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arXiv:2503.22697v1 Announce Type: new
Abstract: Deciphering the neural mechanisms that transform sensory experiences into meaningful semantic representations is a fundamental challenge in cognitive neuroscience. While neuroimaging has mapped a distributed semantic network, the format and neural code of semantic content remain elusive, particularly for complex, naturalistic stimuli. Traditional brain decoding, focused on visual reconstruction, primarily captures low-level perceptual features, missing the deeper semantic essence guiding human cognition. Here, we introduce a paradigm shift by directly decoding fMRI signals into textual descriptions of viewed natural images. Our novel deep learning model, trained without visual input, achieves state-of-the-art semantic decoding performance, generating meaningful captions that capture the core semantic content of complex scenes. Neuroanatomical analysis reveals the critical role of higher-level visual regions, including MT+, ventral stream visual cortex, and inferior parietal cortex, in this semantic transformation. Category-specific decoding further demonstrates nuanced neural representations for semantic dimensions like animacy and motion. This text-based decoding approach provides a more direct and interpretable window into the brain's semantic encoding than visual reconstruction, offering a powerful new methodology for probing the neural basis of complex semantic processing, refining our understanding of the distributed semantic network, and potentially inspiring brain-inspired language models.
in arXiv: Quantitative Biology: Neurons and Cognition on 2025-04-01 04:00:00 UTC.
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arXiv:2503.22808v1 Announce Type: new
Abstract: Setting up a psychedelic study can be a long, arduous, and kafkaesque process. Researchers are faced with a host of challenges in this rapidly-evolving field, necessitating a range of questions that remain largely unstandardised. 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 aims to formalise these unique hurdles by addressing the sociocultural, political, legal, pharmacological, safety, study-design and experiential facets inherent to a psychedelic study. We bring several of the major psychedelic research teams across the United Kingdom, identify continuing areas of debate, and provide a practical, comprehensive, experience-based guide, with recommendations for policymakers and future researchers intending to set up a psychedelic research study or clinical trial.
in arXiv: Quantitative Biology: Neurons and Cognition on 2025-04-01 04:00:00 UTC.
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arXiv:2503.22917v1 Announce Type: new
Abstract: Because organisms are able to sense its passage, it is perhaps tempting to treat time as a sensory modality, akin to vision or audition. Indeed, certain features of sensory estimation, such as Weber's law, apply to timing and sensation alike (Gibbon, 1977; Pardo-Vazquez et al., 2019). However, from an organismal perspective, time is a derived feature of other signals, not a stimulus that can be readily transduced by sensory receptors. Its importance for biology lies in the fact that the physical world comprises a complex dynamical system. The multiscale spatiotemporal structure of sensory and internally generated signals within an organism is the informational fabric underlying its ability to control behavior. Viewed this way, temporal computations assume a more fundamental role than is implied by treating time as just another element of the experienced world (Paton & Buonomano, 2018). Thus, in this review we focus on temporal processing as a means of approaching the more general problem of how the nervous system produces adaptive behavior.
in arXiv: Quantitative Biology: Neurons and Cognition on 2025-04-01 04:00:00 UTC.
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arXiv:2503.23245v1 Announce Type: new
Abstract: The symbolic architecture of non-ordinary consciousness remains largely unmapped in cognitive science and artificial intelligence. While conventional models prioritize rational coherence, altered states such as those induced by psychedelics reveal distinct symbolic regimes characterized by recursive metaphor, ego dissolution, and semantic destabilization. We present \textit{Glyph}, a generative symbolic interface designed to simulate psilocybin-like symbolic cognition in large language models. Rather than modeling perception or mood, Glyph enacts symbolic transformation through recursive reentry, metaphoric modulation, and entropy-scaled destabilization -- a triadic operator formalized within a tensorial linguistic framework. Experimental comparison with baseline GPT-4o reveals that Glyph consistently generates high-entropy, metaphor-saturated, and ego-dissolving language across diverse symbolic prompt categories. These results validate the emergence of non-ordinary cognitive patterns and support a new paradigm for simulating altered consciousness through language. Glyph opens novel pathways for modeling symbolic cognition, exploring metaphor theory, and encoding knowledge in recursively altered semantic spaces.
in arXiv: Quantitative Biology: Neurons and Cognition on 2025-04-01 04:00:00 UTC.
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arXiv:2503.23394v1 Announce Type: new
Abstract: Understanding how the brain's complex nonlinear dynamics give rise to adaptive cognition and behavior is a central challenge in neuroscience. These dynamics exhibit scale-free and multifractal properties, influencing the reconfiguration of neural networks. However, conventional neuroimaging models are constrained by linear and stationary assumptions, limiting their ability to capture these processes. Transformer-based architectures, known for capturing long-range dependencies, align well with the brain's hierarchical and temporal organization. We introduce Multi-Band Brain Net (MBBN), a transformer-based framework that models frequency-specific spatiotemporal brain dynamics from fMRI by integrating scale-free network principles with frequency-resolved multi-band self-attention. Trained on three large-scale neuroimaging cohorts (UK Biobank, ABCD, ABIDE) totaling 45,951 individuals, MBBN reveals previously undetectable frequency-dependent network interactions, shedding light on connectivity disruptions in psychiatric conditions (ADHD, ASD, depression). This validation shows robust generalizability and highlights core neural principles conserved across populations. MBBN achieves up to 30.59% higher predictive accuracy than state-of-the-art methods, demonstrating the advantage of frequency-informed spatiotemporal modeling in capturing latent neural computations. MBBN's interpretability uncovers novel frequency-specific biomarkers for neurodevelopmental disorders, providing insights into the hierarchical organization of brain function. By offering an interpretable framework for spatiotemporal learning, MBBN provides insights into how neural computations underpin cognitive function and psychiatric vulnerability, with implications for brain decoding, cognitive neuroscience, and precision psychiatry.
in arXiv: Quantitative Biology: Neurons and Cognition on 2025-04-01 04:00:00 UTC.
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arXiv:2503.23808v1 Announce Type: new
Abstract: Background: Tinnitus, defined as the conscious awareness of a noise without any identifiable corresponding external acoustic source, can be modulated by various factors. Among these factors, tinnitus patients commonly report drastic increases of tinnitus loudness following nap sleep. Previous studies have suggested that this clinical pattern could be attributed to a somatosensory modulation of tinnitus. To our knowledge, no polysomnographic study has been carried out to assess this hypothesis.
Methods: For this observational prospective study, 37 participants reporting frequent increases of tinnitus following naps were recruited. They participated to six full-polysomnography nap attempts over two days. Audiological and kinesiologic tests were conducted before and after each nap attempt.
Results: 197 naps were collected. Each nap at each time of day elicited an overall significant increase in tinnitus minimum masking level (MML). Each inter nap period elicited an overall significant decrease. Tinnitus modulations were found significantly correlated with nap sleep duration (Visual numeric scale on tinnitus loudness, VNS-L, p < 0.05), with snoring duration (MML, p < 0.001), with snoring average sound level (VNS on tinnitus intrusiveness, VNS-I, p < 0.05) and with sleep apnea count (VNS-I, p < 0.001).
Conclusions: This study confirms objectively that tinnitus may increase following naps. No association was found between these modulations and somatosensory modulations involving the temporomandibular joint and cervical areas. However, it may be possible that nap-induced tinnitus modulations are a hidden form of somatosensory modulation as snoring and sleep apnea events are often related to tensor veli palatini muscle dysfunction.
in arXiv: Quantitative Biology: Neurons and Cognition on 2025-04-01 04:00:00 UTC.
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arXiv:2301.09600v3 Announce Type: replace
Abstract: The critical brain hypothesis posits that neural circuits may operate close to ``critical points'' -- boundaries between different phases of collective activity. This has been argued to have functional benefits for neural computation. Studies investigating whether neural circuits are poised near critical points have largely relied on establishing power laws in neural data, while a fundamental understanding of critical phenomena requires a renormalization group (RG) analysis. However, neural activity is typically non-Gaussian, nonlinear, and non-local, rendering models that capture all of these features difficult to study using standard statistical physics techniques. We overcome these issues and adapt the non-perturbative renormalization group (NPRG) to provide the first RG analysis of networks of stochastic spiking neurons. We show that neural populations can belong to at least two important universality classes: 1) in networks with an absorbing state there is a transition between sustained and extinguished activity that belongs to the directed percolation universality class, and 2) in spontaneously active networks there is a continuous transition between high and low firing rate states that belongs to the Ising model universality class. We verify our theoretical results by simulating the network model on lattices in $2$ and $3$ dimensions, recovering known exponents, and then investigate critical phenomena in networks of sparsely-connected excitatory neurons and densely-connected inhibitory neurons. Depending on the amount of inhibitory feedback, these networks may display mean-field exponents or anomalous exponents close to -- but potentially not equal to -- lattices of the same effective dimension.
in arXiv: Quantitative Biology: Neurons and Cognition on 2025-04-01 04:00:00 UTC.
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arXiv:2307.08758v2 Announce Type: replace
Abstract: This paper introduces a quantum-mechanical model that bridges the realms of cognition and quantum mechanics, offering a novel perspective on decision-making under risk and perceptual reversals. By integrating quantum theories addressing decision-theoretic anomalies with examples from immersive video games like "Deal or No Deal", we seek to elucidate complex human cognitive behaviours. Study 1 showcases the proposed quantum model's superiority over traditional decision-making approaches using the "Deal or No Deal" video game experiment. In Study 2, we apply our model to bistable perceptions, taking the Necker cube from the Necker game as a primary example. While previous works have hinted at connections between quantum mechanics and cognition, Study 3 provides a more tangible link, likening the physics that underpins quantum tunnelling to an eye blink's role in perceptual reversals. Conclusively, our model displays a promising ability to interpret diverse optical illusions and psychological phenomena, marking a significant stride in understanding human decision making.
in arXiv: Quantitative Biology: Neurons and Cognition on 2025-04-01 04:00:00 UTC.
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arXiv:2410.19750v2 Announce Type: replace
Abstract: Sparse autoencoders have recently produced dictionaries of high-dimensional vectors corresponding to the universe of concepts represented by large language models. We find that this concept universe has interesting structure at three levels: 1) The "atomic" small-scale structure contains "crystals" whose faces are parallelograms or trapezoids, generalizing well-known examples such as (man-woman-king-queen). We find that the quality of such parallelograms and associated function vectors improves greatly when projecting out global distractor directions such as word length, which is efficiently done with linear discriminant analysis. 2) The "brain" intermediate-scale structure has significant spatial modularity; for example, math and code features form a "lobe" akin to functional lobes seen in neural fMRI images. We quantify the spatial locality of these lobes with multiple metrics and find that clusters of co-occurring features, at coarse enough scale, also cluster together spatially far more than one would expect if feature geometry were random. 3) The "galaxy" scale large-scale structure of the feature point cloud is not isotropic, but instead has a power law of eigenvalues with steepest slope in middle layers. We also quantify how the clustering entropy depends on the layer.
in arXiv: Quantitative Biology: Neurons and Cognition on 2025-04-01 04:00:00 UTC.
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arXiv:2411.08140v2 Announce Type: replace
Abstract: Exposure therapy, a standard treatment for anxiety disorders, relies on fear extinction. However, extinction recall is often limited to the spatial and temporal context in which extinction is learned, leading to fear relapse in new settings or after delays. Animal studies offer insights into fear extinction in humans. Computational models that integrate these findings into a neurally grounded framework, while generating testable hypotheses for humans, can bridge this gap. Current models either focus on neuron-level activity, limiting their scope, or abstract away entirely from neural mechanisms. They also often overlook the distinct contributions of cue and context in fear extinction and recall. To address these gaps, we present ConFER, a neurally constrained model of fear extinction, recall, and relapse. ConFER integrates findings from the neural fear circuit, modeling distinct pathways for cue and context processing. These pathways independently activate positive and/or negative memory engrams in the basolateral amygdala, competing to determine the fear response. ConFER simulates fear renewal and spontaneous recovery across context combinations, while generating novel, testable predictions. Notably, it predicts counterconditioning may better prevent relapse than extinction in new contexts or after delays. By mechanistically modeling fear relapse, ConFER offers insights to improve exposure therapy outcomes.
in arXiv: Quantitative Biology: Neurons and Cognition on 2025-04-01 04:00:00 UTC.
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arXiv:2503.06374v3 Announce Type: replace
Abstract: One of the central aims of neuroscience is to reliably predict the behavioral response of an organism using its neural activity. If possible, this implies we can causally manipulate the neural response and design brain-computer-interface systems to alter behavior, and vice-versa. Hence, predictions play an important role in both fundamental neuroscience and its applications. Can we predict the neural and behavioral states of an organism at any given time? Can we predict behavioral states using neural states, and vice-versa, and is there a memory-component required to reliably predict such states? Are the predictions computable within a given timescale to meaningfully stimulate and make the system reach the desired states? Through a series of mathematical treatments, such conjectures and questions are discussed. Answering them might be key for future developments in understanding intelligence and designing brain-computer-interfaces.
in arXiv: Quantitative Biology: Neurons and Cognition on 2025-04-01 04:00:00 UTC.
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arXiv:2503.21611v2 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 2025-04-01 04:00:00 UTC.
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arXiv:2502.20779v2 Announce Type: replace-cross
Abstract: Large language models (LLMs) often exhibit abrupt emergent behavior, whereby new abilities arise at certain points during their training. This phenomenon, commonly referred to as a ''phase transition'', remains poorly understood. In this study, we conduct an integrative analysis of such phase transitions by examining three interconnected perspectives: the similarity between LLMs and the human brain, the internal states of LLMs, and downstream task performance. We propose a novel interpretation for the learning dynamics of LLMs that vary in both training data and architecture, revealing that three phase transitions commonly emerge across these models during training: (1) alignment with the entire brain surges as LLMs begin adhering to task instructions Brain Alignment and Instruction Following, (2) unexpectedly, LLMs diverge from the brain during a period in which downstream task accuracy temporarily stagnates Brain Detachment and Stagnation, and (3) alignment with the brain reoccurs as LLMs become capable of solving the downstream tasks Brain Realignment and Consolidation. These findings illuminate the underlying mechanisms of phase transitions in LLMs, while opening new avenues for interdisciplinary research bridging AI and neuroscience.
in arXiv: Quantitative Biology: Neurons and Cognition on 2025-04-01 04:00:00 UTC.
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arXiv:2503.15699v2 Announce Type: replace-cross
Abstract: How do two deep neural networks differ in how they arrive at a decision? Measuring the similarity of deep networks has been a long-standing open question. Most existing methods provide a single number to measure the similarity of two networks at a given layer, but give no insight into what makes them similar or dissimilar. We introduce an interpretable representational similarity method (RSVC) to compare two networks. We use RSVC to discover shared and unique visual concepts between two models. We show that some aspects of model differences can be attributed to unique concepts discovered by one model that are not well represented in the other. Finally, we conduct extensive evaluation across different vision model architectures and training protocols to demonstrate its effectiveness.
in arXiv: Quantitative Biology: Neurons and Cognition on 2025-04-01 04:00:00 UTC.
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arXiv:2405.06851v2 Announce Type: replace-cross
Abstract: Understanding how neural systems efficiently process information through distributed representations is a fundamental challenge at the interface of neuroscience and machine learning. Recent approaches analyze the statistical and geometrical attributes of neural representations as population-level mechanistic descriptors of task implementation. In particular, manifold capacity has emerged as a promising framework linking population geometry to the separability of neural manifolds. However, this metric has been limited to linear readouts. To address this limitation, we introduce a theoretical framework that leverages latent directions in input space, which can be related to contextual information. We derive an exact formula for the context-dependent manifold capacity that depends on manifold geometry and context correlations, and validate it on synthetic and real data. Our framework's increased expressivity captures representation reformatting in deep networks at early stages of the layer hierarchy, previously inaccessible to analysis. As context-dependent nonlinearity is ubiquitous in neural systems, our data-driven and theoretically grounded approach promises to elucidate context-dependent computation across scales, datasets, and models.
in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-04-01 04:00:00 UTC.
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arXiv:2503.23767v1 Announce Type: new
Abstract: Lateral connection is a fundamental feature of biological neural circuits, facilitating local information processing and adaptive learning. In this work, we integrate lateral connections with a substructure selection network to develop a novel diffusion model based on spiking neural networks (SNNs). Unlike conventional artificial neural networks, SNNs employ an intrinsic spiking inner loop to process sequential binary spikes. We leverage this spiking inner loop alongside a lateral connection mechanism to iteratively refine the substructure selection network, enhancing model adaptability and expressivity. Specifically, we design a lateral connection framework comprising a learnable lateral matrix and a lateral mapping function, both implemented using spiking neurons, to dynamically update lateral connections. Through mathematical modeling, we establish that the proposed lateral update mechanism, under a well-defined local objective, aligns with biologically plausible synaptic plasticity principles. Extensive experiments validate the effectiveness of our approach, analyzing the role of substructure selection and lateral connection during training. Furthermore, quantitative comparisons demonstrate that our model consistently surpasses state-of-the-art SNN-based generative models across multiple benchmark datasets.
in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-04-01 04:00:00 UTC.
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arXiv:2503.22722v1 Announce Type: cross
Abstract: The landscape of optimization problems has become increasingly complex, necessitating the development of advanced optimization techniques. Meta-Black-Box Optimization (MetaBBO), which involves refining the optimization algorithms themselves via meta-learning, has emerged as a promising approach. Recognizing the limitations in existing platforms, we presents PlatMetaX, a novel MATLAB platform for MetaBBO with reinforcement learning. PlatMetaX integrates the strengths of MetaBox and PlatEMO, offering a comprehensive framework for developing, evaluating, and comparing optimization algorithms. The platform is designed to handle a wide range of optimization problems, from single-objective to multi-objective, and is equipped with a rich set of baseline algorithms and evaluation metrics. We demonstrate the utility of PlatMetaX through extensive experiments and provide insights into its design and implementation. PlatMetaX is available at: \href{https://github.com/Yxxx616/PlatMetaX}{https://github.com/Yxxx616/PlatMetaX}.
in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-04-01 04:00:00 UTC.
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arXiv:2503.22742v1 Announce Type: cross
Abstract: We propose Adaptive Integrated Layered Attention (AILA), a neural network architecture that combines dense skip connections with different mechanisms for adaptive feature reuse across network layers. We evaluate AILA on three challenging tasks: price forecasting for various commodities and indices (S&P 500, Gold, US dollar Futures, Coffee, Wheat), image recognition using the CIFAR-10 dataset, and sentiment analysis on the IMDB movie review dataset. In all cases, AILA matches strong deep learning baselines (LSTMs, Transformers, and ResNets), achieving it at a fraction of the training and inference time. Notably, we implement and test two versions of the model - AILA-Architecture 1, which uses simple linear layers as the connection mechanism between layers, and AILA-Architecture 2, which implements an attention mechanism to selectively focus on outputs from previous layers. Both architectures are applied in a single-task learning setting, with each model trained separately for individual tasks. Results confirm that AILA's adaptive inter-layer connections yield robust gains by flexibly reusing pertinent features at multiple network depths. The AILA approach thus presents an extension to existing architectures, improving long-range sequence modeling, image recognition with optimised computational speed, and SOTA classification performance in practice.
in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-04-01 04:00:00 UTC.
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arXiv:2503.24389v1 Announce Type: cross
Abstract: Underwater object detection is critical for oceanic research and industrial safety inspections. However, the complex optical environment and the limited resources of underwater equipment pose significant challenges to achieving high accuracy and low power consumption. To address these issues, we propose Spiking Underwater YOLO (SU-YOLO), a Spiking Neural Network (SNN) model. Leveraging the lightweight and energy-efficient properties of SNNs, SU-YOLO incorporates a novel spike-based underwater image denoising method based solely on integer addition, which enhances the quality of feature maps with minimal computational overhead. In addition, we introduce Separated Batch Normalization (SeBN), a technique that normalizes feature maps independently across multiple time steps and is optimized for integration with residual structures to capture the temporal dynamics of SNNs more effectively. The redesigned spiking residual blocks integrate the Cross Stage Partial Network (CSPNet) with the YOLO architecture to mitigate spike degradation and enhance the model's feature extraction capabilities. Experimental results on URPC2019 underwater dataset demonstrate that SU-YOLO achieves mAP of 78.8% with 6.97M parameters and an energy consumption of 2.98 mJ, surpassing mainstream SNN models in both detection accuracy and computational efficiency. These results underscore the potential of SNNs for engineering applications. The code is available in https://github.com/lwxfight/snn-underwater.
in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-04-01 04:00:00 UTC.
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arXiv:2305.18353v4 Announce Type: replace
Abstract: The Backpropagation algorithm has often been criticised for its lack of biological realism. In an attempt to find a more biologically plausible alternative, the recently introduced Forward-Forward algorithm replaces the forward and backward passes of Backpropagation with two forward passes. In this work, we show that the internal representations obtained by the Forward-Forward algorithm can organise into category-specific ensembles exhibiting high sparsity -- composed of a low number of active units. This situation is reminiscent of what has been observed in cortical sensory areas, where neuronal ensembles are suggested to serve as the functional building blocks for perception and action. Interestingly, while this sparse pattern does not typically arise in models trained with standard Backpropagation, it can emerge in networks trained with Backpropagation on the same objective proposed for the Forward-Forward algorithm.
in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-04-01 04:00:00 UTC.
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arXiv:2501.06572v2 Announce Type: replace
Abstract: Deep learning models trained on finite data lack a complete understanding of the physical world. On the other hand, physics-informed neural networks (PINNs) are infused with such knowledge through the incorporation of mathematically expressible laws of nature into their training loss function. By complying with physical laws, PINNs provide advantages over purely data-driven models in limited-data regimes. This feature has propelled them to the forefront of scientific machine learning, a domain characterized by scarce and costly data. However, the vision of accurate physics-informed learning comes with significant challenges. This review examines PINNs for the first time in terms of model optimization and generalization, shedding light on the need for new algorithmic advances to overcome issues pertaining to the training speed, precision, and generalizability of today's PINN models. Of particular interest are the gradient-free methods of neuroevolution for optimizing the uniquely complex loss landscapes arising in PINN training. Methods synergizing gradient descent and neuroevolution for discovering bespoke neural architectures and balancing multiple conflicting terms in physics-informed learning objectives are positioned as important avenues for future research. Yet another exciting track is to cast neuroevolution as a meta-learner of generalizable PINN models.
in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-04-01 04:00:00 UTC.
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arXiv:2209.06119v5 Announce Type: replace-cross
Abstract: Activation Functions introduce non-linearity in the deep neural networks. This nonlinearity helps the neural networks learn faster and efficiently from the dataset. In deep learning, many activation functions are developed and used based on the type of problem statement. ReLU's variants, SWISH, and MISH are goto activation functions. MISH function is considered having similar or even better performance than SWISH, and much better than ReLU. In this paper, we propose an activation function named APTx which behaves similar to MISH, but requires lesser mathematical operations to compute. The lesser computational requirements of APTx does speed up the model training, and thus also reduces the hardware requirement for the deep learning model. Source code: https://github.com/mr-ravin/aptx_activation
in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-04-01 04:00:00 UTC.
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Nature Communications, Published online: 01 April 2025; doi:10.1038/s41467-025-58315-2
The cobalt-catalyzed intermolecular reductive coupling of alkenes and alkynes is attractive due to the unique reactivity and cost-effectiveness of cobalt catalysts. Here, the authors report an asymmetric desymmetric reductive coupling of electronically unbiased succinimide-containing cyclobutenes with internal alkynes via photoredox and cobalt dual catalysis.
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/s41467-025-58458-2
The strength of the Cape-Horn Current, as traced in the sediment cores, varies with sea surface temperature in the Eastern South Pacific. Changes in this current are also associated with North Hemisphere cooling events and atmospheric CO2 outgassing.
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/s41467-025-58432-y
RNF213 is a key player in fighting against various invasive pathogens in mammals. Here, the authors show that pathogenic Shigella flexneri can use its effector IpaH1.4 to directly target and subvert RNF213 to evade host antibacterial immunity.
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/s41467-025-58180-z
This study identifies monoclonal antibodies A138 and B026 targeting MPXV proteins M1R and B6R. Both antibodies exhibit neutralization of MPXV and VACV, and their combination enhances protective efficacy in mice, supporting a dual-targeting strategy.
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/s41467-025-58371-8
Transplantation of allogeneic hematopoietic stem cells (HSCs) is the only reported cure of HIV-1. Here, authors describe an autologous HSC transplant therapy with cells engineered for multilayered resistance to HIV-1 through CCR5 knockout and secretion of HIV inhibiting antibodies by B cell progeny.
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/s41467-025-58341-0
Phylogenetic origin of the Y haplome present in allopolyploid Triticeae species is unclear. Here, the authors report the genome assembly of allohexaploid Elymus nutans, reveal the all likely combinations of St, Y, and H haplomes during the allopolyploid origins, and identify gene responsible for UV-B radiation adaptation.
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/s41467-025-58310-7
Atopic dermatitis is a highly heritable skin condition. Here, the authors perform a GWAS meta-analysis of atopic dermatitis and carry out downstream analyses and functional experiments to understand the impact of the variants they identify.
in Nature Communications on 2025-04-01 00:00:00 UTC.
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Defensive behaviors are essential for survival, with risk assessment enabling organisms to evaluate and respond to potential threats. The dorsal raphe nucleus (DRN), a key neuromodulatory center, is crucial for encoding motivational salience and regulating arousal and sleep-wake states through its diverse neuronal populations, including dopaminergic neurons (DRNDA). While the roles of DRNDA neurons have been studied, their specific contributions to threat evaluation are less understood. Recent research identifies a distinct subset of DRNDA neurons that express vasoactive intestinal peptide (VIP) and project to the central amygdala (CeA) and the oval nucleus of the bed nucleus of the stria terminalis (ovBNST). Together, these two regions comprise the central extended amygdala, a key network regulating adaptive responses to threats. We hypothesized that distinct DRNDA subpopulations exert diverging effects on sleep-wake regulation and that DRNVIP neurons play a pivotal role in coordinating activity between the CeA and ovBNST, thereby influencing risk assessment and defensive response. To test this hypothesis, we used a combination of in situ hybridization, immunochemistry, whole-brain mapping, electrophysiology, and cell-specific genetic tools in mice and non-human primates. Our findings reveal that DRNVIP neurons form a key DRNDA neuronal subset, uniquely positioned to regulate the central extended amygdala through a feedback loop. These neurons receive inputs from Protein Kinase C delta (PKC-{delta}) neurons in the ovBNST and CeA and send glutamate-releasing projections back to these regions, modulating PKC-{delta} neuron excitability. Selective ablation of DRNVIP neurons increases activity in both the BNST and CeA, disrupting active-phase sleep architecture and impairing risk assessment and defensive behaviors. Together, these findings suggest DRNVIP neurons control specific phases of sleep and orchestrate the role of central extended amygdala in risk assessment and defensive responses.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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Clinical features of FXS phenotype include intellectual disability, repetitive behaviors, social communication deficit and also commonly manifested auditory hypersensitivity for acoustic stimuli. The electrophysiological studies have shown that FXS patients and Fmr1KO mice display improper processing of auditory information in the cortical areas of the brain and the spiral ganglion of cochlea. Synapses formed by spiral ganglion neurons on sensory hair cells (HC) are the first connection on the path that conveys the auditory information from the sensory cells to the brain. We confirmed the presence of fragile X mental retardation protein (FMRP) in the inner hair cells of the cochlea. Next, we analyzed the morphology of IHC ribbon synapses in early stages of postnatal development (P5, P14) and detected their delayed development in Fmr1 KO mice. Interestingly the ultrastructure of inner hair cell ribbon synapses studied by electron microscopy in the adult mice have shown no specific dysmorphologies. Delayed development of presynaptic ribbons of auditory hair cells in Fmr1 KO mice may contribute to abnormal development of circuits induced by auditory experience.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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Transcranial magnetic stimulation (TMS) to the dorsolateral prefrontal cortex (DLPFC) is hypothesized to relieve symptoms of depression by inhibiting activity in the subgenual anterior cingulate cortex (sgACC). However, we have a limited understanding of how TMS influences neural activity in the sgACC, owing to its deep location within the brain. To better understand the mechanism of antidepressant response to TMS, we recruited two neurosurgical patients with indwelling electrodes and delivered TMS pulses to the DLPFC while simultaneously recording local field potentials from the sgACC. Spectral analysis revealed a decrease in high-frequency activity (HFA; 70-180 Hz) after each stimulation pulse, which was especially pronounced in the sgACC relative to other regions. TMS-evoked HFA power was generally anticorrelated between the DLPFC and sgACC, even while low-frequency phase locking between the two regions was enhanced. Together, these findings support the notion that TMS to the DLPFC can suppress neural firing in the sgACC, suggesting a possible mechanism by which this treatment regulates mood.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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Spontaneous thoughts, occupying much of one's awake time in daily time, are often colored by emotional qualities. While spontaneous thoughts have been associated with various neural correlates, the relationship between subjective qualities of ongoing experiences and the brain's sensitivity to bodily signals (i.e., interoception) remains largely unexplored. Given the well-established role of interoception in emotion, clarifying this relationship may elucidate how processes relevant to mental health, such as arousal and anxiety, are regulated. We used EEG and ECG to measure the heartbeat evoked potential (HEP), an index of interoceptive processing, while 51 adult participants (34 male, 20 female) visually fixated on a cross image and let their minds wander freely. At pseudo-random intervals, participants reported their momentary level of arousal. This measure of subjective arousal was highly variable within and between individuals but was statistically unrelated to several markers of physiological arousal, including heart rate, heart rate variability, time on task, and EEG alpha power at posterior electrodes. A cluster-based permutation analysis revealed that the HEP amplitude was increased during low relative to high subjective arousal in a set of frontal electrodes during the 0.328 s to 0.364 s window after heartbeat onset. This HEP effect was more pronounced in individuals who reported high, relative to low, levels of state anxiety. Together, our results offer novel evidence that at varying levels of state anxiety, the brain differentially modulates sensitivity to bodily signals in coordination with the momentary, spontaneous experience of subjective arousal, a mechanism that may operate independently of physiological arousal.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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Learning to adapt voluntary movements to an external perturbation, whether mechanical or visual, is faster during a second encounter than during the first. The mechanisms underlying this phenomenon, known as savings, remain unclear. Recent studies propose that the high dimensionality of neural control enables the retention of learning traces that may facilitate savings. To test this idea we used MotorNet, a framework for training recurrent neural networks (RNNs) to control biomechanical models of the human upper limb. RNNs were trained to perform reaching movements with a velocity-dependent force field (FF) and without (NF) in the sequence NF1 (baseline), FF1 (adaptation), NF2 (washout), and FF2 (re-adaptation). RNNs showed behavioural signatures of savings in the absence of any explicit contextual input signalling the presence or absence of the FF. Savings was more robust in RNNs with larger numbers of units. We identified a component of RNN activity associated with savings--a shift in preparatory activity that persisted even after washout. Displacing this preparatory activity in the direction of the shift enhanced savings, whereas perturbations in the opposite direction reduced or eliminated savings. These findings suggest a potential neural basis for motor memory retention underlying savings that is reliant on the high dimensionality of neural space, and is independent of cognitive or strategic learning.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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In two-photon imaging of neuronal activity it is common to acquire 3-dimensional volumes. However, these volumes are typically processed plane by plane, leading to duplicated cells across planes, reduced signal-to-noise ratio per cell, uncorrected axial movement, and missed cells. To overcome these limitations, we introduce Suite3D, a volumetric cell detection pipeline. Suite3D corrects for 3D brain motion, estimating axial motion and improving estimates of lateral motion. It detects neurons using 3D correlation, which improves the signal-to-background ratio and detectability of cells. Finally, it performs 3D segmentation, detecting cells across imaging planes. We validated Suite3D with data from conventional multi-plane microscopes and advanced volumetric microscopes, at various resolutions and in various brain regions. Suite3D successfully detected cells appearing on multiple imaging planes, improving cell detectability and signal quality, avoiding duplications, and running >20x faster than a prior volumetric pipeline. Suite3D offers a powerful solution for analyzing volumetric two-photon data.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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RNA sequencing studies on human dorsal root ganglion (hDRG) from patients suffering from neuropathic pain show upregulation of OSM, linking this IL-6 family cytokine to pain disorders. In mice, however, OSM signaling causes itch behaviors through a direct effect on its cognate receptor expressed uniquely by pruriceptive sensory neurons. We hypothesized that an expansion in function of OSM-OSM receptor (OSMR) in sensory disorders in humans could be explained by species differences in receptor expression and signaling. Our in situ hybridization and immunohistochemical findings demonstrate broad expression of OSMR in DRG nociceptors and afferent fibers innervating the superficial and deep skin of humans. In patch-clamp electrophysiology, OSM directly activates human sensory neurons engaging MAPK signaling to promote action potential firing. Using CRISPR editing we show that OSM activation of MAPK signaling is dependent on OSMR and not LIFR in hDRG. Bulk, single-nuclei, and single-cell RNA-seq of OSM-treated hDRG cultures reveal expansive similarities in the transcriptomic signature observed in pain DRGs from neuropathic patients, indicating that OSM alone can orchestrate transcriptomic signatures associated with pain. We conclude that OSM-OSMR signaling via MAPKs is a critical signaling factor for DRG plasticity that may underlie neuropathic pain in patients.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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Thought disorder, characterized by disruptions in syntactic and semantic elements in language, is a core symptom of psychotic disorders. Understanding this language impairment is key to uncovering the underlying neuropathology and predicting treatment outcomes for individuals with schizophrenia and other psychotic disorders. Binomial ordering preferences (e.g. "salt and pepper" instead of "pepper and salt"), may be a quantifiable correlate of thought disorder and underlying linguistic impairments. We tested whether atypical binomial ordering can serve as a linguistic marker for psychosis symptoms. Participants with early-stage psychotic disorders and controls were recruited, and video-recorded interviews were transcribed for analysis. Identified binomial pairs were assessed using both the Google N-gram database and a logistic regression model to determine ordering preferences. Results showed that while both psychotic participants and controls preferred conventional binomial orderings, participants with psychotic disorders exhibited a higher rate of atypical binomial orderings. The use of atypical orderings was correlated with thought disorder, but not with other psychiatric symptoms or medications. Tracking binomial ordering can be a valuable marker of thought disorder but future studies are needed to determine whether this link remains stable or if it changes with disease progression.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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Plato's Republic, Einstein's Theory of relativity, Vilvadi's Four Seasons are all remarkable examples of humans' unique ability to create and manipulate complex abstract structures, whether in language, mathematics or music. Yet the mechanisms by which children develop such abstract thinking, and the role of education and structured experiences such as musical practice in shaping these abilities remain unclear. To explore these questions, we conducted cross-sectional behavioral experiments with 566 children aged 4 to 8, spanning four educational grades, half of whom participated in a violin training program since the age of four. Two experiments examined how children encode, process and compress auditory sequences and visual patterns, while a third examined their sensitivity to geometric regularities. Our results reveal the emergence of symbolic reasoning as early as the start of formal schooling, yet with deeper abstraction as a function of grade. By first grade, children encoded complex auditory sequences within a Language of Thought (LoT) similar to adults. Additionally, when confronted with quadrilaterals, children showed increasing sensitivity to geometric regularities, suggesting a developmental transition from perceptual to symbolic reasoning. However, we did not observe significant impact of musical practice on abstraction abilities across any of the domains tested. We discuss whether and how the impact of education and extracurricular activities such as music could be enhanced.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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Skillful hand movements are a hallmark of primates, including humans, requiring sophisticated motor planning and execution. Challenging the longstanding paradigm that emphasizes the dominance of the cerebral cortex, our study highlights a pivotal role for spinal excitatory reflex circuits in both planning and executing skillful hand movements. Using a combination of experimental approaches with behaving non-human primates and predictive simulation, we identified a group of excitatory spinal interneurons that orchestrate a closed-loop, positive feedback mechanism during voluntary wrist movements. This mechanism is characterized by a bidirectional interaction between inter-neuronal spiking and muscle activity, mediated by motoneuronal efferent signals and proprioceptive afferent signals from the same agonistic muscles. Furthermore, we demonstrate that the temporal profile of muscle activity during movement execution, including amplitude and duration, is pre-determined during motor planning at the spinal interneurons, functioning as a force-feedback gain within the excitatory circuit. These findings suggest that autogenic spinal excitatory circuits play a predominant role in shaping overall muscle activation during motor execution, provided the proper reflex gain is pre-set by higher neural systems during motor planning. Together, our findings provide a cellular-level perspective on how spinal reflex loops contribute to skilled voluntary movements in primates, extending over a century of spinal reflex research.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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Group III metabotropic glutamate receptors (mGluRIII) are expressed broadly throughout the neocortex and hippocampus but are thought to inhibit neurotransmitter release only at a subset of synapses and in a target cell-specific manner. Accordingly, previous slice physiology experiments in hippocampal area CA1 showed that mGluRIII receptors inhibit glutamate and GABA release only at excitatory and inhibitory synapses formed onto GABAergic interneurons, not onto pyramidal cells. Here, we show that the supposed target cell-specific modulation of GABA release only occurs when the extracellular calcium concentration in the recording solution is higher than its physiological concentration in the cerebrospinal fluid. Under more physiological conditions, mGluRIII receptors inhibit GABA release at synapses formed onto both interneurons and pyramidal cells but limit glutamate release only onto interneurons. This previously unrecognized form of mGluRIII-dependent, pre-synaptic modulation of inhibition onto pyramidal cells is accounted for by a reduction in the size of the readily releasable pool, mediated by protein kinase A and its vesicle-associated target proteins, synapsins. Using in vivo whole-cell recordings in behaving mice, we demonstrate that blocking mGluRIII activation in the intact CA1 network results in net effects consistent with decreased inhibition and significantly alters CA1 place cell activity. Together, these findings challenge our current understanding of the role of mGluRIII receptors in the control of synaptic transmission and encoding of spatial information in the hippocampus.
in bioRxiv: Neuroscience on 2025-04-01 00:00:00 UTC.
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A failure of organized communication in the PFC is thought to contribute to the emergence of cognitive impairments in psychiatric diseases, with attentional deficits occurring as a fundamental symptom across various conditions. The 22q11.2 microdeletion syndrome is a rare genetic condition that confers a high risk for developing psychiatric and neurodevelopmental disorders, and mouse models have been shown to display attention impairments and PFC pathology that are relevant to clinical populations. Abnormalities in prefrontal parvalbumin-expressing neurons (PVNs) are part of the observed pathophysiology, and studies in rodents have shown that the direct manipulation of these cells can induce behavioral deficits that align with the cognitive symptoms observed in psychiatric diseases. In the present study, we expanded on the role of PVNs in supporting cognition by investigating their involvement in multiple aspects of attentional functions using a translationally relevant task of focused visual attention, in both non-pathological mice and a model of the 22q11.2 microdeletion syndrome. We observed that task-evoked prefrontal PVN activity was reduced in mice that exhibited poorer attention and in 22q11.2 mutant mice. While PVN activity was shaped across learning in non-pathological mice, mutant mice exhibited a lack of signal dynamics that coincided with attentional deficits. Importantly, we observed that task performance in both poor performing wild-types and 22q11.2 mutants could be alleviated by gamma frequency stimulation of PVNs. Thus, PVNs appear to be involved in the acquisition of task rules and execution of attention and continue to be a promising therapeutic target for cognitive dysfunction in disease.
in bioRxiv: Neuroscience 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 conversation 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 last 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/d41586-025-00934-2
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 Communications, Published online: 31 March 2025; doi:10.1038/s41467-025-57978-1
Author Correction: A20 controls intestinal homeostasis through cell-specific activities
in Nature Communications 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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Nature Physics, Published online: 31 March 2025; doi:10.1038/s41567-025-02838-4
Circadian disruption can promote tumour formation. Now it is shown that the loss of circadian synchronization can drive this effect by disrupting the coupling between the circadian rhythm and the cell cycle within individual cells.
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/s41567-025-02864-2
Spin-split bands and certain lattice symmetries are required to generate the spin currents needed for spintronics applications. Now a layered room-temperature antiferromagnet is shown to exhibit anisotropic spin splitting between valleys paired by a crystal symmetry.
in Nature Physics on 2025-03-31 00:00:00 UTC.
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Scientific Data, Published online: 31 March 2025; doi:10.1038/s41597-025-04855-7
A high-quality chromosome-level genome assembly for the agricultural pest Mythimna separata
in Nature scientific data on 2025-03-31 00:00:00 UTC.
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Scientific Data, Published online: 31 March 2025; doi:10.1038/s41597-025-04893-1
Near telomere-to-telomere genome assembly of the blackspot tuskfish (Choerodon schoenleinii)
in Nature scientific data on 2025-03-31 00:00:00 UTC.
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Scientific Data, Published online: 31 March 2025; doi:10.1038/s41597-025-04853-9
Chromosome-level genome assembly of Jiaobai (Zizania latifolia, Poceace)
in Nature scientific data on 2025-03-31 00:00:00 UTC.
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Scientific Data, Published online: 31 March 2025; doi:10.1038/s41597-025-04901-4
China’s social fake news database release with brain structural, functional, and behavioural measures
in Nature scientific data on 2025-03-31 00:00:00 UTC.
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Scientific Data, Published online: 31 March 2025; doi:10.1038/s41597-025-04692-8
A Dataset on Linguistic Connectivity Across and Within Countries
in Nature scientific data on 2025-03-31 00:00:00 UTC.
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Scientific Data, Published online: 31 March 2025; doi:10.1038/s41597-024-04207-x
Global Roadkill Data: a dataset on terrestrial vertebrate mortality caused by collision with vehicles
in Nature scientific data on 2025-03-31 00:00:00 UTC.
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Scientific Data, Published online: 31 March 2025; doi:10.1038/s41597-025-04887-z
Haplotype-resolved genome assembly of the tetraploid Youcha tree Camellia meiocarpa Hu
in Nature scientific data on 2025-03-31 00:00:00 UTC.
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Scientific Data, Published online: 31 March 2025; doi:10.1038/s41597-025-04869-1
UrBAN: Urban Beehive Acoustics and PheNotyping Dataset
in Nature scientific data on 2025-03-31 00:00:00 UTC.
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Communications Biology, Published online: 31 March 2025; doi:10.1038/s42003-025-07957-5
Author Correction: 3D genome landscape of primary and metastatic colorectal carcinoma reveals the regulatory mechanism of tumorigenic and metastatic gene expression
in Nature communications biology on 2025-03-31 00:00:00 UTC.
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Communications Biology, Published online: 31 March 2025; doi:10.1038/s42003-025-07958-4
OPN3 interacts with VEGFR2, forming a physical complex in HUVECs, and regulates angiogenesis in vitro and in vivo via the VEGFR2-mediated AKT pathway, offering new mechanistic insights into angiogenesis.
in Nature communications biology on 2025-03-31 00:00:00 UTC.
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Communications Biology, Published online: 31 March 2025; doi:10.1038/s42003-025-07784-8
Grains suppress ovaries in ears of maize to strengthen their sugar utilization advantage for development, potentially through hormone and MAPK signaling.
in Nature communications biology on 2025-03-31 00:00:00 UTC.
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Communications Biology, Published online: 31 March 2025; doi:10.1038/s42003-025-07959-3
SDA4Drug is a semi-supervised, few-shot transfer learning method that improves single-cell drug response predictions by transferring knowledge from bulk-level data. It accurately identifies drug-resistant subpopulations, aiding precision medicine and drug development.
in Nature communications biology on 2025-03-31 00:00:00 UTC.
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Communications Biology, Published online: 31 March 2025; doi:10.1038/s42003-025-07886-3
Using protein covariation network analysis, this study uncovers the mechanism of action for AX-53802, a new ferroptosis inducer, validating GPX4 as its direct target, and proposes combination therapies targeting FAK/Src to enhance cancer cell death.
in Nature communications biology on 2025-03-31 00:00:00 UTC.
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Communications Biology, Published online: 31 March 2025; doi:10.1038/s42003-025-07954-8
Five histone marks and transcriptome are profiled for each tumor or non-neoplastic tissue samples to identify genes and regulatory elements involved in non-small cell lung cancer.
in Nature communications biology on 2025-03-31 00:00:00 UTC.
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Communications Biology, Published online: 31 March 2025; doi:10.1038/s42003-025-07980-6
A paracrine mechanism reveals that activation of nicotinic acetylcholine receptors (nAChRs) in Siberian tiger pituitary somatotrophs enhances GH secretion, a process that is predominantly active during early development.
in Nature communications biology 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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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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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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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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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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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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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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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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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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A critical function of the nervous system is to rapidly process sensory information and initiate appropriate behavioral responses. Defects in sensory processing and behavior selection are commonly observed in neuro-psychiatric conditions including anxiety, autism (ASD), and schizophrenia. The etiology of sensory processing disorders remains equivocal; however, it is hypothesized that extrinsic environmental factors can play fundamental roles. In this study we examine the importance of vitamin D (1, 25-dihydroxyvitamin D3) receptor signaling during early life stage development on sensory processing and neurobehavioral health outcomes. While vitamin D has traditionally been associated with mineral ion homeostasis, accumulating evidence suggests non-calcemic roles for vitamin D including early neurodevelopment. Here we demonstrate that systemic disruption of vitamin D receptor (VDR) signaling with a conditional dominant negative (dnVDR) transgenic zebrafish line results in specific visual and acoustic sensorimotor behavior defects. Induction of dnVDR between 24-72 hours post fertilization (hpf) results in modulation of visual motor response with demonstrate attenuation in acute activity and hypolocomotion across multiple swimming metrics when assayed at 6- and 28-days post fertilization (dpf). Disruption in VDR signaling additionally resulted in a strong and specific attenuation of the Long-Latency C-bends (LLC) within the acoustic startle response at 6 dpf while Short-Latency C-bends (SLC) were moderately impacted. Pre-pulse inhibition (PPI) was not impacted in young larvae however exhibited a significantly attenuated response at 28 dpf suggesting an inability to properly modulate their startle responses later in development and persistent effects of VDR modulation during early development. Overall, our data demonstrate that modulation of vitamin D signaling during critical windows of development irreversibly disrupts the development of neuronal circuitry associated with sensory processing behaviors which may have significant implications to neurobehavioral health outcomes.
in bioRxiv: Neuroscience on 2025-03-31 00:00:00 UTC.
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The amygdala is considered crucial to the formation of emotional episodic memories, but causal evidence in humans is limited due to challenges in non-invasive neuromodulation of deep brain structures. In a double-blind, sham-controlled, repeated measures study, we examined whether transcranial low-intensity focused ultrasound (tFUS) targeting the left amygdala prior to the encoding of emotional and neutral pictures impacted memory for these pictures 24 hours later. We used a putative inhibitory tFUS protocol shown to attenuate amygdala blood-oxygenation-level-dependent signal, thus testing the hypothesis that pre-encoding amygdala inhibition diminishes emotional memory. Surprisingly, active vs. sham sonication enhanced multiple measures of neutral and emotional memory across two memory tests. A secondary test of amygdala function found that active sonication enhanced fear recognition in faces. Computational modeling further supported these results. These findings motivate a novel conceptualization of the amygdala's role in emotional episodic memory. Rather than enhancing memory via amplification of salient stimuli, the amygdala may instead act as a filter that attenuates the maintenance of non-salient stimuli in long-term memory. Finally, the potential to enhance memory serves as an impetus to test tFUS of the amygdala in disorders such as depression and posttraumatic disorder that exhibit comorbid hyperreactive amygdalae and memory impairments.
in bioRxiv: Neuroscience on 2025-03-31 00:00:00 UTC.
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Growing evidence supports a metabolic component in Parkinson's disease (PD). alpha-Synuclein (aSyn), a protein central to the onset and progression of PD, facilitates the accumulation of neuronal lipid droplets, which are implicated in disease pathology. We report that AKT is hyper-phosphorylated in PD brains and show that aSyn enhances p110 activity by facilitating palmitoylated Ras localization to the plasma membrane, driving lipid droplet accumulation through PI3K/AKT/mTOR and PPAR{gamma} activation. Phosphorylation of aSyn at Ser129 correlates positively with the localization of Ras to the membrane fraction and with accumulation of lipid droplets. In-vivo treatment of young, asymptomatic aSynA53T transgenic mice with GDC-0084 (paxalisib), a blood-brain barrier-permeable PI3K inhibitor, restored healthy AKT activity levels, reduced levels of PSer129 and aSyn oligomers, decreased neuronal lipid droplet accumulation, and promoted lysosomal clustering. These findings establish a role for aSyn in p110a activation during early, asymptomatic stages of the disease and highlight the therapeutic potential of PI3K inhibition as a disease-modifying strategy.
in bioRxiv: Neuroscience on 2025-03-31 00:00:00 UTC.
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Genetic defects in glycine decarboxylase (GLDC) cause non-ketotic hyperglycinemia (NKH), a rare and frequently fatal neurometabolic disease, which lacks FDA-approved therapies. We characterized CRISPR Cas9-edited humanized mice expressing a prevalent clinical mutation after administration with a single intraperitoneal dose of a novel recombinant of adeno-associated viral vector 9 expressing GLDC (rAAV9-GLDC). Long term biological activity of rAAV9-GLDC was first validated by assessment of its systemic efficacy over five and ten months in mice. Access of rAAV9 to the brain was confirmed by tracking green fluorescent protein (GFP) after a single intraperitoneal dose of rAAV9-GFP. Over five months, control "mock" treated GFP-mice showed reduction in astrocytes but not microglia, oligodendrocytes or neurons in the brain. 37% of these animals suffered long term neurological disease and/or death. rAAV9-GLDC boosted novel astrocyte proliferation linked to neurogenesis, in absence of inflammation to confer 100% protection against sickness and fatality due to NKH.
in bioRxiv: Neuroscience on 2025-03-31 00:00:00 UTC.
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Human postmortem brain tissues provide an indispensable resource that is crucial for the understanding of neurological conditions, whether related to pathology subtype, burden, distribution or cell-type specificity. Pathology staging protocols provide guidelines for standardized sampling of brain tissues, but cover only a subset of regions affected by pathologies. Thus, to study how various neuropathologies and cell types in highly specialized circuit nodes correlate with functions specifically served by these nodes, additional protocols are necessary. This especially applies to brainstem tissues due to the small dimension of regions of interest and interindividual variability of specimens, whether due to procurement or intrinsic differences. Here we systematically assessed factors contributing to heterogeneity in the length of whole brainstem samples and then presented a standardized approach to reproducibly assign rostrocaudal levels, with standardization relying upon readily identifiable internal landmarks. We validated this approach using postmortem MRI imaging. Standardized brainstem length correlated positively with subject height and negatively with subject age of death. By providing a reference series, reproducible levels can be assigned to individual histological sections or MRI images, i.e. when full brainstem specimens are not available and irrespective of platform, promoting reproducibility.
in bioRxiv: Neuroscience on 2025-03-31 00:00:00 UTC.
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The "sign-tracking" and "goal-tracking" model of individual variation in associative learning permits the identification of rats with different cue-reactivity and predisposition to addiction-like behaviors. Certainly, compared to "goal-trackers" (GTs), "sign-trackers" (STs) show more susceptibility traits such as increased cue-induced 'relapse' of drugs of abuse. Different cue- and reward-evoked patterns of activity in the nucleus accumbens (NAc) have been a hallmark of the ST/GT phenotype. However, it is unknown whether differences in the intrinsic neuronal properties of NAc medium spiny neurons (MSNs) in the core and shell subregions are also a physiological correlate of these phenotypes. We performed whole-cell slice electrophysiology in outbred male rats and found that STs exhibited the lowest excitability in the NAc core, with lower number of action potentials and firing frequency as well as a blunted voltage/current relationship curve in response to hyperpolarized potentials in both the NAc core and shell. Although firing properties of shell MSNs did not differ between STs and GTs, intermediate responders that engage in both behaviors showed greater excitability compared to both STs and GTs. These findings suggest that intrinsic excitability in the NAc may contribute to individual differences in the attribution of incentive salience.
in bioRxiv: Neuroscience on 2025-03-31 00:00:00 UTC.
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Patients with myofascial pain in the head and neck area report widespread and referred pain, including headache. Existing preclinical models fail to replicate this clinical phenotype; therefore, we aimed to develop animal models mimicking referred pain phenomenon and investigate whether referred pain leads to gene plasticity at the referred sites. We modeled masticatory myalgia by stimulation of either the masseter (MM) or temporal muscle (TM) in mice. MM and TM were stimulated with a single high-dose injection of Collagenase-type II (Col), repetitive low-dose Col injections, repetitive gentle MM stimulation, or single or repetitive forceful mouth opening. Referred pain was assessed by measuring mechanical hypersensitivity in the periorbital area (representing headache-like behavior) and another masticatory muscle. Stimulation of the MM, whether through single or repetitive Col injections or mouth opening, produced inconsistent, short-lasting (1-2 days) headache-like behavior in both males and females. In contrast, stimulation of the TM, using different paradigms, triggered mechanical hypersensitivity in both the MM and the periorbital area. Referred headache-like behavior lasted longer in females compared to males, while referred myalgia in the MM was pronouncer in males. The referred pain in the MM and periorbital areas triggered by TM stimulation was associated with significant gene plasticity in the MM and dura mater. Transcriptional changes in the MM following Col injection into the TM resembled those observed after direct MM injections. Presented data imply that referred pain modeled by TM stimulation could be accounted by nociceptive signaling from multiple local sites involved in this referred pain network.
in bioRxiv: Neuroscience on 2025-03-31 00:00:00 UTC.
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The orbitofrontal cortex (OFC) is critical to identifying task structure and to generalizing appropriately across task states with similar underlying or hidden causes. This capability is at the heart of OFCs proposed role in a network responsible for cognitive mapping, and its loss can explain many deficits associated with OFC damage or inactivation. Substance use disorder is defined by behaviors that share much in common with these deficits, such as an inability to modify learned behaviors in the face of new or even anecdotal information about undesired consequences. One explanation for this similarity would be if addictive drugs impacted the ability of OFC to recognize underlying similarities, hidden states, that allow information learned in one setting to be used in another. To explore this possibility, we trained rats to self-administer cocaine and then recorded single unit activity in lateral OFC as these rats performed in an odor sequence task consisting of unique and shared positions. In well-trained controls, we observed chance decoding of sequence at shared positions and near chance decoding even at unique positions, reflecting the irrelevance of distinguishing these positions in the task. By contrast, in cocaine-experienced rats, decoding remained significantly elevated, particularly at the positions that had superficial sensory differences that were collapsed in controls across learning. A tensor component analysis showed that this effect of reduced generalization after cocaine use also extended across positions in the sequences. These results show that prior cocaine use disrupts the normal identification of hidden states by OFC.
in bioRxiv: Neuroscience on 2025-03-31 00:00:00 UTC.
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Memory retrieval is notoriously variable. Various neurocognitive states have been theorized to affect retrieval success from moment to moment, but the presence and catalysts of these states in the human brain remain largely understudied. Building on previous work, we studied how recent memory experiences (i.e. novelty vs. familiarity) and their corresponding neural activity prepare the brain to reactivate memories. Our data uncover a pronounced neural bias, whereby regions representing episodic information fail to reactivate memories following recent experiences of novelty. Drawing on computational models, we hypothesized that novelty-evoked activity in cholinergic nuclei underlie this bias. The data revealed an unexpected alternative mediator of memory reactivation in response to recent novelty, namely recent dopaminergic nuclei activity. By identifying dopamine as a potential mediator of retrieval variability, our results challenge existing models and open new avenues for investigating how neuromodulatory states dynamically shape memory accessibility.
in bioRxiv: Neuroscience on 2025-03-31 00:00:00 UTC.
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A century and a half of neuroscience has yielded many divergent theories of the neurobiology of language. Two factors that likely contribute to this situation include (a) conceptual disagreement about language and its component processes, and (b) intrinsic inter-individual variability in the topography of language areas. Recent functional magnetic imaging (fMRI) studies of small numbers of intensively scanned individuals have argued that a language-selective brain network emerges from correlations (individualized functional connectomics, iFC) in task-free (e.g., rest) or task-regressed activation timecourses. Here we test this hypothesis at scale and evaluate its practical utility for task-agnostic language localization: we apply iFC separately to each of 1,971 (fMRI) scanning sessions (1,199 unique brains), each consisting of diverse tasks. We find that iFC indeed reveals a left-lateralized frontotemporal network that is more stable within individuals than between them, robust to the granularity of the parcellation, and selective for language. These results support the hypothesis that this network is a key structure in the functional organization of the adult brain and show that it can be recovered retrospectively from arbitrary imaging data, with implications for neuroscience, neurosurgery, and neural engineering.
in bioRxiv: Neuroscience on 2025-03-31 00:00:00 UTC.
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Functional lateralization is a ubiquitous trait in the animal kingdom and represents a general and conserved mechanism of the central nervous system. Lateralized processes observed in adult sensory cortices emerge as a function of development and experience, e.g. speech-processing in humans and processing of conspecific vocalizations in songbirds. Adult Zebra finches (ZFs), a species of songbird, exhibit right-lateralized activity in the higher auditory region caudomedial nidopallium (NCM) which depends on normal rearing conditions; auditory deprivation leads to atypical bilateral responses to conspecific song. Here, we investigate the ontogenetic timeline of auditory lateralization and the lasting effects of auditory rearing-environment in the developing ZF (40-120 days post-hatch, phd). ZFs were raised in one of three acoustic environments: 1) a tutor-playback driven paradigm, 2) chronic exposure to a ZF aviary recording (no tutor), and 3) chronic exposure to a canary aviary recording (no tutor). By longitudinally tracking lateralized auditory evoked potentials at the level of the dura, we show that adult right-lateralized activity 1) emerges from an initial left-biased profile; 2) this left-to-right emergence occurs ~60-80phd and does not require the presence of a tutor; and 3) also emerges in ZFs raised in a canary auditory environment. Furthermore, lateralization and song development were positively correlated, although these measurements are not necessarily causally related. Awake, bilateral NCM electrophysiology in the same birds when adult, confirmed they were right-lateralized and that lateralized activity for specific test stimuli depended on rearing experience. Lastly, a decoding assay showed that canary-based rearing led to increased decoding accuracy of canary test stimuli, suggesting that neurons exhibit enhanced encodability for those sounds heard earlier. Together, the results document the ontogenetic timeline of auditory lateralization in the songbird and show that auditory experience in development, including passive exposure, shapes how auditory regions in the brain process stimuli in adulthood. Taken together with earlier results showing 1) the absence of lateral differences in ZFs reared in auditory deprivation and 2) that lateralization reverses dynamically in concert with improved discrimination in adult ZFs exposed to novel auditory environments, our current timeline suggests that the dynamic emergence of lateralization reflects the brains plastic response to novel auditory experiences.
in bioRxiv: Neuroscience on 2025-03-31 00:00:00 UTC.
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Prepulse inhibition (PPI) of the auditory startle reflex task is a widely recognized operational measure of sensorimotor gating. PPI deficits are a hallmark feature of schizophrenia, often associated with attentional and cognitive impairments. Despite its extensive use in preclinical research for screening antipsychotic drugs, the precise cellular and circuit mechanisms underlying PPI remain unclear, even under physiological conditions. Recent evidence suggests that non-cholinergic inputs from the pedunculopontine tegmental nucleus (PPTg) to the caudal pontine reticular nucleus (PnC) mediate PPI. In this study, we investigated the contribution of PPTg glutamatergic neurons to acoustic startle and PPI. Tract-tracing, immuno-histochemical analyses, and in vitro whole-cell recordings in wild-type mice confirmed that PPTg glutamatergic neurons innervate the PnC. Optogenetic inhibition of PPTg-PnC glutamatergic synapses in vivo resulted in increased PPI across various interstimulus intervals. Notably, while optogenetic activation of this pathway had no additional effect on startle and PPI, activation of this connection alone before startle stimulation reduced startle at short interstimulus intervals and increased startle at longer intervals. Furthermore, although PPTg glutamatergic inputs target PnC glycinergic neurons, our in vitro whole-cell recordings combined with optogenetic stimulation at PPTg-PnC synapses revealed that PPTg glutamatergic inputs activate PnC glutamatergic giant neurons. Our findings identify a feed-forward excitatory mechanism within the brainstem startle circuit, whereby PPTg glutamatergic inputs modulate PnC neuronal activity. These results provide new insights into the clinically relevant theoretical construct of PPI, which is disrupted in various neuropsychiatric and neurological disorders.
in bioRxiv: Neuroscience on 2025-03-31 00:00:00 UTC.
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Electrical neuromodulation, the current clinical standard, is invasive, expensive, and prone to malfunction. Electromagnetic waves can perform noninvasive neuromodulation, but existing methods are limited by the tradeoff between penetration depth and spatial precision. Microwaves in the 0.9 - 3 GHz range are widely used for telecommunications and can penetrate to the deep brain. Microwaves have been shown to nonthermally modulate neural activity, but the acute bioeffects remain unclear and under-studied. Here, we employ a microwave rod antenna (MRA) to demonstrate bi-modal neuromodulation via thermal and non-thermal mechanisms. The MRA enabled electrophysiological recordings of neurons exposed to microwaves, which elucidated the differential effects of pulsed and continuous microwaves on neurons. These findings build the foundation for developing microwave-based wireless neuromodulation devices for drug-free treatment of seizures and chronic pain.
in bioRxiv: Neuroscience on 2025-03-31 00:00:00 UTC.
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Oligodendrocyte precursor cells (OPCs) can generate myelinating oligodendrocytes life-long, a process that is dependent on neuronal activity. However, it is possible that OPCs have additional functions, influencing neuronal functions directly. We have used a mouse genetic model of juvenile seizures and chemical induction of neuronal activity to examine the morphological and molecular changes in OPCs around activated principal neurons. We found an increase in process extension of OPCs specifically toward the soma of activated neurons. Moreover, we found that the close proximity of OPC processes around neurons expressing the immediate early gene c-Fos decreased the calcium transients in these neurons, indicating a regulative function of OPCs. Analyses of transcriptome and chromatin accessibility revealed significant changes in genes involved in transforming growth factor beta (TGF beta) signaling. Extracellular matrix genes, particularly those encoding type VI collagen, an established binding partner for the OPC surface protein NG2, was increased around active neurons. Our findings indicate that OPCs are an integral part of the neural network and may help to decrease the activity of neurons that have previously been over-excited, in order to protect these neurons.
in bioRxiv: Neuroscience on 2025-03-31 00:00:00 UTC.
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Male CD-1 mice form linear social hierarchies and can rapidly reform them following social reorganization. Through Tag-based sequencing in the medial amygdala (MeA), we identified several genes regulating cholinergic signaling, myelination, and thyroid signaling that rapidly shift expression 70 minutes after animals change social status. Here, we further characterize the expression patterns of individual genes within these pathways in both stable and reorganized hierarchies. We find that genes related to cholinergic signaling show higher expression in the MeA of dominant males in stable hierarchies as well as when reestablishing dominance in reorganized hierarchies. Dominant males also show higher levels of myelination related genes than socially descending males when reestablishing their social status during social reorganization but less so in stable groups. Conversely, thyroid signaling genes show higher expression in the MeA in subordinate males and previously dominant males who are socially descending. Using RNAscope, we were able to demonstrate broadly similar patterns of gene expression immediately following social reorganization across the MeA, basolateral, and central amygdala for 7 genes of interest (chat, slc5a7, ache, mbp, mog, crym, mybpc1). High levels of co-expression of cholinergic signaling and myelination gene expression in dominant males suggest that these processes work together to promote resilience to the social challenge and promote dominance. In summary, we demonstrate that rapid changes in amygdala gene expression in each pathway are associated with the formation and maintenance of dominance and subordinate social status in stable and reorganized environments.
in bioRxiv: Neuroscience on 2025-03-31 00:00:00 UTC.
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During passive listening, the brain maintains a hierarchy of predictive models to monitor the statistics of its surroundings. The automatic discovery of regular patterns has been associated with a gradual increase in sustained tonic M/EEG activity, sourced in auditory, hippocampal, and frontal areas - reflecting evidence accumulation and establishment of a regularity model. Conversely, when a regular pattern is interrupted, the sustained activity drops - indicating disengagement from the model. However, how such models are established in and retrieved from memory as well as the conditions under which they are activated and interrupted remain underexplored. In this MEG experiment (N=26; both sexes), we examined how neural responses related to model establishment and interruption are influenced by (1) the rate of stimulus presentation (tone presentation rate 20 Hz vs. 40 Hz), and (2) the novelty of the experienced acoustic structure (novel vs resumed REG pattern). The results show that (1) the dynamics of model interruption and establishment are independent of stimulus presentation rate, and that (2) model establishment occurred much faster when an experienced vs novel pattern was presented after pattern interruption, suggesting re-activation of the stored original model. These responses broadly mirrored those of an ideal observer model of prediction. (3) Finally, sustained response rises in response to pattern establishment and interruption were localized in auditory, hippocampal, and frontal sources, supporting top-down model information flow. These results unveil the temporal dynamics and neural network underlying the brain's construction and selection of predictive models to monitor changes in sensory statistics.
in bioRxiv: Neuroscience on 2025-03-31 00:00:00 UTC.
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Neuropsychiatric disorders such as autism spectrum disorder (ASD) and schizophrenia (SCZ) share genetic risk factors, including rare high penetrance single nucleotide variants and copy number variants (CNVs), and exhibit both overlapping and distinct clinical phenotypes. Cognitive deficits and intellectual disability-critical predictors of long-term outcomes-are common to both conditions. To investigate shared and disorder-specific neurobiological impact of highly penetrant rare mutations in ASD and SCZ, we analyzed human single-nucleus whole-brain sequencing data to identify strongly affected brain cell types. Our analysis revealed Caudal Ganglionic Eminence (CGE)-derived GABAergic interneurons as a critical nexus for cognitive deficits across these disorders. Notably, genes within 22q11.2 deletions, known to confer a high risk of SCZ, ASD, and cognitive impairment, showed a strong expression bias toward vasoactive intestinal peptide-expressing cells (VIP+) among CGE subtypes. To explore VIP+ GABAergic interneuron perturbations in the 22q11.2 deletion syndrome in vivo, we examined their activity in the Df(16)A+/- mouse model during a spatial navigation task and observed reduced activity along with altered responses to random rewards. At the population level, VIP+ interneurons exhibited impaired spatial encoding and diminished subtype-specific activity suggesting deficient disinhibition in CA1 microcircuits in the hippocampus, a region essential for learning and memory. Overall, these results demonstrate the crucial role of CGE-derived interneurons in mediating cognitive processes that are disrupted across a range of psychiatric and neurodevelopmental disorders.
in bioRxiv: Neuroscience 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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Communications Biology, Published online: 30 March 2025; doi:10.1038/s42003-025-07906-2
Cryo-EM and tomography of the Hsp70 chaperone system disaggregating amyloid fibrils show that the 2 step activation of the class B J-domain protein DNAJB1 is required for the formation of ordered arrays of chaperones that prime fibril disassembly.
in Nature communications biology on 2025-03-30 00:00:00 UTC.
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Background: Alzheimer's disease is characterized by progressive cognitive decline and neurodegeneration, with cognitive reserve playing a key role in mitigating disease impact. Cognitive stimulation has been suggested as a non-pharmacological approach to enhance cognitive reserve and delay cognitive deterioration, but its underlying mechanism remains to be fully understood. This study investigates the effects of pre-amyloid cognitive intervention on brain connectivity, memory, synaptic plasticity and neuroinflammation in aged TgF344-AD rats, considering sex-specific differences. Methods: Male and female TgF344-AD and wild-type rats were assigned to trained and untrained groups, with cognitive stimulation administered through repetitive delayed nonmatch-to-sample tasks. Longitudinal magnetic resonance imaging acquisitions assessed training-induced changes in whole-brain functional connectomics and in particular entorhinal cortex connectivity. Memory was evaluated using the novel object recognition test. Cellular analysis of neurons (NeuN+, Parvalbumin+) and microglial cells, as well as molecular (PSD95, TrkB, p-RPS6, and VGLUT) analyses were conducted to determine the role of cognitive stimulation in modulating neuronal density, neuroinflammation and neuroplasticity. Results: Male TgF344-AD rats undergoing prolonged cognitive stimulation had preserved global functional connectivity and exhibited improved recognition memory, compared to untrained animals, while TgF344-AD females did not follow this pattern. Entorhinal cortex connectivity was significantly loss in 19-month-old rats compared to wild-type rats and this was completely prevented by training. At a cellular level, cognitive stimulation significantly decreased the number of PV+ neurons in the dentate gyrus of trained rats. Moreover, a greater microglial density around beta amyloid plaques and a less reactive phenotype was clearly observed at 11 in trained rats. These protective effects diminished by 19 months, coinciding with increased neuroinflammation and microglial dysfunction. At a molecular level, cognitive stimulation preserved PSD95 expression in male TgF344-AD and p-RPS6 in both sexes. Conclusions: Pre-amyloid cognitive stimulation enhances synaptic plasticity, sustains brain network integrity, and modulates neuroinflammation, contributing to increased resilience against Alzheimer's disease-related cognitive decline. In general, cognitive stimulation exerted a more protective effect in male TgF344-AD rats showing sex-dependent differences in pathology and cognitive reserve mechanisms. These findings highlight the importance of early cognitive engagement as a potential strategy to delay disease onset and underscore sex-specific differences in cognitive resilience mechanisms.
in bioRxiv: Neuroscience 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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in eNeuro on 2025-03-28 16:30:36 UTC.
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The annual Society for Neuroscience (SfN) meeting is a bonanza of scientific achievement: famous keynote speakers, beautiful scientific results, and award ceremonies. This focus is exciting and invigorating but glosses over the many failures, mistakes, and rejections that typically lead to scientific success. Our goal has been to create a space within the annual SfN meeting for open conversation about scientific failure and, by doing so, increase transparency, resilience, and mental well-being within our community. In this article, we share the materials that we have used at SfN during the past 4 years (2021–2024) to promote discussions of scientific failure, including formal storytelling, individual and interactive games, and confessionals. For each activity, we provide the rationale and practical guidance regarding logistics and usage. We hope this will aid scientists interested in adapting the activities for their own communities or local events. We end with a call for scientific institutions to commit to providing space for open discussions of failure within their educational programs and conferences.
in eNeuro on 2025-03-28 16:30:36 UTC.
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Neurons adapt to chronic activity changes by modifying synaptic properties, including neurotransmitter release. However, whether neuropeptide release via dense core vesicles (DCVs)—a distinct regulated secretory pathway—undergoes similar adaptation remains unclear. Here, we demonstrate that 24 h action potential blockade leads to significant DCV accumulation in primary mouse cortical neurons of both sexes. Reactivation with action potential trains induced enhanced Ca2+ influx and 700% more DCV exocytosis compared with control neurons. Notably, total DCV cargo protein levels were unchanged, while mRNA levels of corresponding genes were reduced. Blocking neurotransmitter release with Tetanus toxin induced DCV accumulation, similar to that induced by network silencing with TTX. Hence, chronic network silencing triggers increased DCV accumulation due to reduced exocytosis during silencing. These accumulated DCVs can be released upon reactivation resulting in a massive potentiation of DCV exocytosis, possibly contributing to homeostatic mechanisms.
in eNeuro on 2025-03-28 16:30:36 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.
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by Peter J. Hotez
The coming decade might see major cuts to the United States Government funding for biomedicine and the mainstreaming of pseudoscience. But your biosciences PhD gives you the problem-solving skills to navigate this maelstrom, especially if you maintain flexibility, optimism, and enthusiasm for uncharted paths.
in PLoS Biology on 2025-03-28 14:00:00 UTC.
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by David Acunzo, Damiano Grignolio, Clayton Hickey
The visual environment is complicated, and humans and other animals accordingly prioritize some sources of information over others through the deployment of spatial attention. Cognitive theories propose that one core purpose of this is to gather information that can be used in downstream cognitive processes, including the development of concepts and categories. However, neuroscientific investigation has focused closely on the identification of the systems and algorithms that support attentional control or that instantiate the effect of attention on sensation and perception. Much less is known about how attention impacts the acquisition and activation of concepts. Here, we use machine learning of EEG and concurrently recorded EEG/MRI to temporally and anatomically characterize the neural network that abstracts from attended perceptual information to activate and construct semantic and conceptual representations. We find that variance in the amplitude of N2pc—an event-related potential (ERP) component closely linked to selective attention—predicts the emergence of conceptual information in a network including VMPFC, posterior parietal cortex, and anterior insula. This network appears to play a key role in the attention-mediated translation of perceptual information to concepts, semantics, and action plans.
in PLoS Biology on 2025-03-28 14:00:00 UTC.
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in Hippocampus on 2025-03-28 12:34:09 UTC.
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Journal of Neurophysiology, Volume 133, Issue 4, Page 1116-1137, April 2025.
in Journal of Neurophysiology on 2025-03-28 11:57:29 UTC.
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Journal of Neurophysiology, Ahead of Print.
in Journal of Neurophysiology on 2025-03-28 11:50:32 UTC.
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Proceedings of the National Academy of Sciences, Volume 122, Issue 13, April 2025.
SignificanceFeeding behaviors of wild animals are influenced by the repetitive cycle of feeding phases: Food procurement, consumption, and termination. However, neural circuits controlling the food consumption phase remain unclear. Here, we found that the ...
in PNAS on 2025-03-28 07:00:00 UTC.
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Science, Volume 387, Issue 6741, March 2025.
in Science on 2025-03-28 07:00:00 UTC.
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Science, Volume 387, Issue 6741, March 2025.
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Science, Volume 387, Issue 6741, March 2025.
in Science on 2025-03-28 07:00:00 UTC.
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Science, Volume 387, Issue 6741, March 2025.
in Science on 2025-03-28 07:00:00 UTC.
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Science, Volume 387, Issue 6741, March 2025.
in Science on 2025-03-28 07:00:00 UTC.
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Science, Volume 387, Issue 6741, March 2025.
in Science on 2025-03-28 07:00:00 UTC.
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Science, Volume 387, Issue 6741, March 2025.
in Science on 2025-03-28 07:00:00 UTC.
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Science Advances, Volume 11, Issue 13, March 2025.
in Science Advances on 2025-03-28 07:00:00 UTC.
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Science Advances, Volume 11, Issue 13, March 2025.
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Science Advances, Volume 11, Issue 13, March 2025.
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Science Advances, Volume 11, Issue 13, March 2025.
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Science Advances, Volume 11, Issue 13, March 2025.
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Science Advances, Volume 11, Issue 13, March 2025.
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Science Advances, Volume 11, Issue 13, March 2025.
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Science Advances, Volume 11, Issue 13, March 2025.
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Science Advances, Volume 11, Issue 13, March 2025.
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Science Advances, Volume 11, Issue 13, March 2025.
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Science Advances, Volume 11, Issue 13, March 2025.
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Science Advances, Volume 11, Issue 13, March 2025.
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Science Advances, Volume 11, Issue 13, March 2025.
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Science Advances, Volume 11, Issue 13, March 2025.
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Science Advances, Volume 11, Issue 13, March 2025.
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Science Advances, Volume 11, Issue 13, March 2025.
in Science Advances on 2025-03-28 07:00:00 UTC.
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Science Advances, Volume 11, Issue 13, March 2025.
in Science Advances on 2025-03-28 07:00:00 UTC.
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- Wallabag.it! - Save to Instapaper - Save to Pocket -
Science Advances, Volume 11, Issue 13, March 2025.
in Science Advances on 2025-03-28 07:00:00 UTC.
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- Wallabag.it! - Save to Instapaper - Save to Pocket -
Science Advances, Volume 11, Issue 13, March 2025.
in Science Advances on 2025-03-28 07:00:00 UTC.
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- Wallabag.it! - Save to Instapaper - Save to Pocket -
Science Advances, Volume 11, Issue 13, March 2025.
in Science Advances on 2025-03-28 07:00:00 UTC.
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- Wallabag.it! - Save to Instapaper - Save to Pocket -
Science Advances, Volume 11, Issue 13, March 2025.
in Science Advances on 2025-03-28 07:00:00 UTC.
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- Wallabag.it! - Save to Instapaper - Save to Pocket -
Science Advances, Volume 11, Issue 13, March 2025.
in Science Advances on 2025-03-28 07:00:00 UTC.
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- Wallabag.it! - Save to Instapaper - Save to Pocket -
Science Advances, Volume 11, Issue 13, March 2025.
in Science Advances on 2025-03-28 07:00:00 UTC.
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- Wallabag.it! - Save to Instapaper - Save to Pocket -
Science Advances, Volume 11, Issue 13, March 2025.
in Science Advances on 2025-03-28 07:00:00 UTC.
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- Wallabag.it! - Save to Instapaper - Save to Pocket -
Science Advances, Volume 11, Issue 13, March 2025.
in Science Advances on 2025-03-28 07:00:00 UTC.
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- Wallabag.it! - Save to Instapaper - Save to Pocket -
Science Advances, Volume 11, Issue 13, March 2025.
in Science Advances on 2025-03-28 07:00:00 UTC.
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- Wallabag.it! - Save to Instapaper - Save to Pocket -
Science Advances, Volume 11, Issue 13, March 2025.
in Science Advances on 2025-03-28 07:00:00 UTC.
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- Wallabag.it! - Save to Instapaper - Save to Pocket -
Science Advances, Volume 11, Issue 13, March 2025.
in Science Advances on 2025-03-28 07:00:00 UTC.
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TDP-43 pathology characterizes neurodegenerative diseases. Scialò et al. use in vitro-generated and patient-derived TDP-43 aggregates as seeds to show that seed-induced TDP-43 cytoplasmic aggregation causes its loss of function and downstream RNA misregulation. This new cell model shows TDP-43 aggregation and loss of function without overexpression or knockdown.
in Neuron: In press on 2025-03-28 00:00:00 UTC.
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Rummens et al. demonstrate that amyloid-like fibrils trigger TDP-43 aggregation and nuclear depletion, key hallmarks of neurodegenerative disorders. This provokes a unique transcriptomic signature with RNA splicing defects, including disease-specific cryptic splicing in human cells. Over time, fibril-induced TDP-43 pathology recapitulates distinct aggregate shapes and causes toxicity in iPSC-derived neurons.
in Neuron: In press on 2025-03-28 00:00:00 UTC.
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Xia et al. identify a mechanism of ovarian cancer resistance to cisplatin (CDDP) that involves arginine methylation of METTL3 by PRMT5, leading to enhanced HR-mediated DSBR. MST4 activates PRMT5 through direct phosphorylation. Inhibition of PRMT5 or METTL3 disrupts HR-DSBR and augments the cytotoxic effects of CDDP in ovarian tumor xenografts.
in Cell Reports: Current Issue on 2025-03-28 00:00:00 UTC.
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Chang et al. report the cryo-EM structures of GPR3 in different oligomerization states, including its dimeric form. The study reveals that dimerization is associated with a possible autoinhibition mechanism by the ICL3 region of GPR3.
in Cell Reports: Current Issue on 2025-03-28 00:00:00 UTC.
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Bick et al. investigate the molecular factors influencing anti-HIV antibody Fc effector functions using AI-assisted protein design. They find that the stoichiometry of antibody binding is the primary determinant of FcγRIIIa signaling and immune responses such as antibody-dependent cellular cytotoxicity and phagocytosis, while epitope location and binding kinetics have minimal impact.
in Cell Reports: Current Issue on 2025-03-28 00:00:00 UTC.
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Yu et al. identify host factors governing placental ZIKV infection using an unbiased CRISPR gene-knockout screen. They unravel that GATA3-hepatitis A virus cellular receptor 1 (HAVCR1)-adaptor protein 2 small σ2 (AP2S1) serves as a placenta-intrinsic regulatory axis indispensable for ZIKV entry and maternal-fetal transmission during pregnancy.
in Cell Reports: Current Issue on 2025-03-28 00:00:00 UTC.
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Transcription factor ZNF410 uniquely activates CHD4 transcription. Xu et al. show that ZNF410 recruits the SWI/SNF complex for its cooperative binding to homotypic clusters of binding sites within the CHD4 enhancers for modulating gene transcription.
in Cell Reports: Current Issue on 2025-03-28 00:00:00 UTC.
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Thakur et al. find that the lipid transfer protein PDZD8 induces synaptic growth. Through in vivo studies, the authors find that PDZD8 functions at neuronal ER-late endosome/lysosome membrane contact sites to promote lysosome maturation and accelerate autophagic flux. Increased autophagy in turn induces activity-dependent synapse formation.
in Cell Reports: Current Issue on 2025-03-28 00:00:00 UTC.
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Nature, Published online: 28 March 2025; doi:10.1038/d41586-025-00984-6
Researchers are looking to improve how ageing is measured, but the field is plagued with uncertainties.
in Nature on 2025-03-28 00:00:00 UTC.
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Nature, Published online: 28 March 2025; doi:10.1038/d41586-025-00879-6
Study of more than 100,000 people supports your parents’ advice: eat your veggies.
in Nature on 2025-03-28 00:00:00 UTC.