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Reassessing prediction in the brain: Pre-onset neural encoding during natural listening does not reflect pre-activation
arXiv:2412.19622v2 Announce Type: replace Abstract: Predictive processing theories propose that the brain continuously anticipates upcoming input. However, direct neural evidence for predictive pre-activation during natural language comprehension remains limited and debated. Previous studies using large language model (LLM)-based encoding models with fMRI and ECoG have reported pre-onset signals that appear to encode upcoming words, but these effects may instead reflect dependencies in the stimulus or autocorrelations in neural activity. Here, we re-examined this question by aligning LLM-derived word embeddings with neural activity recorded during naturalistic listening using magnetoencephalography (MEG) and electrocorticography (ECoG). We replicated pre-onset encoding effects previously observed in ECoG across both modalities, and found that they persist even after controlling for stimulus correlations. Crucially, temporal generalization analyses revealed no stable overlap between pre- and post-onset representations, indicating that pre-onset activity does not reflect pre-activation of the next word. Consistent with this, long-range predictive effects previously reported in fMRI did not replicate in our higher-temporal-resolution data. While we found no evidence for predictive pre-activation, we observed clear signatures of postdiction, with neural activity reflecting persistent encoding of prior words. These results suggest that reported apparent predictive signals do not reflect pre-activation of upcoming input. They call for caution in interpreting LLM-based encoding models and highlight the need for a more nuanced understanding of what constitutes "prediction" in language comprehension.in arXiv: Quantitative Biology: Neurons and Cognition on 2025-11-24 05:00:00 UTC.
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Emergence of psychopathological computations in large language models
arXiv:2504.08016v2 Announce Type: replace Abstract: Can large language models (LLMs) instantiate computations of psychopathology? An effective approach to the question hinges on addressing two factors. First, for conceptual validity, we require a general and computational account of psychopathology that is applicable to computational entities without biological embodiment or subjective experience. Second, psychopathological computations, derived from the adapted theory, need to be empirically identified within the LLM's internal processing. Thus, we establish a computational-theoretical framework to provide an account of psychopathology applicable to LLMs. Based on the framework, we conduct experiments demonstrating two key claims: first, that the computational structure of psychopathology exists in LLMs; and second, that executing this computational structure results in psychopathological functions. We further observe that as LLM size increases, the computational structure of psychopathology becomes denser and that the functions become more effective. Taken together, the empirical results corroborate our hypothesis that network-theoretic computations of psychopathology have already emerged in LLMs. This suggests that certain LLM behaviors mirroring psychopathology may not be a superficial mimicry but a feature of their internal processing. Our work shows the promise of developing a new powerful in silico model of psychopathology and also alludes to the possibility of safety threat from the AI systems with psychopathological behaviors in the near future.in arXiv: Quantitative Biology: Neurons and Cognition on 2025-11-24 05:00:00 UTC.
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Forecasting Future Anatomies: Longitudinal Brain Mri-to-Mri Prediction
arXiv:2511.02558v2 Announce Type: replace-cross Abstract: Predicting future brain state from a baseline magnetic resonance image (MRI) is a central challenge in neuroimaging and has important implications for studying neurodegenerative diseases such as Alzheimer's disease (AD). Most existing approaches predict future cognitive scores or clinical outcomes, such as conversion from mild cognitive impairment to dementia. Instead, here we investigate longitudinal MRI image-to-image prediction that forecasts a participant's entire brain MRI several years into the future, intrinsically modeling complex, spatially distributed neurodegenerative patterns. We implement and evaluate five deep learning architectures (UNet, U2-Net, UNETR, Time-Embedding UNet, and ODE-UNet) on two longitudinal cohorts (ADNI and AIBL). Predicted follow-up MRIs are directly compared with the actual follow-up scans using metrics that capture global similarity and local differences. The best performing models achieve high-fidelity predictions, and all models generalize well to an independent external dataset, demonstrating robust cross-cohort performance. Our results indicate that deep learning can reliably predict participant-specific brain MRI at the voxel level, offering new opportunities for individualized prognosis.in arXiv: Quantitative Biology: Neurons and Cognition on 2025-11-24 05:00:00 UTC.
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Brain-Like Processing Pathways Form in Models With Heterogeneous Experts
arXiv:2506.02813v3 Announce Type: replace-cross Abstract: The brain is made up of a vast set of heterogeneous regions that dynamically organize into pathways as a function of task demands. Examples of such pathways can be found in the interactions between cortical and subcortical networks during learning, or in sub-networks specializing for task characteristics such as difficulty or modality. Despite the large role these pathways play in cognition, the mechanisms through which brain regions organize into pathways remain unclear. In this work, we use an extension of the Heterogeneous Mixture-of-Experts architecture to show that heterogeneous regions do not form processing pathways by themselves, implying that the brain likely implements specific constraints which result in the reliable formation of pathways. We identify three biologically relevant inductive biases that encourage pathway formation: a routing cost imposed on the use of more complex regions, a scaling factor that reduces this cost when task performance is low, and randomized expert dropout. When comparing our resulting \textit{Mixture-of-Pathways} model with the brain, we observe that the artificial pathways in our model match how the brain uses cortical and subcortical systems to learn and solve tasks of varying difficulty. In summary, we introduce a novel framework for investigating how the brain forms task-specific pathways through inductive biases, and the effects these biases have on the behavior of Mixture-of-Experts models.in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-11-24 05:00:00 UTC.
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Fractional Artificial Neural Networks for Growth Models
arXiv:2511.16676v1 Announce Type: new Abstract: In this paper we present a method to solve initial value problems for fractional growth models, such as generalizations of the exponential and logistic with periodic harvesting models. Using a discretization of the Caputo derivative we propose a fractional artificial neural network, which is implemented in the statistical software R. Moreover, we show examples where the analytical solutions and the approximation of the artificial neural network are compared.in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-11-24 05:00:00 UTC.
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Jump-diffusion models of parametric volume-price distributions
arXiv:2511.16838v1 Announce Type: new Abstract: We present a data-driven framework to model the stochastic evolution of volume-price distribution from the New York Stock Exchange (NYSE) equities. The empirical distributions are sampled every 10 minutes over 976 trading days, and fitted to different models, namely Gamma, Inverse Gamma, Weibull, and Log-Normal distributions. Each of these models is parameterized by a shape parameter, $\phi$, and a scale parameter, $\theta$, which are detrended from their daily average behavior. The time series of the detrended parameters is analyzed using adaptive binning and regression-based extraction of the Kramers-Moyal (KM) coefficients, up to their sixth order, enabling to classification of its intrinsic dynamics. We show that (i) $\phi$ is well described as a pure diffusion with a linear mean regression for the Gamma, Inverse Gamma, and Weibull models, while $\theta$ shows dominant jump-diffusion dynamics, with an elevated fourth- and sixth-order moment contributions; (ii) the log-normal model shows however the opposite: $\theta$ is predominantly diffusive, with $\phi$ showing weak jump signatures; (iii) global moment inversion yields jump rates and amplitudes that account for a large share of total variance for $\theta$, confirming that rare discontinuities dominate volatility.in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-11-24 05:00:00 UTC.
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Illuminating the Black Box of Reservoir Computing
arXiv:2511.17003v1 Announce Type: new Abstract: Reservoir computers, based on large recurrent neural networks with fixed random connections, are known to perform a wide range of information processing tasks. However, the nature of data transformations within the reservoir, the interplay of input matrix, reservoir, and readout layer, as well as the effect of varying design parameters remain poorly understood. In this study, we shift the focus from performance maximization to systematic simplification, aiming to identify the minimal computational ingredients required for different model tasks. We examine how many neurons, how much nonlinearity, and which connective structure is necessary and sufficient to perform certain tasks, considering also neurons with non-sigmoidal activation functions and networks with non-random connectivity. Surprisingly, we find non-trivial cases where the readout layer performs the bulk of the computation, with the reservoir merely providing weak nonlinearity and memory. Furthermore, design aspects often considered secondary, such as the structure of the input matrix, the steepness of activation functions, or the precise input/output timing, emerge as critical determinants of system performance in certain tasks.in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-11-24 05:00:00 UTC.
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TDSNNs: Competitive Topographic Deep Spiking Neural Networks for Visual Cortex Modeling
arXiv:2508.04270v2 Announce Type: replace Abstract: The primate visual cortex exhibits topographic organization, where functionally similar neurons are spatially clustered, a structure widely believed to enhance neural processing efficiency. While prior works have demonstrated that conventional deep ANNs can develop topographic representations, these models largely neglect crucial temporal dynamics. This oversight often leads to significant performance degradation in tasks like object recognition and compromises their biological fidelity. To address this, we leverage spiking neural networks (SNNs), which inherently capture spike-based temporal dynamics and offer enhanced biological plausibility. We propose a novel Spatio-Temporal Constraints (STC) loss function for topographic deep spiking neural networks (TDSNNs), successfully replicating the hierarchical spatial functional organization observed in the primate visual cortex from low-level sensory input to high-level abstract representations. Our results show that STC effectively generates representative topographic features across simulated visual cortical areas. While introducing topography typically leads to significant performance degradation in ANNs, our spiking architecture exhibits a remarkably small performance drop (No drop in ImageNet top-1 accuracy, compared to a 3% drop observed in TopoNet, which is the best-performing topographic ANN so far) and outperforms topographic ANNs in brain-likeness. We also reveal that topographic organization facilitates efficient and stable temporal information processing via the spike mechanism in TDSNNs, contributing to model robustness. These findings suggest that TDSNNs offer a compelling balance between computational performance and brain-like features, providing not only a framework for interpreting neural science phenomena but also novel insights for designing more efficient and robust deep learning models.in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-11-24 05:00:00 UTC.
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The Cooperative Network Architecture: Learning Structured Networks as Representation of Sensory Patterns
arXiv:2407.05650v5 Announce Type: replace-cross Abstract: We introduce the Cooperative Network Architecture (CNA), a model that represents sensory signals using structured, recurrently connected networks of neurons, termed "nets." Nets are dynamically assembled from overlapping net fragments, which are learned based on statistical regularities in sensory input. This architecture offers robustness to noise, deformation, and generalization to out-of-distribution data, addressing challenges in current vision systems from a novel perspective. We demonstrate that net fragments can be learned without supervision and flexibly recombined to encode novel patterns, enabling figure completion and resilience to noise. Our findings establish CNA as a promising paradigm for developing neural representations that integrate local feature processing with global structure formation, providing a foundation for future research on invariant object recognition.in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-11-24 05:00:00 UTC.
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MonoKAN: Certified Monotonic Kolmogorov-Arnold Network
arXiv:2409.11078v2 Announce Type: replace-cross Abstract: Artificial Neural Networks (ANNs) have significantly advanced various fields by effectively recognizing patterns and solving complex problems. Despite these advancements, their interpretability remains a critical challenge, especially in applications where transparency and accountability are essential. To address this, explainable AI (XAI) has made progress in demystifying ANNs, yet interpretability alone is often insufficient. In certain applications, model predictions must align with expert-imposed requirements, sometimes exemplified by partial monotonicity constraints. While monotonic approaches are found in the literature for traditional Multi-layer Perceptrons (MLPs), they still face difficulties in achieving both interpretability and certified partial monotonicity. Recently, the Kolmogorov-Arnold Network (KAN) architecture, based on learnable activation functions parametrized as splines, has been proposed as a more interpretable alternative to MLPs. Building on this, we introduce a novel ANN architecture called MonoKAN, which is based on the KAN architecture and achieves certified partial monotonicity while enhancing interpretability. To achieve this, we employ cubic Hermite splines, which guarantee monotonicity through a set of straightforward conditions. Additionally, by using positive weights in the linear combinations of these splines, we ensure that the network preserves the monotonic relationships between input and output. Our experiments demonstrate that MonoKAN not only enhances interpretability but also improves predictive performance across the majority of benchmarks, outperforming state-of-the-art monotonic MLP approaches.in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-11-24 05:00:00 UTC.
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Quantitative Attractor Analysis of High-Capacity Kernel Logistic Regression Hopfield Networks
arXiv:2505.01218v3 Announce Type: replace-cross Abstract: Kernel-based learning methods such as Kernel Logistic Regression (KLR) can dramatically increase the storage capacity of Hopfield networks, but the principles governing their performance and stability remain largely uncharacterized. This paper presents a comprehensive quantitative analysis of the attractor landscape in KLR-trained networks to establish a solid foundation for their design and application. Through extensive, statistically validated simulations, we address critical questions of generality, scalability, and robustness. Our comparative analysis reveals that KLR and Kernel Ridge Regression (KRR) exhibit similarly high storage capacities and clean attractor landscapes, suggesting this is a general property of kernel regression methods, though KRR is computationally much faster. We uncover a non-trivial, scale-dependent scaling law for the kernel width ($\gamma$), demonstrating that optimal capacity requires $\gamma$ to be scaled such that $\gamma \times N$ increases with network size $N$. This implies that larger networks necessitate more localized kernels -- where each pattern's influence is more spatially confined -- to manage inter-pattern interference. Under this optimized scaling, we provide definitive evidence that the storage capacity scales linearly with network size ($P \propto N$). Furthermore, our sensitivity analysis shows that performance is remarkably robust to the choice of the regularization parameter $\lambda$. Collectively, these findings provide a clear set of empirical principles for designing high-capacity, robust associative memories and clarify the mechanisms that enable kernel methods to overcome the classical limitations of Hopfield-type models.in arXiv: Computer Science: Neural and Evolutionary Computing on 2025-11-24 05:00:00 UTC.
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Hydrogen fuel isn’t always the green choice
Nature, Published online: 24 November 2025; doi:10.1038/d41586-025-03695-0
Using hydrogen to power road transportation and heat homes doesn’t save more carbon emissions than direct electrification.in Nature on 2025-11-24 00:00:00 UTC.
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Nickel-catalyzed highly diastereo- and enantioselective hydroaminocarbonylation and hydrocarboxylation of cyclopropenes
Nature Communications, Published online: 24 November 2025; doi:10.1038/s41467-025-66742-4
Here, the authors present a mild nickel-catalyzed asymmetric hydroaminocarbonylation and hydrocarboxylation that use cost-effective NH₄OAc and H₂O as nucleophiles, respectively, which provides rapid access to structurally diverse cyclopropyl amides and carboxylic acids.in Nature Communications on 2025-11-24 00:00:00 UTC.
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Fructose and follistatin potentiate acute MASLD during complete hepatic insulin resistance
Nature Communications, Published online: 24 November 2025; doi:10.1038/s41467-025-66296-5
The authors report that, in mice without hepatic insulin signaling, diets high in fructose cause acute hepatic steatosis without increasing hepatic de novo lipogenesis, dependent upon hepatic follistatin secretion and associated adipose insulin resistance.in Nature Communications on 2025-11-24 00:00:00 UTC.
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WWOX deficiency uncovers a cell-autonomous mechanism impairing myelin repair
Remyelination is essential for neuronal function and plasticity, and its failure contributes to multiple sclerosis (MS) and other neurodegenerative disorders. Yet, the molecular programs governing oligodendrocyte precursor cell (OPC) differentiation and remyelination remain incompletely defined. Here, we identify the WW domain-containing oxidoreductase (WWOX) as a critical cell-autonomous regulator of oligodendrocyte differentiation and myelin repair. Reanalysis of single-nucleus RNA sequencing from MS lesions revealed WWOX as one of the most significantly dysregulated oligodendroglial genes. Conditional deletion of Wwox in oligodendroglia impaired OPC differentiation, favouring aberrant proliferation and blocking myelin regeneration after cuprizone-induced demyelination. Single-nucleus transcriptomics confirmed profound transcriptional reprogramming in WWOX-deficient oligodendroglia during remyelination, with enrichment of WNT and TGFb; signalling and cell cycle programs. Mechanistically, WWOX physically interacts with the master transcription factor SOX10 via its WW1 domain, stabilising SOX10 protein and sustaining its downstream myelin gene network. Loss of WWOX reduced SOX10 stability and activity, providing a direct mechanistic link to defective OPC differentiation. Together, our findings uncover WWOX as an essential orchestrator of remyelination and position the WWOX-SOX10 axis as a promising therapeutic target for enhancing myelin repair in MS and related demyelinating disorders.in bioRxiv: Neuroscience on 2025-11-24 00:00:00 UTC.
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Comparative Analysis of FOXP2 Expression in the Thalamus of Mice, Rats, and Macaques: Implications for the Evolution of Language Circuits.
FOXP2 is a transcription factor essential for the development and function of neural circuits involved in language. Although its expression has been extensively characterized in the cortex and basal ganglia, its organization within the adult thalamus remains poorly understood. In this study, we present a comparative analysis of FoxP2 protein expression across thalamic nuclei in mice, rats, and macaques, with a focus on nuclei associated with higher-order cognitive functions and language-related circuits in humans. We found that FoxP2 is expressed in most thalamic nuclei across species, with a consistent absence in the reticular nucleus and zona incerta. Expression was highest in midline and intralaminar nuclei, whereas the anterior group showed low and variable expression among species. Macaques exhibited broader and, in some nuclei, more intense FoxP2 expression, particularly in associative regions such as the pulvinar, lateral geniculate, and parts of the ventral group, indicating increased specialization of thalamocortical pathways. This distribution suggests a conserved role for FoxP2 in shaping thalamic circuits supporting sensorimotor integration, attention, memory, and linguistic processing. Phylogenetic comparisons further indicate that enhanced FoxP2 expression in associative thalamic territories in primates, likely intensified in humans, may have contributed to the evolution of neural circuits required for speech and language. These findings provide molecular and anatomical insights into how FoxP2 helps organize thalamocortical networks relevant both to language function and to neuropsychiatric disorders involving thalamocortical dysconnectivity.in bioRxiv: Neuroscience on 2025-11-24 00:00:00 UTC.
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Dynamic methylation changes in Alzheimers disease-related genes during mindfulness practice - a proof-of-concept study
Background: Mindfulness meditation has gained significant attention in the context of Alzheimer's disease (AD) due to its potential effects on the prevention of cognitive decline and overall psychological well-being. The epigenetic landscape of this complex neurodegenerative disorder can be influenced by environmental factors. Mindfulness practices could actively shape the biological response to AD by modifying the underlying molecular mechanisms through epigenetic regulation. Methods: A group of 17 long-term mindfulness meditators (MMs) and 17 sex- and age-matched controls were recruited. Experienced MMs participated in a 1-month Vipassana meditation retreat. Blood DNA methylation levels of differentially methylated genes (ABCA7, ADAM10, APOE, HOXA3, NXN, TREM2 and TREML2) previously validated in a predictive AD-model found analyzed by bisulfite pyrosequencing. Results: An increase in DNA methylation was observed for ADAM10, APOE, HOXA3 and TREM2 in MMs with respect to controls. Furthermore, significant differences were found for ABCA7, ADAM10, APOE and HOXA3 in MMs after retreat. Conclusions: DNA methylation changes identified for ADAM10 and HOXA3 in MMs are in the opposite direction to those occurring in AD and may constitute a protective epigenetic alteration. Mindfulness practice could counteract DNA methylation of key AD genes as a possible preventive strategy or non-pharmacological intervention in AD patients.in bioRxiv: Neuroscience on 2025-11-24 00:00:00 UTC.
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Dual inhibition of FACT and RRM2 suppresses the progression of pancreatic ductal adenocarcinoma driven by the oncohistone H2BG53D
Qin et al. investigated the roles, mechanisms, and therapeutics of oncohistone mutation H2BG53D in PDAC. They found that H2BG53D promotes PDAC development in vivo, alters transcriptional profiles governed by the FACT complex, and proposed a potential therapeutic strategy for H2BG53D-mutant PDAC.in Cell Reports: Current Issue on 2025-11-23 00:00:00 UTC.
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Activation of the Yersinia type III secretion system induces large-scale spatial reorganization of chromosomal and virulence plasmid DNA
Activation of the Yersinia type III secretion system triggers rapid, large-scale relocalization of both chromosomal and plasmid DNA. This spatial reorganization links secretion activity to growth inhibition, revealing a new connection between virulence and bacterial cell biology.in Cell Reports: Current Issue on 2025-11-23 00:00:00 UTC.
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In vivo mitochondrial base editing restores genotype and visual function in a mouse model of LHON
Nature Communications, Published online: 23 November 2025; doi:10.1038/s41467-025-66600-3
Leber hereditary optic neuropathy (LHON) is caused by mtDNA mutations. Here, authors generated a mouse model with the common LHON mutation and showed that optimized TALE-like deaminases restored both phenotype and genotype via high-fidelity mitochondrial base editing.in Nature Communications on 2025-11-23 00:00:00 UTC.
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Targeting fibroblast derived thrombospondin 2 disrupts an immune-exclusionary environment at the tumor front in colorectal cancer
Nature Communications, Published online: 23 November 2025; doi:10.1038/s41467-025-66485-2
Desmoplastic stroma is a hallmark of aggressive colorectal cancer. Matrix cancer-associated fibroblasts derived THBS2 establishes a fibrotic, immune-exclusionary barrier that limits CD8+ T cell infiltration, while its inhibition restores CXCR3-mediated T cell recruitment and enhances response to immune checkpoint blockade.in Nature Communications on 2025-11-23 00:00:00 UTC.
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Wavefront Shaping of Scattering Forces Enhances Optical Trapping of Levitated Nanoparticles
Nature Communications, Published online: 23 November 2025; doi:10.1038/s41467-025-66713-9
This work experimentally demonstrates that light-field spatial modulation can be harnessed to substantially increase the forces used to optically levitate nanoparticles in vacuum.in Nature Communications on 2025-11-23 00:00:00 UTC.
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Efficient electrodynamic stripping for 12-inch wafer-scale freestanding ferroelectric oxide membranes
Nature Communications, Published online: 23 November 2025; doi:10.1038/s41467-025-66697-6
A directional electrodynamic decomposition method using a LaNiO3 sacrificial layer is proposed for freestanding films. It boosts oxide film release rate to 600 mm2 /min via electric field-enhanced adsorption energy and electron transfer.in Nature Communications on 2025-11-23 00:00:00 UTC.
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Blood biomarkers of Alzheimer’s disease and progression across different stages of cognitive decline in the community
Nature Communications, Published online: 23 November 2025; doi:10.1038/s41467-025-66728-2
Blood biomarkers of Alzheimer’s disease, including p-tau217, are linked with faster progression from mild cognitive impairment to dementia, supporting their potential for risk stratification at the stage of mild cognitive impairment in the community.in Nature Communications on 2025-11-23 00:00:00 UTC.
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Structural insights into scaffold-guided assembly of the Pseudomonas phage D3 capsid
Nature Communications, Published online: 23 November 2025; doi:10.1038/s41467-025-66648-1
Tailed bacteriophages package their DNA into symmetric protein shells, called “capsids”, that use a common subunit fold. Here, authors visualize such a capsid at the molecular level and identify a key structural motif involved in regulating its size.in Nature Communications on 2025-11-23 00:00:00 UTC.
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Dual-action salivary peptide drives black fly feeding efficiency
Communications Biology, Published online: 23 November 2025; doi:10.1038/s42003-025-09182-6
Discovery of sibanin, a Kunitz-type peptide from black fly venom, reveals dual analgesia and anticoagulation via the NaV1.7 channel and coagulation factor inhibition, highlighting its potential as a lead compound for pain and thrombotic disease therapeutics.in Nature communications biology on 2025-11-23 00:00:00 UTC.
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Dcaf15-mediated EphA2 degradation triggers disruption of the blood-brain barrier during Streptococcus suis meningitis
Communications Biology, Published online: 23 November 2025; doi:10.1038/s42003-025-09213-2
EphA2 protects the blood-brain barrier during Streptococcus suis meningitis by promoting autophagy. S. suis disrupts this protection by inducing EphA2 degradation through DCAF15-mediated ubiquitination.in Nature communications biology on 2025-11-23 00:00:00 UTC.
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Systematic evaluation of tools used for single-cell m6A identification
Communications Biology, Published online: 23 November 2025; doi:10.1038/s42003-025-09246-7
Comparison of single-cell m6A methods and development of a freely accessible database, Scm6A, enabling prediction and visualization of m6A modifications across human and mouse single-cell and spatial transcriptomes.in Nature communications biology on 2025-11-23 00:00:00 UTC.
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Influenza virus and Staphylococcus aureus super-infection disrupts spatially coordinated cellular immunity in the mouse lung
Communications Biology, Published online: 23 November 2025; doi:10.1038/s42003-025-09268-1
The authors report a spatial transcriptomic analysis of mouse lungs following a super-infection of influenza and methicillin-resistant Staphylococcus aureus.in Nature communications biology on 2025-11-23 00:00:00 UTC.
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Transcriptome profiling of tumor-infiltrating lymphocyte-mediated cytotoxicity against patient-derived lung cancer organoids
Communications Biology, Published online: 23 November 2025; doi:10.1038/s42003-025-09188-0
A patient-derived organoid-TIL co-culture system delineates the clonal and molecular dynamics of effective anti-tumor immune responses in NSCLC.in Nature communications biology on 2025-11-23 00:00:00 UTC.
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Metabolic reprogramming and mitochondrial dysfunction underlie β gonia arrest and niche cell dysfunction in sterile triploid oysters
Communications Biology, Published online: 23 November 2025; doi:10.1038/s42003-025-09202-5
Integrative spatial and single-nucleus transcriptomics reveal mitochondrial dysfunction, mitophagy, and disrupted germ-niche signalling underlying germ cell arrest and sterility in triploid oysters.in Nature communications biology on 2025-11-23 00:00:00 UTC.
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Heterogeneous distribution of toxic arsenic modulates the mutualistic interaction between Pteris vittata and soil microbiota
Communications Biology, Published online: 23 November 2025; doi:10.1038/s42003-025-09233-y
The arsenic hyperaccumulator Pteris vittata actively forages arsenic by root proliferation and exudate-mediated recruitment of specific microbes, restoring diminished rhizosphere microbial alpha-diversity under heterogeneous arsenic contamination.in Nature communications biology on 2025-11-23 00:00:00 UTC.
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Host cell KRT-18 as a non-redox dependent interactor of Cryptosporidium parvum PDI enables parasite infection
Communications Biology, Published online: 23 November 2025; doi:10.1038/s42003-025-09238-7
Mechanistic insights into Cryptosporidium parvum invasion identify a non-canonical role for Protein Disulfide Isomerase through interaction with host keratin 18.in Nature communications biology on 2025-11-23 00:00:00 UTC.
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Lipid Nanoparticles Enable mRNA Delivery to Diverse Cell Types of the Inner Retina
Lipid nanoparticles (LNPs) have emerged as a promising platform for retinal genetic therapy, offering a non-viral alternative to adeno-associated viruses (AAVs). While LNPs can transfect outer retinal cells, their tropism for inner retinal cell types remains insufficiently characterized. Here, we systematically assessed cellular tropism of conventional LNPs encapsulating chemically modified mRNA encoding mCherry in murine retinal explants and dissociated retinal cells. We compared quasi-subretinal and quasi-intravitreal administrations and evaluated how retinal degeneration and inner limiting membrane (ILM) integrity influence LNP-mediated transfections. We observed that LNPs efficiently transfected Muller glia under all experimental conditions. In addition, LNPs transfected several other retinal cell types, including neurons in dissociated cells and explants, and vascular cells exclusively in explants. Subretinal delivery resulted in significantly higher transfection rates than intravitreal administration, and overall efficiency was higher in degenerate as compared to non-degenerate healthy retinas. In healthy retinas, removal of ILM-associated barriers significantly increased transfection efficiency following intravitreal administration. Together, these findings demonstrate that conventional LNPs can transfect a broader range of retinal cell types than previously recognized and highlight LNPs as a versatile tool for mRNA delivery to the retina, with applications in gene supplementation, gene editing, and regenerative therapies for inner retinal disorders.in bioRxiv: Neuroscience on 2025-11-23 00:00:00 UTC.
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From Syllables to Words: EEG Evidence of Different Age Trajectories in Speech Tracking and Statistical Learning in Infants at High and Low Likelihood for Autism
Delayed onset of canonical babbling and first words is often reported in infants later diagnosed with autism spectrum disorder (ASD). Identifying the neural mechanisms underlying language acquisition in ASD is therefore critical to inform early diagnosis, prognosis, and intervention strategies. In this study, we investigated two speech processing mechanisms previously identified as atypical in children and adults with ASD: the neural ability to track syllables; and statistical learning (SL), the capacity to detect speech regularities beneath surface variability. We recorded 83 longitudinal high-density EEGs from 44 infants (2.5-22.6 months) at high (HL) and low (LL) likelihood for ASD and assessed their verbal outcomes at 20 months. Neural entrainment was measured at syllable and word frequencies during exposure to a multi-speaker stream of concatenated tri-syllabic words, followed by a word recognition test using ERP recording. Our findings revealed reduced tracking abilities at the syllabic level in HL infants, a measure that correlated with verbal outcomes. While HL infants did not exhibit deficits in SL itself, they displayed reduced novelty orientation during the word recognition test, indicated by a reduced late ERP. By contrast, multi-talker variability temporarily disrupted word segmentation around 12 months in LL infants, but not in HL infants, potentially reflecting decreased sensitivity to human voices in the HL group. These results emphasize the importance of longitudinal protocols employing online, implicit measures to track the hierarchical stages of speech processing in both HL and LL infants.in bioRxiv: Neuroscience on 2025-11-23 00:00:00 UTC.
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Factors associated with postpartum complications: A systematic review to inform early detection strategies [version 2; peer review: 2 approved]
Background Complications during the puerperium present abnormal conditions that can jeopardize the health and well-being of both mother and newborn. These complications are significant contributors to maternal morbidity and mortality worldwide. This systematic review aims to identify and synthesize evidence on the factors associated with postpartum disease complications. Methods This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The protocol was registered in PROSPERO (CRD420251013692). A comprehensive search was performed using electronic databases, including Scopus and PubMed, to identify relevant studies published between 2014 and 2024. Eligible studies included full-text, peer-reviewed articles that used quantitative or qualitative designs and addressed postpartum complications in accordance with the PEO framework. Descriptive analysis was used to synthesize findings. Results A total of 907 records were identified, and 13 studies met the inclusion criteria. The findings highlight a range of factors significantly associated with postpartum complications, including postpartum hemorrhage, maternal age >35 years, depressive and anxiety disorders, preeclampsia, multiple pregnancies, type of vaginal delivery, infant-related health concerns, childhood trauma, low social support, low educational attainment of both mothers and husbands, perceived social isolation, and marital dissatisfaction. While early detection and intervention were not directly evaluated in these studies, the identification of these risk factors suggests that targeted screening and supportive strategies may be beneficial in mitigating postpartum complications. Conclusions This review identifies multiple psychosocial, demographic, and clinical factors associated with postpartum complications. These findings underscore the importance of early detection and comprehensive postpartum care to mitigate risks and improve maternal health outcomes.in F1000Research on 2025-11-22 11:09:10 UTC.
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SARS-CoV-2-ORF3a variant Q57H reduces its pro-apoptotic activity in host cells [version 2; peer review: 1 approved with reservations, 1 not approved]
Background Mutations in the viral genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can enhance its pathogenicity by affecting its transmissibility, disease severity, and overall mortality in human populations. In addition to mutations within the coding region of SARS-CoV-2 structural proteins, there have been reports of mutations in other SARS-CoV-2 proteins that affect virulence, such as open reading frame 3a (ORF3a), which is involved in viral replication. The expression of ORF3a in host cells activates cell death signaling, leading to tissue damage, which affects the severity of COVID-19. The ORF3a-Q57H variant is the most frequent and recurrent variant of ORF3a and is likely associated with increased transmissibility but lower mortality in the 4th epidemic wave of COVID-19 in Hong Kong. Computational structural modeling predicted that the Q57H variant destabilizes the protein structure of ORF3a, which may result in reduced protein expression in human cells. However, it is still unknown how this mutation affects ORF3a protein function and, if so, whether it can change the severity of host cell damage. Methods Plasmids carrying SARS-CoV-2-ORF3a from Wuhan-Hu-1 strain (i.e., wild-type; WT) and its variant Q57H were transiently transfected into HEK293T cells and used for biochemical and cell biological assays. Results SARS-CoV-2-ORF3a-Q57H variant exhibits similar protein expression in whole cell lysates compared to WT, but less expression at the plasma membrane. ORF3a-Q57H expression results in less apoptosis in host cells compared to WT via lower activation of the extrinsic apoptotic pathway. Conclusion The relatively mild phenotype of the SARS-CoV-2-ORF3a-Q57H variant may result from alterations to ORF3a function by this mutation, rather than its protein expression levels in host cells.in F1000Research on 2025-11-22 09:54:15 UTC.
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Airway immunometabolic responses during pulmonary bacterial and viral infections
Wadhwa et al. examine how respiratory bacterial and viral pathogens exploit host metabolism to evade immune responses and influence disease outcomes. They underscore the need for deeper insight into immunometabolic interactions, as host-derived metabolites can shape pathogen fitness/evolution—highlighting both the therapeutic promise and complexity of targeting metabolism in infection.in Cell Reports: Current Issue on 2025-11-22 00:00:00 UTC.
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Glycolysis inhibition functionally reprograms T follicular helper cells and reverses lupus
Choi et al. show that pharmacologically restricting glycolysis improves the cellular, transcriptional, and metabolic machinery in murine lupus TFH cells. Transcript overlaps between TFH cells from lupus patients and experimental mice indicate glycolysis-sensitive mechanisms, thus demonstrating that uncontrolled glycolysis exacerbated TFH cell functions and autoantibody production in lupus.in Cell Reports: Current Issue on 2025-11-22 00:00:00 UTC.
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TREX1 enables viral entry in intestinal epithelia via immunity-independent control of endocytosis
TREX1 is known for degrading cytosolic DNA to prevent unwanted immune activation. However, its role in all human cell types is not fully clear. Here, Liu et al. reveal an unexpected function of TREX1 in intestinal epithelial cells, showing that it regulates endocytosis to aid viral entry without affecting immune status.in Cell Reports: Current Issue on 2025-11-22 00:00:00 UTC.
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Inhibition of respiration prompts commitment to unisexual reproduction in Cryptococcus deneoformans
Yao et al. discovered that inhibition of respiration directs the fungal pathogen Cryptococcus species to undergo unisexual development. This metabolic cue activates the Znf2-Cln1 regulatory circuit that induces G2/M cell-cycle arrest, promoting unisexual self-filamentation while inhibiting α × a heterothallic cell fusion.in Cell Reports: Current Issue on 2025-11-22 00:00:00 UTC.
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Mechanisms governing poly(A)-tail-length specificity of the human PAN2-PAN3 deadenylase complex
PAN2-PAN3 deadenylases are conserved but act on mRNA poly(A) tails of different lengths in yeast and human. Albrecht et al. show how metazoan-specific loops in PAN3 create distinct binding sites for poly(A)-PABPC1 ribonucleoproteins, favoring longer poly(A) tails than in yeast and rationalizing these substrate preferences.in Cell Reports: Current Issue on 2025-11-22 00:00:00 UTC.
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Twenty years (2000–2020) of butterfly monitoring data across the contiguous United States
Scientific Data, Published online: 22 November 2025; doi:10.1038/s41597-025-05513-8
Twenty years (2000–2020) of butterfly monitoring data across the contiguous United Statesin Nature scientific data on 2025-11-22 00:00:00 UTC.
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A dataset of building surface defects collected by UAVs for machine learning-based detection
Scientific Data, Published online: 22 November 2025; doi:10.1038/s41597-025-06318-5
A dataset of building surface defects collected by UAVs for machine learning-based detectionin Nature scientific data on 2025-11-22 00:00:00 UTC.
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Dissociating the neural codes for multiple pitch perception in humans
Pitch is crucial for speech and music perception, yet its neural code remains contested. The classic "rate-place" theory suggests that pitch is computed from spatial patterns of average neural firing rates along the cochlear tonotopic axis. These cues are thought to be robust for isolated harmonic complex tones (HCTs) but degraded for spectrally dense mixtures of simultaneous HCTs (e.g., musical chords) due to auditory filtering. In many cases, pitch perception remains feasible for HCT mixtures, but it is unclear whether listeners utilize residual rate-place cues or alternative neural codes. To adjudicate between these possibilities, we generated rate-place metamers (META), which are synthetic stimuli with simulated auditory-nerve average-rate responses that are nearly identical to those of original pitch-evoking stimuli (ORIG). Using these stimuli, listeners completed four psychophysical experiments that spanned a wide range of acoustic and cognitive complexity, from single-HCT pitch discrimination to harmonic-expectation judgments. Combining the behavioral data with predictive models of listener performance, we found that listener performance on single pitch discrimination tasks could be adequately explained by a rate-place model, with or without simultaneous pitch maskers (Experiments 1 and 2). More complex tasks involving attention to all pitches in a three-pitch mixture (Experiments 3 and 4) showed a pattern of results more difficult to account for with a rate-place model, perhaps suggesting a role for integration of temporal cues.in bioRxiv: Neuroscience on 2025-11-22 00:00:00 UTC.
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Inter-areal coupling for cognition through coincident oscillatory transients
How do large-scale brain networks interact to enable cognition? Correlated oscillations, a mechanism for inter-areal interactions, can be expressed as phase coherence or amplitude co-fluctuations. While considerable work has investigated the functional roles of phase coherence, little is known about whether and how the coincidence of high-amplitude oscillations across the cortex can impact cognition. Here, we demonstrate that inter-areal amplitude-coupling related to cognitive dynamics mainly reflects coincident oscillatory transients, rather than sustained oscillations. Capitalizing on the spatio-temporal resolution of brain-wide magnetoencephalography (MEG) during a behavioral task probing attention and decision-making our findings reveal behaviorally relevant transient oscillatory networks: First, coincidences of oscillatory transients in the alpha and beta frequency range increase prior to correct decisions in a parieto-frontal network. Second, during attention allocation coincident oscillatory transients increase in visual, medial parietal and lateral prefrontal networks in the theta/alpha frequency range. We propose that brain-wide coincident oscillatory events are a key signature of inter-areal interactions during cognition.in bioRxiv: Neuroscience on 2025-11-22 00:00:00 UTC.
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Cannabis-enriched oral Actinomyces induces anxiety-like behavior via impairing mitochondria and GABA signaling
The human oral microbiome is increasingly recognized as a contributor to brain health, yet its mechanisms remain unclear. Our previous work revealed that oral Actinomyces species was enriched in chronic cannabis smokers. Here, we show oral inoculation of cannabis use-associated Actinomyces species, especially A. meyeri, to wildtype C57BL/6 mice leads to anxiety-like behaviors, non-region-specific microglia activation, mitochondrial dysfunction, and reduced GABAergic neurotransmission, without evidence of bacterial translocation to the brain, neuroinflammation, and memory decline. Notably, Actinomyces species producing metabolites, i.e., arginine and argininosuccinate, were increased in both oral swabs and brain following inoculation in vivo. These Actinomyces species-producing metabolites induced mitochondrial dysfunction and oxidative stress in neurons in vitro, indicating a neuropathogenic role and aligning with reduced GABAergic neurotransmission in vivo. Together, these results suggest that oral cannabis-associated dysbiosis impacts behavior through mitochondrial stress and impaired inhibitory signaling, indicating the oral to brain metabolic axis is potentially consequential in neuropsychiatric disorders.in bioRxiv: Neuroscience on 2025-11-22 00:00:00 UTC.
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A gene expression atlas of a juvenile nervous system
Although the fundamental architecture of metazoan nervous systems is typically established in the embryo, substantial numbers of neurons are added during post-natal development while existing neurons expand in size, refine connectivity, and undergo additional differentiation. To reveal the underlying molecular determinants of post-embryonic neurogenesis and maturation, we have produced gene expression profiles of all neuron types and their progenitors in the first larval stage (L1) of C. elegans. Comparisons of the L1 profile to the embryo and to the later L4 larval stage identified thousands of differentially expressed genes across individual neurons throughout the nervous system. Key neuropeptide signaling networks, for example, are remodeled during larval development. Gene regulatory network analysis revealed potential transcription factors driving the temporal changes in gene expression across the nervous system, including a broad role for the heterochronic gene lin-14. We utilized available connectomic data of juvenile animals in combination with our neuron-specific atlas to identify potential molecular determinants of membrane contact and synaptic connectivity. These expression data are available through a user-friendly interface at CeNGEN.org for independent investigations of the maturation, connectivity and function of a developing nervous system.in bioRxiv: Neuroscience on 2025-11-22 00:00:00 UTC.
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Risky Choices After Frontal Brain Injury: Differential Effects in Self vs Other-Decision Contexts
Frontal lobe integrity is crucial for assessing risk and making informed decisions. This study investigated how frontal lobe lesions affect the computational mechanisms underlying risky choice, particularly when decisions impact oneself versus another person. A Patient Group of 20 individuals with frontal cortex damage and a Control Group of 20 matched individuals performed a gambling task, making accept/reject decisions on mixed-outcome gambles for themselves ("Self") or an anonymous other ("Other"). We provide a mechanistic account of choice behavior using Prospect Theory, the leading behavioral model of decision-making under risk, to quantify parameters for utility curvature, loss aversion, and probability weighting. Behaviorally, the Patient Group accepted significantly more disadvantageous gambles for themselves than did the Control Group yet showed a trend toward greater caution when choosing for others. Prospect Theory modeling revealed a specific computational phenotype for this behavior. Compared to the Control Group, the Patient Group exhibited significantly more pronounced utility curvature (lower , {beta}) and more linear, less distorted probability weighting (higher {gamma}). While patients also showed a trend toward lower loss aversion ({lambda}), this difference was not statistically significant. This combination of altered utility and probability processing explains their paradoxical risk-seeking. These findings suggest that frontal cortex damage disrupts the computation of subjective value, leading to a distinctive decision-making profile marked by altered utility curvature and reduced sensitivity to outcome magnitudes. This computational characterization deepens our understanding of frontal lobe contributions to decision-making and can inform targeted rehabilitation strategies.in bioRxiv: Neuroscience on 2025-11-22 00:00:00 UTC.
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Observations of anisotropic paramagnetic and diamagnetic susceptibility in the primate brain
Bulk magnetic susceptibility in the brain white matter is known to be diamagnetic and anisotropic due to the ordered myelin lipids. While paramagnetic iron is widely present in the brain, it is typically not considered to contribute to anisotropy. Using experimental MRI and computational techniques, this study explores the competing contribution of diamagnetic and paramagnetic substances to the susceptibility anisotropy. Multi-echo gradient-echo imaging and diffusion-weighted imaging data from a paraformaldehyde-fixed post-mortem chimpanzee (Pan troglodytes verus) brain was analyzed. A computational method, DECOMPOSE-QSM, was used to separate paramagnetic susceptibility and diamagnetic susceptibility components. As expected, diamagnetic components showed significant anisotropy; unexpectedly, paramagnetic components also exhibited strong anisotropy in deep gray matter and parts of white matter. This may arise from the geometric arrangement of iron-rich cellular compartments, such as oligodendrocytes, astrocytes, and microglia, along nerve fibers. This method enables further exploration of tissue-specific contributions to susceptibility anisotropy.in bioRxiv: Neuroscience on 2025-11-22 00:00:00 UTC.
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The unexpected dual role of S100A9 amyloid protein on neurodegeneration in progressive multiple sclerosis motor cortex
Motor cortical inflammation and neurodegeneration are key features of progressive multiple sclerosis (MS), contributing to irreversible motor disability. However, the precise mechanisms leading to neuronal loss remain poorly understood. While chronic inflammation is a hallmark of MS and contributes to disease progression, the factors linking inflammation to neuronal loss in the cortex are not well defined. One candidate is the calcium-binding protein S100A9, a damage-associated molecular pattern (DAMP) protein, thought to be released by stressed cells and infiltrating monocytes. Through its ability to modulate immune responses and influence neuronal survival, S100A9 may sustain chronic inflammation and participate in neurodegenerative processes. Although its role has been explored in other neurological disorders, its contribution to progressive MS remains largely uncharacterised. Here, we investigated S100A9 expression in the motor cortex of a large post-mortem cohort of MS cases (n=67) and controls (n=9), focusing on its cellular localisation and its relationship with neuronal density and vascular pathology. S100A9 expression was increased in progressive MS cases compared to controls, predominantly localised to intravascular monocytes and as amyloid-like extracellular plaques surrounding blood vessels. These patterns were associated with neurodegeneration and blood-brain barrier (BBB) disruption, as evidenced by correlations with reduced brain weight, decreased neuronal density, and increased fibrin(ogen) deposition. In contrast, S100A9 was also expressed in microglia, where it correlated with increased neuronal density and reduced fibrin(ogen) deposition. Notably, the phosphorylated form of S100A9, linked to pro-inflammatory signaling, was reduced in microglia but enriched in perivascular regions. These findings reveal a dual, compartment-specific role for S100A9 in progressive MS, whereby extracellular aggregates may drive neurotoxicity, while microglial S100A9 may confer neuroprotection. Therapeutic strategies targeting extracellular S100A9 while preserving its intracellular functions may offer new opportunities for treating progressive MS.in bioRxiv: Neuroscience on 2025-11-22 00:00:00 UTC.
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Multiple longitudinal tracts in the cephalopod arm sensorimotor system
Octopuses have an incredibly rich behavioral repertoire, exhibiting complex motor acts that require the coordination of eight highly flexible arms, each with hundreds of suckers. These movements are controlled by an axial nerve cord (ANC), equivalent to the spinal cord, situated in the center of the arm musculature. The ANC has a cell body layer which forms a U-shape around its neuropil and is capped aborally, or opposite the sucker, by the cerebrobrachial tract (CBT), a massive fiber bundle known to interconnect the arms and the brain. In vertebrate spinal cords, in addition to the major fiber tracts that interconnect the brain and spinal cord, there are spinospinal connectives that coordinate complex motor behaviors across the appendages. Here, we asked with tract-tracing and immunohistochemistry, whether an octopus arm's ANC might also have intrinsic longitudinal connections for coordinated arm and sucker movements. We found that the ANC neuropil is enriched in longitudinal fibers. These fibers form distinct tracts, two within the oral (sucker-side) neuropil and two in the aboral (brachial-side) neuropil. In addition, CBT itself demonstrates four major subtracts, and DiI labeling and dextran tracing suggests that (1) the CBT also carries arm-intrinsic longitudinal connections and (2) the CBT and the neuropil tracts can be subcategorized into those that primarily connect with the sucker and those that serve the arm musculature. We also examined the organization of fiber-tracts in the ANC of the arms and tentacles of two species of squid, establishing that an aboral, extra-neuropil tract is a shared feature across all cephalopod species studied. In addition, the squids also had an oral longitudinal tract, though its positioning and size varied with species and appendage. In sum, these findings describe the neural substrate for coordinating motor behaviors across the length of a cephalopod appendage.in bioRxiv: Neuroscience on 2025-11-22 00:00:00 UTC.
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High extraversion enhances attentional control through dynamic network reorganization
The extraversion-introversion dimension of personality is hypothesized to differ based on low or high cortical arousal, respectively. Notably, high cortical arousal in introverts is thought to underlie increased distractibility. Here, we assess fMRI while participants meditate (focused attention to their breath) under three levels of auditory distraction: no, low and high. Whereas introverts exhibited worsening attentional focus on their breath with increasing distraction, extraverts retained their ability to focus attention despite distraction. Dynamic functional connectivity analysis indicated that extraverts exhibited less globally efficient and less modular networks, which may prevent distracting stimuli from creating interference. Furthermore, connectivity strengths amongst the default mode, central executive, and salience networks were increased for extraverts and decreased in introverts during high focused attention; potentially indicating distinct cognitive processes that support attentional control. These findings support the hypothesis regarding differing levels of cortical arousal in extraverts and introverts and extend personality theory by linking the extraversion dimension to attentional control and functional connectivity dynamics.in bioRxiv: Neuroscience on 2025-11-22 00:00:00 UTC.
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Neural dynamics outside task-coding dimensions drive decision trajectories through transient amplification
Most behaviors involve neural dynamics in high-dimensional activity spaces. A common approach is to extract dimensions that capture task-related variability, such as those separating stimuli or choices, yielding low-dimensional, task-aligned neural activity subspaces ("coding dimensions"). However, whether these dimensions actively drive decisions or merely reflect underlying computations remains unclear. Moreover, neural activity outside these coding subspaces ("residual dimensions") is often ignored, though it could also causally shape neural dynamics driving behavior. We developed a recurrent neural network model that fits population activity and uncovers the dynamic interactions between coding and residual subspaces on single trials. Applied to electrophysiological recordings from the anterior lateral motor cortex (ALM) and motor thalamus in mice performing a delayed response task, our model demonstrates that perturbations of residual dimensions reliably alter behavioral choices, whereas perturbations of the choice dimension, which strongly encodes the animal's upcoming decision, are largely ineffective. These perturbation effects arise because residual dimensions drive transient amplification across an intermediate number of coding and residual dimensions (~10), before the dynamics collapse into discrete attractor states corresponding to the animal's choice. By dissecting the low-dimensional variability underlying error trials, we find that it primarily shifts trajectories along residual dimensions, biasing single decisions. Residual activity in thalamus shapes cortical decision dynamics, implicating weakly selective thalamic populations in the emergence of cortical selectivity. Our findings challenge the conventional focus on low-dimensional coding subspaces as sufficient framework for understanding neural computations, demonstrating that dimensions previously considered task-irrelevant and accounting for little variance can have a critical role in driving behavior.in bioRxiv: Neuroscience on 2025-11-22 00:00:00 UTC.
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Two-photon characterisation of long-Stokes-shift dye ATTO 490LS for single-laser multicolour imaging
Long-Stokes-shift fluorophores enable high sensitivity and multiplexed imaging with single-wavelength excitation. Under single-photon conditions ATTO 490LS exhibits a 165-nm Stokes shift, but its two-photon properties remain uncharacterised. Emission and excitation spectral analyses of ATTO 490LS in ex vivo Drosophila melanogaster brains identified two-photon excitation sensitivity at 940 nm, with peak emission at 640 nm. We demonstrate successful duplexed imaging of ATTO 490LS alongside Alexa Fluor 488 using a single 920-nm fibre laser and dual photomultiplier tubes, enabling distinct measurement of red and green fluorescence signals. These findings establish ATTO 490LS as suitable for multicolour two-photon microscopy with single-laser systems.in bioRxiv: Neuroscience on 2025-11-22 00:00:00 UTC.
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Developing a Systemic Framework to Reduce the Bullwhip Effect in the Construction Industry: Empirical Insights and Practical Implications [version 1; peer review: awaiting peer review]
Background The construction industry faces systemic inefficiencies and cost overrun. Many of these issues result from demand amplification, known as the Bullwhip Effect (BWE), within supply chains. Aim To investigate the root causes and impacts of the Bullwhip Effect during construction. Establish a foundation for mitigation strategies using a conceptual framework. This framework was validated using a real-world case study to support effective mitigation. Methods This study systematically identified and analyzed twenty-one underlying causes of the Bullwhip Effect in the supply chain. The effect was calculated for the selected construction materials using data from Mostashar United Company-Kuwait. Results The Bullwhip Effect in the construction industry emerges not from a single cause but from a complex interaction of factors that significantly influence the phenomenon and are deeply embedded within the industry’s structural and operational practices. These causes are grouped into three main dimensions: informational, operational, and behavioral factors. BWE can be quantitatively measured and directly escalates production costs and intensifies over time if mitigating strategies are not implemented. Research has identified several strategies that can effectively prevent the occurrence or reduce the bullwhip effect in the construction industry, such as collaboration and teamwork enhanced strategies between SCM partners, optimizing information exchange and communications among SCM partners, Building SCM Resilience Against Component Shortages, and Strategic Planning for Resource Utilization. Conclusion The causes of Bullwhip Effects and impacts are interconnected rather than segregated or isolated, creating a reinforcing feedback loop where informational opacity sparks behavioral reactions, further intensifying operational instability. A bullwhip mitigation policy should include addressing data transparency, supply chain process coordination, and contractual early incentives, instead of focusing on isolated symptom management, instead of systemic resolution.in F1000Research on 2025-11-21 17:32:31 UTC.
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Building Entrepreneurship Ecosystem: A Systematic Review [version 2; peer review: 1 approved with reservations, 2 not approved]
The primary objective of this study is to advance research by providing a conceptual framework for entrepreneurship ecosystem building and the growth of entrepreneurship intention among students in higher education institutions. The study conducted a comprehensive literature review, selecting peer-reviewed articles on entrepreneurial ecosystem building and entrepreneurial intention growth. A systematic review (SR) method was used to achieve he stated objectives. The PRISMA protocol, searching approach, inclusion and exclusion criteria, and data analysis technique were successfully applied. The research finding shows that developing a robust entrepreneurial ecosystem within universities can stimulate entrepreneurial activities, enhance self-efficacy, and cultivate an entrepreneurial culture. The findings also underscore the importance of creating environments that not only provide knowledge and skills but also practical experiences and support networks essential for nurturing future entrepreneurs. Finally, both empirical and practical implication was identified and a future research direction was suggested for future researchers.in F1000Research on 2025-11-21 17:30:02 UTC.
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Study Protocol: Intrafamily Communication on Mental Disorders (IFACOM) [version 1; peer review: awaiting peer review]
Our study deals with intra-family communication on mental disorders. We plan to develop a questionnaire, which can be used to measure the functionality of intra-family communication. Previous studies have shown that certain forms of communication in families affected by mental disorders impact the further course of the disease. Derogatory or taboo communication content are known to be disease-promoting, while open and positive communication has a preventive effect on the occurrence of further mental disorders. The functionality of communication therefore describes the potential of a health-promoting effect of intra-family communication styles. On the other hand, dysfunctional communication styles might be associated with a higher risk of the new emergence or recurrence of mental health problems in other family members. Following a systematic literature search on data containing information on intra-family communication patterns on mental disorders we plan to collect further data suing qualitative interviews (n=10). Interviewees include family members of individuals affected by mental disorders. We then plan to create a questionnaire with approximately 30 factors and items. This questionnaire will be tested in a large cohort of family members of individuals affected by mental disorders (n=300) and consequently validated by a confirmatory factor analysis. With the help of the planned questionnaire, risk factors of patients could be recognized earlier and taken into account for therapeutic interventions.in F1000Research on 2025-11-21 17:27:44 UTC.
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Barriers and Strategies for Antiretroviral Therapy Appointment Adherence in Rural South Africa: A Narrative Review with a Focus on the Vhembe District [version 1; peer review: awaiting peer review]
Background and Objective Antiretroviral therapy (ART) is the cornerstone of HIV treatment, but its effectiveness depends heavily on consistent patient adherence to scheduled appointments. Rural regions, such as the Vhembe district in South Africa, face persistent structural, economic, and psychosocial challenges that hinder ART adherence and continuity of care. This narrative review synthesizes evidence on the multifaceted barriers affecting ART appointment adherence in rural settings and evaluates intervention strategies that have demonstrated success across sub-Saharan Africa. It emphasizes the relevance of these findings to the Vhembe district context. Methods The review draws on three key evidence sources: a doctoral study evaluating home delivery models for ART, a systematic review on treatment supporter interventions (TSIs), and a meta-analysis on adherence among pregnant women using digital and educational tools. The selected studies were critically examined for their applicability to rural service delivery and adherence outcomes. Results The review identifies major adherence barriers, including poor transport infrastructure, high indirect costs, clinic overcrowding, limited refill durations, stigma, and the impact of public health emergencies. Strategies such as home delivery, multi-month dispensing (MMD), mHealth device reminders, and community-based support programs (TSIs) are shown to mitigate these challenges effectively. Combined socio-structural interventions yield the most substantial improvements in adherence outcomes. Conclusions Improving ART appointment adherence in Vhembe requires an integrated model tailored to local realities. Combining decentralized care, social support structures, mHealth solutions, and financial incentives offers a sustainable path forward. However, research gaps in implementation science, cost-effectiveness, and context-specific interventions must be addressed to scale these solutions effectively.in F1000Research on 2025-11-21 16:24:36 UTC.
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Urban Noise Pollution through Combined Analysis of Sound Levels [version 1; peer review: awaiting peer review]
Introduction Noise pollution has become one of the most frequent urban environmental problems, with negative effects on public health, social well-being, and quality of life in high population density contexts. Within this framework, the present study was developed with the purpose of characterizing environmental noise levels in the Historic Center of Lima, integrating objective measurements and citizens’ perceptions. Methodology The research adopted a quantitative approach, applied type, with a non-experimental and cross-sectional design. Measurements were carried out at thirteen strategic points along Abancay Avenue using a type I integrating sound level meter, while population perception was collected through a structured survey applied to 392 participants selected by non-probabilistic sampling. Data were processed through descriptive and comparative analysis between instrumental records and population responses. Results The findings showed that equivalent noise levels consistently exceeded environmental quality standards for commercial zones, reaching maximum values above 90 dB(A). Vehicular traffic and informal commercial activity were identified as the main noise sources, and most respondents perceived noise as intense and disturbing, especially during the evening-nighttime period. Conclusion Noise pollution in the studied area constitutes a persistent problem that affects environmental quality and the daily lives of the population. Furthermore, the need to design urban management and acoustic control strategies is recognized, aiming to reduce exposure in heritage and commercial corridorsin F1000Research on 2025-11-21 16:14:20 UTC.
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The Genetic Association of Single Nucleotide Polymorphisms of SERPINE1 (rs6092) and IFNAR2 (rs1051393, rs2229207) Genes Is Related to Post Covid-19 Respiratory Syndrome [version 1; peer review: awaiting peer review]
Background Coronavirus disease 2019 (Covid-19) is a disease of the respiratory system caused by the SARS-CoV-2 virus. The severity of Covid-19 can be affected by the presence of single nucleotide polymorphisms (SNPs) in certain genes, such as IFNAR2 and SERPINE-1. This study aimed to identify and analyze the presence of SNP rs6092 in the SERPINE1 gene and rs1051393 and rs2229207 in the IFNAR2 gene relation in Covid-19 respiratory syndrome in Indonesia. Methods DNA was isolated from saliva samples of all patients, and a TaqMan Genotyping Assay with a real-time PCR instrument was used to run the samples. The output data were analyzed for demographic data, allele frequency, genotype frequency, and the association of all SNPs with the Covid-19 respiratory syndrome (case) and control subjects. We also analyzed blood laboratory results, blood gas analyses, coagulation factors, and inflammatory factors using SPSS. Results This study included 85 subjects comprise with Covid-19 respiratory syndrome and control subjects. Our study found no association between subjects with Covid-19 respiratory syndrome and any of the variants. However, based on the symptoms caused by rs1051393, we found that it had an effect on fever symptoms. In addition, a significant relationship between rs2229207 and chest pain symptoms was observed in patients with case group. Furthermore, our study found significant differences (p < 0.05) in several blood laboratory analyses, such as the level of basophils and eGFR for rs6092 and the potassium level for rs2229207. Furthermore, arterial blood gas analysis showed that pCO2 and pH levels were significantly different for rs2229207. Conclusion Our study found an association between rs1051393 and fever and between rs2229207 and chest pain in patients with post Covid-19 respiratory syndrome.in F1000Research on 2025-11-21 16:12:21 UTC.
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Are We Truly Preparing Students for Financial Success? Insights from Economic Education Curricula in Indonesia [version 1; peer review: awaiting peer review]
Background Financial literacy is an essential competency for university students, especially those in economics education programs, as it supports effective money management and responsible decision-making. However, higher education curricula in Indonesia still emphasize theoretical aspects over practical financial skills, raising concerns about whether graduates are adequately prepared for financial challenges. Methods This study employed a qualitative content analysis to evaluate the integration of financial literacy within economics education curricula in Indonesia. Data were collected through curriculum document reviews, semi-structured interviews with economics educators, and student surveys. The analysis focused on identifying the extent of financial literacy integration and perceptions of curriculum effectiveness. Results The findings indicate that while fundamental topics such as budgeting and savings are covered, critical elements including investment diversification, risk management, and digital financial tools remain underdeveloped. Students expressed a strong demand for more experiential learning approaches, such as case studies, financial simulations, and collaboration with industry partners. The results highlight a gap between theoretical instruction and the practical competencies required for effective financial decision-making. Conclusions The study concludes that strengthening economics education curricula requires the integration of applied financial literacy training, digital financial education, and industry collaboration to better prepare students for personal and professional financial challenges. While this research provides valuable insights, its qualitative scope presents limitations. Future studies with broader institutional coverage and quantitative approaches are recommended to generate more generalizable findings.in F1000Research on 2025-11-21 16:09:56 UTC.
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A Systematic Literature Review and Bibliometric Analysis of Workplace Coaching [version 1; peer review: awaiting peer review]
Workplace Coaching has evolved significantly over the last two decades and has become a mainstream global activity in business organizations. The concept has been recognized for its potential in enhancing the well-being and performance of individuals, groups, and leaders, making it a popular intervention in modern organizations. Therefore, this study provides a comprehensive understanding of workplace coaching research from 2000 to 2025 by examining global trends in terms of publications, contributors, keyword co-occurrences, and thematic clusters, utilizing a systematic literature review with bibliometric analysis. The review was conducted to synthesise the available literature on workplace coaching to suggest future trends. The Scopus and Web of Science databases were used to explore and analyze published works using the PRISMA framework and VOSviewer software. A total of 343 published journal articles were considered in the analysis, eliminating duplication and minimizing potential risks during the screening process. The findings reveal a significant growth in academic interest in coaching in workplace research, with four key thematic clusters emerging: Coaching for Workplace Learning and Development, Multifaceted advantages of Executive and Leadership Coaching, Dimensions of Workplace Coaching, and Employee Coaching for Human Resource Management and Development. The study findings serve as a foundation for future studies that explore under-researched areas, such as the application of artificial intelligence in coaching practices, ethical considerations, digital transformation, sustainability in leadership, and employee well-being practices. Moreover, this study reveals the potential of meta-analyses and systematic reviews that incorporate grey literature to provide a more comprehensive understanding of coaching effectiveness. Comparative studies across different sectors, countries, and regions can help consolidate the existing findings and uncover new insights. These limitations and opportunities present avenues for future research, motivating researchers to advance and refine existing literature.in F1000Research on 2025-11-21 16:08:14 UTC.
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Automated and modular protein binder design with BinderFlow
by Nayim González-Rodríguez, Carlos Chacón-Sánchez, Oscar Llorca, Rafael Fernández-Leiro
Deep learning has revolutionised de novo protein design, with new models achieving unprecedented success in creating novel proteins with specific functions, including artificial protein binders. However, current workflows remain computationally demanding and challenging to operate without dedicated infrastructure and expertise. To overcome these limitations, we present BinderFlow, an open, structured, and parallelised pipeline that automates end-to-end protein binder design. Its batch-based architecture enables live monitoring of design campaigns, seamless coexistence with other GPU-intensive processes, and minimal user intervention. BinderFlow’s modular design facilitates the integration of new tools, allowing rapid adaptation to emerging methods. We demonstrate its utility by running automated design campaigns that rapidly generate diverse, high-confidence candidates suitable for experimental validation. To complement the pipeline, we developed BFmonitor, a web-based dashboard for real-time campaign monitoring, design evaluation, and hit selection. Together, BinderFlow and BFmonitor make generative protein design more accessible, scalable, and reproducible, streamlining both exploratory and production-level research. The software is freely available at https://github.com/cryoEM-CNIO/BinderFlow under the GNU LGPL v3.0 license.in PLoS Computational Biology on 2025-11-21 14:00:00 UTC.
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Ten simple rules for maximizing summer research experiences for students, mentors, and research groups
by Miriam B. Goodman
Whether hosted by colleges, universities, stand-alone research institutions, federal research labs, or private companies, immersive summer (6–12 weeks) research experiences build students’ confidence in their scientific capabilities and help to refine their professional trajectories. Such internships are an important tool to introduce students to STEM careers and energize participants, each of whom realizes a powerful benefit. The student gains hands-on research experience, insight into the research process, and clarity regarding their educational and career aspirations. The bench mentor, typically an advanced graduate student, postdoctoral researcher, or staff scientist, acquires essential skills in training and mentoring while incorporating fresh perspectives from an inquisitive novice into their research project. The principal investigator (PI) promotes the professional development of the bench mentor, expands interest in STEM careers, while exploring a focused and compact research question. This set of Ten Simple Rules is a guide for PIs, bench mentors, and research groups and seeks to foster excellence in the design of short-term research experiences for students. They emphasize projects co-created by PIs and bench mentors, accessible techniques that can be mastered in a few weeks, and strategies enabling interns to develop their own mental model of the research question and approach. Although tailored primarily to full-time summer internships for individual students in an academic research setting, this advice may be applicable to short-term, mentored research experiences in multiple settings.in PLoS Computational Biology on 2025-11-21 14:00:00 UTC.
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Nash equilibrium of attack and defense behaviors between predators and prey
by Hiroyuki Ichijo, Yuichiro Kawamura, Tomoya Nakamura
How animals process information, compute, and execute behaviors is a central question in neuroscience and computational biology. Predators attack prey by chasing or ambushing them, while prey respond with escaping or freezing. These behaviors are fundamental for survival. Uncovering functions of such behaviors requires an understanding not only of the implementation of neuronal circuits but also of the underlying algorithms and computation. However, how animals respond to predators or prey depending on whether they can detect them from a distance remains unclear. Here, we modeled and analyzed attack and defense behaviors with game theory. Using encounter probabilities to construct payoff matrices under a sensory–motor algorithm that lacked directional information, we identified the corresponding equilibrium behaviors for the agents (predators and prey). Different detection distances yielded distinct Nash equilibrium behaviors, representing a computational mechanism that can account for diverse attack and defense behaviors. The games based on interactions among multiple predators and prey were, in most cases, non-constant-sum and positive-sum games. Measured payoffs of Nash equilibrium behaviors indicated that the predators were able to increase their payoffs by attacking, and the prey were also able to increase their payoffs even in the presence of predators. These results suggest that each of the agents initiates attack and defense behaviors. Moreover, Nash equilibrium behaviors were also identified under a simpler non-sensory motor algorithm. Despite the similarity, the non-sensory motor algorithm and the sensory–motor algorithm had distinct adaptive significance. The sensory–motor algorithm produced substantially greater prey payoffs. By implementing these algorithms, agents interact in ways that give rise to payoff matrices from which various Nash equilibrium behaviors can be mathematically derived under different conditions. Furthermore, this approach offers an experimental framework for understanding behavioral evolution and suggests a possible difference in evolutionary mechanisms of attack and defense behaviors.in PLoS Computational Biology on 2025-11-21 14:00:00 UTC.
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Parameterization of cell-free systems with time-series data using KETCHUP
by Mengqi Hu, Syed Bilal Jilani, Daniel G. Olson, Costas D. Maranas
Kinetic models mechanistically link enzyme levels, metabolite concentrations, and allosteric regulation to metabolic reaction fluxes. This coupling allows for the quantitative elucidation of the dynamics of the evolution of metabolite concentrations and metabolic fluxes as a function of time. So far, most large-scale kinetic model parameterizations are carried out using mostly steady-state flux measurements supplemented with metabolomics and/or proteomics data when available. Even though the parameterized kinetic model can trace a temporal evolution of the system, lack of anchoring to temporal data reduces confidence in the dynamics predictions. Notably, the simulation of enzymatic cascade reactions requires a full description of the dynamics of the system as a steady-state is not applicable given that all measured metabolite concentrations vary with time. Here we describe how kinetic parameters fitted to the dynamics of single-enzyme assays remain accurate for the simulation of multi-enzyme cell-free systems. Herein, we demonstrate two extensions for the Kinetic Estimation Tool Capturing Heterogeneous datasets Using Pyomo (KETCHUP) software tool for parameterizing a kinetic model of the cell-free kinetics of formate dehydrogenase (FDH) and 2,3-butanediol dehydrogenase (BDH) through the use of time-course data across various initial conditions. An implemented extension of KETCHUP allowing for the reconciliation of measurement time-lag errors present in datasets was used to parameterize kinetic models using multiple datasets. By combining the kinetic parameters identified by the FDH and BDH assays, accurate simulation of the binary FDH-BDH system was achieved.in PLoS Computational Biology on 2025-11-21 14:00:00 UTC.
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Universal scale-free representations in human visual cortex
by Raj Magesh Gauthaman, Brice Ménard, Michael F. Bonner
How does the human brain encode complex visual information? While previous research has characterized individual dimensions of visual representation in cortex, we still lack a comprehensive understanding of how visual information is organized across the full range of neural population activity. Here, analyzing fMRI responses to natural scenes across multiple individuals, we discover that neural representations in human visual cortex follow a remarkably consistent scale-free organization—their variance decay is consistent with a power-law distribution, detected across four orders of magnitude of latent dimensions. This scale-free structure appears consistently across multiple visual regions and across individuals, suggesting it reflects a fundamental organizing principle of visual processing. Critically, when we align neural responses across individuals using hyperalignment, we find that these representational dimensions are largely shared between people, revealing a universal high-dimensional spectrum of visual information that emerges despite individual differences in brain anatomy and visual experience. Traditional analysis approaches in cognitive neuroscience have focused primarily on a small number of high-variance dimensions, potentially missing crucial aspects of visual representation. Our results demonstrate that visual information is distributed across the full dimensionality of cortical activity in a systematic way, thus revealing a key property of neural coding in visual cortex. These findings suggest that we need to move beyond low-dimensional characterizations to fully understand how the brain represents the visual world.in PLoS Computational Biology on 2025-11-21 14:00:00 UTC.
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Protein drift-diffusion in membranes with non-equilibrium fluctuations arising from gradients in concentration or temperature
by Dev Jasuja, Paul J. Atzberger
We investigate proteins within heterogeneous cell membranes where non-equilibrium phenomena arises from spatial variations in concentration and temperature. We develop simulation methods building on non-equilibrium statistical mechanics to obtain stochastic hybrid continuum-discrete descriptions which track individual protein dynamics, spatially varying concentration fluctuations, and thermal exchanges. We investigate biological mechanisms for protein positioning and patterning within membranes and factors in thermal gradient sensing. We also study the kinetics of Brownian motion of particles with temperature variations within energy landscapes arising from heterogeneous microstructures within membranes. The introduced approaches provide self-consistent models for studying biophysical mechanisms involving the drift-diffusion dynamics of individual proteins and energy exchanges and fluctuations between the thermal and mechanical parts of the system. The methods also can be used for studying related non-equilibrium effects in other biological systems and soft materials.in PLoS Computational Biology on 2025-11-21 14:00:00 UTC.
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Emergence of sparse coding, balance and decorrelation from a biologically-grounded spiking neural network model of learning in the primary visual cortex
by Marko A. Ruslim, Martin J. Spencer, Hinze Hogendoorn, Hamish Meffin, Yanbo Lian, Anthony N. Burkitt
Many experimental and computational studies deal with sparseness, balance, and decorrelation in neural networks and explain the presence of these properties as fulfilling requirements related to optimum energy efficiency, network stability, and information representation. These studies leave the question of how these properties arise in the brain unanswered. The present study attempts to address this question using a model built upon the experimentally observed properties of neural responses, homeostasis, and synaptic plasticity. The experimentally observed properties of sparseness, balance, and decorrelation are then expected to emerge from this substrate. A spiking neural model of the primary visual cortex (V1) was investigated. Populations of both inhibitory and excitatory leaky integrate-and-fire neurons with recurrent connections were provided with spiking input from simulated ON and OFF neurons of the lateral geniculate nucleus. This network was provided with natural image stimuli as input. All synapses underwent learning using spike-timing-dependent plasticity learning rules. A homeostatic rule adjusted the weights and thresholds of each neuron based on target homeostatic spiking rates and mean synaptic input values. These experimentally grounded rules resulted in a number of the expected properties of information representation. The network showed a temporally sparse spike response to inputs and this was associated with a sparse code with Gabor-like receptive fields. The network was balanced at both slow and fast time scales; increased excitatory input was balanced by increased inhibition. This balance was associated with decorrelated firing that was observed as population sparseness. This population sparseness was both the cause and result of the decorrelation of receptive fields. These observed emergent properties (balance, temporal sparseness, population sparseness, and decorrelation) indicate that the network is implementing expected principles of information processing: efficient coding, information maximization (’infomax’), and a lateral or single-layer form of predictive coding. These emergent features of the network were shown to be robust to randomized jitter of the values of key simulation parameters.in PLoS Computational Biology on 2025-11-21 14:00:00 UTC.
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The efficacy of longevity interventions in Caenorhabditis elegans is determined by the early life activity of RNA splicing factors
by Sneha Dutta, Maria Camila Perez Matos, Caroline Heintz, Ayse Sena Mutlu, Mary Piper, Meeta Mistry, Arpit Sharma, Christopher S. Morrow, Hannah Smith, Porsha Howell, Rohan Sehgal, Anne Lanjuin, Meng C. Wang, William B. Mair
Geroscience aims to target the aging process to extend healthspan. However, even isogenic individuals show heterogeneity in natural aging rate and responsiveness to pro-longevity interventions, limiting translational potential. Using RNAseq analysis of young, isogenic, subpopulations of Caenorhabditis elegans selected solely on the basis of the splicing pattern of an in vivo minigene reporter that is predictive of future life expectancy, we find a strong correlation in young animals between predicted life span and alternative splicing of mRNAs related to lipid metabolism. The activity of two RNA splicing factors, Reversed Polarity-1 (REPO-1) and Splicing Factor 1 (SFA-1), early in life is necessary for C. elegans response to specific longevity interventions and leads to context-specific changes to fat content that is mirrored by knockdown of their direct target POD-2/ACC1. Moreover, POD-2/ACC1 is required for the same longevity interventions as REPO-1/SFA-1. In addition, early inhibition of REPO-1 renders animals refractory to late onset suppression of the TORC1 pathway. Together, we propose that splicing factor activity establishes a cellular landscape early in life that enables responsiveness to specific longevity interventions and may explain variance in efficacy between individuals.in PLoS Biology on 2025-11-21 14:00:00 UTC.
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Cardiometabolic health and physical robustness map onto distinct patterns of brain structure and neurotransmitter systems
by Eliana Nicolaisen-Sobesky, Somayeh Maleki Balajoo, Mostafa Mahdipour, Agoston Mihalik, Mahnaz Olfati, Felix Hoffstaedter, Janaina Mourao-Miranda, Masoud Tahmasian, Simon B. Eickhoff, Sarah Genon
The link between brain health and risk/protective factors for non-communicable diseases (such as high blood pressure, high body mass index, diet, smoking, physical activity, etc.) is increasingly acknowledged. However, the specific effects that these factors have on brain health are still poorly understood, delaying their implementation in precision brain health. Here, we studied the multivariate relationships between risk factors for non-communicable diseases and brain structure, including cortical thickness (CT) and gray matter volume (GMV). Furthermore, we adopted a systems-level perspective to understand such relationships, by characterizing the cortical patterns (yielded in association to risk factors) with regards to brain morphological and functional features, as well as with neurotransmitter systems. Similarly, we related the pattern of risk/protective factors dimensions with a peripheral marker of inflammation. First, we identified latent dimensions linking a broad set of risk factors for non-communicable diseases to parcel-wise CT and GMV across the whole cortex. Data was obtained from the UK Biobank (n = 7,370, age range = 46–81 years). We used regularized canonical correlation analysis (RCCA) embedded in a machine learning framework. This approach allows us to capture inter-individual variability in a multivariate association and to assess the generalizability of the model. The brain patterns (captured in association with risk/protective factors) were characterized from a multi-level perspective, by performing correlations (spin tests) between them and different brain patterns of structure, function, and neurotransmitter systems. The association between the risk/protective factors pattern and C-reactive protein (CRP, a marker of inflammation) was examined using Spearman correlation. We found two significant and partly replicable latent dimensions. One latent dimension linked cardiometabolic health to brain patterns of CT and GMV and was consistent across sexes. The other latent dimension linked physical robustness (including non-fat mass and strength) to patterns of CT and GMV, with the association to GMV being consistent across sexes and the association to CT appearing only in men. The CT and GMV patterns of both latent dimensions were associated to the binding potentials of several neurotransmitter systems. Finally, the cardiometabolic health dimension was correlated to CRP, while physical robustness was only very weakly associated to it. We observed robust, multi-level and multivariate links between both cardiometabolic health and physical robustness with respect to CT, GMV, and neurotransmitter systems. Interestingly, we found that cardiometabolic health and physical robustness are associated with not only increases in CT or GMV, but also with decreases of CT or GMV in some brain regions. Our results also suggested a role for low-grade chronic inflammation in the association between cardiometabolic health and brain structural health. These findings support the relevance of adopting a holistic perspective in health, by integrating neurocognitive and physical health. Moreover, our findings contribute to the challenge to the classical conceptualization of neuropsychiatric and physical illnesses as categorical entities. In this perspective, future studies should further examine the effects of risk/protective factors on different brain regions in order to deepen our understanding of the clinical significance of such increased and decreased CT and GMV.in PLoS Biology on 2025-11-21 14:00:00 UTC.
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Nanobody-drug conjugates for targeting specific GPCR pairs
by Xianglin Huang, Bryan L. Roth
Bitopic ligands that engage two distinct binding sites offer exciting opportunities for finely tuned control of G protein-coupled receptor signaling. A recent study in PLOS Biology employed click chemistry to generate novel nanobody-small molecule conjugates and demonstrated their logic-gated activity at co-expressed receptor pairs with improved signaling profiles. Bitopic ligands that engage two distinct binding sites offer exciting opportunities for finely tuned control of G protein-coupled receptor signaling. This Primer explores a recent study in PLOS Biology that reports novel nanobody-small molecule conjugates and demonstrates their logic-gated activity at co-expressed receptor pairs with improved signaling profiles.in PLoS Biology on 2025-11-21 14:00:00 UTC.
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Effect of Canal Size on Isthmus Cleaning Efficiency and Safety of High-Frequency Sonic Agitation: An In Vitro Study [version 1; peer review: awaiting peer review]
Objective This study aimed to evaluate the effect of root canal preparation size on isthmus cleaning efficiency and periapical extrusion using high-frequency sonic agitation with the EDDY irrigation system. Materials and Methods Thirty custom-made epoxy split models were used to simulate a root canal system with two curved canals merging at the apical 1 mm and an isthmus extending along their length. A periapical lesion was simulated to assess the extrusion tendency. Canals were prepared using the WaveOne Gold system in small, primary, and medium sizes. The isthmuses were filled with bovine dentin debris, while dyed gelatin was used in the periapical lesion to quantify extruded irrigant volume. EDDY irrigation efficiency was evaluated based on the total cleared surface area (mm2) using ImageJ software. Statistical analysis was performed using one-way ANOVA and post hoc multiple comparisons, with a significance level of P ≤ 0.05. Results Isthmus cleaning efficiency remained consistent across all canal sizes, with no significant differences among groups (P > 0.05). However, periapical extrusion increased significantly with larger canal preparation sizes, with medium-sized preparations showing significantly higher extrusion than small (P = 0.001) and primary (P = 0.026) sizes. Conclusion EDDY irrigation was effective in achieving isthmus cleanliness regardless of canal preparation size. However, larger instrumentation increased the risk of apical extrusion, underscoring the need for careful irrigation management in clinical applications.in F1000Research on 2025-11-21 11:25:21 UTC.
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Association of cancer and outcomes of patients hospitalized for COVID-19 between 2020 and 2023 [version 3; peer review: 1 approved, 2 approved with reservations, 1 not approved]
Background The coronavirus disease 2019 (COVID-19) has caused substantial morbidity and mortality on a global scale. A strong correlation has been found between COVID-19 treatment outcomes and noncommunicable diseases such as cancers. However, there is limited information on the outcomes of cancer patients who were hospitalised for COVID-19. Methods We conducted an analysis on data collected in a large prospective cohort study set-up by the World Health Organisation (WHO) International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC). All patients with laboratory-confirmed or clinically-diagnosed SARS-CoV-2 infection were included. Cancer was defined as having a current solid organ or haematological malignancy. The following outcomes were assessed; The hazard ratio of 30-day in-hospital mortality, intensive care unit (ICU) admission, length of hospitalization and receipt of higher-level care. Results Of the 560,547 hospitalised individuals who were analysed, 27,243 (4.9%) had cancer. Overall, cancer patients were older and had more comorbidities than non-cancer patients. Patients with cancer had a higher hazard ratio of 30-day in-hospital mortality than non-cancer patients (29.1.3% vs 18.0%) and longer hospital stays (median of 12 days vs 8 days). However, patients with cancer were admitted less often to intensive care units than non-cancer patients (12.6% vs 17.1%) and received less invasive mechanical ventilation than non-cancer patients (4.5% vs 7.6%). The hazard ratio of dying from cancer, adjusted for age, sex and country income level was 1.18 (95%CI: 1.15-1.2). Conclusions This study’s findings underscore the heightened vulnerability of hospitalized COVID-19 patients with cancer, revealing a higher mortality rate, longer hospital stays, and an unstructured pattern of care that reflects the complexity of managing severely ill patients during a public health crisis like the COVID-19 pandemic.in F1000Research on 2025-11-21 10:43:08 UTC.
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The complete chloroplast genome of Phyllanthus acidus (L.) Skeels (Phyllanthaceae) [version 3; peer review: 3 approved with reservations]
Phyllanthus acidus (L.) Skeels (Phyllanthaceae) is a potential medicinal plant recognized for its sour and tart-tasting fruits. In this study, the chloroplast genome of P. acidus was sequenced, assembled, and characterized. The chloroplast genome size was 156,331 bp, and the overall GC content was 36.9%. Additionally, the chloroplast genome had a quadripartite structure consisting of a large single copy (LSC; 85,807 bp in length; GC content: 34.6%), a small single copy (SSC; 19,262 bp in length; GC content: 30.6%), and two inverted repeat regions (IR; 25,631 bp in length; GC content: 43.1%). A total of 113 unique genes were annotated in the chloroplast genome, including 79 protein-coding genes, 30 tRNAs, and four rRNAs. The phylogenetic analysis based on 79 protein-coding genes revealed the paraphyly of the Phyllanthus genus. These findings provided additional genetic information for further research on P. acidus and the cp genome in the Phyllanthaceae family.in F1000Research on 2025-11-21 10:39:01 UTC.
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Boundary homogenization and numerical modeling of solute transport across the blood-brain barrier
Author(s): Reza Yousofvand, Gregory Handy, and Jeffrey Tithof
Effective clearance of amyloid- () from the brain is essential for preventing neurodegenerative diseases such as Alzheimer's. A significant portion of this clearance occurs through the blood-brain barrier (BBB) via receptor-mediated transport. However, current models fail to capture the complex k…
[Phys. Rev. E 112, 054410] Published Fri Nov 21, 2025
in Physical Review E: Biological physics on 2025-11-21 10:00:00 UTC.
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Anatomical Associations Between Focal Mitochondrial Metabolism and Patterns of Neurodegeneration in Amyotrophic Lateral Sclerosis
Objective
Amyotrophic lateral sclerosis (ALS) has a very specific neuroimaging signature, but the molecular underpinnings of the strikingly selective anatomic involvement have not elucidated to date. Accordingly, a large neuroimaging study was conducted with 258 participants to evaluate associations between patterns of neurodegeneration and focal metabolic metrics.
Methods
Structural and diffusivity alterations were systematically evaluated in a genetically stratified cohort. Voxelwise associations between neurodegeneration and physiological mitochondrial indices were systematically evaluated over the entire brain and also examined in specific regions.
Results
Significant topological associations were identified between physiological mitochondria tissue density, nicotinamide adenine dinucleotide (NADH)–ubiquinone oxidoreductase, succinate dehydrogenase, cytochrome c oxidase (COX), mitochondrial respiratory capacity (MRC), tissue respiratory capacity (TRC), and propensity to focal atrophy in ALS. Anatomic correlations between mitochondrial metrics and morphometric change were particularly strong in GGGGCC hexanucleotide repeat carriers in C9orf72. Diffusivity analyses also confirmed associations between brain metabolism and microstructural degeneration. Higher focal mitochondria tissue density was associated with higher likelihood of frontal, temporal, cerebellar, opercular, thalamic, cingulum, putamen, corpus callosum, and corona radiata degeneration. Uncinate fasciculus degeneration was associated with higher Complex I, II, COX, and TRC activity. Topological associations were readily replicated in an external validation cohort.
Interpretation
Our data indicate that brain regions with high metabolic activity are particularly vulnerable to neurodegeneration in ALS. Anatomic associations between physiological cerebral metabolism and patterns of neurodegeneration implicate mitochondrial dysfunction in the pathophysiology of ALS. Although mitochondrial dysfunction may not be the primary etiological factor, it may represent a shared bottleneck of multiple converging molecular and genetic pathways, offering a potential opportunity for meaningful pharmacological intervention. ANN NEUROL 2025
in Annals of Neurology on 2025-11-21 08:58:45 UTC.
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Additive Effects of White Matter Hyperintensity and APOE ε4 Status on Risk of Incident Dementia in Two Large Longitudinal Cohorts
Objective
To evaluate whether white matter hyperintensities (WMH) and apolipoprotein E (APOE) ε4 status have an additive or multiplicative effect on the risk of incident all-cause dementia.
Methods
We conducted a prospective cohort study in the Atherosclerosis Risk in Communities (ARIC) study and confirmed findings in the UK Biobank (UKB). The exposures were APOE ε4 status (0 vs. ≥1 allele) and WMH on magnetic resonance imaging (MRI). The primary outcome was incident all-cause dementia. After confirming an additive interaction, we created combined exposure groups: WMH−/ε4−, WMH+/ε4−, WMH−/ε4+, and WMH+/ε4+. Cox proportional hazards models were adjusted for age, sex, race, education, cognition (ARIC only), hypertension, diabetes, and prior stroke.
Results
In ARIC (n = 1,736, mean age 63, 58.8% female, 48.7% non-Hispanic White individuals, median follow-up 18.6 years), the dementia incidence rate was 10.4 (95% CI, 9.2–11.6) per 1,000 person-years. Compared to WMH−/ε4–, adjusted hazard ratios (HRs) for dementia were: WMH−/ε4+, 1.5 (95% CI, 1.1–2.1); WMH+/ε4–, 2.0 (95% CI, 1.4–2.7); and WMH+/ε4+, 3.2 (95% CI, 2.2–4.6). In UKB (n = 40,307, mean age 55, 52.7% female, 97.1% non-Hispanic White individuals, median follow-up 3.2 years), the dementia incidence rate was 0.42 (95% CI, 0.32–0.55) per 1,000 person-years. Adjusted HRs were: WMH−/ε4+, 2.3 (95% CI, 1.2–4.5); WMH+/ε4–, 2.1 (95% CI, 1.0–4.6); and WMH+/ε4+, 6.7 (95% CI, 3.2–13.9).
Interpretation
WMH burden and APOE ε4 status additively increase dementia risk. These findings support the potential benefit of vascular risk management to reduce WMH and delay dementia onset, even among genetically at-risk individuals. ANN NEUROL 2025
in Annals of Neurology on 2025-11-21 08:57:07 UTC.
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Frailty across Neurological Diseases: Why Sex and Gender Matter
Frailty is increasingly recognized as a critical factor in neurology, influencing disease susceptibility, progression, and outcomes. Emerging evidence highlights the pivotal role of sex and gender in shaping frailty trajectories across major neurological disorders, including stroke, Parkinson's disease (PD), dementia, and multiple sclerosis. This systematic review synthesizes current knowledge on the interplay between frailty and neurological disease, with a focus on sex-specific patterns. Recognizing sex- and gender-related differences in frailty expression is critical to advancing a more personalized and equitable model of neurological care, and reducing disparities in a growing population affected by age-related neurological conditions. ANN NEUROL 2025
in Annals of Neurology on 2025-11-21 08:37:51 UTC.
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Interactions between long- and short-term synaptic plasticity transform temporal neural representations into spatial
Proceedings of the National Academy of Sciences, Volume 122, Issue 47, November 2025.
SignificanceNeurons in the brain communicate through spikes that are transmitted via chemical synapses that express both long-term and short-term plasticity. While long-term plasticity is thought to be the central site of learning and memory and has ...in PNAS on 2025-11-21 08:00:00 UTC.
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High-capacity directional information processor using all-optical multilayered neural networks
Science Advances, Volume 11, Issue 47, November 2025.
in Science Advances on 2025-11-21 08:00:00 UTC.
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Antigen-specific B cell response regulation by IL-10–producing tolerogenic dendritic cells
Science Advances, Volume 11, Issue 47, November 2025.
in Science Advances on 2025-11-21 08:00:00 UTC.
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High-entropy nanoalloys anchored on entropy-compensating two-dimensional oxides for enhanced nanomagnetism
Science Advances, Volume 11, Issue 47, November 2025.
in Science Advances on 2025-11-21 08:00:00 UTC.
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Critical windows of prenatal heat exposure and preterm birth: Metabolomic study in the Atlanta African American Maternal-Child Cohort
Science Advances, Volume 11, Issue 47, November 2025.
in Science Advances on 2025-11-21 08:00:00 UTC.
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Experimental characterization of complex atmospheric flows: A wind turbine wake case study
Science Advances, Volume 11, Issue 47, November 2025.
in Science Advances on 2025-11-21 08:00:00 UTC.
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Two-photon induced coherence without induced emission
Science Advances, Volume 11, Issue 47, November 2025.
in Science Advances on 2025-11-21 08:00:00 UTC.
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Proximity-induced chirality at the achiral conductive interface by electrical control of enantiopure ion adsorption
Science Advances, Volume 11, Issue 47, November 2025.
in Science Advances on 2025-11-21 08:00:00 UTC.
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A striosomal accumbens pathway drives stereotyped behavior through an aversive Esr1+ hypothalamic-habenula circuit
Science Advances, Volume 11, Issue 47, November 2025.
in Science Advances on 2025-11-21 08:00:00 UTC.
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Nanofluidic-engineered carbon nanotube ion highways in hydrogels enable high-power aqueous zinc-ion batteries
Science Advances, Volume 11, Issue 47, November 2025.
in Science Advances on 2025-11-21 08:00:00 UTC.
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3D bioprinted human-scale intestine models for physiological and microbial insights through fluid-driven heterogeneity
Science Advances, Volume 11, Issue 47, November 2025.
in Science Advances on 2025-11-21 08:00:00 UTC.
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Observation of proton tunneling correlated with phonons and electrons in Pd
Science Advances, Volume 11, Issue 47, November 2025.
in Science Advances on 2025-11-21 08:00:00 UTC.
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Double-sided annealing to reverse the crystallization direction for efficient and stable flexible FACs-perovskite solar modules
Science Advances, Volume 11, Issue 47, November 2025.
in Science Advances on 2025-11-21 08:00:00 UTC.
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Visualizing the strong field–induced molecular breakup of C60 via x-ray diffraction
Science Advances, Volume 11, Issue 47, November 2025.
in Science Advances on 2025-11-21 08:00:00 UTC.
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Sabatier principle in designing CO2-philic but blocking membranes
Science Advances, Volume 11, Issue 47, November 2025.
in Science Advances on 2025-11-21 08:00:00 UTC.
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A universal 2D-on-SiC platform for heterogeneous integration of epitaxial III-N membranes
Science Advances, Volume 11, Issue 47, November 2025.
in Science Advances on 2025-11-21 08:00:00 UTC.
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Single atom–cluster synergy in Ag catalysts enables chiral glyceric acid from biomass
Science Advances, Volume 11, Issue 47, November 2025.
in Science Advances on 2025-11-21 08:00:00 UTC.
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Stable electron-irradiated [1-13C]alanine radicals for metabolic imaging with dynamic nuclear polarization
Science Advances, Volume 11, Issue 47, November 2025.
in Science Advances on 2025-11-21 08:00:00 UTC.
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Low-waste, single-step, sustainable extraction of critical metals from deep-sea polymetallic nodules
Science Advances, Volume 11, Issue 47, November 2025.
in Science Advances on 2025-11-21 08:00:00 UTC.
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Mitochondrial NAD+ gradient sustained by membrane potential and transport
Science Advances, Volume 11, Issue 47, November 2025.
in Science Advances on 2025-11-21 08:00:00 UTC.
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Benchmarking retrieval-augmented large language models in biomedical NLP: Application, robustness, and self-awareness
Science Advances, Volume 11, Issue 47, November 2025.
in Science Advances on 2025-11-21 08:00:00 UTC.
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A ubiquitin-like protein controls assembly of a bacterial type VIIb secretion system
Science Advances, Volume 11, Issue 47, November 2025.
in Science Advances on 2025-11-21 08:00:00 UTC.
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Renal clearable CRISPR nanosensor targeting mitochondrial DNA mutation for noninvasive monitoring of tumor progression and metastasis
Science Advances, Volume 11, Issue 47, November 2025.
in Science Advances on 2025-11-21 08:00:00 UTC.
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A rapid self-healing polymer mediated by ion aggregates achieves effective encapsulation of sustainable perovskite solar cells
Science Advances, Volume 11, Issue 47, November 2025.
in Science Advances on 2025-11-21 08:00:00 UTC.
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miRNA-loaded biomimetic nanoparticles orchestrate gut microbe to ameliorate inflammatory bowel disease
Science Advances, Volume 11, Issue 47, November 2025.
in Science Advances on 2025-11-21 08:00:00 UTC.
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Electrochemical C4 alkylation of pyridine derivatives: Enhanced regioselectivity via silane assistance
Science Advances, Volume 11, Issue 47, November 2025.
in Science Advances on 2025-11-21 08:00:00 UTC.
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Mapping structures and dynamics with frequency-correlated diffusion exchange
Science Advances, Volume 11, Issue 47, November 2025.
in Science Advances on 2025-11-21 08:00:00 UTC.
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An acyclic nucleoside phosphonate effectively blocks the egress of the malaria parasite by inhibiting the synthesis of cyclic GMP
Science Advances, Volume 11, Issue 47, November 2025.
in Science Advances on 2025-11-21 08:00:00 UTC.
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Rapid cancer diagnosis using deep learning–powered label-free subcellular-resolution photoacoustic histology
Science Advances, Volume 11, Issue 47, November 2025.
in Science Advances on 2025-11-21 08:00:00 UTC.
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Conserved CD8 T cell vaccines without B cell epitopes drive robust protection against SARS-CoV-2 that is enhanced by intranasal boost
Science Advances, Volume 11, Issue 47, November 2025.
in Science Advances on 2025-11-21 08:00:00 UTC.
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Erratum for the Research Article “Heterochronic parabiosis uncovers AdipoR1 as a critical player in retinal rejuvenation” by Y. Liu et al.
Science Advances, Volume 11, Issue 47, November 2025.
in Science Advances on 2025-11-21 08:00:00 UTC.
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Sensory Enrichment and Deprivation During Development: Limited Effects on the Volumes of CNS Neuropils in Two Spiders With Different Ecology
Sensory enrichment did not increase modality-specific brain region volumes in either Parasteatoda tepidariorum or Marpissa muscosa; variation was largely explained by shared maternal origin, suggesting that genetic or developmental factors may outweigh environmental sensory input in shaping spider brain structure.
ABSTRACT
Neuroplasticity is a core property of animal nervous systems, enabling structural changes in the brain in response to environmental stimuli or internal processes such as learning. Among spiders—a diverse group of predators—neuroanatomy varies with hunting strategy: stationary species that build capture webs differ from cursorial species that hunt without webs, reflecting reliance on distinct sensory modalities. While neuroplasticity has been documented in cursorial jumping spiders, its direct drivers remain unclear. In this study, we tested how sensory input influences the central nervous system (CNS) and whether stationary and cursorial hunters differ in their plastic responses. Using sensory deprivation and enrichment, we reared spiders under four treatments: control (CON), vibratory enrichment (VIB), visual enrichment (VIS), and combined enrichment (VISVIB). We examined the stationary hunter Parasteatoda tepidariorum and the cursorial hunter Marpissa muscosa. We predicted that enrichment would enlarge neuropil volumes in modality-specific brain regions, with stronger vibratory effects in P. tepidariorum and stronger visual effects in M. muscosa. Contrary to our expectations, sensory enrichment did not increase the volume of the corresponding CNS neuropils in either species. Although certain neuropils showed significant differences in specific groups, no clear causal link to sensory input emerged. Instead, a substantial proportion of the variation in neuropil volume was explained by family effects (shared maternal origin). We discuss these findings in the context of potential mechanisms underlying environmental plasticity in the spider brain.
in Journal of Comparative Neurology on 2025-11-21 07:25:54 UTC.
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ATHENA: Automatically Tracking Hands Expertly with No Annotations
Journal of Neurophysiology, Ahead of Print.
in Journal of Neurophysiology on 2025-11-21 04:29:56 UTC.
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Activity of protein kinase C controls the efficacy of cannabinoid receptor type 1 in the medial prefrontal cortex after neuropathic pain
Journal of Neurophysiology, Ahead of Print.
in Journal of Neurophysiology on 2025-11-21 04:21:50 UTC.
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MYC inhibition by Omomyc causes DNA damage and overcomes PARPi resistance in breast cancer
Giuntini et al. demonstrate that Omomyc, the only direct MYC inhibitor currently in phase 2 clinical trials, causes DNA damage and synergizes with PARPis in triple-negative breast cancer. Their findings provide compelling evidence for clinical exploration of this combination to overcome PARPi resistance.in Cell Reports: Current Issue on 2025-11-21 00:00:00 UTC.
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Maturation of human intestinal epithelial cell layers fortifies the apical surface against Salmonella attack
van Rijn and Lopes et al. present a resource for live-cell imaging of bacterial infection dynamics atop human enteroid- and colonoid-derived intestinal epithelia, exhibiting varying maturation levels and in the presence or absence of soluble mucus production. Application of this resource reveals how absorptive epithelium maturation fortifies the surface against enterobacterial attack.in Cell Reports: Current Issue on 2025-11-21 00:00:00 UTC.
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MITF, TFEB, and TFE3 drive distinct adaptive gene expression programs and immune infiltration in melanoma
Dias et al. reveal that in melanoma, the transcription factors MITF, TFE3, and TFEB share common binding sites but impose distinct transcriptional programs. Stresses promoting an MITF-to-TFEB-to-TFE3 switch will lead cells to suppress proliferation, reprogram metabolism, and impact tumor immune cell infiltration quantitatively and qualitatively.in Cell Reports: Current Issue on 2025-11-21 00:00:00 UTC.
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Genetic determinants of gene expression noise and its role in complex trait variation
Long et al. mapped expression noise QTLs (enQTLs) across immune cell types in an atlas of 1.23 million cells. These enQTLs are largely independent of eQTLs, exhibit cell-type-specific regulatory mechanisms, and colocalize with GWAS loci for hematopoietic traits and diseases, implicating noise as an underappreciated molecular mediator of complex traits.in Cell Reports: Current Issue on 2025-11-21 00:00:00 UTC.
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Sensory-neuron-derived CGRPα controls white adipocyte differentiation and tissue plasticity
Sensory-neuron-derived CGRPα inhibits subcutaneous white adipocyte differentiation and alters adipogenic gene programs. Ectopic CGRPα expression in iWAT increases adipocyte size, and anti-CGRPα migraine therapy is linked to positive metabolic changes, revealing a neuron-adipose pathway that regulates fat homeostasis and systemic metabolism.in Cell Reports: Current Issue on 2025-11-21 00:00:00 UTC.
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Infection-induced elevation of gut glycosaminoglycans fosters microbiota expansion in Drosophila melanogaster
Arias-Rojas et al. performed a genome-wide association study in Drosophila melanogaster and identified host genetic variants, particularly in heparan sulfate synthesis genes, associated with increased commensal Lactiplantibacillus plantarum abundance. Heparan sulfate enhances bacterial adhesion, biofilm formation, and modulates intestinal homeostasis, microbiota composition, and immune response, thus preventing dysplasia.in Cell Reports: Current Issue on 2025-11-21 00:00:00 UTC.
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Liquid-liquid phase separation of ATXN2L enhances mRNA translation in hepatocellular carcinoma
Wang et al. find that ATXN2L is a novel RBP highly expressed in HCC. LLPS of ATXN2L promotes mRNA translation by recruiting eIFs and their target mRNAs, thereby facilitating HCC progression, and this process is modulated through interactions with SGs.in Cell Reports: Current Issue on 2025-11-21 00:00:00 UTC.
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Pathological tau alters head direction signaling and induces spatial disorientation
Jiang and Hijazi et al. show that an early cognitive biomarker of dementia, spatial disorientation, can be induced in mice by expressing pathological tau in the anterodorsal nucleus of the thalamus. This alters the activity of head direction cells in this nucleus, affecting the animal’s sense of direction during spatial learning.in Cell Reports: Current Issue on 2025-11-21 00:00:00 UTC.
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Bacterial modification of the root cell wall facilitates rice aluminum resistance in acidic soils
Root cell walls integrate microbial cues to shape crop stress resilience. Zhang et al. show that a synthetic microbial community (SynCom) mitigates aluminum toxicity in rice by reducing aluminum binding and promoting brassinosteroid biosynthesis. These coordinated actions reestablish hormonal homeostasis and direct cell-wall remodeling, enhancing root tolerance in acidic soils.in Cell Reports: Current Issue on 2025-11-21 00:00:00 UTC.
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Of masks and Mayans: Books in brief
Nature, Published online: 21 November 2025; doi:10.1038/d41586-025-03868-x
Andrew Robinson reviews five of the best science picks.in Nature on 2025-11-21 00:00:00 UTC.
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Synthetic tongue rates chillies’ heat — and spares human tasters
Nature, Published online: 21 November 2025; doi:10.1038/d41586-025-03767-1
Gel-based device inspired by the cooling powers of milk assesses peppers whose burn ranges from mild to dangerous.in Nature on 2025-11-21 00:00:00 UTC.
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How to defuse a time bomb
Nature, Published online: 21 November 2025; doi:10.1038/d41586-025-03788-w
Career progression.in Nature on 2025-11-21 00:00:00 UTC.
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Psychedelics and immortality: Nature went to a health summit starring RFK and JD Vance
Nature, Published online: 21 November 2025; doi:10.1038/d41586-025-03790-2
The Make America Healthy Again summit, attended by health secretary Robert F. Kennedy Jr and vice-president JD Vance, gave a sense of what’s driving US health policy.in Nature on 2025-11-21 00:00:00 UTC.
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Cyberattacks' harm to universities is growing — and so are their effects on research
Nature, Published online: 21 November 2025; doi:10.1038/d41586-025-03484-9
Hackers are ramping up attacks on academic institutions to access valuable data and to demand ransoms.in Nature on 2025-11-21 00:00:00 UTC.
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I encourage women to claim their space in astrophysics and beyond
Nature, Published online: 21 November 2025; doi:10.1038/d41586-025-03400-1
Debarati Chatterjee’s mission is to make science in India more welcoming towards women.in Nature on 2025-11-21 00:00:00 UTC.
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Astrocytic Sox9 overexpression in Alzheimer’s disease mouse models promotes Aβ plaque phagocytosis and preserves cognitive function
Nature Neuroscience, Published online: 21 November 2025; doi:10.1038/s41593-025-02115-w
Astrocytes are associated with Alzheimer’s disease pathogenesis. We found that the transcription factor Sox9 functions to enhance astrocytic phagocytosis of Aβ plaques via MEGF10, and this clearance of plaques is associated with the preservation of cognitive function in mouse models.in Nature Neuroscience on 2025-11-21 00:00:00 UTC.
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Progress in quantum structured light
Nature Photonics, Published online: 21 November 2025; doi:10.1038/s41566-025-01795-x
This Review provides an overview of the progress in quantum structured light, both as single and entangled photon states, with an emphasis on prospective applications in quantum information science such as quantum communication and quantum imaging.in Nature Photomics on 2025-11-21 00:00:00 UTC.
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Hybrid excitons span two worlds
Nature Physics, Published online: 21 November 2025; doi:10.1038/s41567-025-03097-z
Excitons are bound electron–hole pairs that are usually either tightly bound or spread across a material. Signatures of hybrid excitons that mix both characters have now been observed at organic–semiconductor interfaces.in Nature Physics on 2025-11-21 00:00:00 UTC.
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Dataset on Gait Analysis of Parkinsonian Subjects: Effect of Nordic Walking
Scientific Data, Published online: 21 November 2025; doi:10.1038/s41597-025-06209-9
Dataset on Gait Analysis of Parkinsonian Subjects: Effect of Nordic Walkingin Nature scientific data on 2025-11-21 00:00:00 UTC.
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Southern Spitsbergen coastal permafrost - repeated seismic survey supported by GPR
Scientific Data, Published online: 21 November 2025; doi:10.1038/s41597-025-06327-4
Southern Spitsbergen coastal permafrost - repeated seismic survey supported by GPRin Nature scientific data on 2025-11-21 00:00:00 UTC.
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Adaptive immune response to West Nile virus infection in the Collaborative Cross mouse model: A database of cellular phenotypes and Quantitative Trait Loci
Scientific Data, Published online: 21 November 2025; doi:10.1038/s41597-025-06293-x
Adaptive immune response to West Nile virus infection in the Collaborative Cross mouse model: A database of cellular phenotypes and Quantitative Trait Lociin Nature scientific data on 2025-11-21 00:00:00 UTC.
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Comparative transcriptomic profiling of field-grown cassava genotypes across season transitions
Scientific Data, Published online: 21 November 2025; doi:10.1038/s41597-025-06119-w
Comparative transcriptomic profiling of field-grown cassava genotypes across season transitionsin Nature scientific data on 2025-11-21 00:00:00 UTC.
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A Question Answering Dataset for Temporal-Sensitive Retrieval-Augmented Generation
Scientific Data, Published online: 21 November 2025; doi:10.1038/s41597-025-06098-y
A Question Answering Dataset for Temporal-Sensitive Retrieval-Augmented Generationin Nature scientific data on 2025-11-21 00:00:00 UTC.
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Chromosome-Level Genome Assembly and Annotation of the Japanese Cutlassfish (Trichiurus japonicus): A High-Quality Genomic Resource Featuring Nuclear and Mitochondrial Completeness for Future Studies
Scientific Data, Published online: 21 November 2025; doi:10.1038/s41597-025-06112-3
Chromosome-Level Genome Assembly and Annotation of the Japanese Cutlassfish (Trichiurus japonicus): A High-Quality Genomic Resource Featuring Nuclear and Mitochondrial Completeness for Future Studiesin Nature scientific data on 2025-11-21 00:00:00 UTC.
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Hierarchical Bayesian modeling of multiregion brain cell count data
We can now collect cell-count data across whole animal brains quantifying recent neuronal activity, gene expression, or anatomical connectivity. This is a powerful approach since it is a multiregion measurement, but because the imaging is done postmortem, each animal only provides one set of counts. Experiments are expensive, and since cells are counted by imaging and aligning a large number of brain sections, they are time-intensive. The resulting datasets tend to be undersampled with fewer animals than brain regions. As a consequence, these data are a challenge for traditional statistical approaches. We present a ‘standard’ partially pooled Bayesian model for multiregion cell-count data and apply it to two example datasets. These examples demonstrate that hierarchical Bayesian methods are well suited to these data. In both cases, the Bayesian model outperformed standard parallel t-tests. Overall, inference for cell-count data is substantially improved by the ability of the Bayesian approach to capture nested data and by its rigorous handling of uncertainty in undersampled data.in eLife on 2025-11-21 00:00:00 UTC.
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PTBP1 depletion in mature astrocytes reveals distinct splicing alterations without neuronal features
Astrocyte-to-neuron reprogramming via depletion of PTBP1, a potent repressor of neuronal splicing, has been proposed as a therapeutic strategy, but its efficacy remains debated. While some reported successful conversion, others disputed this, citing a lack of neuronal gene expression as evidence of failed reprogramming. This interpretation was further challenged, attributed to incomplete PTBP1 inactivation, fueling ongoing controversy. Mechanistic understanding of the conversion, or the lack thereof, requires investigating, in conjunction with lineage tracing, the effect of Ptbp1 loss of function in mature astrocytes on RNA splicing, which has not yet been examined. Here, we genetically ablated PTBP1 in adult Aldh1l1-Cre/ERT2 Ai14 mice to determine whether lineage-traced Ptbp1 knockout astrocytes exhibited RNA splicing alterations congruent with neuronal differentiation. We found no widespread induction of neurons, despite a minuscule fraction of knockout cells showing neuron-like transcriptomic signatures. Importantly, PTBP1 loss in mature astrocytes induced splicing alterations unlike neuronal splicing patterns. These findings suggest that targeting PTBP1 alone is ineffective to drive neuronal reprogramming and highlight the need for combining splicing and lineage analyses. Loss of astrocytic PTBP1 is insufficient to induce neuronal splicing, contrasting with its well-known role in other non-neuronal cells, and instead affects a distinct astrocytic splicing program.in eLife on 2025-11-21 00:00:00 UTC.
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Functional characterization of neuropeptides that act as ligands for both calcitonin-type and pigment-dispersing factor-type receptors in a deuterostome
The calcitonin (CT) family of related peptides exerts diverse physiological effects in mammals via two G-protein-coupled receptors: CTR and the CTR-like receptor CLR. Phylogenetic analysis of CT-type signaling has revealed the presence of CT-type peptides and CTR/CLR-type proteins in both deuterostome and protostome invertebrates. Furthermore, experimental studies have demonstrated that in the protostome Drosophila melanogaster, the CT-like peptide DH31 can act as a ligand for a CTR/CLR-type receptor and a pigment-dispersing factor (PDF) receptor. Here, we investigated the signaling mechanisms and functions of CT-type neuropeptides in a deuterostome invertebrate, the sea cucumber Apostichopus japonicus (phylum Echinodermata). In A. japonicus, a single gene encodes two CT-type peptides (AjCT1 and AjCT2), and both peptides act as ligands for a CTR/CLR-type receptor (AjCTR) and two PDF-type receptors (AjPDFR1, AjPDFR2), but with differential activation of downstream cAMP/PKA, Gαq/Ca2+/PKC, and ERK1/2 signaling pathways. AjCT1/AjCT2-encoding transcripts were detected in the central nervous system and a variety of organ systems, and neuropeptide expression was visualized immunohistochemically using an antiserum to a starfish CT-type peptide (ArCT). In vitro pharmacological experiments demonstrated that AjCT1 and/or AjCT2 cause dose-dependent relaxation of longitudinal muscle and intestine preparations. Furthermore, in vivo pharmacological experiments, combined with gain- and loss-of-function experiments, revealed a potential physiological role for AjCT2/AjPDFR2 signaling in promoting feeding and growth in A. japonicus. To our knowledge, this is the first study to obtain evidence that CT-type peptides can act as ligands for both CTR/CLR-type and PDF-type receptors in a deuterostome. Moreover, it provides the first evidence for appetite-stimulating and growth-promoting effects of CT-type neuropeptides in bilaterians. Given the economic importance of A. japonicus as a foodstuff, the discovery of CT-type peptides as potential regulators of feeding and growth in this species may offer novel strategies for aquaculture applications.in eLife on 2025-11-21 00:00:00 UTC.
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HoxB-derived hoxba and hoxbb clusters are essential for the anterior–posterior positioning of zebrafish pectoral fins
Vertebrate paired appendages, such as the pectoral fins in fish and the forelimbs in tetrapods, arise at specific regions along the anterior–posterior axis of the body. Hox genes have long been considered prime candidates for determining the anteroposterior positioning of these paired appendages during development. Evidence from various model organisms, including mouse and chick, supports a role for Hox genes in limb positioning. However, despite extensive phenotypic analyses of numerous single and compound Hox knockout mice, clear genetic evidence for substantial defects in limb positioning has been limited, leaving questions unresolved. In a previous study, we generated seven distinct hox cluster-deficient mutants in zebrafish. Here, we provide genetic evidence that zebrafish hoxba;hoxbb cluster-deleted mutants specifically exhibit a complete lack of pectoral fins, accompanied by the absence of tbx5a expression in pectoral fin buds. In these mutants, tbx5a expression in the pectoral fin field of the lateral plate mesoderm fails to be induced at an early stage, suggesting a loss of pectoral fin precursor cells. Furthermore, the competence to respond to retinoic acid is lost in hoxba;hoxbb cluster mutants, indicating that tbx5a expression cannot be induced in the pectoral fin buds. We further identify hoxb4a, hoxb5a, and hoxb5b as pivotal genes underlying this process. Although the frameshift mutations in these hox genes do not recapitulate the absence of pectoral fins, we demonstrate that deletion mutants at these genomic loci show the absence of pectoral fins with low penetrance. Our results suggest that, by establishing the expression domains along the anteroposterior axis, hoxb4a, hoxb5a, and hoxb5b within hoxba and hoxbb clusters cooperatively determine the positioning of zebrafish pectoral fins through the induction of tbx5a expression in the restricted pectoral fin field. Our findings also provide insights into the evolutionary origin of paired appendages in vertebrates.in eLife on 2025-11-21 00:00:00 UTC.
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Progressive remote memory decline coincides with parvalbumin interneuron hyperexcitability and enhanced inhibition of cortical engram cells in a mouse model of Alzheimer’s disease
Patients with Alzheimer’s disease (AD) initially show temporally graded retrograde amnesia, which gradually progresses into more severe retrograde amnesia. Although mouse models of AD have provided insight into neurobiological mechanisms contributing to impaired formation and retrieval of new memories, the process underlying the progressive loss of remote memories in AD has remained elusive. Here, we demonstrate age-dependent remote memory decline in APP/PS1 mice, which coincides with progressive hyperexcitability of parvalbumin (PV) interneurons in the medial prefrontal cortex (mPFC). Analysis of Fos expression showed that the remote memory deficit is not mirrored by changes in reactivation of memory-encoding neurons, so-called engram cells, nor PV interneuron (re)activation, in the mPFC. However, inhibitory input is enhanced onto engram cells compared to non-engram cells specifically in APP/PS1 mice. Our data indicate that age-dependent remote memory impairment in APP/PS1 mice is due to increased innervation of cortical engram cells by hyperexcitable PV interneurons, suggesting that dysfunctional inhibitory microcircuits in the neocortex mediate progressive retrograde amnesia in AD.in eLife on 2025-11-21 00:00:00 UTC.
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Peripheral glia and neurons jointly regulate activity-induced synaptic remodeling at the Drosophila neuromuscular junction
In the nervous system, reliable communication depends on the ability of neurons to adaptively remodel their synaptic structure and function in response to changes in neuronal activity. While neurons are the main drivers of synaptic plasticity, glial cells are increasingly recognized for their roles as active modulators. However, the underlying molecular mechanisms remain unclear. Here, using Drosophila neuromuscular junction (NMJ) as a model system for a tripartite synapse, we show that peripheral glial cells collaborate with neurons at the NMJ to regulate activity-induced synaptic remodeling, in part through a protein called shriveled (Shv). Shv is an activator of integrin signaling previously shown to be released by neurons during intense stimulation at the fly NMJ to regulate activity-induced synaptic remodeling. We demonstrate that Shv is also present in peripheral glia, and glial Shv is both necessary and sufficient for synaptic remodeling. However, unlike neuronal Shv, glial Shv does not activate integrin signaling at the NMJ. Instead, it regulates synaptic plasticity in two ways: (1) maintaining the extracellular balance of neuronal Shv proteins to regulate integrin signaling, and (2) controlling ambient extracellular glutamate concentration to regulate postsynaptic glutamate receptor abundance. Loss of glial cells showed the same phenotype as loss of Shv in glia. Together, these results reveal that neurons and glial cells homeostatically regulate extracellular Shv protein levels to control activity-induced synaptic remodeling. Additionally, peripheral glia maintain postsynaptic glutamate receptor abundance and contribute to activity-induced synaptic remodeling by regulating ambient glutamate concentration at the fly NMJ.in eLife on 2025-11-21 00:00:00 UTC.
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Neural Sensitivity to Word Frequency Modulated by Morphological Structure: Univariate and Multivariate fMRI Evidence from Korean
A fundamental question in psycholinguistics concerns whether morphological decomposition is obligatory during visual word recognition or whether whole-word access can occur under conditions of high frequency and familiarity. The present study aimed to examine how morphological complexity and lexical frequency jointly influence neural representations during visual word recognition. We addressed this question using rapid event-related fMRI with both univariate and multivariate analyses. Twenty-five native Korean speakers performed lexical decisions on simple and inflected nouns that varied parametrically in surface frequency (token frequency of the full word form) and base frequency (cumulative stem frequency). Korean's transparent agglutinative morphology enabled a principled dissociation of these frequency measures. MVPA failed to decode morphological condition from activation patterns in any region, suggesting that simple and inflected forms are not represented as discrete neural categories. Crucially, RSA demonstrated robust encoding of surface frequency-but not base frequency-in inferior frontal gyrus (IFG) pars opercularis and supramarginal gyrus (SMG), with significantly stronger correlations for inflected than simple nouns. Univariate analyses confirmed this pattern: surface frequency interacted with morphological condition in inferior parietal lobule (IPL), such that higher surface frequency increased activation selectively for inflected forms, while base frequency showed no reliable effects. These results challenge obligatory decomposition and support a distributional framework in which lexical statistics guide the processing of morphologically complex words. Taken together, our findings suggest that morphological complexity modulates neural sensitivity to whole-word rather than stem-level statistics, underscoring how structural and statistical factors interact to support morphological processing.in bioRxiv: Neuroscience on 2025-11-21 00:00:00 UTC.
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Most early-born subplate neurons persist as Layer 6b neurons in the adult mouse neocortex
Subplate neurons (SpNs) are among the earliest-born neurons in the mammalian neocortex and play key roles in radial migration and transient circuit formation. It has long been assumed that most SpNs undergo extensive postnatal cell death, leaving only a small remnant population that contributes to layer 6b (L6b) in adulthood. However, the extent to which SpNs actually persist as L6b neurons has remained unresolved, partly because previous studies lacked quantitative, whole-cortex analyses that account for postnatal cortical expansion. Here, we performed a comprehensive birthdating analysis using multiple EdU injections spanning the entire neurogenic window of SpNs in mice, combined with whole-neocortex 3D tissue clearing to measure subplate and L6b volumes. This approach allowed us to directly estimate the total number and distribution of SpN-derived neurons in adulthood. We found that most early-born SpNs persist as L6b neurons, and that the apparent postnatal reduction in SpN density reflects tangential cortical expansion rather than neuronal loss. Moreover, surviving SpNs comprise diverse neuronal subtypes reminiscent of those present at early postnatal stages. Together, these findings demonstrate that, in rodents, the majority of adult L6b neurons originate from SpNs, revising the long-held view that the subplate is a largely transient neuronal population.in bioRxiv: Neuroscience on 2025-11-21 00:00:00 UTC.
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O-GlcNAc Transferase Regulates GABAergic Synapse Organization and Receptor Composition.
Neural circuits must integrate metabolic information to maintain stable activity and appropriate behavioral responses. While metabolic regulation of excitatory synapses has been well studied, far less is known about how inhibitory synapses respond to changes in energy state. In this study, we show that O-GlcNAc transferase (OGT), a dynamic sensor of cellular nutrient flux, localizes to postsynaptic sites of the inhibitory synapses where it modulates synapse morphology and receptor composition. OGT over-expression reduced the size and intensity of vGAT and gephyrin puncta, whereas conditional OGT deletion produced a converse enlargement and redistribution of inhibitory scaffolds and vesicular proteins. Furthermore, OGT deletion accelerated inhibitory postsynaptic current decay kinetics and induced subunit-specific shifts in GABAA receptor surface expression: {beta}3 subunits decreased, whereas {gamma}2 subunit total and surface levels increased. Together, these findings identify OGT as a metabolic regulator that modulates inhibitory synapse structure and signaling, providing a mechanistic link between energy state and GABAergic circuit function in health and disease.in bioRxiv: Neuroscience on 2025-11-21 00:00:00 UTC.
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Hippocampal sequences traverse a memory space
Highly reliable sequential dynamics organize neural activity in the hippocampus and progress with changes in physical, sensory, or cognitive variables, typified by place cells during active exploration. But sensory and behavioral variables are often confounded, and so it remains intensely debated whether hippocampal sequences are driven by sensory content directly or rather reflect the alignment of internally generated dynamics to external perception. Here we used mouse virtual reality to characterize hippocampal dynamics in environments of systematically different sensory complexity, and to test the robustness of neural sequences to manipulations of exact sensory content. The structure of neural sequences was perturbed by changes in both moment-to-moment sensation and ongoing behavior, in a pattern that was best explained by the different memory strategies employed by the animal in each context. Neural subsequences could be flexibly interrupted, inserted, and resumed wherever a memory of prior experience was violated, indicating that the propagation of hippocampal dynamics was not rigidly fixed by internal networks and initial conditions. Rather, we argue that hippocampal sequences explore an abstract memory space of selectively remembered experiences, which flexibly encompasses both sensory and internal factors in a context-dependent manner.in bioRxiv: Neuroscience on 2025-11-21 00:00:00 UTC.
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Lipid droplets promote the aberrant liquid-liquid phase separation of alpha-synuclein leading to impaired energy homeostasis
Alpha-synuclein (Syn) inclusions, termed Lewy bodies, are the characteristic neuropathological feature of Parkinson's disease. Growing evidence points towards a role of aberrant liquid-liquid phase separation in the dysregulation of Syn and sequence of events that lead to the formation of Lewy bodies. However, the triggers leading to aberrant phase separation are unknown, as is the relevance of this phenomenon to the neurodegeneration process. In this study, we showed that Syn spontaneously phase separates into condensates in the presence of lipid droplets. These lipid droplet-rich condensates represent a toxic species of Syn that prevents the turnover of the entrapped lipid droplets; they are also toxic to neighboring mitochondria which are depolarized and undergo increased mitophagy. These findings underscore the increasing importance of lipid droplets in the pathogenesis of neurodegenerative diseases, and Parkinson's disease in particular. The lipid droplets are significantly enriched within the neuromelanin in midbrain dopaminergic neurons in the substantia nigra and could therefore uniquely facilitate the early Syn-associated neurodegeneration of this region in PD. Our findings reveal a novel pathway implicated in the dysregulation of Syn that connects aberrant liquid-liquid phase separation, lipid droplets and mitochondrial toxicity.in bioRxiv: Neuroscience on 2025-11-21 00:00:00 UTC.
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Deep White-Matter Pathways Mediate the Link Between Docosahexaenoic Acid (DHA) Status and Cognitive Performance in Adolescence
Docosahexaenoic acid (DHA) is a polyunsaturated fatty acid enriched in neuronal membranes and myelin and associated with cognitive performance. However, nutritional interventions show inconsistent cognitive effects, partly due to limited knowledge of the neural pathways linking DHA status to human cognition during sensitive periods of white-matter maturation, such as adolescence. We addressed this gap by studying 99 adolescents drawn from both extremes of performance on a national scholastic examination. Participants completed assessments of scholastic achievement (SA) and intellectual ability (IA), provided erythrocyte DHA samples, and underwent multimodal MRI, including diffusion, T1-weighted, and T2-weighted imaging. Independent component analysis and Bayesian multivariate LASSO models identified brain components jointly associated with DHA and cognition. Across four MRI modalities, a single deep white-matter component consistently emerged as the strongest shared pathway linking DHA with cognition. Tract-resolved analyses highlighted predominant contributions from the fornix and thalamus - temporal fasciculus, with additional subcortical and cortical involvement. In joint models, these components predicted SA and IA after accounting for DHA and other fatty acids, consistent with an indirect, mediation-like pathway. These findings move beyond DHA - behavior correlations by identifying specific neuroanatomical pathways through which a modifiable dietary factor relates to adolescent learning and intellectual performance, offering mechanistic insight relevant to neuroscience, nutrition, and education.in bioRxiv: Neuroscience on 2025-11-21 00:00:00 UTC.
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Cognitive Performance and Brain-Predicted Age Difference in Bipolar Disorder
Neuroimaging-derived brain-predicted age difference (brain-PAD) is a promising marker of advanced brain aging, but its link to cognitive function in bipolar disorder (BD) is not well understood, especially when comparing across publicly available algorithms trained on diverse, large sample datasets and to algorithms trained on local cohorts with rich multimodal imaging data. Our study compares algorithms used to estimate brain-PAD in terms of their clinical relevance to cognition in BD. We included 44 euthymic BD I individuals and 73 HCs who completed the Delis-Kaplan Executive Function System, and we selected nine scores from this battery for further analyses. Raw scores were log-transformed, scaled, and subjected to PCA; PC1 indexed overall executive function. Four brain-PAD algorithms (PHOTON, BrainageR, DenseNet, Multimodal) were applied to T1-weighted MRI data; the multimodal algorithm also included Diffussion Tensor Imaging (DTI), Arterial Spin Labeling (ASL), functional Magnetic resonance imaging (fMRI) and resting state Magnetic resonance imaging (rsMRI) data. For each algorithm, we regressed brain-PAD on age, sex, and their interaction to obtain residuals, then used those residualized brain-PADs (which we refer to subsequently as brain-PADs throughout the text) to predict PC1. We then directly assessed if there were group differences in the relationship of brain-PAD to cognitive function by including an interaction term between group x brain-PAD. We found no significant group x brain-PAD interaction across all four algorithms. Given that, we then combined BD and HC and explored whether brain-PAD was a meaningful predictor of cognitive performance. Multimodal brain-PAD emerged as a strong negative predictor of cognitive performance (Beta Estimate = -0.084, SE = 0.024, t = -3.50, p < 0.001), indicating that those with older-appearing brains, as indexed by the brain-PAD, scored lower on PC1. BrainageR brain-PAD also significantly predicted PC1 (Beta Estimate = -0.031, SE = 0.0116, t = -2.71, p < 0.01), and DenseNet brain-PAD showed a modest effect (Beta Estimate = -0.0355, SE = 0.0177, t = -2.00, p < 0.05). PHOTON brain-PAD demonstrated a negative trend with PC1 (Beta Estimate = -0.024, SE = 0.0127, t = -1.92, p = 0.06). Residualized brain-PAD, after accounting for age and sex, was inversely associated with a composite metric of executive functioning, particularly for an algorithm integrating a range of imaging modalities. Our findings demonstrate how brain aging patterns captured by a neuroimaging-based, ML-derived composite metric could be associated with cognitive performance across algorithms trained on a variety of data granularity and sample sizes.in bioRxiv: Neuroscience on 2025-11-21 00:00:00 UTC.
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Four new Duchenne muscular dystrophy mouse models with clinically relevant exon deletions in the human DMD gene
Mutation specific therapeutic approaches, like exon skipping or gene-editing, hold promise for the treatment of Duchenne muscular dystrophy (DMD). Translatability of preclinical studies investigating these approaches could greatly be improved through the use of humanized mouse models, as these allow preclinical testing of human specific sequences. We developed four novel humanized DMD mouse models with either a deletion of exon 44, 45, 51 or 53 in the human DMD gene, in a mouse dystrophin negative background (mdx mouse; exon 23 nonsense mutation). Our optimized prescreening pipeline allowed us to do so very efficiently with the CRISPR-Cas9 technology. We confirmed either complete lack of dystrophin, or expression of trace levels, which led to development of muscle pathology consisting of muscle fiber de-, and regeneration, inflammation and fibrosis in young adult mice. Intramuscular treatment with vivo-morpholinos targeting a flanking exon induced exon skipping in the DMD strains, which restored the disrupted open reading frame and subsequently dystrophin expression. This validates these models as valuable tools for preclinical studies investigating human sequence specific therapeutic approaches for DMD.in bioRxiv: Neuroscience on 2025-11-21 00:00:00 UTC.
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Comparison of Brain Age Algorithms in Bipolar Disorder
Advances in computational methods have accelerated the application of machine learning to analyze large complex biological data. By applying machine learning algorithms to neuroimaging data, researchers have estimated the "biological age of the brain" i.e., brain age, and used it as a composite metric for indexing brain health, as opposed to using individual features of the brain extracted from neuroimaging data. These machine learning algorithms/models, often known as "brain age" algorithms/models, may take supervised or unsupervised approaches and may utilize one or many imaging modalities during training. We applied 3 regression-based algorithm and 1 neural network-based algorithm trained on varying sample sizes of healthy comparison (HC) participants to estimate the brain age of 73 HC and 44 individuals with bipolar disorder (BD) in our neuroimaging study. Out of the four, 3 were pre-trained off-the-shelf algorithms and 1 was developed and trained on multimodal neuroimaging data from a local cohort. The multimodal algorithm was trained on 51 age-matched HCs and tested on the remaining 22 HCs and 44 BDs. The brain predicted age difference (brain-PAD) score was calculated by subtracting the chronological age from the predicted age. Across four brain age prediction algorithms evaluated in HC, BrainageR and DenseNet demonstrated the highest predictive accuracy (r = 0.83; 0.89) and lowest mean absolute errors (MAE = 5.94; 7.26). However, PHOTON (r = 0.65, MAE = 7.71) showed greatest sensitivity to BD as demonstrated by our logistic regression model where the PHOTON brain-PAD was a significant predictor (beta = 0.064, p < 0.05) of BD. Analyses using ICC revealed that agreement levels varied, with PHOTON achieving the highest ICC with DenseNet (0.78) and BrainageR (0.73), which suggests they may pick up similar brain features as opposed to the multimodal algorithm (0.17- 0.43) These results suggest that regularized linear models trained on large samples that explicitly exclude individuals with psychiatric diagnoses (i.e., PHOTON in this case) may be most sensitive to case-control differences despite having lower predictive accuracy. Our findings can serve as a starting point and quantitative reference for future efforts for researchers working with datasets that are similarly constrained by sample size but include unique combinations of imaging modalities.in bioRxiv: Neuroscience on 2025-11-21 00:00:00 UTC.
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Constraining inference of across-region interactions using neural activity perturbations
Functional interactions between brain regions are often inferred from multi-region models fit to neural activity recorded in behaving animals. Here, we show that inference of across-region interactions is hindered by the wide breadth of model fits consistent with naturally occurring neural activity. In contrast, models fit to activity that includes region-wide activity perturbations provide well-constrained estimates of across-region interactions; simulations suggest these estimates can be accurate.in bioRxiv: Neuroscience on 2025-11-21 00:00:00 UTC.
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Impact of chronic alcohol and stress on mid-life cognition and locus coeruleus integrity
Background: Excessive alcohol consumption and stress are associated with structural and functional alterations in the brain and impaired cognition. However, the persistence of long-term neural impacts after alcohol and stress are less understood. This study investigated midlife cognition and neuropathological changes following a history of alcohol and stress exposure. Methods: C57BL/6J mice acclimated to ethanol drinking (15% v/v) before exposure to four cycles of alternating chronic intermittent ethanol (CIE) vapor exposure and repeated forced swim stress (FSS), with control groups exposed to air and no stress (AIR/NS). After three months of abstinence, mice were evaluated at midlife (11 months old) on volitional drinking and a final CIE/FSS challenge for stress induced drinking. Spatial learning and cognitive flexibility were assessed using the Barnes maze before brains were collected to evaluate locus coeruleus integrity at 12 months old. Results: CIE/FSS increased volitional alcohol intake, and this drinking phenotype persisted through to midlife despite extended abstinence. CIE/FSS mice showed intact spatial learning but impaired flexibility in the Barnes maze reversal phase. Flexibility impairments were driven by decreased time in the target quadrant and increased errors during the reversal test compared to AIR/NS. Furthermore, CIE/FSS mice showed pathological measures of reduced locus coeruleus integrity common to dementia related disorders, including elevated markers of oxidative stress, apoptosis and reduced autoinhibitory function. Conclusions: Our findings highlight the long-lasting impact of alcohol and stress exposure on cognition, with flexibility impairments persisting into midlife. In addition to cognitive changes, alcohol and stress history produced pathological changes in the locus coeruleus, an area known to mediate cognitive flexibility via its forebrain projections. Together, these results give an insight into the long-lasting impacts of chronic alcohol and stress and how they may accelerate age-related cognitive decline.in bioRxiv: Neuroscience on 2025-11-21 00:00:00 UTC.
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The polypharmacological profiles of xanomeline and N-desmethylxanomeline
The muscarinic agonist xanomeline in combination with the peripherally restricted muscarinic antagonist trospium has recently been approved for treatment of schizophrenia. Xanomeline represents the first approved antipsychotic drug without apparent activity at D2-dopamine receptors. In humans, xanomeline is reported to be metabolized to N-desmethylxanomeline, which has a similar pharmacokinetic profile to xanomeline, although its pharmacology has not been reported. We discovered that xanomeline and N-desmethylxanomeline have potent agonist and antagonist actions at many biogenic amine G protein coupled receptors. These results suggest that at least some of the actions of xanomeline and N-desmethylxanomeline could be mediated by off-target actions at serotonergic, dopaminergic, histaminergic, adrenergic and other receptors. We discuss the potential implications of these findings.in bioRxiv: Neuroscience on 2025-11-21 00:00:00 UTC.
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Aging reveals divergent responses of AgRP/NPY neurons to diet in male and female mice.
Objectives: Neurons coexpressing Agouti-related peptide (AgRP) and Neuropeptide Y (NPY) are an essential component of an interoceptive circuit regulating hunger and metabolism. Their activity is closely linked to metabolic state and their output is sensitive to diet-induced plasticity, which may influence the development of obesity and associated metabolic diseases. However, most studies use young male mice, even though obesity and its comorbidities are sensitive to both biological sex and aging, leaving a significant gap in our understanding of the role of these neurons in females and in older animals. Our goal was to begin to address this gap by investigating the effects of diet and age on AgRP/NPY neuronal activity in female mice in both early adulthood and midlife. Methods: Female transgenic NPY-GFP mice aged 8-32 weeks were fed either a standard control chow diet or a high-fat, high-sugar diet (HFD) for 8-24 weeks and brain slice patch clamp electrophysiology was used to measure the response of AgRP/NPY neurons. Results: We found that in young, lean female mice, the baseline firing rate of AgRP/NPY neurons is significantly elevated compared to age-matched males, thus the impact of HFD on the output of these neurons is blunted relative to control. However, in the baseline firing rate of neurons from lean middle-aged female mice is significantly lower, resulting in a greater relative impact of HFD on AgRP/NPY neuronal output, the development of neuronal leptin resistance, and significant weight gain. Conclusions: Both sex and age significantly impact the function and modulation of AgRP/NPY neurons, emphasizing the need to include these biological variables in experimental design.in bioRxiv: Neuroscience on 2025-11-21 00:00:00 UTC.
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Genetic dissection of microglia cannibalism reveals an IL10 signaling axis controls microglia lifespan
The development of complex organs, like the brain, demands a robust system for tissue remodeling and cellular debris clearance. In the brain, this function is performed by microglia, which must clear diverse debris substrates, including that caused by cell death. Although the subsequent fate of these phagocytic microglia is a critical regulatory point that impacts whether the brain resolves a debris environment, the genetic mechanisms that control microglia fate after debris clearance remain mostly unknown. To address this, we conducted a large-scale CRISPR screen in zebrafish using a custom-built robotic confocal microscope. We selected candidate genes from a single-cell RNA sequencing dataset of embryonic mouse microglia. This screen identified several modulators of microglial lifespan and cannibalism that are enriched in mouse and zebrafish microglia, including interleukin-10 receptor beta (il10rb), a receptor subunit for the cytokine IL10. Perturbation of il10, il10rb, and downstream signaling molecules JAK/STAT in zebrafish reduced microglial death. Expression analysis in mouse and zebrafish confirmed that microglia express both il10 and il10rb. Given the established role of IL10 in lysosomal remodeling, we hypothesized that it regulates microglial survival through lysosomal acidification. While il10rb perturbation did not alter lysosome number or size, it caused a significant reduction in LysoTracker-positive lysosomes, indicating decreased lysosomal acidification. Inhibiting v-ATPase also reduced microglial death, reinforcing the link between lysosomal pH and cell fate. Our findings reveal a cytokine-regulated mechanism where lysosomal dynamics determine the survival of phagocytic microglia. We propose that a necroptosis-cannibalism process functions as a quality control mechanism for microglial turnover, which is critical for refining neuroimmune cell function in the brain.in bioRxiv: Neuroscience on 2025-11-21 00:00:00 UTC.
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Altered Dopamine Signaling in Extinction-Deficient Mice
A central mechanism of exposure-based cognitive behavioral therapy for anxiety and trauma-related disorders is fear extinction. However, the mechanisms underlying fear extinction are deficient in some individuals, leading to treatment resistance. Recent animal studies demonstrate that upon omission of the aversive, unconditioned stimulus (US) during fear extinction, dopamine (DA) neurons in the ventral tegmental area (VTA) produce a prediction error (PE)-like signal. However, whether this VTA-DA neuronal PE-like signal is altered in animals exhibiting deficient fear extinction has not been studied. Here, we used a mouse model of impaired fear extinction [129S1/SvImJ (S1) inbred mouse strain] to monitor and manipulate VTA-DA neurons during extinction. Male DAT-Cre mice backcrossed onto an S1 background (S1-DAT-Cre) exhibited impaired extinction but normal VTA-DA neuron number, as compared with BL6-DAT-Cre mice. In vivo fiber photometry showed that impaired extinction in male S1-DAT-Cre mice was associated with abnormally sustained US omission-related VTA-DA neuronal calcium activity during extinction training and retrieval. Neither in vivo optogenetic photoexcitation of VTA-DA neuronal cell bodies nor their axons in the infralimbic cortex was sufficient to rescue deficient extinction in male S1-DAT-Cre mice, at least within the optogenetic and behavioral parameters used. These data suggest that alterations in the activity of VTA-DA neurons during extinction learning and retrieval may be associated with deficient fear extinction in male S1 mice and could potentially contribute to extinction impairments in patient populations.
in eNeuro on 2025-11-20 17:30:20 UTC.
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Open Data In Neurophysiology: Advancements, Solutions & Challenges
Ongoing efforts over the last 50 years have made data and methods more reproducible and transparent across the life sciences. This openness has led to transformative insights and vastly accelerated scientific progress (
Gražulis et al., 2012 ;Munafó et al., 2017 ). For example, structural biology (Bruno and Groom, 2014 ) and genomics (Benson et al., 2013 ;Porter and Hajibabaei, 2018 ) have undertaken systematic collection and publication of protein sequences and structures over the past half century. These data, in turn, have led to scientific breakthroughs that were unthinkable when data collection first began (Jumper et al., 2021 ). We believe that neuroscience is poised to follow the same path, and that principles of open data and open science will transform our understanding of the nervous system in ways that are impossible to predict at the moment. New social structures supporting an active and open scientific community are essential (Saunders, 2022 ) to facilitate and expand the still limited adoption of open science practices in our field (Schottdorf et al., 2024 ). Unified by shared values of openness, we set out to organize a symposium for open data in neurophysiology (ODIN) to strengthen our community and facilitate transformative open neuroscience research at large. In this report, we synthesize insights from this first ODIN event. We also lay out plans for how to grow this movement, document emerging conversations, and propose a path toward a better and more transparent science of tomorrow.in eNeuro on 2025-11-20 17:30:20 UTC.
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Impact and diagnostic accuracy of 18F-FDG PET/CT in malignant melanoma staging and restaging: First Tunisian clinical report [version 1; peer review: awaiting peer review]
Background Accurate staging guides melanoma treatment. Conventional imaging modalities like contrast-enhanced CT (CECT) is widely used but relies on morphology which may miss early spread. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) combines metabolic and anatomic data and may improve detection. Methods We conducted a single-centre retrospective diagnostic accuracy study at a tertiary university hospital in Tunisia (December 2019-February 2024). All adults with histologically confirmed melanoma undergoing whole body 18F-FDG PET/CT as well as CECT for initial staging or restaging were included. The reference standard was histopathology, otherwise composite verification with clinical/imaging follow-up ≥6 months. Outcomes were per-patient sensitivity, specificity, predictive values, and accuracy, inter-modality agreement (Cohen’s κ), and management change attributable to 18F-FDG PET/CT. Results Of 51 screened, 35 patients were included (23 staging and 12 restaging). Compared with CECT, 18F-FDG PET/CT reclassified stage in 22/35 (62.9%), upstaging 14 (40.0%) and downstaging 8 (22.9%). For nodal disease, 18F-FDG PET/CT showed higher specificity (95.2%, 95% CI [77.3-99.8] versus 66.7%, 95% CI [44.7–84.4]) and accuracy (88.6%, 95% CI [73.3-96.8], versus 65.7%, 95% CI [47.8-80.9]) with similar sensitivity (78.6%, 95% CI [49.2-95.3] versus 64.3%, 95% CI [35.1-87.2]). For distant metastases, 18F-FDG PET/CT achieved markedly higher sensitivity (92.9%, 95% CI [66.1–99.8] versus 50.0%, 95% CI [23.0-77.0]) and accuracy (91.4%, 95% CI [76.9-98.2] versus 68.6%, CI [50.7-83.1]), with high specificity for both (90.5%, 95% CI [69.6-98.8] versus 81.0%, 95% CI [58.1–94.6]). Agreement with CECT was fair for nodes (κ=0.27) and poor for distant sites (κ=0.16). Management decisions were available in 32/35. 18F-FDG PET/CT changed treatment in 15/32 (46.9%). No adverse events occurred. Conclusions In this first Tunisian series, 18F-FDG PET/CT improved diagnostic performance over CECT, especially for distant metastases, and frequently redirects management. Findings support integrating its integration into melanoma care pathways when results may influence therapy.in F1000Research on 2025-11-20 16:05:57 UTC.
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Thalamic Stimulation Induced Changes in Network Connectivity and Excitability in Epilepsy
Objective
The effects of deep brain stimulation (DBS) manifest across multiple timescales, spanning seconds to months, and involve direct electrical effects, neuroplasticity, and network reorganization. In epilepsy, the delayed impact of DBS on seizures presents challenges for optimization. Single-pulse stimulation and resulting brain stimulation evoked potentials (BSEPs) provide a means to assess effective connectivity and network excitability. This study integrates BSEPs and short trials of DBS during stereoelectroencephalography (sEEG) to map seizure network engagement, modulate network dynamics, and monitor excitability and interictal abnormalities for biomarker informed neuromodulation.
Methods
Ten individuals with drug resistant epilepsy undergoing clinical sEEG were enrolled in this retrospective cohort study of epilepsy neuromodulation biomarkers. Each patient underwent a trial of high frequency (145Hz) thalamic DBS. BSEPs were acquired before and after DBS trials. Baseline BSEP amplitude assessed seizure network engagement, and modulation of amplitude (pre vs post DBS) assessed change in network excitability. Interictal epileptiform discharges were tracked by an automated classifier.
Results
Baseline BSEPs delineated distinct patterns of network engagement between thalamic subfields with maximal frontotemporal engagement achieved with stimulation of the anterior nucleus of the thalamus-ventral anterior nucleus junction. DBS delivered for >1.5 hours reduced BSEP amplitudes compared to baseline, and the degree of modulation correlated with baseline connectivity strength. Shorter DBS trials did not induce reliable BSEP amplitude suppression, but did immediately suppress interictal epileptiform discharge rates in well-connected seizure networks.
Interpretation
BSEPs and trials of DBS during sEEG provide novel network biomarkers to evaluate the modulation of large-scale networks across multiple timescales, advancing biomarker informed neuromodulation. ANN NEUROL 2025
in Annals of Neurology on 2025-11-20 14:00:55 UTC.
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How cortico-basal ganglia-thalamic subnetworks can shift decision policies to increase reward rate
by Jyotika Bahuguna, Timothy Verstynen, Jonathan E. Rubin
All mammals exhibit flexible decision policies that depend, at least in part, on the cortico-basal ganglia-thalamic (CBGT) pathways. Yet understanding how the complex connectivity, dynamics, and plasticity of CBGT circuits translate into experience-dependent shifts of decision policies represents a longstanding challenge in neuroscience. Here we present the results of a computational approach to address this problem. Specifically, we simulated decisions during the early learning process driven by CBGT circuits under baseline, unrewarded conditions using a spiking neural network, and fit an evidence accumulation model to the resulting behavior. Using canonical correlation analysis, we then replicated the identification of three control ensembles (responsiveness, pliancy and choice) within CBGT circuits, with each of these subnetworks mapping to a specific configuration of the evidence accumulation process. We subsequently simulated learning in a simple two-choice task with one optimal (i.e., rewarded) target and found that, during early stages of learning, feedback-driven dopaminergic plasticity on cortico-striatal synapses effectively increases reward rate over time. The learning-related changes in the decision policy can be decomposed in terms of the contributions of each control ensemble, whose influence is driven by sequential reward prediction errors on individual trials. Our results provide a clear and simple mechanism for how dopaminergic plasticity shifts subnetworks within CBGT circuits so as to increase reward rate by strategically modulating how evidence is used to drive decisions.in PLoS Computational Biology on 2025-11-20 14:00:00 UTC.
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Real-time forecasting of data revisions in epidemic surveillance streams
by Jingjing Tang, Aaron Rumack, Bryan Wilder, Roni Rosenfeld
Epidemic data streams undergo frequent revisions due to reporting delays (“backfill”) and other factors. Relying on tentative surveillance values can seriously degrade the quality of situational awareness, forecasting accuracy and decision-making. We introduce Delphi Revision Forecast (Delphi-RF), a real-time data revision forecasting framework using nonparametric quantile regression, applicable to both counts and proportions (fractions) in public health reporting. By incorporating all available revisions up to a given estimation date, Delphi-RF models revision dynamics and generates distributional forecasts of finalized surveillance values. Applied to daily COVID-19 data (insurance claims, antigen tests, confirmed cases) and weekly dengue and influenza-like illness (ILI) case counts, Delphi-RF delivers accurate revision forecasts, particularly in early reporting stages. In addition, it improves computational efficiency by more than 10-100x compared to existing methods, making it a scalable solution for real-time public health surveillance.in PLoS Computational Biology on 2025-11-20 14:00:00 UTC.
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CrossLabFit: A novel framework for integrating qualitative and quantitative data across multiple labs for model calibration
by Rodolfo Blanco-Rodriguez, Tanya A. Miura, Esteban Hernandez-Vargas
The integration of computational models with experimental data is a cornerstone for gaining insight into biomedical applications. However, parameter fitting procedures often require a vast availability and frequency of data that are challenging to obtain from a single source. Here, we present a novel methodology called “CrossLabFit”, which is designed to integrate data from multiple laboratories, overcoming the constraints of single-lab data collection. Our approach harmonizes disparate qualitative assessments, ranging from different experimental labs to categorical observations, into a unified framework for parameter estimation. By using machine learning clustering, these qualitative constraints are represented as dynamic “feasible windows” that capture significant trends to which models must adhere. For numerical implementation, we developed a GPU-accelerated version of differential evolution to navigate the cost function that integrated quantitative and qualitative information. We validate our approach across a series of case studies, demonstrating significant improvements in model accuracy and parameter identifiability. This work opens a new paradigm for collaborative science, enabling a methodological roadmap to combine and compare findings between studies to improve our understanding of biological systems and beyond.in PLoS Computational Biology on 2025-11-20 14:00:00 UTC.
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PseudoknotVisualizer: Visualization of pseudoknots on three-dimensional RNA structures
by Takumi Otagaki, Goro Terai, Kiyoshi Asai, Junichi Iwakiri
Summary: We introduce the PseudoknotVisualizer, a specialized software designed to identify and visualize pseudoknots within RNA three-dimensional structures. Typically, RNA secondary structures containing pseudoknots can be decomposed into multiple pseudoknot-free layers. Our software colors the base pairs in each pseudoknot layer, enabling the visualization of pseudoknot distribution within three-dimensional structures. Specifically, users can utilize the PseudoknotVisualizer as a PyMOL extension, applying it directly to RNA molecules loaded in PyMOL. Additionally, a Command Line Interface (CLI) is provided, allowing users to generate coloring commands in Chimera or PyMOL formats, which can then be manually copied and pasted for visualization. By facilitating the clear depiction of pseudoknots in RNA tertiary structures, this tool addresses significant challenges in the identification and visualization of pseudoknots in RNA structural analysis, thereby enhancing research productivity and expanding potential applications in molecular biology. Availability and implementation: PseudoknotVisualizer is freely available at https://github.com/TakumiOtagaki/PseudoknotVisualizer.in PLoS Computational Biology on 2025-11-20 14:00:00 UTC.
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Multi-physics modeling for ion homeostasis in multi-compartment plant cells using an energy function
by Guillaume Mestdagh, Alexis De Angeli, Christophe Godin
Plant cells control their volume by regulating the osmotic potential of their cytoplasm and vacuole. Water is attracted into the cell as the result of a cascade of solute exchanges between the cell subcompartments and the cell surroundings, which are governed by chemical, electrostatic and mechanical forces. Due to this multi-physics aspect and to couplings between volume changes and chemical effects, modeling these exchanges remains a challenge that has only been partially addressed. As interest for multi-compartment models grows in the plant cell community, this challenge calls for new modeling strategies. In this paper, we introduce an energy-based approach to couple chemical, electrical and mechanical processes taking place between several subcompartments of a plant cell. The contributions of all physical effects are gathered in an energy function, which allows us to derive the equations satisfied by each variable in a systematic way. We illustrate the properties of this modular, unified approach on the modeling of ion and water transport in a guard cell during stoma opening. We represent the stoma opening process as a quasi-static evolution driven by hydrogen pumps in the plasma and vacuolar membranes, and we show that the new formalism explains why the system varies in a particular direction in response to perturbations. Additional numerical simulations allow us to investigate the role of each hydrogen pump in this process. Altogether, we show that this energy-based approach highlights a hierarchy between the forces involved in the system, and to dissect the role of each physical effect in the complex behavior of the system.in PLoS Computational Biology on 2025-11-20 14:00:00 UTC.
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Unlocking plant health survey data: An approach to quantify the sensitivity and specificity of visual inspections
by Matt Combes, Nathan Brown, Robin N. Thompson, Alexander Mastin, Peter Crow, Stephen Parnell
Invasive plant pests and pathogens cause substantial environmental and economic damage. Visual inspection remains a central tenet of plant health surveys, but its sensitivity (probability of correctly identifying the presence of a pest) and specificity (probability of correctly identifying the absence of a pest) are not routinely quantified. As knowing sensitivity and specificity of visual inspection is critical for effective contingency planning and outbreak management, we address this deficiency using empirical data and statistical analyses. Twenty-three citizen scientist surveyors assessed up to 175 labelled oak trees for three symptoms of acute oak decline. The same trees were also assessed by an expert who has monitored these individual trees annually for over a decade. The sensitivity and specificity of surveyors was calculated using the expert data as the ‘gold-standard’ (i.e., assuming perfect sensitivity and specificity). The utility of an approach using Bayesian modelling to estimate the sensitivity and specificity of visual inspection in the absence of a rarely available ‘gold-standard’ dataset was then examined with simulated plant health survey datasets. There was large variation in sensitivity and specificity between surveyors and between different symptoms, although the sensitivity of detecting a symptom was positively related to the frequency of the symptom on a tree. By leveraging surveyor observations of two symptoms from a minimum of 80 trees on two sites, with reliable prior knowledge of sites with a higher (~0.6) and lower (~0.3) true disease prevalence we show that sensitivity and specificity can be estimated without ‘gold-standard’ data using Bayesian modelling. We highlight that sensitivity and specificity will depend on the symptoms of a pest or disease, the individual surveyor, and the survey protocol. This has consequences for how surveys are designed to detect and monitor outbreaks, as well as the interpretation of survey data that is used to inform outbreak management.in PLoS Computational Biology on 2025-11-20 14:00:00 UTC.
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Benchmarking with synthetic communities provides a baseline for virus-host inferences from Hi-C proximity linking
by Rokaiya Nurani Shatadru, Natalie E. Solonenko, Christine L. Sun, Matthew B. Sullivan
Microbiomes influence diverse ecosystems, and viruses increasingly appear to impose key constraints. While viromics has expanded genomic catalogs, host identification for these viruses remains challenging due to the limitations in scaling cultivation-based approaches and the uncertain reliability and relative low resolution of in silico predictions – particularly for understudied viral taxa. Towards this, Hi-C proximity ligation uses sequenced, cross-linked virus and host genomic fragments to infer virus-host linkages and has now been applied in at least 10 studies. However, its accuracy remains unknown. Here we assess Hi-C performance in recovering virus-host interactions using synthetic communities (SynComs) composed of four marine bacterial strains and nine phages with known interactions and then apply optimized bioinformatic protocols to natural soil samples. In SynComs, standard Hi-C sample preparations and analyses showed poor normalized contact score performance (26% specificity, 100% sensitivity, incorrect matches up to class level) that could be dramatically improved by Z-score filtering (Z ≥ 0.5, 99% specificity), though at reduced sensitivity (62% down from 100%). Detection limits were established as reproducibility was poor below minimal phage abundances of 105 PFU/mL. Applying optimized bioinformatic protocols to natural soil samples, we compared virus-host linkages inferred from proximity-ligated Hi-C sequencing with predictions generated by in silico homology-based and machine learning-based bioinformatic approaches. Prior to Z-score thresholding, agreement was relatively high at the phylum to family levels (72%), but not at the genus (43%) or species (15%) levels. Z-score thresholding reduced sensitivity (only 34% of predictions were retained), with only modest improvements in congruence with bioinformatic methods (48% or 18% at genus or species levels, respectively). Regardless, this led to 79 genus-level-congruent virus-host linkages and 293 new ones revealed by Hi-C alone, i.e., providing many new virus-host interactions to explore in already well-studied climate-critical soils. Overall, these findings provide empirical benchmarks and methodological guidelines to improve the accuracy and reliability of Hi-C for virus-host linkage studies in complex microbial communities.in PLoS Biology on 2025-11-20 14:00:00 UTC.
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Editorial Note: Global Regulator SATB1 Recruits β-Catenin and Regulates TH2 Differentiation in Wnt-Dependent Manner
by The PLOS Biology Editors
in PLoS Biology on 2025-11-20 14:00:00 UTC.
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Sleep deprivation and sleep intensity exert distinct effects on cerebral vasomotion and brain pulsations driven by the respiratory and cardiac cycles
by Sara Marie Ulv Larsen, Sebastian Camillo Holst, Anders Stevnhoved Olsen, Brice Ozenne, Dorte Bonde Zilstorff, Kristoffer Brendstrup-Brix, Pia Weikop, Simone Pleinert, Vesa Kiviniemi, Poul Jørgen Jennum, Maiken Nedergaard, Gitte Moos Knudsen
The flow of cerebrospinal fluid (CSF) through the brain is driven by cerebral vasomotion, along with respiratory and cardiac forces. Growing evidence suggests that sleep facilitates this flow, yet the role of homeostatic sleep mechanisms remains largely unknown. In a circadian-controlled sleep and sleep deprivation study in humans, we used accelerated neuroimaging to investigate how sleep pressure and slow-wave-rich sleep affect low-frequency brain pulsations (LFPs; 0.012–0.034 Hz) as well as brain pulsations originating from the respiratory and cardiac cycles. These pulsations cause movement of CSF and brain tissue which may facilitate waste clearance. We also examined the origin of LFPs through pharmacological vasodilation of the cerebral vasculature with the adrenergic antagonist carvedilol in a randomized, cross-over, double-blinded, placebo-controlled design (NCT03576664). We find that sleep deprivation increases LFPs more than nonrapid eye movement (NREM) sleep does, with LFPs during sleep correlating with cognitive measures of sleep pressure. Conversely, NREM sleep (combined stages N2 and N3) enhances brain pulsations driven by the respiration and cardiac cycles, with more pronounced effects in gray and white matter than in the ventricles. The strength of these brain pulsations escalates with sleep depth (N3 > N2) and correlates with EEG delta power, a measure of slow wave activity. Moreover, carvedilol dampens LFPs, supporting that these reflect cerebral vasomotion. In summary, our findings indicate that heightened sleep pressure promotes vasomotion, whereas slow-wave-rich sleep amplifies respiration- and cardiac-driven brain pulsations, possibly indicating increased CSF flow to the brain. Together, this suggests that homeostatic sleep mechanisms are integral to human brain fluid dynamics and potentially also waste clearance.in PLoS Biology on 2025-11-20 14:00:00 UTC.
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Development of bitopic nanobody-ligand conjugates targeting G protein-coupled receptors and exhibiting logic-gated signaling
by Shivani Sachdev, Swarnali Roy, Ross W. Cheloha
G protein-coupled receptors (GPCRs) are the largest family of plasma membrane-embedded signaling proteins. These receptors are involved in a wide array of physiological processes, marking them as attractive targets for drug development. Bitopic ligands, which are comprised of a pharmacophore that targets the receptor orthosteric site and a linked moiety that binds to a separate site, have considerable potential for addressing GPCR function. Here, we report the synthesis and evaluation of novel bitopic conjugates consisting of a small molecule pharmacophore that activates the adenosine A2A receptor (A2AR) linked to antibody fragments (nanobodies, Nbs). This approach leverages the high-affinity and specificity binding of Nbs to non orthosteric sites on engineered A2AR variants to provide bitopic Nb-ligand conjugates that stimulate strong and enduring signaling responses. We further demonstrate that such bitopic conjugates can induce activation by spanning two distinct receptor protomers. This property enables the selective targeting of receptor pairs over either individual receptor, as a form of “logic-gated” activity. We showcase the broad applicability of bitopic conjugates in this context by demonstrating their activity in targeting several pairs of co-expressed receptors, including GPCR monomers from different classes. Furthermore, we demonstrate that this dual-targeting strategy initiates signaling responses that diverge from those induced by monovalent ligands. The ability to target receptor pairs using Nb-ligand conjugates offers a powerful strategy with potential for cell type-selective signaling and implications for GPCR drug discovery efforts more broadly.in PLoS Biology on 2025-11-20 14:00:00 UTC.
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Online interference of declarative memory on fast and slow adaptive processes in force field motor learning
Journal of Neurophysiology, Ahead of Print.
in Journal of Neurophysiology on 2025-11-20 12:31:18 UTC.
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Motor variability predicts motor learning of improved trunk postural control through repeated trunk perturbations during walking in children with cerebral palsy
Journal of Neurophysiology, Ahead of Print.
in Journal of Neurophysiology on 2025-11-20 12:21:15 UTC.
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Autism-associated Scn2a haploinsufficiency disrupts in vivo dendritic signaling and impairs flexible decision-making
Proceedings of the National Academy of Sciences, Volume 122, Issue 47, November 2025.
SignificanceSCN2Ais one of the strongest known genetic risk factors for autism spectrum disorder (ASD). Previous studies using brain slices showed that losing this gene lowers the excitability in dendrites of pyramidal cells in the cortex. However, it ...in PNAS on 2025-11-20 08:00:00 UTC.
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Rebalancing viral and immune damage versus repair prevents death from lethal influenza infection
Science, Volume 390, Issue 6775, November 2025.
in Science on 2025-11-20 08:00:00 UTC.
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Noncanonical agonist-dependent and -independent arrestin recruitment of GPR1
Science, Volume 390, Issue 6775, November 2025.
in Science on 2025-11-20 08:00:00 UTC.
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An archaeal genetic code with all TAG codons as pyrrolysine
Science, Volume 390, Issue 6775, November 2025.
in Science on 2025-11-20 08:00:00 UTC.
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An Aeromonas variant that produces aerolysin promotes susceptibility to ulcerative colitis
Science, Volume 390, Issue 6775, November 2025.
in Science on 2025-11-20 08:00:00 UTC.
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The 2025 Santorini unrest unveiled: Rebounding magmatic dike intrusion with triggered seismicity
Science, Volume 390, Issue 6775, November 2025.
in Science on 2025-11-20 08:00:00 UTC.
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Retinal calcium waves coordinate uniform tissue patterning of the Drosophila eye
Science, Volume 390, Issue 6775, November 2025.
in Science on 2025-11-20 08:00:00 UTC.
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The synaptic ectokinase VLK triggers the EphB2–NMDAR interaction to drive injury-induced pain
Science, Volume 390, Issue 6775, November 2025.
in Science on 2025-11-20 08:00:00 UTC.
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What enables human language? A biocultural framework
Science, Volume 390, Issue 6775, November 2025.
in Science on 2025-11-20 08:00:00 UTC.
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Erratum for the Research Article “ER-mitochondria contacts couple mtDNA synthesis with mitochondrial division in human cells” by S. C. Lewis et al.
Science, Volume 390, Issue 6775, November 2025.
in Science on 2025-11-20 08:00:00 UTC.
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Erratum for the Research Article “Cdc48 and a ubiquitin ligase drive disassembly of the CMG helicase at the end of DNA replication” by M. Maric et al.
Science, Volume 390, Issue 6775, November 2025.
in Science on 2025-11-20 08:00:00 UTC.
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The demographic future that we do not know about
Science, Volume 390, Issue 6775, November 2025.
in Science on 2025-11-20 08:00:00 UTC.
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In defense of the know-it-all
Science, Volume 390, Issue 6775, Page 793-793, November 2025.
in Science on 2025-11-20 07:00:09 UTC.
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An ode to change
Science, Volume 390, Issue 6775, Page 792-792, November 2025.
in Science on 2025-11-20 07:00:09 UTC.
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The Moon-forming impactor Theia originated from the inner Solar System
Science, Volume 390, Issue 6775, Page 819-823, November 2025.
in Science on 2025-11-20 07:00:09 UTC.
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Increasing the dimensionality of transistors with hydrogels
Science, Volume 390, Issue 6775, Page 824-830, November 2025.
in Science on 2025-11-20 07:00:09 UTC.
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Multigas adsorption with single-site cooperativity in a metal–organic framework
Science, Volume 390, Issue 6775, Page 808-812, November 2025.
in Science on 2025-11-20 07:00:09 UTC.
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A cross-linked molecular contact for stable operation of perovskite/silicon tandem solar cells
Science, Volume 390, Issue 6775, Page 837-842, November 2025.
in Science on 2025-11-20 07:00:09 UTC.
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Atomic layer bonding contacts in two-dimensional semiconductors
Science, Volume 390, Issue 6775, Page 813-818, November 2025.
in Science on 2025-11-20 07:00:09 UTC.
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An anion-binding approach to enantioselective photoredox catalysis
Science, Volume 390, Issue 6775, Page 831-836, November 2025.
in Science on 2025-11-20 07:00:09 UTC.
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Realization of a Rydberg-dressed extended Bose-Hubbard model
Science, Volume 390, Issue 6775, Page 849-853, November 2025.
in Science on 2025-11-20 07:00:09 UTC.
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CRISPR-Cas–mediated heritable chromosome fusions in Arabidopsis
Science, Volume 390, Issue 6775, Page 843-848, November 2025.
in Science on 2025-11-20 07:00:09 UTC.
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Time to laugh
Science, Volume 390, Issue 6775, Page 858-858, November 2025.
in Science on 2025-11-20 07:00:09 UTC.
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In Other Journals
Science, Volume 390, Issue 6775, Page 800-800, November 2025.
in Science on 2025-11-20 07:00:09 UTC.
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Engineering chromosome number in plants
Science, Volume 390, Issue 6775, Page 786-787, November 2025.
in Science on 2025-11-20 07:00:09 UTC.
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Tracking magma with earthquakes
Science, Volume 390, Issue 6775, Page 790-791, November 2025.
in Science on 2025-11-20 07:00:09 UTC.
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