bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disentangling the contributions of stress fibres and the unbundled actin meshwork to the anisotropy of cortical tension in response to cell shape
Authors: Fage F. , Asnacios S. , Pluta A. , Richert A. , Vias C. , Fouchard J. , Enslen H. , Etienne J. , Callan-Jones A. , Thery M. , Pereira D. , Asnacios A. 
Published: October 2024

ABSTRACTMany fundamental biological processes, in particular development and morphogenetic movements, involve tissue and cell deformation, as well as the generation of anisotropic mechanical stresses. They are often accompanied by the appearance of oriented contractile actomyosin structures resembling the stress fibres (SF) observedin vitro. Here, we investigate, at the single cell level, how cell shape — by itself — could control the structure and tension of the actomyosin cortex. Using a unique combination of 3D micropatterning, single peripheral SF (PSF) tension measurement, laser ablation and image analysis, we show that cell shape anisotropy, e.g. its 2D aspect ratio, is indeed sufficient to induce anisotropy of the cortical structure and tension. In particular, taking into account the experimentally measured anisotropy of the cortical meshwork, we could quantify cortical tension and decouple the contribution originating from bundled actin (oriented cortical stress fibres, CSF) and the contribution of the unbundled actin meshwork (UAM). We show that the increase of cortical tension anisotropy with the cell’s aspect ratio depends on the CSF alignment and orientation, the contribution of the isotropic mesh being independent of cell shape. Remarkably, while experimental data from single stress fibre measurements and laser ablation were analysed through different theoretical frameworks, namely that of negative pressure in nematics and hole drilling in prestressed materials, we found quantitatively the same composite material behaviour. In sum, we decipher here the very material properties of the actomyosin cortex, and its sensitivity to cell shape which is at the root of many mechanobiological processes, in particular morphogenesis.
Deep structural analysis of rhamnogalacturonan-I (RG-I) in Arabidopsis reveals new insights into pectin diversity
Authors: Zhang Liang , Vlach Jiri , Black Ian M. , Archer-Hartmann Stephanie , Heiss Christian , Azadi Parastoo , Urbanowicz Breeanna R. 
Published: October 2024

AbstractPectic polysaccharides are an integral part of primary plant cell walls, where they are perfrom crucial structural and biological functions. Pectin is generally divided into four distinct structural categories, including homogalacturonan, xylogalacturonan, rhamnogalacturonan I (RG-I) and rhamnogalacturonan II. Among the four main pectin domains, the structural intricacies of rhamnogalacturonan-I (RG-I) remain the least understood, especially in widely employed plant models. We employed multiple complementary analytical techniques to present a detailed structural analysis of RG-I in the model systemArabidopsis thaliana.Using highly purified RG-I from different tissues, we conducted comparative linkage and NMR analyses, complemented by mass spectrometry of enzymatically digested RG-I oligosaccharides. Our findings present the most comprehensive structural overview of Arabidopsis RG-I to date, revealing novel structural features. Notably, we identifiedO-acetylation of rhamnose backbone residues as a predominant feature, a modification previously unreported in this species. The combined results present a comprehensive structural overview ofArabidopsis thalianaRG-I that will serve as a roadmap for studying pectin biosynthesis and function.
Identification and characterization of UBA5 inhibitors
Authors: Singh Vigyasa , Wan Yuansong , Ahmed Tahsin Reaz , Wang Si-Yu , Samrat Subodh Kumar , Li Zhong , Sinha Subhash , Gan Li , Li Hongmin 
Published: October 2024

ABSTRACTUBA5 is a critical E1-activating enzyme in the UFMylation pathway, a post-translational modification process implicated in neurodegenerative diseases and cancers. In this study, we developed a high-throughput screening (HTS) assay to identify inhibitors of UBA5 from a library of blood-brain barrier (BBB)-permeable compounds. The assay, based on the AMP-Glo™ kit, enabled the identification of five novel UBA5 inhibitors belonging to three distinct chemical scaffolds with low micromolarIC50values. These inhibitors demonstrated selectivity for UBA5 over other E1 enzymes, such as UBA1, and showed efficacy in inhibiting endogenous UFMylation in HEK293T cells. The identified inhibitors not only provided valuable tools for studying UFMylation but also represent potential therapeutic candidates for diseases associated with dysregulated UFMylation, such as Alzheimer’s disease and cancer. Further optimization of these compounds is necessary to enhance their potency and pharmacokinetic properties. Our findings highlight UBA5 as a promising therapeutic target and pave the way for the development of selective inhibitors that can modulate UFMylation in human diseases.
Automated Harmonization and Large-Scale Integration of Heterogeneous Biomedical Sample Metadata Using Large Language Models
Authors: Higashi Koichi , Nakagawa Zenichi , Yamada Takuji , Mori Hiroshi 
Published: October 2024

AbstractThe exponential growth of biomedical data has created an urgent need for efficient integration and analysis of heterogeneous sample metadata across studies. However, current methods for harmonizing and standardizing these metadata are largely manual, time-consuming, and prone to inconsistencies. Here, we present a novel computational framework that leverages large language models (LLMs) to automate the harmonization and large-scale integration of diverse biomedical sample metadata. Our approach combines semantic clustering techniques with LLM-driven natural language processing to extract, interpret, and standardize metadata from various sources, including research papers, supplementary tables, and text data from public databases. We demonstrate the efficacy of our framework by applying it to thousands of human gut microbiome papers, successfully extracting and integrating metadata from over 400,000 samples. Our method achieved a 50% recovery rate of manually curated metadata, significantly outperforming traditional rule-based methods. Furthermore, our framework enabled the creation of a unified, searchable database of standardized metadata, facilitating cross-study analyses and revealing previously obscured patterns in microbiome composition across diverse populations and conditions. The scalability and adaptability of our approach suggest its potential applicability to a wide range of biomedical fields, potentially accelerating meta-analyses and fostering new insights from existing data. This work represents a significant advancement in biomedical data integration, offering a powerful tool for researchers to unlock the full potential of accumulated scientific knowledge.
C9orf72expansion creates the unstable folate-sensitive fragile site FRA9A
Authors: Mirceta Mila , Schmidt Monika H.M. , Shum Natalie , Prasolava Tanya K. , Meikle Bryanna , Lanni Stella , Mohiuddin Mohiuddin , Mckeever Paul M. , Zhang Ming , Liang Minggao , van der Werf Ilse , Scheers Stefaan , Dion Patrick A. , Wang Peixiang , Wilson Michael D. , Abell Theresa , Philips Elliot A. , Sznajder Łukasz J. , Swanson Maurice S. , Mehkary Mustafa , Khan Mahreen , Yokoi Katsuyuki , Jung Christine , de Jong Pieter J. , Freudenreich Catherine H. , McGoldrick Philip , Yuen Ryan K.C. , Abrahão Agessandro , Keith Julia , Zinman Lorne , Robertson Janice , Rogaeva Ekaterina , Rouleau Guy A. , Kooy R. Frank , Pearson Christopher E. 
Published: October 2024

AbstractThe hyper-unstable Chr9p21 locus, harbouring the interferon gene cluster, oncogenes andC9orf72,is linked to multiple diseases.C9orf72(GGGGCC)n expansions (C9orf72Exp) are associated with incompletely penetrant amyotrophic lateral sclerosis, frontotemporal dementia and autoimmune disorders.C9orf72Exp patients display hyperactive cGAS-STING-linked interferon immune and DNA damage responses, but the source of immuno-stimulatory or damaged DNA is unknown. Here, we showC9orf72Exp in pre-symptomatic and ALS-FTD patient cells and brains cause the folate-sensitive chromosomal fragile site, FRA9A. FRA9A centers on >33kb ofC9orf72as highly-compacted chromatin embedded in an 8.2Mb fragility zone spanning 9p21, encompassing 46 genes, making FRA9A one of the largest fragile sites.C9orf72Exp cells show chromosomal instability, heightened global- and Chr9p-enriched sister-chromatid exchanges, truncated-Chr9s, acentric-Chr9s and Chr9-containing micronuclei, providing endogenous sources of damaged and immunostimulatory DNA. Cells from oneC9orf72Exp patient contained highly-rearranged FRA9A-expressing Chr9 with Chr9-wide dysregulated gene expression. SomaticC9orf72Exp repeat instability and chromosomal fragility are sensitive to folate-deficiency. Age-dependent repeat instability, chromosomal fragility, and chromosomal instability can be transferred to CNS and peripheral tissues of transgenicC9orf72Exp mice, implicatingC9orf72Exp as the source. Our results highlight unappreciated effects ofC9orf72expansions that trigger vitamin-sensitive chromosome fragility, adding structural variations to the disease-enriched 9p21 locus, and likely elsewhere.
Effects of one-night partial sleep deprivation on perivascular space volume fraction: Findings from the Stockholm Sleepy Brain Study
Authors: Custer Rachel M. , Lynch Kirsten M. , Barisano Giuseppe , Herting Megan M. , Åkerstedt Torbjörn , Nilsonne Gustav , Ahmadi Hedyeh , Choupan Jeiran 
Published: October 2024

AbstractIncreased waste clearance in the brain is thought to occur most readily during late-stage sleep (stage N3). Sleep deprivation disrupts time spent in deeper sleep stages, fragmenting the clearance process. Here, we have utilized the publicly available Stockholm Sleepy Brain Study to investigate whether various sleep-related measures are associated with changes in perivascular space (PVS) volume fraction following a late-night short-sleep experiment. Our sample consisted of 60 participants divided into old (65-75 years) and young (20-30 years) age groups. We found that partial sleep deprivation was not significantly associated with major PVS changes. In the centrum semiovale, we observed an interaction between percentage of total sleep time spent in N3 and sleep deprivation status on PVS volume fraction. In the basal ganglia, we saw an interaction between N2 (both percentage of total sleep time and absolute time in minutes) and sleep deprivation status. However, the significance of these findings did not survive multiple comparisons corrections. This work highlights the need for future longitudinal studies of PVS and sleep, allowing for quantification of within-subject morphological changes occurring in PVS due to patterns of poor sleep. Our findings here provide insight on the impacts that a single night of late-night short-sleep has on the perivascular waste clearance system.Statement of SignificanceSleep issues have been known to be associated with a variety of health risks. Recent research has shown the importance of sleep for brain clearance, with increases in brain clearance occurring during sleep. PVS seen on MRI are known to represent both influx and efflux pathways for the exchange of cerebrospinal fluid (CSF) and interstitial fluid (ISF) in the brain parenchyma, a key process underlying the waste clearance system.1Numerous recent studies have found links between sleep disruption and PVS volume changes. However, no study to date has been able to examine within-subject changes in PVS resulting from experimental manipulation of sleep. Our study represents the first within-subject study looking at the effects of partial sleep deprivation on PVS volume fraction using an automated PVS segmentation technique.
Benchmarking unsupervised methods for inferring TCR specificity
Authors: Jouannet Charline , Vantomme Hélène , Klatzmann David , Mariotti-Ferrandiz Encarnita 
Published: October 2024

AbstractIdentifying T cell receptor (TCR) specificity is crucial for advancing the understanding of adaptive immunity. Despite the development of computational methods to infer TCR specificity, their performance has not been thoroughly compared. We addressed this by curating a unified database of 190,670 human TCRs with known specificities for 2,313 epitopes across 121 organisms, combining data from IEDB, McPAS-TCR, and VDJdb. Nine methods for clustering TCRs based on similarity were benchmarked against this dataset. DeepTCR demonstrated the best retention, while ClusTCR, TCRMatch, and GLIPH2 excelled in cluster purity but had lower retention. DeepTCR, Levenshtein distance, and TCRdist3 generated large clusters, with DeepTCR showing high purity. Smaller, antigen-specific clusters were produced by Hamming distance, GIANA, and iSMART. GLIPH2 and DeepTCR were the most sensitive in capturing antigen-specific TCRs. This study offers a unified TCR database and a benchmark of specificity inference methods, guiding researchers in selecting appropriate tools.
Spatial quantitative metabolomics enables identification of remote and sustained ipsilateral cortical metabolic reprogramming after stroke
Authors: Wang Gangqi , van den Berg Bernard M. , Kostidis Sarantos , Pinkham Kelsey , Jacobs Marleen E. , Liesz Arthur , Giera Martin , Rabelink Ton J. 
Published: October 2024

AbstractMass spectrometry imaging (MSI) has become a cornerstone of spatial biology research. However, various factors that are intrinsic to the technology limit quantitative capacity of MSI-based spatial metabolomics and thus reliable interpretation. Here, we developed a quantitative MSI workflow (Q-MSI), based on isotopically13C-labeled yeast extract as internal standards, to overcome these pitfalls. Using brain and kidney tissue, we demonstrate that this approach allows for (absolute) quantification of hundreds of metabolites and lipids. Applying our workflow to a stroke model allowed us to not only map metabolic remodeling of the infarct and peri-infarct area over time, but also discover hitherto unnoted remote metabolic remodeling in the histologically unaffected ipsilateral sensorimotor cortex. At day 7 post-stroke, increased levels of neuroprotective lysine and reduced excitatory glutamate levels were found compared to the contralateral cortex. By day 28 post-stroke, lysine and glutamate levels had been normalized, while decreased precursor pools of UDP-GlcNAc and linoleate persisted that have previously been associated with vulnerability. Importantly, traditional normalization strategies not employing internal standards were unable to visualize these differences. Using13C-labeled yeast extracts as a normalization strategy establishes a new paradigm in quantitative MSI-based spatial metabolomics that greatly enhances reliability and interpretive strength.
Gb3 trisaccharide-bearing exosomes as a novel neutralizer for Shiga toxin type 1
Authors: Mikołajczyk Krzysztof 
Published: October 2024

AbstractShiga toxin types 1 (Stx1) and 2 (Stx2), produced by Shiga toxin-producingEscherichia coli(STEC) andShigella dysenteriae, are key virulence factors responsible for severe foodborne diseases, such as hemorrhagic colitis and hemolytic uremic syndrome (HUS). The receptors for Stxs are Gb3 and P1 glycotope, which contain the Galα1→4Gal epitope and are synthesized by human α1,4-galactosyltransferase (A4galt). Stx-related infections pose a global public health challenge, owing to the limited therapeutic options due to the restricted use of antibiotics. Therefore, there is an urgent need to develop novel therapeutic strategies. This study proposes an innovative strategy utilizing exosomes derived from CHO-Lec2 cells, which were modified with Functional-Spacer-Lipid (FSL) conjugates bearing the Gb3 carbohydrate epitope (exo-Gb3-FSL). Flow cytometry analysis confirmed the presence of Galα1→4Gal disaccharides on exo-Gb3-FSL constructs, enabling them to bind Stx1. Moreover, using CHO-Lec2 cells evaluated the ability of exo-Gb3-FSL agents to bind Stx1 and protect these cells from Stx1-mediated cytotoxicity. For Stx1-treated CHO-Lec2 cells, increased cell survival was observed when using 25 µM exo-Gb3-FSL constructs, compared to control cells. These findings highlight the potential of exosome-based anti-Stx1 agents as promising alternatives to conventional therapies. This innovative strategy may provide novel directions for studies on Stx1 neutralization, offering a valuable strategy for the treatment of Stx-related diseases.Highlights-Exo-Gb3-FSL constructs hold Stx1 binding Galα1→4Gal epitope.-Stx1 was effectively bound by exo-Gb3-FSL constructs.-Exo-Gb3-FSL protected CHO-Lec2 cells from Stx1.-Exo-Gb3-FSL is a promising anti-Stx1 agent.
Genomic landscape of antiviral defense systems in prokaryotes and phages
Authors: Li Jinquan , Gu Jiazheng , Xia Runyue , Li Meng 
Published: October 2024

AbstractProkaryotes and their viruses have co-evolved for billions of years, resulting in emergence of numerous antiviral defense systems. With the development of bioinformatic technologies and experimental studies, more and more novel defense systems have been discovered in the near decades. However, the origin and mechanism of these systems are still largely unknown. This study provides a systematic analysis of 132 defense systems within 212,599 prokaryotic genomes, which should be the largest analyzed data so far, revealing the diversity and distribution of these systems across different taxonomic units. Our findings also reveal that not only well-studied bacteria, but also archaea and virus encode diverse antiviral defense systems with specific features. In summary, this work classify 132 known defense systems, provides a comprehensive view of prokaryotic defense systems and insights into the evolution of immune responses.
Low Intestinal Doses of Botulinum Neurotoxins types A and B favour infection bySalmonellaandShigellawithout the flaccid paralysis of botulism
Authors: Fabris Federico , Brun Paola , Megighian Aram , Bernabè G , Castagliuolo Ignazio , Drigo Ilenia , Bano Luca , Lista Florigio , Bernardini Maria Lina , Montecucco Cesare , Rossetto Ornella 
Published: October 2024

AbstractBotulism is a life-threatening disease characterized by a descending flaccid paralysis caused by a protein neurotoxin (BoNT) released by different anaerobic bacterial species of the genusClostridium. The paralysis results from blockade of neurotransmitter release from the terminals of peripheral cholinergic, skeletal and autonomic neurons exerted by BoNT through the cleavage of SNARE proteins, which are essential for neuroexocytosis. Here, we investigated the effect of different doses of BoNT serotypes A and B, the serotypes most commonly associated with human botulism, on enteric nervous system neurons which play an important role in gut health and physiology. We found that BoNT/A and BoNT/B enter cholinergic neurons where they cleave SNARE proteins even at doses that do not cause signs of flaccid neuroparalysis. However, these low BoNT doses favour the invasion and infection of the mouse body bySalmonella thyphimuriumandShigella flexneri. This may have significant animal health implications.
Spatially global effects of feature-based attention in functional subdivisions of human subcortical nuclei
Authors: Lin Weiru , Zhang Yan-Yu , Zhang Xilin , Fang Fang , Qian Chencan , Zhang Peng 
Published: October 2024

AbstractAttention can prioritize the processing of non-spatial features throughout the visual field. While human subcortical nuclei are known to play important roles in spatial attention, the subcortical mechanisms of feature-based attention remain elusive. Using high-resolution 7T fMRI, we investigated the spatially global effects of color-based attention in functional subdivisions of human subcortical nuclei. Paying attention to a color matching the unattended stimulus across the visual field selectively modulated BOLD signals in the parvocellular (P) layers of the lateral geniculate nucleus (LGN) of the thalamus, enhancing the response to the unattended stimulus while reducing the response to the attended stimulus. The spatially global effects of color-based attention were also found in the deeper layers of the superior colliculus (SC), early visual cortices, and the intraparietal sulcus (IPS) of the parietal lobe. Effective connectivity analyses further revealed enhanced feedforward and feedback connectivity between LGN and V1, along with top-down modulation from IPS through the SC and ventral pulvinar. Finally, attended color can be decoded from multi-voxel response patterns in frontoparietal regions. These findings demonstrate that color-based attention selectively modulates color processing in P subdivisions of the LGN of the thalamus throughout the visual field, controlled by top-down signals from the parietal cortex through the SC and pulvinar.HighlightsColor-based attention selectively modulates parvocellular activity in the LGN throughout the visual field.Spatially global effect of feature-based attention significantly modulates activity in the deeper layers of the SC.Feature-based attention enhances both feedforward and feedback connectivity between the LGN and V1.Top-down signals from IPS through the SC and pulvinar controls feature-based attention.
A novel male accessory gland peptide reduces female post-mating receptivity in the brown planthopper
Authors: Zhang Yi-Jie , Zhang Ning , Bu Ruo-Tong , Nässel Dick R. , Gao Cong-Fen , Wu Shun-Fan 
Published: October 2024

AbstractMating in insects commonly induces a profound change in the physiology and behavior of the female that serves to secure numerous and viable offspring and to ensure paternity for the male by reducing receptivity of the female to further mating attempts. Here, we set out to characterize the post-mating response (PMR) in a pest insect, the brown planthopper (BPH)Nilaparvata lugensand to identify a functional analog of sex peptide (SP) and/or other seminal fluid factors that contribute to the PMR inDrosophila. We find that BPHs display a distinct PMR that lasts for about 4 days and includes a change in female behavior with decreased receptivity to males and increased oviposition. Extract from male accessory glands (MAG) injected into virgin females triggers a similar PMR, lasting about 24h. Since SP does not exist in BPHs, we screened for candidate mediators by performing a transcriptional and proteomics analysis of MAG extract. We identified a novel 51 amino acid peptide present only in the MAG and not in female BPHs. This peptide, that we designate maccessin (macc), affects the female PMR. Females mated by males withmaccknockdown display receptivity to wild type males in a second mating, which does not occur in controls. However, oviposition is not affected. Injection of recombinant macc reduces female receptivity, with no effect on oviposition. Thus, macc is so far the only candidate seminal fluid peptide that promotes a PMR in BPHs. Our analysis suggests that the gene encoding the macc precursor is restricted to species closely related to BPHs.Author summaryIn insects, mating often induces a long-lasting change in the female behavior and physiology, called a post-mating response (PMR). This ensures numerous and viable offspring, but also serves to secure paternity for the male by inhibiting the female receptivity to further mating attempts. Here, we demonstrate that a pest insect, the brown planthopper (BPH)Nilaparvata lugens, also displays a PMR with decreased receptivity to further mating and increased egg laying. We furthermore find that seminal fluid extracted from the male accessory gland of BPHs injected into females generates a PMR. Next, we identified a novel peptide unique to the male accessory gland (designated maccessin) and demonstrate that this peptide is responsible for the reduced receptivity in the PMR, but does not affect egg laying. The gene encoding maccessin appears unique to close relatives ofN. lugens. This is similar to aDrosophilamale accessory gland factor, sex peptide, which is known to induce a PMR, and occurs only in a limited number ofDrosophilaspecies.