bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mean exercise torque is a critical factor influencing neuromuscular fatigability induced by exhausting contractions
Authors: Lebesque Loïc , Scaglioni Gil , Manckoundia Patrick , Martin Alain 
Published: March 2024

ABSTRACTPURPOSETo get a more detailed description of neuromuscular fatigability, maximal torque sustainability (i.e., the ability to maintain a high torque level) can be assessed in addition to the classically used maximal voluntary contraction (MVC). Since this parameter appears to be affected by mean exercise torque (MET), the present study aims to examine the relationship between MET and neuromuscular fatigability induced by exhausting contractions.METHODSThirteen participants sustained a plantar flexors MVC for 1 min (MVC1-MIN) before and after exhausting exercises designed to produce a similar MET (30% MVC), and following a 10-min rest period. Exercises consisted of intermittent (INT), continuous (CON) or variable (continuous contraction alternating between moderate and low intensity, VAR) contractions performed until task failure.RESULTSAlthough the INT resulted in greater exercise duration and torque-time integral than CON and VAR, MVC similarly decreased after all exercises due to neural and muscular impairments. The torque loss during the MVC1-MINincreased after all exercises to a similar extent, mainly because of neural alterations. Contrary to MVC, the torque loss during the MVC1-MINreturned to baseline value after the recovery period.CONCLUSIONBy considering both maximal torque production and sustainability, INT, CON and VAR exercises, performed with identical mean torque and until exhaustion, led to a similar neuromuscular fatigability. Results confirm the independence of maximal torque production from the contraction pattern and support the impact of MET on maximal torque sustainability. The present findings are crucial to consider for the management of neuromuscular fatigability in both athletes and patients.
Non-invasive MRI of Blood-Cerebrospinal Fluid-Barrier Function: a Functional Biomarker of Early Alzheimer’s Disease Pathology
Authors: Perera Charith , Cruz Renata , Shemesh Noam , Carvalho Tania , Thomas David L. , Wells Jack , Ianus Andrada 
Published: March 2024

AbstractINTRODUCTIONChoroid plexus (CP) dysfunction is thought to contribute to toxic protein build-up in neurodegenerative disorders, including Alzheimer’s disease (AD). However, the dynamics of this process remain unknown, mainly due to the paucity of in-vivo methods capable of assessing CP function.METHODSHere, we harness recent developments in Arterial Spin Labelling MRI to measure water delivery across the blood cerebrospinal fluid barrier (BCSFB) as a proxy for CP function, as well as cerebral blood flow (CBF), at different stages of AD progression in the widely used triple transgenic mouse model (3Tg), which recapitulates aspects of disease pathology.RESULTSTotal BCSFB-mediated water delivery is significantly higher in 3Tg mice (>50%) from 8 weeks (preclinical stage), while tissue parameters such as CBF and T1 are not different between groups at all ages.DISCUSSIONOur work shows changes in BCSFB function in the early stages of AD, providing a novel biomarker of pathology.
Ectomycorrhizal fungi are influenced by ecoregion boundaries across Europe
Authors: Delhaye Guillaume , van der Linde Sietse , Bauman David , Orme C. David L. , Suz Laura M. , Bidartondo Martin I. 
Published: March 2024

AbstractAimEcoregions and the distance decay in community similarity are fundamental concepts in biogeography and conservation biology that are well supported across plants and animals, but not fungi. Here we test the relevance of these concepts for ectomycorrhizal (ECM) fungi in temperate and boreal regions.LocationEurope.Time period2008 – 2015.Major taxa studiedEctomycorrhizal fungi.MethodsWe used a large dataset of ∼ 24,000 ectomycorrhizas, assigned to 1,350 operational taxonomic units, collected from 129 forest plots via a standardised protocol. We investigated the relevance of ecoregion delimitations for ECM fungi through complementary methodological approaches based on distance decay models, multivariate analyses, and indicator species analyses. We then evaluated the effects of host tree and climate on the observed biogeographical distributions.ResultsEcoregions predict large-scale ECM fungal biodiversity patterns. This is partly explained by climate differences between ecoregions but independent from host tree distribution. Basidiomycetes in the orders Russulales and Atheliales and producing epigeous fruiting bodies, with potentially short-distance dispersal, show the best agreement with ecoregion boundaries. Host tree distribution and fungal abundance (as opposed to presence/absence only) are important to uncover biogeographical patterns in mycorrhizas.Main conclusionsEcoregions are useful units to investigate eco-evolutionary processes in mycorrhizal fungal communities and for conservation decision-making that includes fungi.
Learning tissue representation by identification of persistent local patterns in spatial omics data
Authors: Tanevski Jovan , Vulliard Loan , Hartmann Felix , Saez-Rodriguez Julio 
Published: March 2024

AbstractSpatial omics data provide rich molecular and structural information about tissues, enabling novel insights into the structure-function relationship. In particular, it facilitates the analysis of the local heterogeneity of tissues and holds promise to improve patient stratification by association of finer-grained representations with clinically relevant features. Here, we introduce Kasumi, a method for the identification of spatially localized neighborhoods of intra- and intercellular relationships, persistent across samples and conditions. We learn compressed explainable representations while preserving relevant biological signals that are readily deployable for data exploration and hypothesis generation, facilitating translational tasks. We address tasks of patient stratification for disease progression and response to treatment in cancer on data coming from different spatial antibody-based multiplexed proteomics platforms. Kasumi outperforms related neighborhood analysis approaches and offers explanations at the level of cell types or directly from the measurements, of the spatial coordination and multivariate relationships underlying observed disease progression and response to treatment. We show that persistent local patterns form spatially contiguous regions of different sizes. However, the abundance of the persistent local patterns is not associated with their relative importance in downstream tasks. We show that non-abundant, localized structural and functional relationships in the tissue are strongly associated with unfavorable outcomes in disease progression and response to treatment.
Ecological diversification in sexual and asexual lineages
Authors: Chaparro-Pedraza P. Catalina , Roth Gregory , Melián Carlos J. 
Published: March 2024

AbstractThe presence or absence of sex can have a strong influence on the processes whereby species arise. Yet, the mechanistic underpinnings of this influence are poorly understood. To gain insights into the mechanisms whereby the reproductive mode may influence diversification, we investigate how natural selection, genetic mixing and the reproductive mode interact and how this interaction affects the evolutionary dynamics of diversifying lineages. To do so, we formulate and analyze trait-based eco-evolutionary models of ecological diversification for sexual and asexual lineages, in which diversification is driven by intraspecific resource competition. We find that the reproductive mode strongly influences the diversification rate and thus the ensuing diversity of a lineage. Our results reveal that natural selection is stronger in asexual lineages because asexual organisms have a higher reproductive potential than sexual ones. As a consequence, an asexual population can reach a higher population density than a sexual population under the very same ecological conditions. This causes competition, and thus ecologically-based selection, to be stronger in asexual lineages, promoting faster diversification. However, a small amount of genetic mixing accelerates the trait expansion process in sexual lineages, overturning the effect of selection alone and enabling a faster niche occupancy than asexual lineages. As a consequence, sexual lineages can occupy more ecological niches, eventually resulting in higher diversity. This suggests that sexual reproduction may be widespread among species because it increases rates of diversification.
U-FISH: a universal deep learning approach for accurate FISH spot detection across diverse datasets
Authors: Xu Weize , Cai Huaiyuan , Zhang Qian , Mueller Florian , Ouyang Wei , Cao Gang 
Published: March 2024

AbstractIn the rapidly advancing landscape of fluorescence in situ hybridization (FISH) technologies, there is a critical need for sophisticated yet adaptable methods for spot detection. This study introduces U-FISH, a deep learning approach that significantly improves accuracy and generalization capabilities. Our method utilizes a U-Net model to transform noisy and ambiguous FISH images into a standardized representation with consistent signal characteristics, facilitating efficient spot detection. For the training and evaluation of the U-FISH model, we have constructed a comprehensive dataset comprising over 4,000 images and more than 1.6 million manually annotated spots, sourced from both experimental and simulated environments. Our benchmarks demonstrate that U-FISH outperforms existing methods for FISH spot detection, offering improved versatility by eliminating the need for laborious manual parameter adjustments. This allows for its application across a broad spectrum of datasets and formats. Furthermore, U-FISH is designed for high scalability and is capable of processing 3D data, supporting the latest generation of file formats for large and complex datasets. To promote community adoption and ensure accessibility, we provide a user-friendly interfaces: Napari plugin, web application and command-line interface. The complete training dataset is made publicly available, laying a solid foundation for future research in this field.
High-resolution climate data reveals increased risk of Pierce’s Disease for grapevines worldwide
Authors: Giménez-Romero Àlex , Moralejo Eduardo , Matías Manuel A. 
Published: March 2024

AbstractRange shifts in plant disease distributions are sensitive to scaling processes, but few crop case studies have included these predictions under climate change. High-quality wines are increasingly produced in topographically heterogeneous river valleys, whereby disease models that capture steep relief gradients become especially relevant. Here we show how non-linear epidemiological models more accurately reflect the threat of an emerging grapevine pathogen in areas with significant spatial gradients. By comparing the results of simulations using climate data with different spatial resolutions, we identify an increased risk of Pierce’s disease (PD), caused by the vector-borne bacteriumXylella fastidiosa, in wine regions globally. Over 100,000 vine presence records worldwide were analysed with respect to their closer risk-grid cell, observing an increase from 21.8% to 41.2% of the area at risk in European vineyards, from 5.6% to 47.2% in South Africa and to a lesser extent in other wine-growing regions. This general trend has been preceded by an accelerating rate of increase in risk within wine-growing areas. Our analysis demonstrates the importance of microclimatic conditions, highlighting previously unresolved risk zones in areas close to rivers and valleys, and the insufficiency of lower resolution data sets to capture complex climatic variations.
High Frequency Terahertz Stimulation Alleviates Neuropathic Pain by Inhibiting the Pyramidal Neuron Activity in the Anterior Cingulate Cortex of mice
Authors: Peng Wenyu , Wang Pan , Tan Chaoyang , Zhao Han , Chen Kun , Si Huaxing , Tian Yuchen , Lou Anxin , Zhu Zhi , Yuan Yifang , Wu Kaijie , Chang Chao , Wu Yuanming , Chen Tao 
Published: March 2024

AbstractNeuropathic pain (NP) is caused by a lesion or disease of the somatosensory system and is characterized by abnormal hypersensitivity to stimuli and nociceptive responses to non-noxious stimuli, affecting approximately 7–10% of the general population. However, current first-line drugs like non-steroidal anti-inflammatory agents and opioids have limitations, including dose-limiting side effects, dependence, and tolerability issues. Therefore, developing new interventions for the management of NP is urgent. In this study, we discovered that the high-frequency terahertz stimulation (HFTS) at approximate 36 THz effectively alleviates NP symptoms in mice with spared nerve injury. Computational simulation suggests that the frequency resonates with the carbonyl group in the filter region of Kv1.2 channels, facilitating the translocation of potassium ions.In vivoandin vitroresults demonstrate that HFTS reduces the excitability of pyramidal neurons in the anterior cingulate cortex through enhancing the voltage-gated K+and also the leak K+conductance. This research presents a novel optical intervention strategy with terahertz waves for the treatment of NP and holds promising application in other nervous system diseases.
Longevity of Implantable Silicon-ICs for Emerging Neural Applications: Evaluation of Bare Die and PDMS-Coated ICs After Accelerated Aging and Implantation Studies
Authors: Nanbakhsh Kambiz , Idil Ahmad Shah , Lamont Callum , Dücső Csaba , Akgun Ömer Can , Horváth Domonkos , Tóth Kinga , Ulbert István , Mazza Federico , Constandinou Timothy G. , Serdijn Wouter , Vanhoestenberghe Anne , Donaldson Nick , Giagka Vasiliki 
Published: March 2024

AbstractSilicon integrated circuits (ICs) are central to the next-generation miniature active neural implants, whether packaged in soft polymers for flexible bioelectronics or implanted as bare die for neural probes. These emerging applications bring the IC closer to the corrosive body environment, raising reliability concerns, particularly for long-term clinical use. Here, we evaluated the long-term electrical and material stability of silicon-ICs from two foundries, after one-year acceleratedin vitroandin vivoanimal studies. The ICs featured various custom-designed test structures and were partially PDMS coated, creating two regions on each chip, uncoated “bare die” and “PDMS-coated”. During the acceleratedin vitrostudy, ICs were electrically biased and periodically monitored. Results demonstrated stable electrical performance for at least a year, suggesting that bare die ICs can function in the body for months. Despite electrical stability, material analysis revealed chemical and electrically driven degradation of the IC passivation in the bare die regions. In contrast, PDMS-coated regions revealed no such degradation, making PDMS a highly suitable encapsulant for ICs intended for years-long implantation. Based on the new insights, guidelines are proposed that may enhance the longevity of implantable ICs, significantly broadening their applications in the biomedical field.
Clinical factors associated with SFTS diagnosis and severity in cats
Authors: Osako Hiromu , Xu Qiang , Nabeshima Takeshi , Balingit Jean Claude , Nwe Khine Mya , Yu Fuxun , Inoue Shingo , Hayasaka Daisuke , Tun Mya Myat Ngwe , Morita Kouichi , Takamatsu Yuki 
Published: March 2024

SummarySevere fever with thrombocytopenia syndrome (SFTS) is a potentially fatal tick-borne zoonosis caused by SFTS virus (SFTSV). In addition to tick bites, animal-to-human transmission of SFTSV has been reported, but little is known about feline SFTSV infection. In this study, we analyzed data on 187 cats with suspected SFTS to identify biomarkers for SFTS diagnosis and clinical outcome., Body weight, red and white blood cell and platelet counts, serum aspartate aminotransferase and total bilirubin levels, were useful for SFTS diagnosis, and alanine aminotransferase, aspartate aminotransferase and serum SFTSV RNA levels were associated with the clinical outcome. We developed a scoring model to predict SFTSV infection. In addition, we performed a phylogenetic analysis to reveal the relationship between disease severity and viral strain. This study provides comprehensive information on feline SFTS and could contribute to the protection of cat owners, community members, and veterinarians from the risk of cat-transmitted SFTSV infection.
Screening of functional maternal-specific chromatin regulators in early embryonic development
Authors: Liu Guifen , Wang Yiman , Wang Xiangxiu , Wang Wen , Cao Zheng , Zhang Yong 
Published: March 2024

AbstractThe early stages of embryonic development rely on maternal products for proper regulation. However, systematic screening for functional maternal-specific factors has been challenging due to the time- and labor-intensive nature of traditional approaches. Here, we combined a computational pipeline and F0 homozygous mutation technology to screen for functional maternal-specific chromatin regulators in zebrafish embryogenesis and identified Mcm3l, Mcm6l, and Npm2a as playing essential roles in DNA replication and cell division. Our results contribute to understanding the molecular mechanisms underlying early embryo development and highlight the importance of maternal-specific chromatin regulators in this critical stage.
3D quantification of viral transduction efficiency in living human retinal organoids
Authors: Rogler Teresa S. , Salbaum Katja A. , Sonntag Selina M. , James Rebecca , Shelton Elijah R. , Brinkop Achim T. , Klopstock Thomas , Babutzka Sabrina , Michalakis Stylianos , Serwane Friedhelm 
Published: March 2024

AbstractThe development of therapeutics relies on testing their efficiency and specificity in animals and humanin vitromodels. To optimize the efficiency of a gene therapy, for example, fluorescent reporters expressed by treated cells are often utilized as readouts. Traditionally, the overall fluorescence signal provides an estimate for the global transduction efficiency. However, detailed analysis of the transduction efficiency in individual cells within a tissue remains a challenge. Readout on a single cell level can be realized via fluorescence-activated cell sorting at the cost of tissue dissociation into single cells and loss of spatial information. Complementary, spatial information is accessible via immunofluorescence characterization of fixed samples. However, those approaches impede time-dependent studies and prevent the recording of the dynamic interplay between the viral vector and the target cells in a 3D tissue.Here, we provide a quantitative, three-dimensional characterization of viral transduction efficiencies in living retinal organoids. We combine engineered adeno-associated virus (AAV) vectors, confocal live-imaging, and deep learning-based image segmentation to establish a quantitative test platform for gene delivery. To establish this, we transduced human retinal organoids with specific AAV vectors and imaged the fluorescent reporter expression in 3D. We measured a faster onset (7 days) and higher transduction efficiency (82%) of an AAV vector with optimized serotype (AAV2.NN) compared to two other AAV serotypes (AAV2.7m8, AAV9.NN). This highlights the practicality and functionality of our platform as a testbed for future treatments. The combination of optimized viral vectors, live-imaging, and deep learning-based image processing has the potential to guide the development of therapies in a variety of biomedical applications.
Unlocking the Potential of High-Quality Dopamine Transporter Pharmacological Data: Advancing Robust Machine Learning-Based QSAR Modeling
Authors: Lee Kuo Hao , Won Sung Joon , Oyinloye Precious , Shi Lei 
Published: March 2024

AbstractThe dopamine transporter (DAT) plays a critical role in the central nervous system and has been implicated in numerous psychiatric disorders. The ligand-based approaches are instrumental to decipher the structure-activity relationship (SAR) of DAT ligands, especially the quantitative SAR (QSAR) modeling. By gathering and analyzing data from literature and databases, we systematically assemble a diverse range of ligands binding to DAT, aiming to discern the general features of DAT ligands and uncover the chemical space for potential novel DAT ligand scaffolds. The aggregation of DAT pharmacological activity data, particularly from databases like ChEMBL, provides a foundation for constructing robust QSAR models. The compilation and meticulous filtering of these data, establishing high-quality training datasets with specific divisions of pharmacological assays and data types, along with the application of QSAR modeling, prove to be a promising strategy for navigating the pertinent chemical space. Through a systematic comparison of DAT QSAR models using training datasets from various ChEMBL releases, we underscore the positive impact of enhanced data set quality and increased data set size on the predictive power of DAT QSAR models.
Functional Diversification of Gene Duplicates under the Constraint of Protein Structure
Authors: Guo Kangning , Yang Yuqing , You Tingting , Zhu Kangli 
Published: March 2024

AbstractGene differentiation following duplication plays a crucial role in evolution, driving the emergence of new functional genes. This process involves changes in key gene traits, such as protein structure, expression patterns, subcellular localization, and enzymatic activity, which together contribute to the development of novel functions. Here, we identified a group of homologous Glycoside Hydrolase Family 50 (GH50) agarases in the deep-sea bacteriumAgarivorans ablusstrain JK6, providing an ideal model for studying gene differentiation following duplication. Phylogenetic analysis revealed that these enzymes arose through gene duplication and subsequent divergence. Experimental assays demonstrated that, while they retained similar glycoside hydrolase activity, their agarolytic activity diverged significantly. We further explored their structural variations constrained by the protein’s 3D structural limitations, the development of specific localization linked to changes in enzymatic activity, and distinct expression patterns induced by different sugars. Notably, structural variations were primarily concentrated in the active site, while the overall backbone remained highly conserved. This study highlights gene differentiation following duplication as a key evolutionary strategy, facilitating the transition from single enzymes to complex functional systems.