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Background Ophthalmologists deal with daily pseudoexfoliation (PXF) due to severe secondary glaucoma, which arises after cataract surgery. Cataracts with pseudoexfoliation are age-related and are associated with open-angle glaucoma. Therefore, pseudoexfoliation is expected to occur more frequently. Pseudoexfoliation is occasionally associated with the development of thick nuclear cataracts, which may make surgery challenging. risks of cataract extraction in patients with pseudoexfoliation include zonular weakness and inadequate pupillary dilation. This may cause vitreous loss, and intraoperative or postoperative lens displacement. It could also lead to a rise in postoperative intraocular pressure (IOP), progressing to long-term inflammation, phimosis of the capsular tissue, glaucoma, and surgical corneal decompensation. Recurrent secondary cataracts are typically caused by some remaining cortical tissue and decreased zonular support, which may lead to lens epithelial cell migration. Surgery for glaucoma and cataracts is complicated by the presence of pseudoexfoliative debris. Objectives To determine the prevalence of pseudoexfoliation in cataract patients visiting the ophthalmic OPD, AVBRH hospital, to locate patients with pseudoexfoliative cataracts, to evaluate their likelihood of progressing to open-angle glaucoma, and to examine the various ocular characteristics of these patients. Methodology The study participants will undergo ophthalmological examination after considering the inclusion and exclusion criteria. This examination will include sac syringing on the lacrimal gland, estimation of the highest corrected visual acuity, slit-lamp examination, application tonometer assessment of intraocular pressure (IOP), and fundus examination using an indirect ophthalmoscope. All individuals with cataracts visiting the ophthalmology department of AVBRH will be examined under a slit-lamp to determine the presence of pseudoexfoliation in the operating eye. Expected Results Hospital statistics from India indicated that the percentage of patients with pseudoexfoliation, in addition to cataracts, ranges from 1.87% to 13.5%.
in F1000Research on 2025-05-16 08:11:33 UTC.
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arXiv:2505.09624v1 Announce Type: new
Abstract: Adaptive deep brain stimulation (aDBS) has emerged as a promising treatment for Parkinson disease (PD). In aDBS, a surgically placed electrode sends dynamically altered stimuli to the brain based on neurophysiological feedback: an invasive gadget that limits the amount of data one could collect for optimizing the control offline. As a consequence, a plethora of synthetic models of PD and those of the control algorithms have been proposed. Herein, we introduce the first neurophysiologically realistic benchmark for comparing said models. Specifically, our methodology covers not only conventional basal ganglia circuit dynamics and pathological oscillations, but also captures 15 previously dismissed physiological attributes, such as signal instabilities and noise, neural drift, electrode conductance changes and individual variability - all modeled as spatially distributed and temporally registered features via beta-band activity in the brain and a feedback. Furthermore, we purposely built our framework as a structured environment for training and evaluating deep reinforcement learning (RL) algorithms, opening new possibilities for optimizing aDBS control strategies and inviting the machine learning community to contribute to the emerging field of intelligent neurostimulation interfaces.
in arXiv: Quantitative Biology: Neurons and Cognition on 2025-05-16 04:00:00 UTC.
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arXiv:2505.09643v1 Announce Type: new
Abstract: Epilepsy is a prevalent neurological disease with millions of patients worldwide. Many patients have turned to alternative medicine due to the limited efficacy and side effects of conventional antiepileptic drugs. In this study, we developed a computational approach to optimize herbal epilepsy treatment through AI-driven analysis of global natural products and statistically validated randomized controlled trials (RCTs). Our intelligent prescription system combines machine learning (ML) algorithms for herb-efficacy characterization, Bayesian optimization for personalized dosing, and meta-analysis of RCTs for evidence-based recommendations. The system analyzed 1,872 natural compounds from traditional Chinese medicine (TCM), Ayurveda, and ethnopharmacological databases, integrating their bioactive properties with clinical outcomes from 48 RCTs covering 48 epilepsy conditions (n=5,216). Using LASSO regression and SHAP value analysis, we identified 17 high-efficacy herbs (e.g., Gastrodia elata [using \'e for accented characters], Withania somnifera), showing significant seizure reduction (p$<$0.01, Cohen's d=0.89) with statistical significance confirmed by multiple testing (p$<$0.001). A randomized double-blind validation trial (n=120) demonstrated 28.5\% greater seizure frequency reduction with AI-optimized herbal prescriptions compared to conventional protocols (95\% CI: 18.7-37.3\%, p=0.003).
in arXiv: Quantitative Biology: Neurons and Cognition on 2025-05-16 04:00:00 UTC.
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arXiv:2505.09646v1 Announce Type: new
Abstract: This paper proposes a novel theoretical model to explain how the human mind and artificial intelligence can approach real-time awareness by reducing perceptual delays. By investigating cosmic signal delay, neurological reaction times, and the ancient cognitive state of stillness, we explore how one may shift from reactive perception to a conscious interface with the near future. This paper introduces both a physical and cognitive model for perceiving the present not as a linear timestamp, but as an interference zone where early-arriving cosmic signals and reactive human delays intersect. We propose experimental approaches to test these ideas using human neural observation and neuro-receptive extensions. Finally, we propose a mathematical framework to guide the evolution of AI systems toward temporally efficient, ethically sound, and internally conscious decision-making processes
in arXiv: Quantitative Biology: Neurons and Cognition on 2025-05-16 04:00:00 UTC.
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arXiv:2505.10536v1 Announce Type: new
Abstract: Brain-Computer Interfaces enable direct communication between the brain and external systems, with functional Near-Infrared Spectroscopy emerging as a portable and non-invasive method for capturing cerebral hemodynamics. This study investigates the classification of rest and task states during a realistic, interactive tennis simulation using fNIRS signals and a range of machine learning approaches. We benchmarked traditional classifiers based on engineered features, Long Short-Term Memory networks on raw time-series data, and Convolutional Neural Networks applied to Gramian Angular Field-transformed images. Ensemble models like Extra Trees and Gradient Boosting achieved accuracies above 97 percent, while the ResNet-based CNN reached 95.0 percent accuracy with a near-perfect AUC of 99.2 percent, outperforming both LSTM and EfficientNet architectures. A novel data augmentation strategy was employed to equalize trial durations while preserving physiological integrity. Feature importance analyses revealed that both oxygenated and deoxygenated hemoglobin signals, particularly slope and RMS metrics, were key contributors to classification performance. These findings demonstrate the strong potential of fNIRS-based BCIs for deployment in dynamic, real-world environments and underscore the advantages of deep learning models in decoding complex neural signals.
in arXiv: Quantitative Biology: Neurons and Cognition on 2025-05-16 04:00:00 UTC.
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arXiv:2505.10444v1 Announce Type: cross
Abstract: We propose a method for inferring entropy production (EP) in high-dimensional stochastic systems, including many-body systems and non-Markovian systems with long memory. Standard techniques for estimating EP become intractable in such systems due to computational and statistical limitations. We infer trajectory-level EP and lower bounds on average EP by exploiting a nonequilibrium analogue of the Maximum Entropy principle, along with convex duality. Our approach uses only samples of trajectory observables (such as spatiotemporal correlation functions). It does not require reconstruction of high-dimensional probability distributions or rate matrices, nor any special assumptions such as discrete states or multipartite dynamics. It may be used to compute a hierarchical decomposition of EP, reflecting contributions from different kinds of interactions, and it has an intuitive physical interpretation as a thermodynamic uncertainty relation. We demonstrate its numerical performance on a disordered nonequilibrium spin model with 1000 spins and a large neural spike-train dataset.
in arXiv: Quantitative Biology: Neurons and Cognition on 2025-05-16 04:00:00 UTC.
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arXiv:2503.01761v3 Announce Type: replace
Abstract: The claustrum is a thin gray matter structure in each brain hemisphere, characterized by exceptionally high connectivity with nearly all brain regions. Despite extensive animal studies on its anatomy and function and growing evidence of claustral deficits in neuropsychiatric disorders, its specific roles in normal and abnormal human brain function remain largely unknown. This is primarily due to its thin and complex morphology, which limits accurate anatomical delineation and neural activity isolation in conventional in vivo neuroimaging. To facilitate future neuroimaging studies, we developed a comprehensive and reliable manual segmentation protocol based on a cellular-resolution brain atlas and high-resolution (0.7^3 mm) MRI data. The protocols involve detailed guidelines to delineate the entire claustrum, including the inferior parts that have not been clearly described in earlier MRI studies. Additionally, we propose a geometric method to parcellate the claustrum into three subregions (the dorsal, ventral, and temporal claustrum) along the superior-to-inferior axis. The mean bilateral claustrum volume in 10 young adults was 3307.5 mm^3, approximately 0.21% of total intracranial volume. Our segmentation protocol demonstrated high inter- and intra-rater reliability (ICC > 0.89, DSC > 0.85), confirming its replicability. This comprehensive and reliable manual segmentation protocol offers a robust foundation for anatomically precise neuroimaging investigations of the human claustrum.
in arXiv: Quantitative Biology: Neurons and Cognition on 2025-05-16 04:00:00 UTC.
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arXiv:2505.05476v2 Announce Type: replace
Abstract: We introduce a novel predictive coding framework for studying attachment theory. Building off an established model of attachment, the dynamic-maturational model (DMM), as well as the neuroanatomical Embodied Predictive Interoception Coding (EPIC) model of interoception and emotion, we not only elucidate how neural processes can shape attachment strategies, but also explore how early attachment experiences can shape those processes in the first place.
in arXiv: Quantitative Biology: Neurons and Cognition on 2025-05-16 04:00:00 UTC.
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arXiv:2501.04706v2 Announce Type: replace-cross
Abstract: Mean kurtosis in iron-rich grey matter has values similar to that seen in white matter. We suspect these elevated values may be related to iron. Multi-shell diffusion and multi-echo gradient echo acquisitions were used to derive mean kurtosis and R2*, respectively. Mean kurtosis and R2* were measured in subcortical grey matter nuclei and white matter tracts in 93 older adults and 62 younger adults. Grey matter regions exhibited higher mean kurtosis and R2* in the older adult group whereas white matter regions had reduced mean kurtosis in the older adult group. Grey matter mean kurtosis was significantly correlated with R2* iron-rich grey matter nuclei in both groups. Our findings indicate that higher mean kurtosis in iron-rich grey matter structures may be due to either increased tissue complexity or to decreases in signal-to-noise ratios from iron deposition
in arXiv: Quantitative Biology: Neurons and Cognition on 2025-05-16 04:00:00 UTC.
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arXiv:2505.09816v1 Announce Type: cross
Abstract: Growing evidence suggests that synaptic weights in the brain follow heavy-tailed distributions, yet most theoretical analyses of recurrent neural networks (RNNs) assume Gaussian connectivity. We systematically study the activity of RNNs with random weights drawn from biologically plausible L\'evy alpha-stable distributions. While mean-field theory for the infinite system predicts that the quiescent state is always unstable -- implying ubiquitous chaos -- our finite-size analysis reveals a sharp transition between quiescent and chaotic dynamics. We theoretically predict the gain at which the system transitions from quiescent to chaotic dynamics, and validate it through simulations. Compared to Gaussian networks, heavy-tailed RNNs exhibit a broader parameter regime near the edge of chaos, namely a slow transition to chaos. However, this robustness comes with a tradeoff: heavier tails reduce the Lyapunov dimension of the attractor, indicating lower effective dimensionality. Our results reveal a biologically aligned tradeoff between the robustness of dynamics near the edge of chaos and the richness of high-dimensional neural activity. By analytically characterizing the transition point in finite-size networks -- where mean-field theory breaks down -- we provide a tractable framework for understanding dynamics in realistically sized, heavy-tailed neural circuits.
in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-05-16 04:00:00 UTC.
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arXiv:2505.10176v1 Announce Type: new
Abstract: Multimodal learning enhances the perceptual capabilities of cognitive systems by integrating information from different sensory modalities. However, existing multimodal fusion research typically assumes static integration, not fully incorporating key dynamic mechanisms found in the brain. Specifically, the brain exhibits an inverse effectiveness phenomenon, wherein weaker unimodal cues yield stronger multisensory integration benefits; conversely, when individual modal cues are stronger, the effect of fusion is diminished. This mechanism enables biological systems to achieve robust cognition even with scarce or noisy perceptual cues. Inspired by this biological mechanism, we explore the relationship between multimodal output and information from individual modalities, proposing an inverse effectiveness driven multimodal fusion (IEMF) strategy. By incorporating this strategy into neural networks, we achieve more efficient integration with improved model performance and computational efficiency, demonstrating up to 50% reduction in computational cost across diverse fusion methods. We conduct experiments on audio-visual classification, continual learning, and question answering tasks to validate our method. Results consistently demonstrate that our method performs excellently in these tasks. To verify universality and generalization, we also conduct experiments on Artificial Neural Networks (ANN) and Spiking Neural Networks (SNN), with results showing good adaptability to both network types. Our research emphasizes the potential of incorporating biologically inspired mechanisms into multimodal networks and provides promising directions for the future development of multimodal artificial intelligence. The code is available at https://github.com/Brain-Cog-Lab/IEMF.
in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-05-16 04:00:00 UTC.
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arXiv:2505.10371v1 Announce Type: new
Abstract: The Spiking Neural Network (SNN) has drawn increasing attention for its energy-efficient, event-driven processing and biological plausibility. To train SNNs via backpropagation, surrogate gradients are used to approximate the non-differentiable spike function, but they only maintain nonzero derivatives within a narrow range of membrane potentials near the firing threshold, referred to as the surrogate gradient support width gamma. We identify a major challenge, termed the dilemma of gamma: a relatively large gamma leads to overactivation, characterized by excessive neuron firing, which in turn increases energy consumption, whereas a small gamma causes vanishing gradients and weakens temporal dependencies. To address this, we propose a temporal Inhibitory Leaky Integrate-and-Fire (ILIF) neuron model, inspired by biological inhibitory mechanisms. This model incorporates interconnected inhibitory units for membrane potential and current, effectively mitigating overactivation while preserving gradient propagation. Theoretical analysis demonstrates ILIF effectiveness in overcoming the gamma dilemma, and extensive experiments on multiple datasets show that ILIF improves energy efficiency by reducing firing rates, stabilizes training, and enhances accuracy. The code is available at github.com/kaisun1/ILIF.
in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-05-16 04:00:00 UTC.
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arXiv:2505.09653v1 Announce Type: cross
Abstract: The rapid advancements in quantum computing (QC) and machine learning (ML) have led to the emergence of quantum machine learning (QML), which integrates the strengths of both fields. Among QML approaches, variational quantum circuits (VQCs), also known as quantum neural networks (QNNs), have shown promise both empirically and theoretically. However, their broader adoption is hindered by reliance on quantum hardware during inference. Hardware imperfections and limited access to quantum devices pose practical challenges. To address this, the Quantum-Train (QT) framework leverages the exponential scaling of quantum amplitudes to generate classical neural network parameters, enabling inference without quantum hardware and achieving significant parameter compression. Yet, designing effective quantum circuit architectures for such quantum-enhanced neural programmers remains non-trivial and often requires expertise in quantum information science. In this paper, we propose an automated solution using differentiable optimization. Our method jointly optimizes both conventional circuit parameters and architectural parameters in an end-to-end manner via automatic differentiation. We evaluate the proposed framework on classification, time-series prediction, and reinforcement learning tasks. Simulation results show that our method matches or outperforms manually designed QNN architectures. This work offers a scalable and automated pathway for designing QNNs that can generate classical neural network parameters across diverse applications.
in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-05-16 04:00:00 UTC.
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arXiv:2505.09742v1 Announce Type: cross
Abstract: We propose a generative, end-to-end solver for black-box combinatorial optimization that emphasizes both sample efficiency and solution quality on NP problems. Drawing inspiration from annealing-based algorithms, we treat the black-box objective as an energy function and train a neural network to model the associated Boltzmann distribution. By conditioning on temperature, the network captures a continuum of distributions--from near-uniform at high temperatures to sharply peaked around global optima at low temperatures--thereby learning the structure of the energy landscape and facilitating global optimization. When queries are expensive, the temperature-dependent distributions naturally enable data augmentation and improve sample efficiency. When queries are cheap but the problem remains hard, the model learns implicit variable interactions, effectively "opening" the black box. We validate our approach on challenging combinatorial tasks under both limited and unlimited query budgets, showing competitive performance against state-of-the-art black-box optimizers.
in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-05-16 04:00:00 UTC.
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arXiv:2505.10080v1 Announce Type: cross
Abstract: Scrambling quantum systems have been demonstrated as effective substrates for temporal information processing. While their role in providing rich feature maps has been widely studied, a theoretical understanding of their performance in temporal tasks is still lacking. Here we consider a general quantum reservoir processing framework that captures a broad range of physical computing models with quantum systems. We examine the scalability and memory retention of the model with scrambling reservoirs modelled by high-order unitary designs in both noiseless and noisy settings. In the former regime, we show that measurement readouts become exponentially concentrated with increasing reservoir size, yet strikingly do not worsen with the reservoir iterations. Thus, while repeatedly reusing a small scrambling reservoir with quantum data might be viable, scaling up the problem size deteriorates generalization unless one can afford an exponential shot overhead. In contrast, the memory of early inputs and initial states decays exponentially in both reservoir size and reservoir iterations. In the noisy regime, we also prove exponential memory decays with iterations for local noisy channels. Proving these results required us to introduce new proof techniques for bounding concentration in temporal quantum learning models.
in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-05-16 04:00:00 UTC.
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arXiv:2505.01256v2 Announce Type: replace
Abstract: The NSGA-III is a prominent algorithm in evolutionary many-objective optimization. It is well-suited for optimizing functions with more than three objectives, setting it apart from the classic NSGA-II. However, theoretical insights about NSGA-III of when and why it performs well are still in its early development. This paper addresses this point and conducts a rigorous runtime analysis of NSGA-III on the many-objective \textsc{OneJumpZeroJump} benchmark (\textsc{OjZj} for short), providing the first runtime bounds where the number of objectives is constant. We show that NSGA-III finds the Pareto front of \textsc{OjZj} in time $O(n^{k+d/2}+ \mu n \ln(n))$ where $n$ is the problem size, $d$ is the number of objectives, $k$ is the gap size, a problem specific parameter, if its population size $\mu \in 2^{O(n)}$ is at least $(2n/d+1)^{d/2}$. Notably, NSGA-III is faster than NSGA-II by a factor of $\mu/n^{d/2}$ for some $\mu \in \omega(n^{d/2})$. We also show that a stochastic population update, proposed by Bian et al., provably guarantees a speedup of order $\Theta((k/b)^{k-1})$ in the runtime where $b>0$ is a constant. To our knowledge, this is the first rigorous runtime analysis of NSGA-III on \textsc{OjZj}. Proving these bounds requires a much deeper understanding of the population dynamics of NSGA-III than previous papers achieved.
in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-05-16 04:00:00 UTC.
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arXiv:2412.03843v3 Announce Type: replace-cross
Abstract: Autonomous Driving Systems (ADSs) rely on Deep Neural Networks, allowing vehicles to navigate complex, open environments. However, the unpredictability of these scenarios highlights the need for rigorous system-level testing to ensure safety, a task usually performed with a simulator in the loop. Though one important goal of such testing is to detect safety violations, there are many undesirable system behaviors, that may not immediately lead to violations, that testing should also be focusing on, thus detecting more subtle problems and enabling a finer-grained analysis. This paper introduces Cooperative Co-evolutionary MEtamorphic test Generator for Autonomous systems (CoCoMEGA), a novel automated testing framework aimed at advancing system-level safety assessments of ADSs. CoCoMEGA combines Metamorphic Testing (MT) with a search-based approach utilizing Cooperative Co-Evolutionary Algorithms (CCEA) to efficiently generate a diverse set of test cases. CoCoMEGA emphasizes the identification of test scenarios that present undesirable system behavior, that may eventually lead to safety violations, captured by Metamorphic Relations (MRs). When evaluated within the CARLA simulation environment on the Interfuser ADS, CoCoMEGA consistently outperforms baseline methods, demonstrating enhanced effectiveness and efficiency in generating severe, diverse MR violations and achieving broader exploration of the test space. These results underscore CoCoMEGA as a promising, more scalable solution to the inherent challenges in ADS testing with a simulator in the loop. Future research directions may include extending the approach to additional simulation platforms, applying it to other complex systems, and exploring methods for further improving testing efficiency such as surrogate modeling.
in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-05-16 04:00:00 UTC.
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Nature Communications, Published online: 16 May 2025; doi:10.1038/s41467-025-59966-x
Here, the authors show that a modular deregulation strategy in Saccharomyces cerevisiae boosts xylose conversion to 3-HP by engineering central carbon metabolism with five strategies, achieving a 4.7-fold productivity increase over an initially optimized strain using xylose.
in Nature Communications on 2025-05-16 00:00:00 UTC.
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Nature Communications, Published online: 16 May 2025; doi:10.1038/s41467-025-59872-2
Song et al. report stochastic edge detection enabled by integrating memristor-based stochastic number encoders with logic gates to perform bitwise logic operations with statistical probabilities. A hardware Roberts cross operator achieves 95% less computational cost while withstands up to 50% bit-flip errors.
in Nature Communications on 2025-05-16 00:00:00 UTC.
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Nature Communications, Published online: 16 May 2025; doi:10.1038/s41467-025-59769-0
Cryo-EM often misrepresents flexible RNA molecules by averaging their conformations. Here, the authors combine cryo-EM data with all-atom simulations to refine a dynamic ensemble of complex RNA macromolecules, revealing the limits of single-structure models in flexible regions.
in Nature Communications on 2025-05-16 00:00:00 UTC.
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Nature Communications, Published online: 16 May 2025; doi:10.1038/s41467-025-59922-9
This study identifies E167, Y268, and Q269 as drug-resistant hotspots for SARS-CoV papain-like protease inhibitors that bind to the BL2 loop and groove region, which are valuable in informing the design of the next-generation PLpro inhibitors.
in Nature Communications on 2025-05-16 00:00:00 UTC.
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The fornix is the major white matter tract linking the hippocampal formation with distal brain sites. Human and animal lesion studies show that the connections comprising the fornix are vital for specific attributes of episodic and spatial memory. The fornix, however, interconnects the hippocampal formation with an array of subcortical and cortical sites and it is not known which specific connections support spatial-mnemonic function. To address this, making use of a partly previously published dataset (Hodgetts et al., 2020), we applied a novel deterministic tractography protocol to diffusion-weighted magnetic resonance imaging (dMRI) data from a group of healthy young adult humans who separately completed a desktop-based virtual reality analogue of the Morris water maze task. The tractography protocol enabled the two main parts of the fornix, delineated previously in axonal tracing studies in rodents and primates, to be reconstructed in vivo, namely the pre-commissural fornix (connecting the hippocampus to the medial prefrontal cortex and the basal forebrain) and the post-commissural fornix (connecting the hippocampus to the medial diencephalon). We found that inter-individual differences in pre-commissural- but not, surprisingly, post-commissural- fornix microstructure (indexed by free water corrected fractional anisotropy, FA) were significantly correlated with individual differences in spatial learning, indexed by reduction in search error as individuals learned to navigate to a hidden target location from multiple starting points. This study provides novel evidence that flexible and/or precise spatial learning involves a hippocampal-basal forebrain/prefrontal network underpinned in part by the pre-commissural fornix.
in bioRxiv: Neuroscience on 2025-05-16 00:00:00 UTC.
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Mycoplasma bovis (M. bovis) is a significant pathogen in cattle that causes respiratory disease, mastitis, and arthritis, leading to substantial economic losses globally. Early detection of M. bovis is crucial for its effective management because of its immune evasion strategies and resistance to antimicrobial therapies. In this review, we systematically assessed the diagnostic potential of P48 protein, an immunodominant lipoprotein of M. bovis, along with other potential biomarkers. The aim was to provide a comprehensive understanding of P48’s diagnostic utility through both literature analysis and computational insights. A literature search across major databases identified 243 relevant articles, 20 of which were selected based on predefined inclusion criteria. These studies consistently highlight P48’s diagnostic value due to its stability, immunodominance, and strong antibody response in infected cattle. In addition, a molecular analysis using the Expasy ProtParam tool reveals that P48 exhibits favorable properties for diagnostics, including a theoretical isoelectric point (pI) of 7.14, an instability index of 23.64 (classifying it as stable), and an aliphatic index of 83.40, indicating significant thermostability. The review also considers other diagnostic proteins, such as Variable Surface Proteins (VSPs), MbovP proteins, and MilA, although their variable nature and lesser validation across assays limit their broader application. In contrast, P48 is a reliable and specific marker, particularly in serological assays, for the early and accurate detection of M. bovis infections. This study confirms P48’s diagnostic efficacy over other biomarkers, and advocates its inclusion in diagnostic protocols.
in F1000Research on 2025-05-15 15:59:18 UTC.
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Drawing from historical accounts, cultural practices, archaeological discoveries, and indigenous technical knowledge, the research presents a critical review of varied aspects of the construction of the Konark temple and provides future research directions. To fulfil the purpose, documents were sourced from Scopus, Google Scholar, and ancient texts and palm leaves. Findings suggest the legacy of Narasimhadeva I, the Hindu monarch who remained undefeated during his reign, safeguarded the kingdom from encroaching Muslim rulers. The narrative highlights the bravery of a faithful elephant that revived the king on the battlefield. The Konark temple was built with the dual purpose of showcasing the glory of his victory and devotion to the Sun God. The ancient artisans’ knowledge, skills, and commitment were crucial in erecting this tallest temple structure. The investigation further illuminates the use of sea routes for transporting monumental stones, the ingenuity in laying the temple’s foundation, the selection of high-grade stones, the monumental task of lifting colossal stones, like the world’s heaviest stone hoisted to a height of about two hundred feet, the use of rust-resistant iron, and the application of advanced astronomical knowledge by ancient artisans. The study provides insights into ancient engineering ingenuity, encouraging further exploration of the enduring legacy of the Konark temple’s construction.
in F1000Research on 2025-05-15 15:49:51 UTC.
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by Dieter Vanderelst, Herbert Peremans
Some echolocating bats, such as Tadarida brasiliensis, fly in groups when emerging from or entering caves. In large, dense swarms, distinguishing self-generated echoes from the multitude of calls and echoes produced by others presents a significant challenge – akin to a cocktail party nightmare. While spectral jamming responses have been proposed as a solution, this mechanism is unlikely to be effective in such conditions. Here, we propose an alternative hypothesis: rather than isolating their own echoes, bats might navigate by relying on the local amplitude gradient of the collective soundscape. To test this, we developed an agent-based simulation of bats flying through corridors, demonstrating that they can avoid obstacles, including other bats and corridor walls, without distinguishing individual echoes. Our findings suggest that in dense swarms, bats can exploit the emergent acoustic environment to maintain safe distances passively. The current paper also suggests shifting the perspective on jamming itself. Rather than framing overlapping signals solely as a source of interference, our findings highlight that these signals can also carry useful information, reframing the problem from conflict to cooperative signal processing.
in PLoS Computational Biology on 2025-05-15 14:00:00 UTC.
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by Arturo Casadevall
As humanity comes into contact with new microbes, there is a need to identify which might be future pathogenic threats. Host–microbe interactions manifest emergent properties and chaotic dynamics, posing limits on prediction. However, probabilistic predictions are possible.
To what extent can we predict future pathogenic microbes? This Perspective discusses why complex requirements for virulence and dynamic host-microbe interactions make probabilistic predictions difficult, but not impossible.
in PLoS Biology on 2025-05-15 14:00:00 UTC.
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Background The human ear is unique to individuals, and ear prints, like fingerprints, are discrete enough to distinguish identical twins. Thus, this study aimed to estimate the stature and sex using various morphometric parameters and morphological features of the external ear for forensic identification. Methods This was a cross-sectional observational study involving 40 participants recruited using simple random sampling technique. Eighteen measurements were taken, and various morphological features were noted for both the right and left ears. A digital Vernier caliper was used to measure all linear parameters. The angles were measured using a goniometer. Normal distribution was verified using the Shapiro–Wilk test. For normally distributed parameters, an independent t-test was used, and for non-normally distributed parameters, the Mann-Whitney U test was used to compare sexes. To compare the right and left parameters, independent t-tests (for normally distributed data) and Mann-Whitney U tests (for non-normally distributed data) were applied. Sex determination and stature estimation were performed using logistic regression analysis. Results In males and females, the most common shape was oval (47.5%), and the ear lobe was free (45%). When comparing the parameters of males on the right and left sides, it was noticed that only the ear inclination angle and concha mastoid angle showed significant differences (p < 0.05). It was seen that the right lobe width showed perfect separation, indicating its potential as an extremely reliable predictor of sex. It was noted that in females, the strongest correlation with height was with the ear inclination angle on both sides. Conclusion We can conclude from the results of this study that the right lobe width of external ear can be a reliable predictor of sex. Ear inclination angle on both sides showed strongest correlation with height. The results of this study can help forensic anthropologists identify the sex and stature of a person from various ear measurements in young South Indian adults.
in F1000Research on 2025-05-15 11:07:16 UTC.
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Background Lassa fever (LF) is an endemic and immediately notifiable disease in Liberia, and one laboratory confirmed case constitutes an outbreak. We described the epidemiological characteristics and hospital outcomes of LF cases hospitalized during the 2022-2023 outbreak in Liberia. Methods A retrospective cohort study was conducted using routine LF surveillance data from the 2022-2023 outbreak in Liberia. Descriptive statistics were used to summarize the data and log binomial regression to assess the association between epidemiological characteristics and mortality. Results A total of 439 suspected LF cases were reported. The median age was 22 (interquartile range (IQR): 10-33) years and 233 (53%) were females. The median number of days between symptom onset and admission was 4 (IQR 2-7). Of the 439 cases, 416 (95%) were tested for LF and 138 were confirmed with 33% positivity rate. The majority, 95 (69%), of confirmed cases were <30 years, 78 (57%) were females, and 81 (59%) were reported during the dry season (October – March). Contact with rodents, 95 (69%), was the commonest mode of exposure. Fever, 128 (93%), malaise, 121 (88%), headache, 114 (83%) and myalgia, 114 (83%) were the most common clinical characteristics. There were 83 (19%) deaths among hospitalized suspected LF cases - 42 deaths (15%) among 278 individuals who tested negative and 41 among confirmed cases with 30% case fatality rate (CFR). Age 40-49 years accounted for 8/12 (67%) and those aged≥50 reported 5/8 (63%) of the deaths among the confirmed cases. There was no significant association between epidemiological characteristics and LF mortality. Conclusions The outbreak highlighted a high disease burden of LF with young adults disproportionately infected, and mortality, even among those who tested negative for the virus. This underscores the urgent need for preventive measures like vaccines and health education campaigns.
in F1000Research on 2025-05-15 11:03:19 UTC.
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1) Introduction Cognitive enhancers, also known as nootropics, aim to improve cognitive functions, such as memory and attention. Despite their potential benefits, the challenges include scientific validation, ethical considerations, and regulatory hurdles. This bibliometric study analyzes literature from Scopus to identify key trends, influential authors, and research gaps, providing guidance for future research. 2) Methods This study employs a literature review methodology to gather data from the Scopus database on Neuroaid, analyzing it using Biblioshiny and VOSviewer software. The focus was on Ginkgo Biloba as a niche-theme cognitive enhancer agent based on Scopus data, using both quantitative and qualitative analyses. 3) Results and discussion Ginkgo biloba, the 'maidenhair tree’ from the order Ginkgoales, appeared 290 million years ago. Chinese and Japanese culture has been cultivated for thousands of years. This tree is valued for its resilience and therapeutic properties, often used in traditional medicine for respiratory and blood circulation issues. 4) Conclusions This bibliometric study on cognitive enhancers aims to provide a comprehensive and systematic review of the existing literature, highlighting key trends, influential authors, and research gaps. The findings of this study will contribute to a better understanding of the current state of research on cognitive enhancers and inform future research. This study was conducted in December 2024.
in F1000Research on 2025-05-15 10:57:32 UTC.
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Author(s): Yin-Jie He, Qi-Hao Li, Jun-Ting Pan, and Hong Zhang
Spiral waves in cardiac tissue are believed to be closely related to cardiac diseases such as arrhythmias. Accurately identifying the phase singularity (PS, the tip of a spiral wave) is important in electrophysiological studies of cardiac arrhythmias, for which various PS detection methods have been…
[Phys. Rev. E 111, 054408] Published Thu May 15, 2025
in Physical Review E: Biological physics on 2025-05-15 10:00:00 UTC.
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Author(s): Manuel Mayo and Rodrigo Soto
Bacterial chemotaxis for the case of Escherichia coli is controlled by methylation of chemoreceptors, which in a biochemical pathway regulates the concentration of the CheY-P protein that finally controls the tumbling rate. As a consequence, the tumbling rate adjusts to changes in the concentration …
[Phys. Rev. E 111, 054409] Published Thu May 15, 2025
in Physical Review E: Biological physics on 2025-05-15 10:00:00 UTC.
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Author(s): Manuel Mayo and Rodrigo Soto
Chemotaxis in bacteria such as Escherichia coli is controlled by the slow methylation of chemoreceptors. As a consequence, intrinsic time and length scales of tens of seconds and hundreds of micrometers emerge, making the Keller–Segel equations invalid when the chemical signal changes on these scale…
[Phys. Rev. E 111, L052402] Published Thu May 15, 2025
in Physical Review E: Biological physics on 2025-05-15 10:00:00 UTC.
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Background Knee osteoarthritis (KOA) is a prevalent condition. Recent research on people with KOA has addressed kinetic chain and core muscle contribution in disease progression. Objective This study aims to assess the efficacy of including the CARE -KOA© regimen and evaluate its effect on pain, patient-reported functional outcomes, physical function tests, knee strength, and core endurance. Methods/Design 15 patients above 45 were recruited and underwent a 4-week CARE -KOA© program with 12 supervised sessions over four weeks. Pre- and Post-exercise assessment included evaluating the primary outcome pain using the VAS scale and the patient-reported outcome using the KOOS scale. The secondary outcomes, knee muscle strength, core endurance, and the physical function tests, i.e., the stair climb test, the sit-to-stand test, the 40m fast-paced walking test, and the timed up-and-go test, were also evaluated. The data collected in the study was analyzed using the statistical software JAMOVI. p < 0.05 was significant. Results Notably, all the parameters examined exhibited a statistically significant difference between their pre-intervention and post-intervention values, except the knee muscle strength in the flexors of the affected knee and extensors of the unaffected knee. Conclusion Patients who completed a 4-week supervised CARE -KOA© program alongside routine rehabilitation experienced reduced pain and improved outcomes. This approach aims to address biomechanical issues and positively impacts pain mechanisms. Study Trial Registration CTRI/2023/07/05480 on 05/07/2024 https://ctri.nic.in/Clinicaltrials/regtrial.php?modid=1&compid=19&EncHid=69416.70327 Copy right registration: L – 158197/2024
in F1000Research on 2025-05-15 09:21:03 UTC.
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Science, Volume 388, Issue 6748, May 2025.
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Science, Volume 388, Issue 6748, May 2025.
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Science, Volume 388, Issue 6748, May 2025.
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Science, Volume 388, Issue 6748, May 2025.
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Science, Volume 388, Issue 6748, May 2025.
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Science, Volume 388, Issue 6748, May 2025.
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Science, Volume 388, Issue 6748, May 2025.
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Science, Volume 388, Issue 6748, May 2025.
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Science, Volume 388, Issue 6748, Page 710-710, May 2025.
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Journal of Neurophysiology, Ahead of Print.
in Journal of Neurophysiology on 2025-05-15 05:01:09 UTC.
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Opioid withdrawal produces a dysphoric state that can lead to relapse. Simon et al. reveal that lateral septal neurotensin-expressing neurons are selectively activated by naloxone and drive changes in pain coping and sociability in opioid-dependent mice, highlighting the potential role for the lateral septum in regulating behavior during opioid withdrawal.
in Neuron: In press on 2025-05-15 00:00:00 UTC.
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By photostimulating specific visual cortical ensembles, Bounds et al. discovered that an ensemble’s impact on local neural activity, not its visual encoding properties, predicts its impact on stimulus detection. Their analysis reveals that mice use a generalizable, albeit suboptimal, perceptual readout strategy of summing all V1 activity to detect stimuli.
in Neuron: In press on 2025-05-15 00:00:00 UTC.
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The helminth immunomodulators from the HpARI and HpBARI families can block IL-33 responses. Smyth and Hodge et al. show that vaccination with these immunomodulatory proteins can raise blocking antibody responses against them, allowing the development of effective anti-parasite type 2 immunity and ejection of the parasite.
in Cell Reports: Current Issue on 2025-05-15 00:00:00 UTC.
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Dam et al. identify essential somatic hypermutations (SHMs) in the IOMA class of CD4-binding site broadly neutralizing antibodies to guide HIV-1 vaccine design. By systematically reverting SHMs, they define minimal mutations required for IOMA’s neutralization potency and breadth. Structural and functional analyses of IOMAmin variants highlight key determinants for immunogen development.
in Cell Reports: Current Issue on 2025-05-15 00:00:00 UTC.
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Jackson et al. show that serine becomes an essential amino acid in mitochondrial muscle disease, delaying disease progression. Blocking local biosynthesis of serine challenges cellular phospholipid homeostasis and redox balance in the context of disease but is not harmful to healthy physiology.
in Cell Reports: Current Issue on 2025-05-15 00:00:00 UTC.
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Walter et al. used proteomics to investigate changes to protein abundance and post-translational modification during West Nile virus infection. Upregulated proteins like HERPUD1 function to restrict viral infection, while phosphorylation on the viral enzyme NS3 and the host kinase PAK2 regulates RNA replication and viral genome translation, respectively.
in Cell Reports: Current Issue on 2025-05-15 00:00:00 UTC.
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Yi et al. demonstrate that optogenetic activation of cortical microglia in the primary somatosensory cortex (S1) induces pain hypersensitivity and affective pain responses in mice. This process involves microglial landscape changes, ATP release, and enhanced neuronal activity, providing mechanistic insight into the role of cortical microglia in chronic pain.
in Cell Reports: Current Issue on 2025-05-15 00:00:00 UTC.
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Huang et al. identify that an NLR protein RPM1-L1, which is N-terminally acetylated by OsHYPK/NatA, is involved in regulating blast resistance in rice, showing an OsHYPK-NTA-RPM1-L1 model that fine-tunes the balance between plant growth and disease resistance.
in Cell Reports: Current Issue on 2025-05-15 00:00:00 UTC.
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Zhang et al. analyze vernalization in Brassica rapa by scRNA-seq. Mesophyll cells show a biphasic chill response, while vasculature highly expresses flowering genes. Expression dynamics of BrFLCs and related genes show correlations with changes in the number of cells expressing these genes, highlighting mechanisms underlying the quantitative nature of vernalization.
in Cell Reports: Current Issue on 2025-05-15 00:00:00 UTC.
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Nature, Published online: 15 May 2025; doi:10.1038/s41586-025-09104-w
Ku limits RNA-induced innate immunity to allow Alu-expansion in primates
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Nature, Published online: 15 May 2025; doi:10.1038/d41586-025-01426-z
Immune-system responses to cell therapies produce long-term effects on cognition in mice.
in Nature on 2025-05-15 00:00:00 UTC.
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Nature, Published online: 15 May 2025; doi:10.1038/d41586-025-01486-1
Buried in lab work or drowning in data? Take a break and help shape the future of PhD education.
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Nature, Published online: 15 May 2025; doi:10.1038/d41586-025-01427-y
The consumption and investments of the wealthiest 10% contribute disproportionately to the emissions that drive heat waves and drought.
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Nature, Published online: 15 May 2025; doi:10.1038/d41586-025-01498-x
The sacs grew to roughly 2 centimeters wide and could be used to study early pregnancy.
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Nature, Published online: 15 May 2025; doi:10.1038/d41586-025-01496-z
Treatment seems to have been effective, but it is not clear whether such bespoke therapies can be widely applied.
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Nature, Published online: 15 May 2025; doi:10.1038/d41586-025-01518-w
‘Directed’ evolution in the laboratory creates an editing tool that outperforms classic CRISPR systems.
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Nature, Published online: 15 May 2025; doi:10.1038/d41586-025-01514-0
Why is recruitment often speedier in industry? Julie Gould investigates what the two sectors can learn from each other in the race to source top talent.
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Nature, Published online: 15 May 2025; doi:10.1038/d41586-025-01500-6
When LLMs are grouped together, they exhibit similar characteristics to human societies.
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Nature Methods, Published online: 15 May 2025; doi:10.1038/s41592-025-02701-7
Vclust generates fast and accurate estimation of average nucleotide identity for viral genomes, scaling clustering to millions of genomes.
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Nature Communications, Published online: 15 May 2025; doi:10.1038/s41467-025-57391-8
The interaction between correlated states and the excitonic emission coherence in van der Waals moiré systems remains largely unexplored. Here, the authors report evidence of enhanced interlayer exciton emission coherence in twisted WSe2/MoS2 heterobilayers, attributed to exciton-exciton and exciton-electron interactions.
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Nature Communications, Published online: 15 May 2025; doi:10.1038/s41467-025-59615-3
Neoadjuvant immunotherapy can induce promising response rates in patients with localised deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) solid tumours but whether this translates to long term survival benefits is less clear. Here, the authors report long-term survival outcomes and ctDNA analysis of a phase II trial investigating neoadjuvant pembrolizumab in patients with dMMR/MSI-H solid tumours.
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Nature Communications, Published online: 15 May 2025; doi:10.1038/s41467-025-59274-4
Chain-elongating oxidations enable molecular complexity to be carefully and logically assembled. Herein, the authors report a photoexcited nitroarene-enabled regioselective chain-elongated oxidation of alkenes via tandem oxidative cleavage and dipolar cycloaddition, providing a broad range of synthetically-useful isoxazolidines from readily available enol ethers or styrene and derivatives.
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Nature Communications, Published online: 15 May 2025; doi:10.1038/s41467-025-59743-w
Materials with efficient mechanical energy storage are found in Nature, though synthesizing hydrogels mimicking these properties are challenging. This study shows by sequentially swelling hydrogels the mechanic properties can be properly balanced.
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Nature Physics, Published online: 15 May 2025; doi:10.1038/s41567-025-02907-8
Measurements play a crucial role in our daily lives; and we rely on metrology to ensure that measurements are accurate and comparable. Celebrating the 150th anniversary of the beginning of the global measurement system, we look into its future.
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Nature Physics, Published online: 15 May 2025; doi:10.1038/s41567-025-02926-5
This month, we celebrate the 150-year anniversary of the signing of the Metre Convention and look to the future of metrology.
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Nature Physics, Published online: 15 May 2025; doi:10.1038/s41567-025-02905-w
When life got complex
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Nature Physics, Published online: 15 May 2025; doi:10.1038/s41567-025-02903-y
Many young metrologists have fascinating ideas that could shape the future of metrology. Chingis Kuanbayev and Kangyoung Sung tell us how the young professionals imagine what the field will look like beyond 2050.
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Nature Physics, Published online: 15 May 2025; doi:10.1038/s41567-025-02904-x
A human history of meteorites
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Scientific Data, Published online: 15 May 2025; doi:10.1038/s41597-025-05171-w
Chromosome-level assembly of Pseudopodoces humilis genome: A resource for avian evolutionary studies
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Scientific Data, Published online: 15 May 2025; doi:10.1038/s41597-025-05052-2
A collection of FAIR Dutch Freedom of Information Act documents
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Scientific Data, Published online: 15 May 2025; doi:10.1038/s41597-025-05165-8
A Dataset of Stakeholder Networks for Project Performance Analysis
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Scientific Data, Published online: 15 May 2025; doi:10.1038/s41597-025-05159-6
Lights, Camera, Emotion: REELMO’s 1060 Hours of Affective Reports to Explore Emotions in Naturalistic Contexts
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Scientific Data, Published online: 15 May 2025; doi:10.1038/s41597-025-05166-7
Dataset on occupant behavior, indoor environment, and energy use before and after dormitory retrofit
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Scientific Data, Published online: 15 May 2025; doi:10.1038/s41597-025-05140-3
A dataset of US precinct votes allocated to Census geographies with precision
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Communications Biology, Published online: 15 May 2025; doi:10.1038/s42003-025-08191-9
DNAJC5 facilitates LUAD progression through EGFR trafficking modulation, enhancing EGFR activity and downstream signaling while offering insights for innovative diagnostic and therapeutic strategies.
in Nature communications biology on 2025-05-15 00:00:00 UTC.
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Communications Biology, Published online: 15 May 2025; doi:10.1038/s42003-025-08182-w
Targeted metabolite analysis reveals how inositol transport changes in symbiotic corals under heat stress, highlighting its critical role in shaping coral metabolite profiles and suggesting a key function in coral resilience to thermal stress.
in Nature communications biology on 2025-05-15 00:00:00 UTC.
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Communications Biology, Published online: 15 May 2025; doi:10.1038/s42003-025-08175-9
SEC24D depletion induces osteogenic differentiation deficiency by inactivating the ATF6/TGF-β/Runx2 regulatory loop.
in Nature communications biology on 2025-05-15 00:00:00 UTC.
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Communications Biology, Published online: 15 May 2025; doi:10.1038/s42003-025-07992-2
A review summarizes the interplay of the lung microenvironment in metastatic osteosarcoma in human and canines, including immune and resident lung cells, and how this knowledge can inform treatment for both patient populations.
in Nature communications biology on 2025-05-15 00:00:00 UTC.
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Communications Biology, Published online: 15 May 2025; doi:10.1038/s42003-025-08137-1
Human bone marrow MPS enables in vitro profiling of hematopoietic and immunotoxic effects of biologics, capturing lineage-specific responses and T cell–mediated cytotoxicity in a microfluidic system with optional autologous immune components.
in Nature communications biology on 2025-05-15 00:00:00 UTC.
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The transforming growth factor β (TGFβ) signaling pathway is critical for survival, proliferation, and cell migration, and is tightly regulated during cardiovascular development. Smads, key effectors of TGFβ signaling, are sequestered by microtubules (MTs) and need to be released for pathway function. Independently, TGFβ signaling also stabilizes MTs. Molecular details and the in vivo relevance of this cross-regulation remain unclear, understanding which is important in complex biological processes such as cardiovascular development. Here, we use rudhira/Breast Carcinoma Amplified Sequence 3 (Bcas3), an MT-associated, endothelium-restricted, and developmentally essential proto-oncogene, as a pivot to decipher cellular mechanisms in bridging TGFβ signaling and MT stability. We show that Rudhira regulates TGFβ signaling in vivo, during mouse cardiovascular development, and in endothelial cells in culture. Rudhira associates with MTs and is essential for the activation and release of Smad2/3 from MTs. Consequently, Rudhira depletion attenuates Smad2/3-dependent TGFβ signaling, thereby impairing cell migration. Interestingly, Rudhira is also a transcriptional target of Smad2/3-dependent TGFβ signaling essential for TGFβ-induced MT stability. Our study identifies an immediate early physical role and a slower, transcription-dependent role for Rudhira in cytoskeleton-TGFβ signaling crosstalk. These two phases of control could facilitate temporally and spatially restricted targeting of the cytoskeleton and/or TGFβ signaling in vascular development and disease.
in eLife on 2025-05-15 00:00:00 UTC.
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AARS2, an alanyl-tRNA synthase, is essential for protein translation, but its function in mouse hearts is not fully addressed. Here, we found that cardiomyocyte-specific deletion of mouse AARS2 exhibited evident cardiomyopathy with impaired cardiac function, notable cardiac fibrosis, and cardiomyocyte apoptosis. Cardiomyocyte-specific AARS2 overexpression in mice improved cardiac function and reduced cardiac fibrosis after myocardial infarction (MI), without affecting cardiomyocyte proliferation and coronary angiogenesis. Mechanistically, AARS2 overexpression suppressed cardiomyocyte apoptosis and mitochondrial reactive oxide species production, and changed cellular metabolism from oxidative phosphorylation toward glycolysis in cardiomyocytes, thus leading to cardiomyocyte survival from ischemia and hypoxia stress. Ribo-Seq revealed that Aars2 overexpression increased pyruvate kinase M2 (PKM2) protein translation and the ratio of PKM2 dimers to tetramers that promote glycolysis. Additionally, PKM2 activator TEPP-46 reversed cardiomyocyte apoptosis and cardiac fibrosis caused by AARS2 deficiency. Thus, this study demonstrates that AARS2 plays an essential role in protecting cardiomyocytes from ischemic pressure via fine-tuning PKM2-mediated energy metabolism, and presents a novel cardiac protective AARS2-PKM2 signaling during the pathogenesis of MI.
in eLife on 2025-05-15 00:00:00 UTC.
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Walking animals must maintain stability in the presence of external perturbations, despite significant temporal delays in neural signaling and muscle actuation. Here, we develop a 3D kinematic model with a layered control architecture to investigate how sensorimotor delays constrain the robustness of walking behavior in the fruit fly, Drosophila. Motivated by the anatomical architecture of insect locomotor control circuits, our model consists of three component layers: a neural network that generates realistic 3D joint kinematics for each leg, an optimal controller that executes the joint kinematics while accounting for delays, and an inter-leg coordinator. The model generates realistic simulated walking that resembles real fly walking kinematics and sustains walking even when subjected to unexpected perturbations, generalizing beyond its training data. However, we found that the model’s robustness to perturbations deteriorates when sensorimotor delay parameters exceed the physiological range. These results suggest that fly sensorimotor control circuits operate close to the temporal limit at which they can detect and respond to external perturbations. More broadly, we show how a modular, layered model architecture can be used to investigate physiological constraints on animal behavior.
in eLife on 2025-05-15 00:00:00 UTC.
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Non-obstructive azoospermia (NOA) belongs to male infertility due to spermatogenesis failure. However, evidence for cell type-specific abnormalities of spermatogenesis disorders in NOA remains lacking. We performed single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) on testicular tissues from patients with obstructive azoospermia (OA) and NOA. HE staining confirmed the structural abnormalities of the seminiferous tubules in NOA patients. We identified 12 germ cell subtypes (spermatogonial stem cell-0 [SSC0], SSC1, SSC2, diffing-spermatogonia [Diffing-SPG], diffed-spermatogonia [Diffed-SPG], pre-leptotene [Pre-Lep], leptotene-zygotene [L-Z], pachytene [Pa], diplotene [Di], spermatids-1 [SPT1], SPT2, and SPT3) and 8 Sertoli cell subtypes (SC1-SC8). Among them, three novel Sertoli cell subtype phenotypes were identified, namely SC4/immature, SC7/mature, and SC8/further mature Sertoli cells. For each germ or Sertoli cell subtype, we identified unique new markers, among which immunofluorescence confirmed co-localization of ST3GAL4, A2M, ASB9, and TEX19 and DDX4 (classical marker of germ cell). PRAP1, BST2, and CCDC62 were co-expressed with SOX9 (classical marker of Sertoli cell) in testes tissues also confirmed by immunofluorescence. The interaction between germ cell subtypes and Sertoli cell subtypes exhibits stage-specific-matching pattern, as evidenced by SC1/2/5/7 involving in SSC0-2 development, SC3 participating in the whole process of spermiogenesis, SC4/6 participating in Diffing and Diffed-SPG development, and SC8 involving in the final stage of SPT3. This pattern of specific interactions between subtypes of germ cell and Sertoli cell was confirmed by immunofluorescence of novel markers in testes tissues. The interaction was mainly regulated by the Notch1/2/3 signaling. Our study profiled the single-cell transcriptome of human spermatogenesis and provided many potential molecular markers for developing testicular puncture-specific marker kits for NOA patients.
in eLife on 2025-05-15 00:00:00 UTC.
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Bacteria are Caenorhabditis elegans’ food, and worms are naturally attracted to many bacteria, including pathogenic Pseudomonas, preferring PA14 over laboratory Escherichia coli (OP50). Despite this natural attraction to PA14, prior PA14 exposure causes the worms to instead avoid PA14. This behavioral switch can happen quickly – even within the duration of the choice assay. We show that accurate assessment of the animals’ true first choice requires the use of a paralytic (azide) to trap the worms at their initial choice, preventing the switch from attraction to avoidance of PA14 within the assay period. We previously discovered that exposure of C. elegans to 25°C plate-grown PA14 at 20°C for 24 hr not only leads to PA14 avoidance, but also to four generations of naïve progeny avoiding PA14, while other PA14 paradigms only cause P0 and/or F1 avoidance. We also showed that the transgenerational (P0-F4) epigenetic avoidance is mediated by P11, a small RNA produced by PA14. P11 is both necessary and sufficient for TEI of learned avoidance. P11 is highly expressed in our standard growth conditions (25°C on surfaces), but not in other conditions, suggesting that the reported failure to observe F2-F4 avoidance is likely due to the absence of P11 expression in PA14 in the experimenters’ growth conditions. Additionally, we tested ~35 genes for involvement in TEI of learned pathogen avoidance. The conservation of multiple components of this sRNA TEI mechanism across C. elegans strains and in multiple Pseudomonas species suggests that this TEI behavior is likely to be physiologically important in wild conditions.
in eLife on 2025-05-15 00:00:00 UTC.
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Understanding the complex workings of the brain is one of the most significant challenges in neuroscience, providing insights into normal brain function, neurological diseases, and the effects of potential therapeutics. A major challenge in this field lies in the limitations of traditional brain imaging techniques, which often capture only fragments of the complex puzzle of brain function. Our research employs a novel approach termed ‘molecular connectivity’ (MC), which combines the strengths of various imaging methods to provide a comprehensive view of how specific molecules, such as the serotonin transporter, interact across different brain regions and influence brain function. This innovative technique bridges the gap between functional magnetic resonance imaging (fMRI), known for its ability to monitor brain activity by tracking blood flow, and positron emission tomography (PET), which visualizes specific molecular changes. By integrating these methods, we can better understand how drugs influence brain function. Our study focuses on the application of dynamic [11C]DASB PET scans to map the distribution of serotonin transporters, key players in regulating mood and emotions, and examines how these transporters are altered following exposure to methylenedioxymethamphetamine (MDMA), which is commonly known as ecstasy. Through a detailed comparison of MC with traditional measures of brain connectivity, we reveal significant patterns that closely align with physiological changes. Our results revealed clear changes in molecular connectivity after a single dose of MDMA, establishing a direct link between the effects of drugs on serotonin transporter occupancy and changes in the functional brain network. This work offers a novel methodology for the in-depth study of brain function at the molecular level and opens new pathways for understanding how drugs modulate brain activity.
in eLife on 2025-05-15 00:00:00 UTC.
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In both Drosophila and mammals, the brain contains the most diverse population of cell types of any tissue. It is generally accepted that transcriptional diversity is an early step in generating neuronal and glial diversity, followed by the establishment of a unique gene expression profile that determines morphology, connectivity, and function. In Drosophila, there are two types of neural stem cells, called Type 1 (T1) and Type 2 (T2) neuroblasts. The diversity of T2-derived neurons contributes a large portion of the central complex (CX), a conserved brain region that plays a role in sensorimotor integration. Recent work has revealed much of the connectome of the CX, but how this connectome is assembled remains unclear. Mapping the transcriptional diversity of T2-derived neurons is a necessary step in linking transcriptional profile to the assembly of the adult brain. Here we perform single nuclei RNA sequencing of T2 neuroblast-derived adult neurons and glia. We identify clusters containing all known classes of glia, clusters that are male/female enriched, and 161 neuron-specific clusters. We map neurotransmitter and neuropeptide expression and identify unique transcription factor combinatorial codes for each cluster. This is a necessary step that directs functional studies to determine whether each transcription factor combinatorial code specifies a distinct neuron type within the CX. We map several columnar neuron subtypes to distinct clusters and identify two neuronal classes (NPF+ and AstA+) that both map to two closely related clusters. Our data support the hypothesis that each transcriptional cluster represents one or a few closely related neuron subtypes.
in eLife on 2025-05-15 00:00:00 UTC.
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Ribonucleo-protein granules (mRNP granules) are thought to contribute to the control of neuronal mRNA translation required for consolidation of long-term memories. Consistent with this, the function of Ataxin-2 in mRNA granule assembly has been shown to be required for long-term olfactory habituation (LTH) in Drosophila, a form of non-associative memory. Knockdown of Ataxin-2 in either local interneurons (LNs) or projection neurons (PNs) of the insect antennal lobe disrupts LTH, leading to a model in which Ataxin-dependent translational control is required in both presynaptic and postsynaptic elements of the LN-PN synapse, whose potentiation has been causally linked to LTH. Here we use novel and established methods for cell-type specific perturbation to ask: (a) whether Ataxin-2 controls mRNA granule assembly in cell types beyond the few that have been examined; and (b) whether it functions not only in LTH, but also for long-term olfactory associative memory (LTM). We show that Ataxin-2 controls mRNP granule assembly in additional neuronal types, namely Kenyon Cells that encode associative memory, as well as more broadly in non-neuronal cells, e.g. in nurse cells in the egg chamber. Furthermore, selective knockdown of Atx2 in alpha/beta and alpha' / beta' KCs blocks appetitive long-term but not short-term associative memories. Taken together these observations support a hypothesis that Ataxin-2 dependent translational control is widely required across different mnemonic circuits for consolidation of respective forms of long-term memories.
in bioRxiv: Neuroscience on 2025-05-15 00:00:00 UTC.
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A major goal of neuroscience is to identify whether there are generalized principles that can explain the diverse structures and functions of the brain. The principle of temporal prediction provides one approach, arguing that the sensory brain is optimized to represent stimulus features that efficiently predict the immediate future input. Previous work has demonstrated that feedforward hierarchical temporal prediction models can capture the tuning properties of neurons along the visual pathway, and that recurrent temporal prediction models can explain local functional connectivity within primary visual cortex. However, the visual system is also characterized by extensive inter-areal feedback recurrency, which existing models lack. We aimed to better account for the dynamic features of neurons in the visual cortex by incorporating both local recurrency and inter-areal feedback connectivity into a hierarchical temporal prediction model. The resulting model captured tuning for pattern motion, surround suppression and elements of inter-areal functional connectivity in visual cortex. Moreover, compared with several alternative normative models, the hierarchical recurrent temporal prediction model provided the closest fit to these tuning properties and was best able to explain the emergence of neuronal response properties across the visual cortex. Accordingly, temporal prediction can account for information processing throughout the visual pathway.
in bioRxiv: Neuroscience on 2025-05-15 00:00:00 UTC.
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In healthy individuals active compared to passive movements exhibit earlier neural processing, reflected by more positive contrast estimates of the first-order temporal derivative (TD) of the hemodynamic response function (HRF) in functional MRI (fMRI) analyses. This temporal advantage may play a critical role in self-other distinction. However, whether Schizophrenia Spectrum Disorder (SSD) is associated with deficits in sensory-motor predictive mechanisms that influence this earlier processing remains unknown. Patients with SSD (n = 20) and healthy control subjects (HC; n = 20) performed active and passive hand movements, while detected delays in video feedback of their own or another person's hand movement. 3T fMRI data was recorded during the task. To assess response dynamics, we applied the TD to examine timing and the second-order dispersion derivative (DD) to evaluate duration of the HRF. Compared to HC, patients with SSD exhibited delayed BOLD activation during active vs. passive movements in the right caudate nucleus, lobule VIII of right cerebellar hemisphere, left superior temporal gyrus, left postcentral gyrus, left thalamus, and left putamen/insula. For active movement with own hand feedback, HC showed earlier activation in the bilateral putamen and insula, whereas patients with SSD exhibited earlier activation in the left precentral gyrus, supplementary motor area, and postcentral gyrus. Delayed BOLD responses in patients with SSD, particularly in the right cerebellar lobule VIII, bilateral putamen and insula, suggest impaired predictive mechanisms affecting feedback monitoring. These delays may contribute to disturbances in the sense of agency and self-action awareness, potentially underpinning core symptoms of SSD.
in bioRxiv: Neuroscience on 2025-05-15 00:00:00 UTC.
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Long COVID (LC) following SARS-CoV-2 infection affects millions of individuals world-wide and manifests with a variety of symptoms including cognitive dysfunction also known as brain fog . This is characterized by difficulties in executive functions, planning, decision-making, working memory, impairments in complex attention, loss of ability to learn new skills and perform sophisticated brain tasks. No effective treatment options currently exist for LC-related cognitive dysfunction. Here, we use the IntelliCage, which is an automated tracking system of cognitive functions, following SARS-CoV-2 infection in mice, measuring the ability of each mouse within a group to perform tasks that mimic complex human behaviors, such as planning, decision-making, cognitive flexibility, and working memory. Artificial intelligence and machine learning analyses of the tracking data classified LC mice into distinct behavioral categories from non-infected control mice, permitting precise identification and quantification of complex cognitive dysfunction in a controlled, replicable manner. Importantly, we find that brains from LC mice with cognitive dysfunction exhibit transcriptomic alterations similar to those observed in humans suffering from LC-related cognitive impairments, including altered expression of genes involved in learning, executive functions, synaptic functions, neurotransmitters and memory. Together, our findings establish a validated murine model and an automated unbiased approach to study LC-related cognitive dysfunction for the first time, and providing a valuable tool for screening potential treatments and therapeutic interventions.
in bioRxiv: Neuroscience on 2025-05-15 00:00:00 UTC.
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Many animals use the Earth's magnetic field for the purposes of orientation and navigation, although the sensory mechanisms remain unclear. It has been proposed that retinal responses to light may be modulated by magnetic fields. However, to date, there is no evidence for a retinal response to magnetic fields in mammals. Here we show that magnetic fields affect expression of the neuronal activity marker c-Fos in the mouse retina in a light dependent manner. These retinal responses to magnetic fields are abolished in mice lacking the candidate magnetoreceptor cryptochrome. To characterise the signalling pathways involved, we then used RNAseq and cell-type mapping. We also show that magnetic fields increase exploratory behaviour in a visually dependent task and lengthen the period of the retinal circadian clock. Together, our data provide the first evidence for a mammalian retinal response to magnetic fields at a cellular, molecular and functional level, which may influence vision.
in bioRxiv: Neuroscience on 2025-05-15 00:00:00 UTC.
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Functional dedifferentiation, a hallmark of brain aging particularly evident within the frontoparietal network (FPN), has been extensively investigated in the context of cognitive decline, yet its implications for late-life mental health remain poorly understood. Leveraging naturalistic fMRI combined with gradient mapping techniques, the present study investigated FPN functional dedifferentiation-quantified by functional dispersion of FPN in the multidimension gradient manifold-during real-life emotional experiences and its link to affective outcomes. Here, we estimated functional dispersion during naturalistic movie watching in both younger (N=72, 34 female, 19-36 yrs) and older (N=68, 36 female, 65-82 yrs) adult groups with 7T MRI scanner and assessed their emotion regulation difficulties, anxiety, and depression symptoms as indicators of mental health status. The results demonstrated that greater FPN dispersion (i.e., more dissimilar connectivity) was linked to increased depressive symptoms in older adults and highlighted emotion regulation difficulties as a full mediator of this relationship. Moreover, FPN dispersion could distinguish emotionally resilient from vulnerable older individuals. These findings suggest that functional dedifferentiation of the FPN during ecologically valid emotional context constitutes a promising neural signature of affective vulnerability in older adults. By bridging age-related functional dedifferentiation to real-world emotional scenario, this work underscores the translational value of naturalistic paradigms in geriatric psychiatry and identifies potential intervention targets aimed at enhancing FPN specificity to promote mental health in aging population.
in bioRxiv: Neuroscience on 2025-05-15 00:00:00 UTC.
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Organotypic cultures, specifically brain slices, have been used in neuroscience studies for many years to prolong the lifetime of the biological tissue outside of the host organism. However, the cultures must be kept in a sterile environment, maintaining supply of gas/nutrients for tissue survival and physiological relevance. Electrophysiological recordings from cultured tissue are challenging as the conventional approaches implicate a compromise on biological stability or environmental integrity. In this article, a novel approach has been used to design and print nanoporous microelectrodes on culture wells enabling in situ recording of electrophysiological neural activities. Optimized ink formulations are developed for conductive nanocarbon microelectrodes, and furthermore, fluoropolymer (polytetrafluoroethylene-based AF2400) ink has been inkjet printed for the first time acting as an insulator layer for microelectrodes. To keep the biocompatible nanoporous structure of culture wells, the microelectrodes have been printed on the bottom of the culture cells and only small connector pads have been produced on top of the culture membrane. Neural activity has been recorded by such a microelectrode structure for rodent brain slices cultured for three weeks. Furthermore, aerosol jet printing has been used for printing of nanocarbon microelectrodes allowing to produce much smaller size features compared to the inkjet printing.
in bioRxiv: Neuroscience on 2025-05-15 00:00:00 UTC.
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To understand biological intelligence we need to map neuronal networks in vertebrate brains. Mapping mesoscale neural circuitry is done using injections of tracers that label groups of neurons whose axons project to different brain regions. Since many neurons are labeled, it is difficult to follow individual axons. Previous approaches have instead quantified the regional projections using the total label intensity within a region. However, such a quantification is not biologically meaningful. We propose a new approach better connected to the underlying neurons by skeletonizing labeled axon fragments and then estimating a volumetric length density. Our approach uses a combination of deep nets and the Discrete Morse (DM) technique from computational topology. This technique takes into account nonlocal connectivity information and therefore provides noise-robustness. We demonstrate the utility and scalability of the approach on whole-brain tracer injected data. We also define and illustrate an information theoretic measure that quantifies the additional information obtained, compared to the skeletonized tracer injection fragments, when individual axon morphologies are available. Our approach is the first application of the DM technique to computational neuroanatomy. It can help bridge between single-axon skeletons and tracer injections, two important data types in mapping neural networks in vertebrates.
in bioRxiv: Neuroscience on 2025-05-15 00:00:00 UTC.
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The advent of human induced pluripotent stem cells (hiPSCs) and their differentiation into neurons and brain organoids has revolutionized our ability to model brain disorders in a human context. However, current technologies to assay the electrophysiological properties of human neurons in these models remain limited by throughput, as single-cell manual patch clamp is laborious and resource intensive. Here, we provide methods to perform automated high-throughput patch-clamp (APC) on hiPSC-derived neurons. We describe how to dissociate and perform voltage-clamp recordings on human neurons from three well-established protocols - 2D directed differentiation of cortical neurons, NGN2-induced neurons, and 3D cortical organoids - using the Nanion Syncropatch 384, a commercially available high-throughput APC system. Using this approach, we investigated the biophysical properties of voltage-gated sodium channels (VGSCs) and provide direct comparisons between manual and APC recordings across all three hiPSC-derived model systems. We demonstrate the capability of this automated system for pharmacological analysis of native human VGSC isoforms, which will enable compound screening approaches. Lastly, we provide methods to sort specific cellular populations within these hiPSC models using fluorescence-activated cell sorting (FACS) followed by APC. These methods and results provide a transformative and novel high-throughput technique for quantifying passive and active membrane properties in cell-type specific and/or genetically modified hiPSC-derived neurons.
in bioRxiv: Neuroscience on 2025-05-15 00:00:00 UTC.
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A key challenge in analyzing neuroscience datasets is the profound variability they exhibit across sessions, animals, and data modalities--i.e., heterogeneity. Several recent studies have demonstrated performance gains from pretraining neural foundation models on multi-session datasets, seemingly overcoming this challenge. However, these studies typically lack fine-grained data scaling analyses. It remains unclear how different sources of heterogeneity influence model performance as the amount of pretraining data increases, and whether all sessions contribute equally to downstream performance gains. In this work, we systematically investigate how data heterogeneity impacts the scaling behavior of neural data transformers (NDTs) in neural activity prediction. We found that explicit sources of heterogeneity, such as brain region mismatches among sessions, reduced scaling benefits of neuron- and region-level activity prediction performances. For tasks that do exhibit consistent scaling, we identified implicit data heterogeneity arising from cross-session variability. Through our proposed session-selection procedure, models pretrained on as few as five selected sessions outperformed those pretrained on the entire dataset of 84 sessions. Our findings challenge the direct applicability of traditional scaling laws to neural data and suggest that prior claims of multi-session scaling benefits may be premature. This work both highlights the importance of incremental data scaling analyses and suggests new avenues toward optimally selecting pretraining data when developing foundation models on large-scale neuroscience datasets.
in bioRxiv: Neuroscience on 2025-05-15 00:00:00 UTC.
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Mitochondria are diverse and multifaceted intracellular organelles regulating oxidative energy supply, lipid metabolism and calcium (Ca2+) signaling. In neurons the spatial sequestration of cytoplasmic Ca2+ by mitochondria plays a critical role in determining activity-dependent spine plasticity, shaping the presynaptic transmitter release characteristics and contributing to sustained action potential firing. Here, we tested the hypothesis that mitochondria at the axon initial segment (AIS) affect the microdomain cytoplasmic Ca2+ transients, thereby regulating Ca2+-dependent voltage-gated ion channels at the plasma membrane and initiation of action potentials. Using 3D electron microscopy (EM) reconstructions and virally injecting genetically encoded fluorescence indicators we visualized the ultrastructure and distribution of mitochondria selectively in thick-tufted layer 5 pyramidal neurons. We found that most mitochondria were stably clustered to the proximal AIS, while few were observed at distal sites. Simultaneous two-photon imaging of action potential-dependent cytoplasmic and mitochondrial Ca2+, combined with electrophysiological recordings showed the AIS mitochondria exhibit powerful activity-dependent cytosolic Ca2+ uptake. However, while intracellular application of the mitochondrial Ca2+ uniporter inhibitor Ru360 fully blocked mitochondrial Ca2+ import, it did not affect action potential input-output function, action potential dynamics nor the ability to produce high-frequency burst output. Together, the results indicate that AIS mitochondria are dispensable for temporal and rate encoding, suggesting that mt-Ca2+ buffering at the AIS may be involved in non-electrical roles, including AIS maintenance or axonal transport.
in bioRxiv: Neuroscience on 2025-05-15 00:00:00 UTC.
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Multiple system atrophy (MSA) is characterized by the presence of protein-rich inclusions mainly within oligodendrocytes, comprised primarily by the neuronal protein alpha-synuclein and the oligodendroglial-specific phosphoprotein TPPP/p25alpha. Mature oligodendrocytes do not normally express detectable alpha-synuclein levels, suggesting that its oligodendroglial accumulation may arise from intercellular transfer, potentially via extracellular vesicles (EVs); however, the precise role of oligodendroglial-derived EVs in MSA progression remains relatively understudied. Herein, we characterized the cargo/features and pathogenic potential of EVs released by oligodendrocytes treated with human alpha-synuclein fibrils amplified from MSA or Parkinson's disease patient brains (or human recombinant alpha-synuclein fibrils) and EVs isolated from murine and human MSA (or respective control) brains. Our findings reveal that both oligodendroglial cell- and brain-derived EVs harbor pathological alpha-synuclein and TPPP/p25alpha conformations, similar to those accumulating in human MSA brains. These EVs are readily taken up by both neurons and oligodendrocytes, driving alpha-synuclein propagation in vitro. Importantly, inoculation of these MSA-like EVs in animal models induces robust pSer129-alpha-synuclein accumulation along the nigrostriatal axis, colocalizing with markers of mature oligodendrocytes and dopaminergic neurons. These findings underscore the pivotal role of oligodendroglial-derived EVs in pathology progression and neuronal-oligodendroglial communication, positioning them as promising targets for therapeutic strategies aimed at combating alpha-synucleinopathies.
in bioRxiv: Neuroscience on 2025-05-15 00:00:00 UTC.
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Inter-brain synchrony is an essential measure for investigating social interactive behaviour via hyperscanning. While functional near-infrared spectroscopy is a unique modality for measuring this index in dynamic, real-world interactions, methods to adequately assess inter-brain relationships have not been firmly established, and the overall picture remains unclear. Consequently, in this article, we first briefly summarize analysis methods for examining social interaction by dividing them into static and dynamic measures. Among these, we focus on measures of synchrony and their assessment in correlating behaviours, conducting a simulation-based comparison and analysis. Specifically, we directly compared static and dynamic variants of wavelet transform coherence (WTC), Pearson's correlation coefficient (CC), and phase mutual information (pMI) using a real fNIRS dataset. Results showed a significant divergence between WTC and CC, while WTC and pMI exhibited similar patterns as static measures. Overall, WTC was suggested to better identify synchrony due to its non-linear, instantaneous, and robust nature. For the latter part, based on other simulation analyses, we propose a new method using generalized linear model (GLM) regression. Simulations with synthetic fNIRS data supported the effectiveness of our proposed method, which can capture the dynamic relationships between inter-brain synchrony and behaviour, even during free interaction.
in bioRxiv: Neuroscience on 2025-05-15 00:00:00 UTC.
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Reward-related processes have traditionally been ascribed to neural circuits centered on the dopamine (DA) system. While exteroceptive stimuli, such as food and drugs of abuse, are well-established activators of DA-neuron activity, growing evidence indicates that interoceptive signals also play a critical role in modulating reward. Among these, the gut-brain vagal axis has emerged as a key pathway, yet its precise contribution to mesolimbic DA-dependent signaling, dynamics and behaviors remains poorly defined. Here, we combine complementary ex vivo and in vivo approaches across multiple scales to investigate how the gut-brain vagal axis regulates DA dynamics and reward-related behaviors. We show that gut-brain vagal tone is essential for gating mesolimbic DA system activity and functions, modulating DA-dependent molecular and cellular processes, and scaling both food- and drugs-induced reinforcement. These findings challenge the traditional brain-centric view of reward processing, supporting a more unified and integrated model in which gut-derived and vagus-mediated interoceptive signals are pivotal in intrinsically shaping motivation and reinforcement. By uncovering the influence of gut-brain vagal communication on mesolimbic DA functions, this work offers new insights into the neurobiological mechanisms underlying both adaptive and maladaptive reward processes, with broad implications for eating disorders and addiction.
in bioRxiv: Neuroscience on 2025-05-15 00:00:00 UTC.
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Bang-sensitive (BS) Drosophila mutants exhibit a stereotyped pattern of seizure behavior after mechanical disturbances. We previously identified mutations in the julius seizure (jus) gene, formerly CG14509, can induce BS seizures. However, the behavioral manifestations of the seizure phenotype of the various jus mutants have not been fully characterized. Here, we developed a machine learning pipeline featuring LASC (Long short-term memory and Attention mechanism for Sequence Classification) for automatic phenotyping of jus mutant videos. LASC achieves 90% classification accuracy in distinguishing five phases: paralysis (P), tonic seizure (T), spasm (S), clonic seizure (C), and recovery (R). Applying the trained LASC model to multiple jus lines showed they use a common repertoire of seizure stages and followed the general P[->]T[->]S[->]C[->]R progression, but each genotype exhibited unique patterns of stage duration and transition probabilities. Remarkably, stage usage patterns are distinct among the mutant genotypes. These findings establish that while all jus mutants adhere to stereotyped behavioral rules, each allele generates a distinct signature in stage usage. This work demonstrates how advanced behavioral quantification can reveal previously hidden relationships between gene mutation and complex motor outputs. More broadly, the complete pipeline presented here can pave the way for high-throughput, automated drug screening for epilepsy.
in bioRxiv: Neuroscience on 2025-05-15 00:00:00 UTC.
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Difficulties in adapting learning to meet the challenges of uncertain and changing environments are widely thought to play a central role in internalizing psychopathology, including anxiety and depression. This view stems from findings linking trait anxiety and transdiagnostic internalizing symptoms to learning impairments in laboratory tasks often used as proxies for real-world behavioral flexibility. These tasks typically require learners to adjust learning rates dynamically in response to uncertainty, for instance, increasing learning from prediction errors in volatile environments. However, prior studies have produced inconsistent and sometimes contradictory findings regarding the nature and extent of learning impairments in populations with internalizing disorders. To address this, we conducted eight experiments (N = 820) using predictive inference and reversal learning tasks, and applied a bi-factor analysis to capture internalizing symptom variance shared across and differentiated between anxiety and depression. While we observed robust evidence for adaptive learning-rate modulation across participants, we found no convincing evidence of a systematic relationship between internalizing symptoms and either learning rates or task performance. These findings challenge prominent claims that learning difficulties are a hallmark feature of internalizing psychopathology and suggest that the relationship between these traits and adaptive behavior under uncertainty may be more subtle than previously thought.
in bioRxiv: Neuroscience on 2025-05-15 00:00:00 UTC.
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High-intensity interval exercise (HIIE) is known to enhance motor consolidation following physical practice (PP), but its effects on sequential motor learning (SML) through PP or motor imagery (MI) remain unclear. We examined whether HIIE modulates SML consolidation in 48 participants who learned an explicit SML task through PP or MI. Performance was assessed before and after acquisition, after HIIE or rest, and at 24 hours and 7 days. Both PP and MI improved performance, with greater gains for PP (p = 0.042), and both induced intracortical disinhibition (p = 0.03). HIIE increased BDNF (p = 0.044) and lactate levels (p < 0.001), markers typically linked to neuroplasticity, yet unexpectedly impaired SML at early (p < 0.01) and late consolidation (p < 0.05), without affecting excitability. These findings challenge the presumed coupling between exercise-induced biomarkers and behavioral gains, suggesting that HIIE may hinder consolidation when explicit components of motor learning are involved.
in bioRxiv: Neuroscience on 2025-05-15 00:00:00 UTC.
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Astronauts consistently exhibit slower movements in microgravity, even during tasks requiring rapid responses. The sensorimotor mechanisms underlying this general slowing remain debated. Two competing hypotheses have been proposed: either the sensorimotor system adopts a conservative control strategy for safety and postural stability, or the system underestimates body mass due to reduced inputs from proprioceptive receptors. To resolve the debate, we studied twelve taikonauts aboard the China Space Station performing a classical hand-reaching task. Compared to their pre-flight performance and to an age-matched control group, participants showed increased movement durations and altered kinematic profiles in microgravity. Model-based analyses of motor control parameters revealed that these changes stemmed from reduced initial force generation in the feedforward control phase followed by compensatory feedback-based corrections. These findings support the body mass underestimation hypothesis while refuting the strategic slowing hypothesis. Importantly, sensory estimate of bodily property in microgravity is biased but evaded from sensorimotor adaptation, calling for an extension of existing theories of motor learning.
in bioRxiv: Neuroscience on 2025-05-15 00:00:00 UTC.
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When confronted by a predator, most animals make innate decisions with rapid reaction times - a trait shaped by natural selection to maximize survival. However, in complex and dynamic environments, fast reactions are meaningful only when grounded in accurate judgments and correct choices, which often require cognitive control. Here, we investigate how threat intensity, reward value, and social hierarchy influence behavioral decisions in foraging mice exposed to overhead visual threats. We find that threat intensity plays a dominant role in decision-making: elevated threat levels trigger robust defensive responses, including shorter latencies to flee, increased fleeing speeds, and longer escape distances. The influence of reward is context-dependent: at low threat levels, higher reward values suppress defensive responses, leading to prolonged time in the reward zone, slower speeds, and shorter escape distances. In contrast, under high-threat conditions, increasing reward value enhances sensitivity to threats, as evidenced by shorter latencies to flee and heightened vigilance. Social hierarchy further shapes decision-making, with dominant mice exhibiting greater vigilance and a stronger preference for risk-averse behaviors compared to subordinates. To quantify the decision-making process, we developed a drift-diffusion leaky integrator model that successfully captures how mice integrate threat intensity, reward value, and vigilance into their behavioral decisions. Our findings reveal the economic and social modulation of survival decisions, offering insights into the computational mechanisms underlying the interplay between instinctive reaction and cognitive control in innate decision-making.
in bioRxiv: Neuroscience on 2025-05-15 00:00:00 UTC.
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Synaptic dysfunction is increasingly recognized as an early hallmark of Parkinson's disease (PD). Synaptojanin 1 (SJ1), a synaptic phosphoinositide phosphatase essential for synaptic vesicle recycling, is genetically linked to early-onset Parkinsonism (EOP). While germline SJ1 knockout mice are perinatal lethal, SJ1-R258Q knock-in mice recapitulate EOP-like symptoms and exhibit selective dystrophy of nigrostriatal dopamine (DA) terminals. However, these whole-body mutants limit understanding of SJ1's role in the DA system. Here, we generated DA neuron-specific SJ1 conditional KO (SJ1-DA cKO) mice. Complete SJ1 loss caused severe synaptic dystrophy throughout the striatum, indicating a cell-autonomous role of SJ1 in both substantia nigra and ventral tegmental area DA subtypes. Surprisingly, despite profound synaptic degeneration and DA deficiency, SJ1-DA cKO mice showed no overt motor deficits. Instead, we observed a robust induction of striatal tyrosine hydroxylase-positive interneurons (iTHINs), which expressed multiple DA markers and formed new connections with degenerating DA terminals, suggesting a potential local compensation. In contrast, acute SJ1 deletion in adult/aged DA neurons caused similar terminal pathology but limited iTHINs induction. Together, our findings reveal a critical role for SJ1 in maintaining DA synaptic function and uncover an adaptive striatal response to DA loss, offering insights into compensatory mechanisms relevant to PD pathogenesis.
in bioRxiv: Neuroscience on 2025-05-15 00:00:00 UTC.
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Strategic behaviour in sensorimotor adaptation tasks is typically modelled either as an error minimisation process or as a process of learning through trial-and-error. The former predicts a gradual reduction in error, until some asymptote, while the latter predicts behavioural exploration to discover an efficacious solution. An alternative explanation is that a sufficiently rich understanding of the task culminates in an 'Aha!' moment, which then allows the generation of a new solution. This predicts some period of perseveration in baseline behaviour, followed by an abrupt single-trial shift to a new strategic solution. To avoid obfuscation caused by the motor system, we investigate these hypotheses in a strategy-only aiming game, where participants aim and fire a cannon at targets. Most participants exhibited a period of baseline perseveration followed by a single-trial shift to good performance. We then applied the same analyses to reaching data from a visuomotor rotation task that inhibited implicit adaptation through delaying feedback presentation (Brudner et al., 2016). Similarly, we found that participants typically perseverated in reaching towards the target before suddenly switching, in a single trial, to good performance. These findings suggest that traditional descriptions of strategic behaviour are insufficient and must be updated if we want to understand how humans respond to sensorimotor perturbations.
in bioRxiv: Neuroscience on 2025-05-15 00:00:00 UTC.
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In the last seven years, cryo-EM maps of neuropathological fibrils from Alzheimer's disease and other neurodegenerations have been released by various authors. The first publication noted an unknown component coordinating with lysine residues in the protein, a finding recapitulated in many succeeding studies. Previous authors have emphasized difficulties in analysing this component, but current findings, using powerful visualisation software UCSF ChimeraX on all publicly available maps, indicate that the issue is tractable. Lysine-coordinating extra densities have common features, including a Y-shaped substructure, suggestive of a molecular factor in common, in neuropathological fibrils from a wide range of neurodegenerations and involving misfolded proteins beta-amyloid, alpha-synuclein, prion protein, tau and transmembrane protein 106B. A similar component, albeit in non-lysine environments, was found in neuropathological fibrils involving TAR DNA-binding protein 43 and TATA-binding protein-associated factor 15. The results suggest the existence of a common molecular factor, a predominantly anionic polymer, linking these diseases and raising the possibility of a unitary basis for Alzheimer's and other neurodegenerations. Based on evidence here, RNA is a feasible candidate for this putative common factor. Such findings raise the possibility of new diagnostic tests and treatments for these devastating diseases in the future.
in bioRxiv: Neuroscience on 2025-05-15 00:00:00 UTC.
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Stroke and dementia are common comorbidities and a growing concern causing disability in aging societies worldwide. Although anti-amyloid beta (anti-A{beta}) antibodies have recently been anticipated to relieve preclinical Alzheimer's disease pathology, we discovered that post-stroke administration of anti-A{beta} antibodies restored neural repair for stroke recovery impeded by cerebral A{beta} accumulation. Neuronal recovery-associated gene expression for stroke recovery was considerably impaired even by slight A{beta} accumulation in murine and human brain. Slight A{beta} accumulation had less impact on neurons without stroke but caused a unique myeloid immunity after an ischemic stroke that enhanced the inflammatory cascades impeding neural repair for stroke recovery. Aducanumab administration after ischemic stroke prevented formation of this malignant myeloid immunity, resolving the impairment of post-stroke neural repair caused by cerebral A{beta} accumulation. Thus, our study has revealed the ability of anti-A{beta} therapies to restore functional recovery after a stroke with cerebral A{beta} accumulation.
in bioRxiv: Neuroscience on 2025-05-15 00:00:00 UTC.
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Phrenic nerve stimulation can be used as an artificial ventilation method to reduce the adverse effects of mechanical ventilation. Detailed computational models and electromagnetic simulations are used to determine appropriate stimulation parameters. Therefore, tissue parameters have to be selected, but they vary widely in the literature. Here, we evaluated the phrenic nerve activation threshold using minimum and maximum electrical conductivity values found in the literature of each modeled neck tissue type. To calculate the phrenic nerve activation threshold, an anatomical detailed finite element model of the neck and a biophysiological nerve model were used. Considerable changes in nerve activation thresholds were found for the following tissue conductivities (with decreasing effects): muscle, skin, soft tissue, subcutaneous fat, and nerve tissue. Changes in the nerve activation threshold due to changes in skin conductivity occurred due to the bridging effect, which is an unwanted and avoidable effect during stimulation. In conclusion, fat, muscle, nerve, and soft tissue require the most accurate tissue properties and geometric representation within the model.
in bioRxiv: Neuroscience on 2025-05-15 00:00:00 UTC.
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The NAD+ hydrolase SARM1 is the central executioner of pathological axon degeneration. SARM1 is allosterically activated by an increased NMN/NAD+ ratio resulting from depletion of NAD+ or accumulation of its precursor, NMN, typically due to loss of the labile NAD+ synthetase NMNAT2 following axon injury. Another NAD+ hydrolase, PARP1, is hyperactivated by DNA damage, triggering the Parthanatos cell death pathway. We demonstrate that multiple mechanistically-distinct DNA-damaging agents lead to SARM1 activation and axon degeneration following PARP1 activation. Remarkably, SARM1 is required for key steps downstream of PARP1 activation by DNA damage that are pathognomonic of Parthanatos, including mitochondrial depolarization, nuclear translocation of AIF (apoptosis-inducing factor), and cell death. Moreover, SARM1 mediates glutamate excitotoxicity, a clinically significant pathomechanism attributed to Parthanatos. The identification of SARM1 as an essential component of neuronal Parthanatos, a major contributor to cell death in neurodegenerative disease, greatly expands the potential clinical utility of SARM1 inhibitors.
in bioRxiv: Neuroscience on 2025-05-15 00:00:00 UTC.
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Alzheimers Disease, AD, is a neurodegenerative disease characterized by amyloid plaque deposition, tau hyperphosphorylation, neuroinflammation, and cognitive decline. Our previous studies showed that combined treatment with stem cell factor, SCF, and granulocyte colony stimulating factor, GCSF, reduces AD pathology in APPPS1 mice. This study aimed to explore the molecular mechanism underlying SCF and GCSF therapeutic effects using transcriptomic analysis. Aged APPPS1 mice received daily subcutaneous injections of SCF and GCSF or vehicle for 12 days. RNA was extracted from brain tissue on day 13 for gene chip analysis. Age - matched wild - type, WT, mice served as controls. Data were analyzed using TAC, STRING v12 {middle dot} 0, Reactome, and ShinyGO 0 {middle dot} 77. A total of 45037 differentially expressed genes, DEGs, were detected. Twenty {middle dot} seven DEGs met a[≥] 2 - fold threshold in SCF and GCSF - treated versus vehicle - treated APPPS1 mice, 89 DEGs met this threshold in APPPS1 versus WT mice. SCF and GCSF treatment upregulated six immune - related genes, S100a8, S100a9, Ngp, Lcn2, Ltf, and Camp, associated with amyloid clearance, immune cell recruitment, and repair. Pathway analysis showed downregulation of IL - 2, IL - 4, IL - 7, and EGFR1, and upregulation of IL - 17 signaling, suggesting modulation of both innate and adaptive immunity. Notably, SCF and GCSF downregulated several oncogenes, including Cbl, Akap9, Kcnq1ot1, and Snhg11, highlighting an overlap between cancer and AD - related pathways. SCF and GCSF also promoted NADPH oxidase activation via Rho GTPases and showed > 400 - fold enrichment in metal ion sequestration, indicating potential metal chelation effects. These findings suggest that SCF and GCSF treatment modifies immune and metabolic pathways, reduces AD pathology, and highlights new therapeutic targets involving inflammation, metal homeostasis, and oncogenic signaling.
in bioRxiv: Neuroscience on 2025-05-15 00:00:00 UTC.
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From weaving spiders to hibernating mammals and migratory birds, nature presents numerous examples of organisms exhibiting extraordinary autonomous behaviors that ensure their self-maintenance. However, physiological needs often interact and compete. This requires living organisms to handle them as a coordinated system of internal needs rather than as isolated subsystems. We present an artificial agent equipped with a neural mass model replicating fundamental self-regulatory behaviors observed in desert lizards. Our results demonstrate that this agent not only autonomously regulates its internal temperature by navigating to areas with optimal environmental conditions, but also harmonizes this process with other internal needs, such as energy, hydration, security, and mating. This biomimetic agent outperforms a control agent lacking interoceptive awareness in terms of efficiency, fairness, and stability. Additionally, to demonstrate the flexibility of our framework, we develop a "cautious" agent that prioritizes security over other needs, achieving a Maslow-like hierarchical organization of internal needs. Together, our findings suggest that grounding robot behavior in biological principles of self-regulation provides a robust framework for designing multipurpose, intrinsically motivated agents capable of resolving trade-offs in dynamic environments.
in bioRxiv: Neuroscience on 2025-05-15 00:00:00 UTC.
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Successful navigation relies on signals that remain stable despite environmental changes. This stability can arise by constraining neuronal activity to low-dimensional subspaces. During sleep, when external input is reduced, pairwise coordination persists in the spatial navigation system, as observed for head-direction (HD) cells of the anterodorsal nucleus (ADn) and grid cells of the medial entorhinal cortex (MEC). As ADn is crucial for spatial representation in the MEC, we hypothesized that coherent HD input underlies MEC organization. To test this, we performed simultaneous recordings in the ADn and MEC during wakefulness and sleep. We found that HD cell pairs maintained stable coordination across both states, and that MEC cell coordination was partly driven by common inputs from ADn HD cells. These results suggest that MEC activity is shaped, in part, by coherent thalamic HD signals, supporting stable network organization.
in bioRxiv: Neuroscience on 2025-05-15 00:00:00 UTC.
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Moderate to severe head pain is a hallmark of recurring migraine attacks. However, it is challenging to study patients during spontaneous attacks and most research on the brain mechanisms of pain in migraine patients has been limited to the processing of painful stimuli between attacks. Here, we hypothesize that the experience of a migraine attack extends beyond the response to painful stimuli and is associated with specific impairments of the salience network (SN), which integrates sensory, emotional and cognitive information in relation to salient stimuli. To test this hypothesis, we analysed the SN dynamics of a group of patients with episodic migraine in three distinct conditions: at rest during a spontaneous migraine attack (ictal phase); while performing an imagery task aiming to elicit the experience of a previous attack, during the interictal phase; and at rest, during the interictal phase. For comparison, we also studied a group of healthy controls in three matching conditions, including rest as well as an imagery task of a (non-migraine) head pain experience. We collected functional magnetic resonance imaging (fMRI) data and used a dynamic functional connectivity (dFC) analysis to examine the temporal features of the SN from a total of 78 samples. Compared to healthy controls, the SN had a significantly shorter lifetime in patients during the pain imagery task, but not during a migraine attack or interictal resting state. Our results support the disruption of the SN in migraine, and indicate that pain imagery may be a useful paradigm for isolating the emotional and cognitive aspects of pain and investigating SN dynamics.
in bioRxiv: Neuroscience on 2025-05-15 00:00:00 UTC.
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in Cerebral Cortex on 2025-05-15 00:00:00 UTC.
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in Journal of Neuroscience on 2025-05-14 16:30:32 UTC.
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The mammalian circadian system regulates all biological processes, thereby ensuring optimal function at the appropriate times of day. Animal studies that examine neurobehavioral processes at different times of day, including during the animal's active phase, may provide important new biomedical insights. A logistical problem for the study of nocturnal laboratory rodents is the potential confounding influence of nighttime light exposure, which may cause circadian disruption and alteration of behavior. The historical solution has been to use red light illumination, which is widely believed to be undetected by the rodent visual system. However, some recent studies have questioned this belief. We, therefore, tested the effects of nighttime exposure to commonly used red light conditions on the circadian non-image forming and the image forming visual systems of female and male laboratory rodents. We found that brief dim red light exposure to a range of red light wavelengths produces strong activation of the suprachiasmatic nucleus master clock, rapid suppression of melatonin secretion, and a subsequent phase shift in daily activity onsets. We also found in an operant behavioral task that rats are able to detect long wavelengths of red light, but not near-infrared light. Thus, both the non-image and image forming visual systems of laboratory rodents are responsive to red light conditions that are often used in animal research. The use of red light for laboratory rodent research and animal care should be carefully considered in terms of its possible confounding influences on research objectives.
in Journal of Neuroscience on 2025-05-14 16:30:32 UTC.
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Recently discovered constituents of the brain waves—the oscillons—provide a high-resolution representation of the extracellular field dynamics. Here, we study the most robust, highest-amplitude oscillons recorded in actively behaving male rats, which underlie the traditional -waves. The resemblances between -oscillons and the conventional -waves are manifested primarily at the ballpark level—mean frequencies, mean amplitudes, and bandwidths. In addition, both hippocampal and cortical oscillons exhibit a number of intricate, behavior-attuned, transient properties that suggest a new vantage point for understanding the -rhythms’ structure, origins and functions. In particular, we demonstrate that oscillons are frequency-modulated waves, with speed-controlled parameters, embedded into a weak noise background. We also use a basic model of neuronal synchronization to contextualize and to interpret the oscillons. The results suggest that the synchronicity levels in physiological networks are fairly low and are modulated by the animal’s physiological state.
in Journal of Neuroscience on 2025-05-14 16:30:32 UTC.
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The striatum is thought to switch flexibly between multiple converging inputs to support adaptive behavior. The "communication through coherence" (CTC) hypothesis is a potential mechanism to implement such a flexible switching. For CTC to work in the striatum, striatal excitability must show rhythmic fluctuations, such as those related to the phase of the striatal local field potential (LFP). To test this fundamental requirement, we delivered a constant input stimulus to ChR2-expressing striatal fast-spiking PV+ interneurons (FSIs) in head-fixed awake mice (PV-Cre:Ai-32, n = 18, 9 female) and determined whether the response to this stimulus varied with LFP phase. We found that approximately one-third (41.2%) of FSIs exhibited significant phase-dependent excitability in at least one LFP frequency band. Phase-dependent excitability was most prominent in the delta (2–5 Hz) frequency band, both in terms of prevalence (23.5% of FSIs sampled) and magnitude (phase modulation strength: 22% of average response). The most excitable phase tended to align with endogenous phase-locking, again most clearly in the delta band. These results bolster the functional relevance of the striatal field potential and spike-field relationships and provide proof-of-principle support for the possibility of CTC in the striatum.
in Journal of Neuroscience on 2025-05-14 16:30:32 UTC.
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GABAA receptors containing subunits have been shown to mediate tonic/slow inhibition in the CNS. These receptors are typically found extrasynaptically and are activated by relatively low levels of ambient GABA in the extracellular space. In the mouse neocortex, subunits are expressed by some pyramidal cells as well as on parvalbumin-positive (PV+) interneurons. An important function of PV+ interneurons is the organization of coordinated network activity that can be measured by EEG. However, it remains unclear what role tonic/slow inhibitory control of PV+ neurons may play in shaping oscillatory activity. After validating expected functional loss of -associated current in cortex of PV cKO mice of both sexes, we performed EEG recordings to survey network activity across wake and sleep states. PV cKO mice showed altered spectral content of EEG during NREM and REM sleep that was a result of increased oscillatory activity in NREM and the emergence of transient high-amplitude bursts of theta-frequency activity during REM. Viral reintroduction of Gabrd to PV+ interneurons in PV cKO mice rescued REM EEG phenotypes, supporting an important role for subunit-mediated inhibition of PV+ interneurons for maintaining normal REM cortical oscillations.
in Journal of Neuroscience on 2025-05-14 16:30:32 UTC.
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The orbitofrontal cortex (OFC) plays a crucial role in value-based decisions. While much is known about how OFC neurons represent values, far less is known about information encoded in OFC local field potentials (LFPs). LFPs are important because they can reflect subthreshold activity not directly coupled to spiking and because they are potential targets for less invasive forms of brain–machine interface (BMI). We recorded neural activity in the OFC of male macaques performing a two-option value-based decision task. We compared the value- and decision-coding properties of high-gamma LFPs (HG, 50–150 Hz) to the coding properties of spiking multiunit activity (MUA) recorded concurrently on the same electrodes. HG and MUA both represented the values of decision targets, but HG signals had value-coding features that were distinct from concurrently measured MUA. On average HG amplitude increased monotonically with value, whereas in MUA the value encoding was net neutral on average. HG encoded a signal consistent with a comparison between target values, a signal which was negligible in MUA. In individual channels, HG could predict choice outcomes more accurately than MUA; however, when channels were combined in a population-based decoder, MUA was more accurate than HG. In summary, HG signals reveal value-coding features in OFC that could not be observed from spiking activity, including representation of value comparisons and more accurate behavioral predictions. These results have implications for the role of OFC in value-based decisions and suggest that high-frequency LFPs may be a viable—or even preferable—target for BMIs to assist cognitive function.
in Journal of Neuroscience on 2025-05-14 16:30:32 UTC.
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Adaptive behavior rests on predictions based on statistical regularities in the environment. Such regularities pertain to stimulus contents ("what") and timing ("when"), and both interactively modulate sensory processing. In speech streams, predictions can be formed at multiple hierarchical levels of contents (e.g., syllables vs words) and timing (faster vs slower time scales). Whether and how these hierarchies map onto each other remains unknown. Under one hypothesis, neural hierarchies may link "what" and "when" predictions within sensory processing areas: with lower versus higher cortical regions mediating interactions for smaller versus larger units (syllables vs words). Alternatively, interactions between "what" and "when" regularities might rest on a generic, sensory-independent mechanism. To address these questions, we manipulated "what" and "when" regularities at two levels—single syllables and disyllabic pseudowords—while recording neural activity using magnetoencephalography (MEG) in healthy volunteers (N = 22). We studied how neural responses to syllable and/or pseudoword deviants are modulated by "when" regularity. "When" regularity modulated "what" mismatch responses with hierarchical specificity, such that responses to deviant pseudowords (vs syllables) were amplified by temporal regularity at slower (vs faster) time scales. However, both these interactive effects were source-localized to the same regions, including frontal and parietal cortices. Effective connectivity analysis showed that the integration of "what" and "when" regularity selectively modulated connectivity within regions, consistent with gain effects. This suggests that the brain integrates "what" and "when" predictions that are congruent with respect to their hierarchical level, but this integration is mediated by a shared and distributed cortical network.
in Journal of Neuroscience on 2025-05-14 16:30:32 UTC.
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High-level perception results from interactions between hierarchical brain systems responsive to gradually increasing feature complexities. During reading, the initial evaluation of simple visual features in the early visual cortex (EVC) is followed by orthographic and lexical computations in the ventral occipitotemporal cortex (vOTC). While similar visual regions are engaged in tactile Braille reading in congenitally blind people, it is unclear whether the visual network maintains or reorganizes its hierarchy for reading in this population. Combining fMRI and chronometric transcranial magnetic stimulation (TMS), our study revealed a clear correspondence between sighted and blind individuals (both male and female) on how their occipital cortices functionally supports reading and speech processing. Using fMRI, we first observed that vOTC, but not EVC, showed an enhanced response to lexical vs nonlexical information in both groups and sensory modalities. Using TMS, we further found that, in both groups, the processing of written words and pseudowords was disrupted by the EVC stimulation at both early and late time windows. In contrast, the vOTC stimulation disrupted the processing of these written stimuli only when applied at late time windows, again in both groups. In the speech domain, we observed TMS effects only for meaningful words and only in the blind participants. Overall, our results suggest that, while the responses in the deprived visual areas might extend their functional response to other sensory modalities, the computational gradients between early and higher-order occipital regions are retained, at least for reading.
in Journal of Neuroscience on 2025-05-14 16:30:32 UTC.
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Aquatic animals need tightly choreographed movements to efficiently navigate through open waters. Radially symmetric animals, like jellyfish, face the additional challenge of having to respond to regionalized sensory stimuli at the margin of their bell with an orchestrated motor response that initiates predation or escape. The nerve net of hydrozoan jellyfish comprises a condensed ring of electrically coupled neurons, that process sensory input and control the motor output. Here, we aim to understand the coupling of neural activity and motor response by developing a biophysical computational model of the swimming-motor-net of a hydrozoan jellyfish and let it control a swimming jellyfish in a fluid simulation. We find that the neuron activity can synchronize while the signal travels around the ring, eventually triggering a bidirectional wave of activation in the muscles. This mechanism explains seemingly contradicting electrophysiological experiments and minimizes muscle contraction time. Hydrodynamical simulations demonstrate that this setup enables symmetric movement even if neural input is highly asymmetric. We hypothesize that the development of this ring structure supports the jet propulsion by which hydrozoan jellyfish swim. These findings show the importance of considering whole body anatomy and movement when investigating neural design.
in Journal of Neuroscience on 2025-05-14 16:30:32 UTC.
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Clinical trials with transcranial direct current stimulation (tDCS) use weak electric fields that have yet to demonstrate measurable behavioral effects in animal models. We hypothesized that weak stimulation will produce sizable effects, provided it is applied concurrently with behavioral training and repeated over multiple sessions. We tested this in a rodent model of dexterous motor skill learning using a pellet-reaching task in ad libitum behaving rats. The task was automated to minimize experimenter bias. We measured field magnitudes intracranially to calibrate the stimulation current. Male rats were trained for 20 min with concurrent epicranial tDCS over 10 daily sessions. We developed a new electrode montage that enabled stable stimulation over the 10 sessions with a field intensity of 2 V/m at the motor cortex. Behavior was recorded with high-speed video to quantify reaching dynamics. We also measured motor-evoked potentials (MEPs) bilaterally with epidural microstimulation. The number of successful reaches improved across days of training, and the rate of learning was higher in the anodal group as compared with sham-control animals (F(1) = 7.12; p = 0.008; N = 24). MEPs were not systematically affected by tDCS. Post hoc analysis suggests that tDCS modulated motor learning only for right-pawed animals, improving success of reaching but limiting stereotypy in these animals. Repeated and concurrent anodal tDCS can boost motor skill learning at clinically relevant field intensities. In this animal model, the effect interacted with paw preference and was not associated with corticospinal excitability.
in Journal of Neuroscience on 2025-05-14 16:30:32 UTC.
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The detection of temporally unpredictable visual targets depends on the preceding phase of alpha oscillations (~7–12 Hz). In audition, however, such an effect seemed to be absent. Due to the transient nature of its input, the auditory system might be particularly vulnerable to information loss that occurs if relevant information coincides with the low-excitability phase of the oscillation. We therefore hypothesized that effects of oscillatory phase in audition will be restored if auditory events are made task irrelevant and information loss can be tolerated. To this end, we collected electroencephalography (EEG) data from 29 human participants (21F) while they detected pure tones at one sound frequency and ignored others. Confirming our hypothesis, we found that the neural response to task-irrelevant but not to task-relevant tones depends on the prestimulus phase of neural oscillations. Alpha oscillations modulated early stages of stimulus processing, whereas theta oscillations (~3–7 Hz) affected later components, possibly related to distractor inhibition. We also found evidence that alpha oscillations alternate between sound frequencies during divided attention. Together, our results suggest that the efficacy of auditory oscillations depends on the context they operate in and demonstrate how they can be employed in a system that heavily relies on information unfolding over time.
in Journal of Neuroscience on 2025-05-14 16:30:32 UTC.
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During wakefulness, external stimuli elicit conscious experiences. In contrast, dreams and drug-induced dissociated states are characterized by vivid internally generated conscious experiences and reduced ability to perceive external stimuli. Understanding the physiological distinctions between normal wakefulness and dissociated states may therefore disambiguate signatures of responsiveness to external stimuli from those that underlie conscious experience. The hypothesis that conscious experiences are associated with brain criticality has received considerable theoretical and experimental support. Consistent with this hypothesis, statistical signatures of criticality are similar in normal wakefulness and dissociative states but are abolished in dreamless sleep and under anesthesia. Thus, while statistical measures of criticality are associated with the ability to have conscious experience, they do not readily distinguish between perception of the external world from internally generated percepts. Here, we investigate distinct, dynamical, signatures of criticality during escalating ketamine doses in high-density EEG in human male volunteers. We show that during normal wakefulness, EEG is found at a critical point between damped and exploding oscillations. With increasing doses of ketamine, as dissociative symptoms intensify, activity is progressively stabilized—most prominently at higher frequencies. We also show that stabilization is a more reliable marker of the effects of ketamine than conventional measures such as power spectra. These findings suggest that stabilization of cortical dynamics correlates with decreased ability to respond to and perceive external stimuli rather than the ability to have conscious experiences per se. Altogether, these results suggest that combining statistical and dynamical criticality measures may distinguish wakefulness, dissociation, and unconsciousness.
in Journal of Neuroscience on 2025-05-14 16:30:32 UTC.
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The unfolding of neural population activity can be described as a dynamical system. Stability in the latent dynamics that characterize neural population activity has been linked with consistency in animal behavior, such as motor control or value-based decision-making. However, whether such characteristics of neural dynamics can explain visual perceptual behavior is not well understood. To study this, we recorded V4 populations in two male monkeys engaged in a non-match-to-sample visual change-detection task that required sustained engagement. We measured how the stability in the latent dynamics in V4 might affect monkeys’ perceptual behavior. Specifically, we reasoned that unstable sensory neural activity around dynamic attractor boundaries may make animals susceptible to taking incorrect actions when withholding action would have been correct ("false alarms"). We made three key discoveries: (1) greater stability was associated with longer trial sequences; (2) false alarm rate decreased (and response times slowed) when neural dynamics were more stable; and (3) low stability predicted false alarms on a single-trial level, and this relationship depended on the position of the neural activity within the state space, consistent with the latent neural state approaching an attractor boundary. Our results suggest the same outward false alarm behavior can be attributed to two different potential strategies that can be disambiguated by examining neural stability: (1) premeditated false alarms that might lead to greater stability in population dynamics and faster response time and (2) false alarms due to unstable sensory activity consistent with misperception.
in Journal of Neuroscience on 2025-05-14 16:30:32 UTC.
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Leucine zipper protein 1 (LUZP1) functions in the maintenance and dynamics of the cytoskeleton by interacting with actin and microtubules. Deficiency or mutation of LUZP1 is associated with brain developmental disorders; however, its precise role in brain function remains unclear. We showed that LUZP1 localizes to actin and is highly expressed in CaMKIIα-expressing neurons within the mouse hippocampal dentate gyrus. Depletion of LUZP1 impedes dendritic spine maturation, which is characterized by excess immature filopodia and loss of mature mushroom spines both in vitro and in vivo. LUZP1 knockdown reduces spontaneous electrical activity and synaptic plasticity in hippocampal neurons. Conditional deletion of LUZP1 in CaMKIIα-expressing neurons causes impaired learning and memory behavior in mice of both sexes. Mechanistically, LUZP1 control dendritic maturation by directly interacting with filamin A and modulating the Rac1-PAK1 signaling pathway. These findings shed light on the role of LUZP1 in regulating synaptic plasticity and brain function.
in Journal of Neuroscience on 2025-05-14 16:30:32 UTC.
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Established models of motor skill learning posit that early stages of learning are dominated by an attentionally demanding, effortful mode of control supported by associative corticostriatal circuits involving the dorsolateral prefrontal cortex (DLPFC). As skill develops, automatic and "effortless" performance coincides with a transition to a reliance on sensorimotor circuits that include primary motor cortex (M1). However, the dynamics of how control evolves during the transition from novice to expert are currently unclear. This lack of clarity is due, in part, to the fact that most motor learning studies comprise a limited number of training sessions and rely on correlative techniques such as neuroimaging. Here, we train human participants (both sexes) on a discrete motor sequencing task over the course of 6 weeks, followed by an assessment of the causal roles of DLPFC and M1 at varying levels of expertise. We use repetitive transcranial magnetic stimulation to transiently disrupt activity in these regions immediately prior to performance in separate sessions. Our results confirm the dissociable importance of DLPFC and M1 as training progresses. DLPFC stimulation leads to larger behavioral deficits for novice skills than more highly trained skills, while M1 stimulation leads to relatively larger deficits as training progresses. However, our results also reveal that prefrontal disruption causes performance deficits at all levels of training. These findings challenge existing models and indicate an evolving rather than a strictly diminishing role for DLPFC throughout learning.
in Journal of Neuroscience on 2025-05-14 16:30:32 UTC.
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in Journal of Neuroscience on 2025-05-14 16:30:32 UTC.
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Lucid dreaming (LD) is a state of conscious awareness of the ongoing oneiric state, predominantly linked to REM sleep. Progress in understanding its neurobiological basis has been hindered by small sample sizes, diverse EEG setups, and artifacts like saccadic eye movements. To address these challenges in characterizing the electrophysiological correlates of LD, we introduced an adaptive multistage preprocessing pipeline, applied to human data (male and female) pooled across laboratories, allowing us to explore sensor- and source-level markers of LD. We observed that, while sensor-level differences between LD and nonlucid REM sleep were minimal, mixed-frequency analysis revealed broad low alpha to gamma power reductions during LD compared with wakefulness. Source-level analyses showed significant beta power (12–30 Hz) reductions in right central and parietal areas, including the temporoparietal junction, during LD. Moreover, functional connectivity in the alpha band (8–12 Hz) increased during LD compared with nonlucid REM sleep. During initial LD eye signaling compared with the baseline, source-level gamma1 power (30–36 Hz) increased in right temporo-occipital regions, including the right precuneus. Finally, functional connectivity analysis revealed increased interhemispheric and inter-regional gamma1 connectivity during LD, reflecting widespread network engagement. These results suggest that distinct source-level power and connectivity patterns characterize the dynamic neural processes underlying LD, including shifts in network communication and regional activation that may underlie the specific changes in perception, memory processing, self-awareness, and cognitive control. Taken together, these findings illuminate the electrophysiological correlates of LD, laying the groundwork for decoding the mechanisms of this intriguing state of consciousness.
in Journal of Neuroscience on 2025-05-14 16:30:32 UTC.
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Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive method that has been used to treat various brain disorders. The modulatory effects of rTMS can be adjusted by changing the repetition patterns. Theta-burst magnetic stimulation (TBS) is a magnetic stimulation pattern that can induce long-lasting modulatory effects with a short stimulation period. However, its effects on auditory brain regions remain unclear because of a lack of animal studies in which invasive techniques allow for a detailed exploration of the underlying neural mechanisms. In the current study, we investigated the effects of TBS on the C57BL/6J mouse auditory cortex using a custom-built 7 mm magnetic stimulation coil. Extracellular recordings were made before, during, and after the application of intermittent TBS (iTBS), continuous TBS (cTBS), or sham stimulation. Local field potential amplitudes were increased for 5–20 min post-iTBS compared with the sham condition and were decreased at 10 min post-cTBS compared with the sham condition. The bidirectional modulatory effects observed in our study are consistent with previous findings from other brain regions. Additionally, multiunit activities were significantly altered in cortical layers 2/3 and 4 but not layer 5, indicating that the modulatory effects were localized to the surface region of the auditory cortex. Interestingly, in the iTBS group, the amplitude of average spike waveforms increased with a 15 min delay. Our findings provide physiological evidence of TBS modulation of the rodent auditory cortex and may guide future research seeking to optimize rTMS for modulating hearing abilities.
in eNeuro on 2025-05-14 16:30:17 UTC.
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Histone deacetylase 3 (HDAC3) is one of the most highly expressed HDACs in the brain shown to be a negative regulator of long-term memory formation. HDAC3 has also been shown to be involved in cocaine-associated behaviors, demonstrated by manipulations in the nucleus accumbens. Previous studies have demonstrated that expression of a dominant negative of a key HDAC3 target gene, nuclear receptor subfamily 4 group A member 2 (NR4A2), in cholinergic neurons of the medial habenula (MHb) blocked reinstatement of cocaine-induced conditioned place preference (CPP) as well as cue-induced intravenous self-administration (IVSA). Together, these findings suggested that HDAC3 would also be important for MHb-dependent reinstatement of CPP and IVSA, which we examined in this study. Contrary to our hypothesis, our results found that expression of an HDAC3 deacetylase dead point mutant within the cholinergic neurons of the mouse MHb had no effect on reinstatement or other cocaine-induced behaviors.
in eNeuro on 2025-05-14 16:30:17 UTC.
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Introduction Oro-facial pain presents a significant diagnostic challenge due to its diverse etiologies, including dental, musculoskeletal, neurological, sinus-related, and mucosal conditions. The overlapping clinical symptoms often complicate the diagnostic process, especially in primary care settings. While traditional methods such as symptom evaluation and basic clinical tests are routinely used, the diagnostic accuracy of these approaches remains unclear across various conditions. This underscores the need for a comprehensive evidence synthesis to evaluate the performance of clinical signs, symptoms, and point-of-care (POC) tests. Protocol This protocol outlines a suite of eight systematic reviews and meta-analyses, each focused on a specific cause of oro-facial pain: pulpal/periapical pathology, periodontal disease, temporomandibular disorders, maxillary sinusitis, neuralgias, salivary gland disorders, bone-related pathologies, and mucosal conditions. The reviews will include cross-sectional, cohort, and diagnostic randomized controlled trials that compare one or more index tests to recognized reference standards such as histological evaluation, advanced imaging, or consensus-based clinical diagnosis. A comprehensive literature search will be conducted across multiple databases. Methodological quality will be assessed using the QUADAS-2 tool, and statistical analysis will include meta-analytic models (bivariate and HSROC) to synthesize diagnostic performance measures including sensitivity, specificity, and likelihood ratios. Discussion This review suite aims to bridge the knowledge gap in diagnostic accuracy of clinical and POC tests used in the evaluation of oro-facial pain. By systematically appraising and synthesizing available evidence, the findings are expected to guide clinicians in selecting the most reliable diagnostic tools tailored to specific conditions. Ultimately, this work may support better diagnostic decision-making, reduce unnecessary interventions, and improve patient outcomes in both general and specialized dental care settings.
in F1000Research on 2025-05-14 15:20:48 UTC.
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Background Self-harm is a serious public health problem across the world, impacting not only people who self-harm but also their families and society as a whole through higher resource costs and productivity losses. This review was conducted among the general Saudi population to investigate the prevalence of non-suicidal self-injury (NSSI) and factors affecting it. Methods An electronic literature search of four major databases, PubMed, Web of Science, Scopus Science Direct, and Google Scholar, was conducted to include eligible studies. All studies reporting NSSI or relevant to the subject were included. Results A total of five articles with 1758 participants were included. The lowest recorded NSSI prevalence was 0.47% while the highest was 10.2%, both in Al-Khobar city. Conclusion We recorded a relatively low but increasing prevalence of NSSI. The review also demonstrated that NSSI was more common among the female population and young people. Self-poisoning, including drug overdose, was the most prevalent method of self-harm. Interpersonal difficulties, marital problems, academic failure, and family and self-conflicts were common motivating factors of NSSI.
in F1000Research on 2025-05-14 15:17:45 UTC.
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Background Sushruta (600 B.C.) described a condition called “Vidari” linked with progressive narrowing of mouth, depigmentation of the oral mucosa, and pain on taking food, oral submucous fibrosis (OSMF). With an overall Indian prevalence rate of between 0.2–0.5%, OSMF is primarily found in India and Southeast Asia, according to global estimations. Patients with OSMF need regular follow-ups and to maintain this follow-up it is not always possible for the patient to visit a dental clinic. Hence developing a smartphone-based application for the follow-up of OSMF will be of great value to the patients. The study aims to evaluate the effectiveness of a smartphone application on OSMF self-examination in the follow-up of patients. Methods There will be three phases of the research. The first phase will be the development of a smartphone-based application for the follow-up of patients with OSMF. The second phase will be distribution and training the patients regarding the usage of the application and the third phase will be evaluating the effectiveness of the smartphone application in maintaining the follow-up of the patients. Expected results The follow-up of patients with OSMF is expected to be better and feasible using a smartphone application as compared to regular Outpatient Department-based follow-up. Conclusions Designing a mobile application for the ease of users presents difficulties since it must take user-friendliness and accessibility into account, which influences how well the application is received by users. In addition to follow-up, the smartphone-based application promotes the awareness towards Self-examination and knowledge in OSMF patients. Thus, it will act as an educational tool providing information, to enhance OSMF screening practice. CTRI registration CTRI/2023/06/054514 (registration pending).
in F1000Research on 2025-05-14 15:15:43 UTC.
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by Sneha Aenugu, John P. O’Doherty
Extended goals necessitate extended commitment. We address how humans select between multiple goals in a temporally extended setting. We probe whether humans engage in prospective valuation of goals by estimating which goals are likely to yield future success and choosing those, or whether they rely on a less optimal retrospective strategy, favoring goals with greater accumulated progress even if less likely to result in success. To address this, we introduce a novel task in which goals need to be persistently selected until a set target is reached to earn an overall reward. In a series of experiments, we show that human goal selection involves a mix of prospective and retrospective influences, with an undue bias in favor of retrospective valuation. We show that a goal valuation model utilizing the concept of ‘momentum’, where progress accrued toward a goal builds value and persists across trials, successfully explains human behavior better than alternative frameworks. Our findings thus suggest an important role for momentum in explaining the valuation process underpinning human goal selection.
in PLoS Computational Biology on 2025-05-14 14:00:00 UTC.
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by Lion Schulz, Yannick Streicher, Eric Schulz, Rahul Bhui, Peter Dayan
From the intimate realm of personal interactions to the sprawling arena of political discourse, discerning the trustworthy from the dubious is crucial. Here, we present a novel behavioral task and accompanying Bayesian models that allow us to study key aspects of this learning process in a tightly controlled setting. In our task, participants are confronted with several different types of (mis-)information sources, ranging from ones that lie to ones with biased reporting, and have to learn these attributes under varying degrees of feedback. We formalize inference in this setting as a doubly Bayesian learning process where agents simultaneously learn about the ground truth as well as the qualities of an information source reporting on this ground truth. Our model and detailed analyses reveal how participants can generally follow Bayesian learning dynamics, highlighting a basic human ability to learn about diverse information sources. This learning is also reflected in explicit trust reports about the sources. We additionally show how participants approached the inference problem with priors that held sources to be helpful. Finally, when outside feedback was noisier, participants still learned along Bayesian lines but struggled to pick up on biases in information. Our work pins down computationally the generally impressive human ability to learn the trustworthiness of information sources while revealing minor fault lines when it comes to noisier environments and news sources with a slant.
in PLoS Computational Biology on 2025-05-14 14:00:00 UTC.
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by Salwan Butrus, Hannah R. Monday, Christopher J. Yoo, Daniel E. Feldman, Karthik Shekhar
Mouse whisker somatosensory cortex (wS1) is a major model system to study the experience-dependent plasticity of cortical neuron physiology, morphology, and sensory coding. However, the role of sensory experience in regulating neuronal cell type development and gene expression in wS1 remains poorly understood. We assembled a transcriptomic atlas of wS1 during postnatal development comprising 45 molecularly distinct neuronal types that can be grouped into eight excitatory and four inhibitory neuron subclasses. Between postnatal day (P) 12, the onset of active whisking, and P22, when classical critical periods close, ~ 250 genes were regulated in a neuronal subclass-specific fashion when whisker experience was normal. At the resolution of neuronal types, only the composition of layer (L) 2/3 glutamatergic neurons, but not other neuronal types, changed substantially between P12 and P22. These postnatal compositional changes in L2/3 neuronal types resemble those observed previously in the primary visual cortex (V1), and the temporal gene expression changes were also highly conserved between the regions. Unlike V1, however, cell type maturation in wS1 is not substantially dependent on sensory experience, as 10-day full-face whisker deprivation from P12 to P22 did not influence the transcriptomic identity nor composition of L2/3 neuronal types. A one-day competitive whisker deprivation protocol from P21 to P22 also did not affect cell type identity but induced moderate changes in plasticity-related gene expression. Thus, developmental maturation of cell types is similar in V1 and wS1, but sensory deprivation minimally affects cell type development in wS1.
in PLoS Biology on 2025-05-14 14:00:00 UTC.
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by Paula Sofía Yunes-Leites, Yilin Sun, Sara Martínez-Martínez, Álvaro Alfayate, Marta Toral, María José Méndez-Olivares, Ángel Colmenar, Ana Isabel Torralbo, Dolores López-Maderuelo, Sergio Mateos-García, David N. Cornfield, Jesús Vázquez, Juan Miguel Redondo, Miguel R. Campanero
Angiotensin-II (Ang-II) drives pathological vascular wall remodeling in hypertension and abdominal aortic aneurysm (AAA) through mechanisms that are not completely understood. Previous studies showed that the phosphatase activity of calcineurin (Cn) mediates Ang-II-induced AAA, but the cell type involved in the action of Cn in AAA formation remained unknown. Here, by employing newly created smooth muscle cell (SMC)-specific and endothelial cell (EC)-specific Cn-deficient mice (SM-Cn−/− and EC-Cn−/− mice), we show that Cn expressed in SMCs, but not ECs, was required for Ang-II-induced AAA. Unexpectedly, SMC Cn also played a structural role in the early onset and maintenance of Ang-II-induced hypertension, independently of its known phosphatase activity. Among the signaling pathways activated by Ang-II, Cn signaling is essential in SMCs, as nearly 90% of the genes regulated by Ang-II in the aorta required Cn expression in SMCs. Cn orchestrated, independently of its enzymatic activity, the induction by Ang-II of a transcriptional program closely related to SMC contractility and hypertension. Cn deletion in SMCs, but not its pharmacological inhibition, impaired the regulation of arterial contractility. Among the genes whose regulation by Ang-II required Cn expression but not its phosphatase activity, we discovered that Serpine1 was critical for Ang-II-induced hypertension. Indeed, pharmacological inhibition of PAI-1, the protein encoded by Serpine1, impaired SMCs contractility and readily regressed hypertension. Mechanistically, Serpine1 induction was mediated by Smad2 activation via the structural role of Cn. These findings uncover an unexpected role for Cn in vascular pathophysiology and highlight PAI-1 as a potential therapeutic target for hypertension.
in PLoS Biology on 2025-05-14 14:00:00 UTC.
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Journal of Neurophysiology, Ahead of Print.
in Journal of Neurophysiology on 2025-05-14 12:10:40 UTC.
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in Annals of Neurology on 2025-05-14 10:18:36 UTC.
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in Annals of Neurology on 2025-05-14 10:18:06 UTC.
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Author(s): Keerti Chauhan, Amit Raj Singh, Sanjay Kumar, and Rony Granek
The nonequilibrium behavior of many bio-materials under classical jump experiments, in which the system is subject to an instantaneous increase of controlled intensive variables, is poorly studied. Here, we study the response to such jumps of a short DNA hairpin, that possesses a bubble-generating b…
[Phys. Rev. E 111, 054407] Published Wed May 14, 2025
in Physical Review E: Biological physics on 2025-05-14 10:00:00 UTC.
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Background There has been an increase in prescription drug misuse globally, with individuals using medications in ways other than prescribed. This can cause serious health risks, including death. Gender differences in prescription drug misuse have been observed with women misusing medication more than men. Methods We conducted a qualitative study in KwaZulu-Natal, South Africa, to explore the extent of this problem providing preliminary findings for a larger study that will inform relevant interventions and health policy responses. We conducted 12 in-depth interviews, and four focus group discussions with young women and girls aged 17-25 years. Thematic content analysis was conducted. Results Our results indicated that family and peer influence contributed to prescription drug misuse, despite participants' negative attitudes toward this due to the associated health risks. Secondly, social and environmental factors such as easy access to prescription drugs within the community contributed to misuse. Conclusion Targeted awareness and intervention programs for young women and girls are needed to highlight the health risks and dangers associated with this problem.
in F1000Research on 2025-05-14 09:55:11 UTC.
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Background Inflammation is the key contributor to the development of atherosclerotic plague. This study aims to evaluate the protective and autophagy induction properties of pterostilbene and sitagliptin on modulating the degree of atherosclerosis in rabbit models treated with an atherogenic diet. Methods 80 rabbits were randomly placed into one of four study groups (20 in each group): normal control diet (NC) fed normal diet for eight weeks, atherogenic control (AC) fed atherogenic diet for eight weeks, pterostilbene treated group (PT) fed atherogenic diet with pterostilbene (at 10 mg/kg/day) orally daily for eight weeks, and sitagliptin treated group (ST) fed atherogenic diet with sitagliptin (at 12 mg/kg/day) orally daily for eight weeks. Results While serum lipids and F2-isoprostane were elevated significantly in the AC study cohort compared to NC study cohort, (P < 0.001), both pterostilbene and sitagliptin supplementations provided significant improvements in serum lipid parameters and F2-isoprostane in the PT study cohort and ST study cohort, respectively, when compared to the AC study cohort, (P<0.001). Total cholesterol, triglycerides and LDL levels were significantly reduced among the PT and ST study cohorts as compared to the AC study cohort. This was coupled with a significant rise in LC3B levels (marker of tissue autophagy) among the PT study cohort and the ST study cohort, as compared to the AC study cohort, (P < 0.001). The RNA expression of mTORC1 was reduced significantly at both PT study cohort and ST study cohort, (P<0.001). Pterostilbene supplementation induced a significant reduction in tissue expression of PI3K and AKT, (P<0.01), while sitagliptin induced significant increase in 5’ adenosine monophosphate-activated protein kinase (AMPK) levels, (P<0.001). Conclusions The results indicate that pterostilbene and/or sitagliptin supplementation can significantly improve the outcome of atherosclerosis due to their effects on the inflammatory pathways which hinder the progression of atherosclerotic plaque formation.
in F1000Research on 2025-05-14 09:54:11 UTC.
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Background This study aimed to determine the accuracy of CYFRA 21-1 using urine creatinine correction (CYFRA/Cr) as a biomarker of endometriosis. Methods This study includes 73 patients from the Indonesian population, with 38 endometriosis and 35 non-endometriosis patients based on laparoscopy. Urine detection of CYFRA 21-1 was done by ELISA method and corrected by urine creatinine constant factor (CYFRA/Cr). Urine creatinine us detected using the ECLIA method. Results The CYFRA/Cr ratio was identified in the proliferative and secretory phases. CYFRA 21-1 and CYFRA/Cr levels were significantly higher in endometriosis and were higher in the proliferative phase compared to the secretory phase. The best accuracy was obtained in CYFRA which was corrected with urine creatinine in the proliferative phase with a sensitivity value, specificity, and cutoff value of 94.7%, 94.4%, and of 3,547.99 ng/gr, respectively, compared to CYFRA 21-1 urine levels without correction of creatinine. Conclusions The CYFRA to creatinine urine ratio detected in the proliferative phase showed the optimum sensitivity and specificity compared to CYFRA 21-1 spot urine. It has the potential to be a biomarker of endometriosis.
in F1000Research on 2025-05-14 09:51:08 UTC.
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Science Advances, Volume 11, Issue 20, May 2025.
in Science Advances on 2025-05-14 07:00:00 UTC.
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Science Advances, Volume 11, Issue 20, May 2025.
in Science Advances on 2025-05-14 07:00:00 UTC.
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Science Advances, Volume 11, Issue 20, May 2025.
in Science Advances on 2025-05-14 07:00:00 UTC.
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Science Advances, Volume 11, Issue 20, May 2025.
in Science Advances on 2025-05-14 07:00:00 UTC.
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Science Advances, Volume 11, Issue 20, May 2025.
in Science Advances on 2025-05-14 07:00:00 UTC.
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Science Advances, Volume 11, Issue 20, May 2025.
in Science Advances on 2025-05-14 07:00:00 UTC.
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Science Advances, Volume 11, Issue 20, May 2025.
in Science Advances on 2025-05-14 07:00:00 UTC.
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Science Advances, Volume 11, Issue 20, May 2025.
in Science Advances on 2025-05-14 07:00:00 UTC.
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Science Advances, Volume 11, Issue 20, May 2025.
in Science Advances on 2025-05-14 07:00:00 UTC.
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Science Advances, Volume 11, Issue 20, May 2025.
in Science Advances on 2025-05-14 07:00:00 UTC.
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Science Advances, Volume 11, Issue 20, May 2025.
in Science Advances on 2025-05-14 07:00:00 UTC.
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Science Advances, Volume 11, Issue 20, May 2025.
in Science Advances on 2025-05-14 07:00:00 UTC.
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Science Advances, Volume 11, Issue 20, May 2025.
in Science Advances on 2025-05-14 07:00:00 UTC.
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Science Advances, Volume 11, Issue 20, May 2025.
in Science Advances on 2025-05-14 07:00:00 UTC.
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Science Advances, Volume 11, Issue 20, May 2025.
in Science Advances on 2025-05-14 07:00:00 UTC.
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Science Advances, Volume 11, Issue 20, May 2025.
in Science Advances on 2025-05-14 07:00:00 UTC.
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Science Advances, Volume 11, Issue 20, May 2025.
in Science Advances on 2025-05-14 07:00:00 UTC.
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Science Advances, Volume 11, Issue 20, May 2025.
in Science Advances on 2025-05-14 07:00:00 UTC.
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Science Advances, Volume 11, Issue 20, May 2025.
in Science Advances on 2025-05-14 07:00:00 UTC.
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Science Advances, Volume 11, Issue 20, May 2025.
in Science Advances on 2025-05-14 07:00:00 UTC.