammatory cytokines, including IL-6, and TNF-α, by microglia, the resident immune cells of the central nervous system. Emerging research highlights the involvement of the endocannabinoid system (ECS) in neuroinflammation, proposing cannabinoids as potential therapeutic agents owing to their immunosuppressive and anti-inflammatory properties. Methods This study used an in vitro model, specifically the BV-2 murine microglial cell line, to assess neuroinflammation. Cell viability was measured using the MTT assay, and cytokine production was quantified using advanced nanobiosensor technologies, including Surface Plasmon Resonance (SPR). Immunocytochemistry (ICC) was used to evaluate protein expression. Microglial cells were treated with varying concentrations of dexamethasone sodium phosphate (Dex-SP), cannabidiol (CBD), a full-spectrum tetrahydrocannabinol (FSE-THC) extract (70% THC), or a combination of the two at a 1:1 ratio (FSE-THC/CBD). Results The treatments did not affect BV-2 microglial cell viability. Nitric oxide (NO) production remained unaltered following treatment with Dex-SP, CBD, FSE-THC 70%, or FSE-THC:CBD in LPS-stimulated BV-2 microglia. However, CBD and FSE-THC:CBD significantly reduced TNF-α levels, whereas Dex-SP and CBD decreased IL-6 expression. Furthermore, Dex-SP, CBD, FSE-THC (70%), and FSE-THC:CBD modulated the activation of Bcl-2, Bax, TNF-α, IFN-γ, NF-κB, and iNOS in concentration- and treatment-specific manners. Conclusions Dex-SPs demonstrate acute anti-inflammatory effects in LPS-stimulated BV2 microglial cells. Specific cannabinoids at particular concentrations exhibit comparable or superior efficacy in modulating key inflammatory mediators. These findings suggest the therapeutic potential of cannabinoids in neuroinflammation, and emphasize the need for further investigation to optimize their application.
in F1000Research on 2025-03-28 15:25:46 UTC.
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The fields of epidemiology and viral phylodynamics share the ultimate goal of disease control, but concepts, methodologies and data employed by each differ in ways that confer complementary strengths and different areas of weakness. We recently introduced EpiFusion, a model for joint inference of outbreak characteristics using phylogenetic and case incidence data via particle filtering and demonstrated its usage to infer the effective reproduction number of simulated and real outbreaks. Here we provide a series of vignettes demonstrating data analysis using the EpiFusion Analysis Framework, consisting of the R package EpiFusionUtilities and the Java program in which the model is implemented, including an example using a new feature incorporated since EpiFusion’s last description: the option to provide a phylogenetic tree posterior as the phylogenetic data input to the program. By outlining these examples, we aim to improve the usability of our model, and promote workflow reproducibility and open research.
in F1000Research on 2025-03-28 15:24:31 UTC.
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Background Motivational variables are of critical importance concerning students' performance. The objective of the present study was to investigate the interrelationships between extrinsic and intrinsic motivation, self-efficacy, self-regulation, critical thinking, and academic performance among university students. Methods The participants were 250 students enrolled in university programs in education and psychology. The research instrument was a self-report questionnaire designed to assess intrinsic and extrinsic motivation, critical thinking, self-regulation, and academic achievement among university students. A path model analysis was employed to identify the relationships among the investigated variables. Results The results demonstrated that self-efficacy was predicted by intrinsic and extrinsic motivation, critical thinking was predicted by self-efficacy, and self-regulation was predicted by self-efficacy and critical thinking, thereby underscoring the pivotal role of self-efficacy. The findings indicate that academic achievement is predicted by critical thinking, and self-regulation, thereby underscoring the pivotal role of these variables in academic contexts. Conclusions The contributions of the present research are twofold, both theoretical and practical. On the one hand, the findings offer a more nuanced understanding of the interconnections between motivation, self-efficacy, critical thinking, and self-regulation. On the other hand, they provide valuable insights for developing educational strategies that enhance academic achievement by fostering these key factors.
in F1000Research on 2025-03-28 15:15:38 UTC.
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by Barry Ryan, Riccardo Marioni, T. Ian Simpson
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor symptoms resulting from the loss of dopamine-producing neurons in the brain. Currently, there is no cure for the disease which is in part due to the heterogeneity in patient symptoms, trajectories and manifestations. There is a known genetic component of PD and genomic datasets have helped to uncover some aspects of the disease. Understanding the longitudinal variability of PD is essential as it has been theorised that there are different triggers and underlying disease mechanisms at different points during disease progression. In this paper, we perform longitudinal and cross-sectional experiments to identify which data modalities or combinations of modalities are informative at different time points. We use clinical, genomic, and proteomic data from the Parkinson’s Progression Markers Initiative. We validate the importance of flexible data integration by highlighting the varying combinations of data modalities for optimal stratification at different disease stages in idiopathic PD. We show there is a shared signal in the DNAm signatures of participants with a mutation in a causal gene of PD and participants with idiopathic PD. We also show that integration of SNPs and DNAm data modalities has potential for use as an early diagnostic tool for individuals with a genetic cause of PD.
in PLoS Computational Biology on 2025-03-28 14:00:00 UTC.
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by Raheel Asghar, Nan Wu, Noman Ali, Yulei Wang, Mahinur Akkaya
Understanding the biological functions of Puccinia striiformis f. sp. tritici (Pst) effectors is fundamental for uncovering the mechanisms of pathogenicity and variability, thereby paving the way for developing durable and effective control strategies for stripe rust. However, due to the lack of an efficient genetic transformation system in Pst, progress in effector function studies has been slow. Here, we modeled the structures of 15,201 effectors from twelve Pst races or isolates, a Puccinia striiformis isolate, and one Puccinia striiformis f. sp. hordei isolate using AlphaFold2. Of these, 8,102 folds were successfully predicted, and we performed sequence- and structure-based annotations of these effectors. These effectors were classified into 410 structure clusters and 1,005 sequence clusters. Sequence lengths varied widely, with a concentration between 101-250 amino acids, and motif analysis revealed that 47% and 5.81% of the predicted effectors contain known effector motifs [Y/F/W]xC and RxLR, respectively highlighting the structural conservation across a substantial portion of the effectors. Subcellular localization predictions indicated a predominant cytoplasmic localization, with notable chloroplast and nuclear presence. Structure-guided analysis significantly enhances effector prediction efficiency as demonstrated by the 75% among 8,102 have structural annotation. The clustering and annotation prediction both based on the sequence and structure homologies allowed us to determine the adopted folding or fold families of the effectors. A common feature observed was the formation of structural homologies from different sequences. In our study, one of the comparative structural analyses revealed a new structure family with a core structure of four helices, including Pst27791, PstGSRE4, and PstSIE1, which target key wheat immune pathway proteins, impacting the host immune functions. Further comparative structural analysis showed similarities between Pst effectors and effectors from other pathogens, such as AvrSr35, AvrSr50, Zt-KP4-1, and MoHrip2, highlighting a possibility of convergent evolutionary strategies, yet to be supported by further data encompassing on some evolutionarily distant species. Currently, our initial analysis is the most one on Pst effectors’ sequence, structural and annotation relationships providing a novel foundation to advance our future understanding of Pst pathogenicity and evolution.
in PLoS Computational Biology on 2025-03-28 14:00:00 UTC.