bluuebunny/crossref_metadata_2025_split huggingface dataset:
The immune profile of circulating autoreactive CD4 T cells is imprinted through tissue activation during autoimmune liver diseases
Authors: Cardon Anaïs , Guinebretière Thomas , Dong Chuang , Gil Laurine , Ado Sakina , Gavlovsky Pierre-jean , Braud Martin , Danger Richard , Schultheiß Christoph , Doméné Aurélie , Paul-Gilloteaux Perrine , Chevalier Caroline , Bernier Laura , Judor Jean-Paul , Fourgeux Cynthia , Imbert Astrid , Khaldi Marion , Bardou-Jacquet Edouard , Elkrief Laure , Lannes Adrien , Silvain Christine , Schnee Matthieu , Tanne Florence , Vavasseur Fabienne , Brusselle Lucas , Brouard Sophie , Kwok William W , Mosnier Jean-François , Lohse Ansgar , Poschmann Jeremie , Binder Mascha , Gournay Jérôme , Conchon Sophie , Milpied Pierre , Renand Amédée 
Published: March 2024

AbstractAutoimmune liver diseases (AILD) are immune-mediated disorders in which CD4 T cells play a central role. However, the link between circulating self-antigen-specific CD4 T cells and the targeted tissue has not been extensively studied in AILD. We hypothesized that circulating autoreactive CD4 T cells were clonally and functionally related to dominant intra-hepatic pathogenic CD4 T cell clones. Single cell transcriptomic analysis of circulating self-antigen-specific CD4 T cells revealed a specific B-helper and immuno-exhausted transcriptional profile, which was conserved for different autoantigens, but distinct from several other types of foreign antigen specificities. In the blood, the dominant hepatic CD4 T cell clones had a similar transcriptomic signature and were enriched in the PD-1+TIGIT+HLA-DR+CD4 T cell subset. In a mouse model, antigen-specific CD4 T cells acquired the immuno-exhausted transcriptional profile when they accumulated in the liver after local antigen reactivity. Locally, immune checkpoint molecules controlled the response of antigen-specific CD4 T cells responsible for liver damage. Our study reveals the origin and biology of liver-derived autoreactive CD4 T cells in the blood of AILD patients that are imprinted by the liver environment, and suggest a dysregulation of the immune checkpoint molecules pathways. Our study enables tracking and isolating circulating autoreactive CD4 T cells for future diagnostic and therapeutic purposes.
Cellects, a software to quantify cell expansion and motion
Authors: Boussard Aurèle , Arrufat Patrick , Dussutour Audrey , Pérez-Escudero Alfonso 
Published: March 2024

MotivationGrowth and motion quantification is a crucial step in studying the evolution, growth and behavior of many species. However, there is no free and easy to use software to automatically quantify the growth of an organism, and that works across a wide range of species. To fill this gap, we developed Cellects, an open-source software that quantifies growth and motion under any conditions and for any species.SummaryAutomated quantification offers unique opportunities to study biological phenomena, increasing reproducibility, replicability, accuracy, and throughput, while reducing observer biases. We present Cellects, a tool to quantify growth and motion in 2D. This software operates with image sequences containing specimens growing and moving on an immobile flat surface. Its user-friendly interface makes it easy to adjust the quantification parameters to cover a wide range of species and conditions, and includes tools to validate the results and correct mistakes if necessary. The software provides the region covered by the specimens at each point of time, as well as many geometrical descriptors that characterize it. We validated Cellects withPhysarum polycephalum, which is particularly difficult to detect because of its complex shape and internal heterogeneity. This validation covered five different conditions with different background and lighting, and found Cellects to be highly accurate in all cases. Cellects’ main strengths are its broad scope of action, automated computation of a variety of geometrical descriptors, easy installation and user-friendly interface.github link:https://github.com/Aurele-B/CellectsHighlightsWe present Cellects, a tool to quantify growth and motion of organisms automatically.Cellects is easy to install and use thanks to its user-friendly interface.It works with a wide range of organisms, providing many geometrical descriptors.Our validation showed high accuracy even in challenging experimental conditions.
Airway succinate chemosensing induces CFTR-dependent anion secretion and mucus clearance which is impaired in cystic fibrosis
Authors: Apablaza Tábata , Barros-Poblete Marisol , Delpiano Livia , Villanueva Sandra , Guequen Anita , Tapia-Balladares Bárbara , Haq Iram , Tribiños Felipe , Hernández-Rivas Sebastián , Verdon Bernard , Biggart Matthew G.S. , Sánchez Yenniffer , Ward Christopher , Baxter B Dnate’ , Restrepo Diego , Cornejo Isabel , Tarran Robert , Catalán Marcelo A. , Gray Michael A. , Flores Carlos A. 
Published: March 2024

ABSTRACTThe respiratory tract possesses a highly regulated innate defense system which includes efficient cilia-mediated mucus transport or mucociliary clearance (MCC). This essential process relies on appropriate hydration of airway surfaces which is controlled by a blend of transepithelial sodium and liquid absorption via the epithelial sodium channel (ENaC), and anion and liquid secretion, primarily regulated by the cystic fibrosis transmembrane conductance regulator (CFTR) channel. MCC is tightly regulated by second messenger signalling pathways. Succinate is derived from parasites, microorganisms and inflammatory cells, and its concentration increases in the airway surface liquid (ASL) during infections. Increases in ASL succinate activates the G-protein coupled succinate receptor (SUCNR1), which acts as a succinate sensor. Here, we tested the hypothesis that succinate signalling was linked to CFTR activity, ASL hydration and increased MCC.We observed that SUCNR1 activation stimulated anion secretion, increased mucus transport and induced bronchoconstriction in mouse airways. In parallel, stimulation of human bronchial epithelial cells (HBEC) with succinate activated anion secretion and increased ASL height. All functions activated by succinate/SUCNR1 were impeded when working with tissues and cells isolated from animal models or individuals affected cystic fibrosis (CF) or when CFTR was inhibited. Moreover, when HBECs derived from ΔF508 individuals were incubated with the triple drug combination of elexacaftor/tezacaftor/ivacaftor (ETI), succinate-induced anion secretion was restored, confirming the tight relationship between SUCNR1 signalling and CFTR function. Our results identify a novel activation pathway for CFTR that participates in the defence response of the airways, which is defective in CF. We propose that succinate acts as a danger molecule that alerts the airways to the presence of pathogens leading to a flushing out of the airways.
KAT6A deficiency impairs cognitive functions through suppressing RSPO2/Wnt signaling in hippocampal CA3
Authors: Liu Yongqing , Fan Minghua , Yang Junhua , Mihaljević Ljubica , Chen Kevin Hong , Ye Yingzhi , Sun Shuying , Qiu Zhaozhu 
Published: March 2024

ABSTRACTIntellectual disability (ID) affects ∼2% of the general population and is often genetic in origin. ID-associated genes are enriched for epigenetic factors, including those encoding the largest family of histone lysine acetyltransferases (KAT5-KAT8). Among them isKAT6A, whosede novoheterozygous mutations cause KAT6A Syndrome (or Arboleda-Tham Syndrome), with ID as a common clinical feature. However, the underlying molecular mechanisms remain elusive. Here, we show that haploinsufficiency ofKat6aimpairs learning and memory in mice, and specific deletion ofKat6ain excitatory neurons recapitulates the hippocampus-dependent memory deficits. Unexpectedly, KAT6A deficiency results in impaired synaptic structure and plasticity in hippocampal CA3, but not in CA1 region. Combining single-nucleus RNA-sequencing and chromatin analysis, we identify a CA3-enriched geneRspo2, encoding a Wnt activator R-spondin 2, as a key transcriptional target of KAT6A. Moreover, deletion ofRspo2in excitatory neurons phenocopies the loss ofKat6a, resulting in defective Wnt/β-catenin signaling and synaptic plasticity in CA3, and abnormal cognitive behaviors in mice. Importantly, restoring RSPO2 expression in CA3 pyramidal neurons rescues the deficits in Wnt signaling and learning-associated behaviors inKat6amutant mice. Collectively, our results demonstrate that KAT6A plays a critical role in regulating synaptic plasticity and memory formation through RSPO2-mediated Wnt signaling in hippocampal CA3, shedding new light on the fundamental mechanisms of ID and providing potential therapeutic targets for the treatment of KAT6A Syndrome and related neurodevelopmental diseases.
Evaluating Species at Risk in Data-Limited Fisheries: A Comprehensive Productivity-Susceptibility Analysis of the Most Traded Marine Aquarium Fish
Authors: Baillargeon Gabrielle A. , Wynn Alice A. , Baldisimo Jemelyn Grace P. , Tlusty Michael F. , Rhyne Andrew 
Published: March 2024

AbstractThe marine aquarium trade is a significant global industry harvesting millions of live coral reef fishes annually. Wild-caught fish dominate public and private aquaria markets in the USA and Europe, supporting fisher livelihoods in the Indo-Pacific. This diverse and species-rich trade is considered data-limited, creating barriers to quantify the sustainability of this fishery to the net benefit of the coral reef socio-ecological system. We present a revised and expanded productivity-susceptibility analysis (PSA) framework to assess the vulnerability to overharvesting of the top 258 traded species, an estimated 92.5% of all import volume into the USA in 2011. Vulnerability was calculated based on various productivity and susceptibility factors, tailored to the unique life-history and fishery selectivity characteristics of the marine aquarium trade. We present novel factors that improve model accuracy, methods to overcome missing data for individual factors, and apply an improved Gaussian mixture model clustering algorithm to objectively classify species as least, moderately, or most vulnerable. Our results show that an overwhelming 85% of species evaluated fall into the least or moderately vulnerable classification, with the remaining species designated as high priority for localized assessment and management initiatives. A comparative case study between our PSA and the popular FishBase Vulnerability assessment illustrates how it is ill-suited to handle data limitations of non-food fishes. The results of our PSA, at a species and family level, provide useful information to stakeholders and serves as a robust and accessible risk assessment tool to prioritize species for management based on their vulnerability scores.
Comprehensive prediction and analysis of human protein essentiality based on a pre-trained protein large language model
Authors: Kang Boming , Fan Rui , Cui Chunmei , Cui Qinghua 
Published: March 2024

AbstractHuman essential genes and their protein products are indispensable for the viability and development of the individuals. Thus, it is quite important to decipher the essential proteins and up to now numerous computational methods have been developed for the above purpose. However, the current methods failed to comprehensively measure human protein essentiality at levels of humans, human cell lines, and mice orthologues. For doing so, here we developed Protein Importance Calculator (PIC), a sequence-based deep learning model, which was built by fine-tuning a pre-trained protein language model. As a result, PIC outperformed existing methods by increasing 5.13%-12.10% AUROC for predicting essential proteins at human cell-line level. In addition, it improved an average of 9.64% AUROC on 323 human cell lines compared to the only existing cell line-specific method, DeepCellEss. Moreover, we defined Protein Essential Score (PES) to quantify protein essentiality based on PIC and confirmed its power of measuring human protein essentiality and functional divergence across the above three levels. Finally, we successfully used PES to identify prognostic biomarkers of breast cancer and at the first time to quantify the essentiality of 617462 human microproteins.Key PointsPIC outperformed existing computational methods for predicting essential proteins.PIC could comprehensively predict human protein essentiality at levels of human, human cell lines and mice orthologues at the same time.PES could serve as a potential metric to quantify the essentiality of both human proteins and human microproteins.
Local nutrient addition drives plant diversity losses but not biotic homogenization in global grasslands
Authors: Chen Qingqing , Blowes Shane A. , Harpole W. Stanley , Ladouceur Emma , Borer Elizabeth T. , MacDougall Andrew , Martina Jason P. , Bakker Jonathan D. , Tognetti Pedro M. , Seabloom Eric W. , Daleo Pedro , Power Sally A. , Roscher Christiane , Adler Peter , Donohue Ian , Wheeler George , Stevens Carly , Veen Ciska , Risch Anita C. , Wardle Glenda M. , Hautier Yann , Estrada Catalina , Hersch-Green Erika , Niu Yujie , Peri Pablo L. , Eskelinen Anu , Gruner Daniel S , Olde Venterink Harry , D’Antonio Carla , Cadotte Marc W. , Haider Sylvia , Eisenhauer Nico , Catford Jane , Virtanen Risto , Morgan John W. , Tedder Michelle , Bagchi Sumanta , Caldeira Maria C. , Bugalho Miguel , Knops Johannes M. H. , Dickman Chris R. , Hagenah Nicole , Jentsch Anke , Macek Petr , Osborne Brooke B. , Laanisto Lauri , Chase Jonathan M. 
Published: March 2024

AbstractNutrient enrichment typically causes local plant diversity decline. A common but untested expectation is that it reduces variation in nutrient conditions among localities and selects for a smaller pool of species, causing greater diversity declines at larger scales and biotic homogenization. We apply a topology linking changes in species richness across scales that characterizes changes in the numbers of spatially restricted and widespread species to a standardized experiment adding nutrients across 72 grasslands on six continents. Overall, we found similar declines of spatially restricted and widespread species, and proportional species loss at local and larger scales, and no biotic homogenization after 4 years and up to 14 years of treatment. These patterns of diversity changes were generally consistent across species groups (e.g., native species, graminoids and legume species). Thus, nutrient enrichment poses threats to plant diversity that includes widespread species that are often critical for ecosystem functions.
An EEG Signature of MCH Neuron Activities Predicts Cocaine Seeking
Authors: Wang Yao , Li Danyang , Widjaja Joseph , Guo Rong , Cai Li , Yan Rongzhen , Ozsoy Sahin , Allocca Giancarlo , Fang Jidong , Dong Yan , Tseng George C. , Huang Chengcheng , Huang Yanhua H. 
Published: March 2024

AbstractBackgroundIdentifying biomarkers that predict substance use disorder (SUD) propensity may better strategize anti-addiction treatment. The melanin-concentrating hormone (MCH) neurons in the lateral hypothalamus (LH) critically mediates interactions between sleep and substance use; however, their activities are largely obscured in surface electroencephalogram (EEG) measures, hindering the development of biomarkers.MethodsSurface EEG signals and real-time Ca2+activities of LH MCH neurons (Ca2+MCH) were simultaneously recorded in male and female adult rats. Mathematical modeling and machine learning were then applied to predict Ca2+MCHusing EEG derivatives. The robustness of the predictions was tested across sex and treatment conditions. Finally, features extracted from the EEG-predicted Ca2+MCHeither before or after cocaine experience were used to predict future drug-seeking behaviors.ResultsAn EEG waveform derivative – a modified theta-to-delta ratio (EEG Ratio) – accurately tracks real-time Ca2+MCHin rats. The prediction was robust during rapid eye movement sleep (REMS), persisted through REMS manipulations, wakefulness, circadian phases, and was consistent across sex. Moreover, cocaine self-administration and long-term withdrawal altered EEG Ratio suggesting shortening and circadian redistribution of synchronous MCH neuron activities. In addition, features of EEG Ratio indicative of prolonged synchronous MCH neuron activities predicted lower subsequent cocaine seeking. EEG Ratio also exhibited advantages over conventional REMS measures for the predictions.ConclusionsThe identified EEG Ratio may serve as a non-invasive measure for assessing MCH neuron activitiesin vivoand evaluating REMS; it may also serve as a potential biomarker predicting drug use propensity.
Reliable estimates of Japanese encephalitis virus evolutionary rate supported by a formal test of temporal signal
Authors: Ukraintceva Polina I. , Bondaryuk Artem N. , Sakhabeev Rodion G. 
Published: March 2024

AbstractJapanese encephalitis virus (JEV) is a positive-strand RNA virus, that causing encephalitis in humans, which is highly spread in East and Southeast Asia, Western Pacific countries and Australia. The main vector of JEV isCulexspp. (mainlyC. tritaeniorhynchus). The intraspecies structure of JEV comprises five genotypes (GI-GV). In the previous studies, the substitution rate and the age of the JEV most recent common ancestor (MRCA) based on complete open reading frame (ORF) / whole genome sequences were reported, however, the estimates are significantly different between some of the studies. Most importantly, the temporal signal in nucleotide data as the key aspect of the molecular clock application was evaluated by neither formal nor informal tests. In February 2023, we found 325 non-recombinant nucleotide sequences of ORF with known collection dates. The purpose of our study is the evaluation of temporal signal in the JEV ORF nucleotide data set using the Bayesian approach with the subsequent re-estimation of substitution rate and the age of the JEV common clade (GI-GV) and two JEV genotypes (GI and GIII) characterized by the number of sequences enough for reliable estimates. Results showed the presence of temporal signal in all analyzed data set. The substitution rate of the JEV GI-GV was 2.41×10−4(95% highest posterior density (HPD) interval, 1.67×10−4–3.14×10−4) or approximately 2.5 nucleotide substitutions per ORF (10,296 nucleotides) per year that is one the lowest substitution rate among the species closely related to JEV and other well-studied members of mosquito-borne flaviviruses. The substitution rate of GI and GIII evaluated as 4.13×10−4(95% HPD interval, 3.45×10−4– 4.82×10−4) and 6.17×10−5(95% HPD interval 3.84×10−5–8.62×10−5), accordingly, with the ages of clades of 153 (95% HPD, 87–237) and 216 (95% HPD, 139–317), respectively. The root height of JEV is 1234 years (95% HPD, 407–2333). To the best of our knowledge, this study provides the first reliable substitution rate assessment of the global clade of JEV embracing all five genotypes.
In situstructure and rotary states of mitochondrial ATP synthase in whole cells
Authors: Dietrich Lea , Agip Ahmed-Noor Adam , Schwarz Andre , Kunz Christina , Kühlbrandt Werner 
Published: March 2024

ABSTRACTCells depend on a continuous supply of ATP, the universal energy currency. In mitochondria, ATP is produced by a series of redox reactions, whereby an electrochemical gradient is established across the inner mitochondrial membrane. The ATP synthase harnesses the energy of the gradient to generate ATP from ADP and inorganic phosphate. We determined the structure of ATP synthase within mitochondria of the unicellular algaPolytomellaby electron cryo-tomography. Sub-tomogram averaging revealed six rotary positions of the central stalk, subclassified into 21 substates of the F1head. ThePolytomellaATP synthase forms helical arrays with multiple adjacent rows defining the cristae ridges. The structure of ATP synthase under native operating conditions in the presence of a membrane potential represents a pivotal step toward the analysis of membrane protein complexesin situ.
Quantitative differences in anaerobic growth and metabolism of three differentE. colistrains using13C-Metabolic Flux Analysis
Authors: Pachauri Piyush , Desai Trunil , Ahmad Ahmad , Srivastava Shireesh 
Published: March 2024

AbstractEscherichia coliare model organisms for biotechnological research owing to their abilities to grow on defined media and consume a variety of carbon sources, as well as a vast knowledge base and tools available for their manipulation. SeveralE. colistrains and their derivatives are available. However, the quantitative metabolic differences between the strains could be better characterized. In this study, we investigated the differences in the intracellular flux distribution between three commonly used strains ofE. coli(K-12 MG1655, C, and W) using13C-Metabolic flux analysis (13C-MFA), the gold standard in fluxomics. The labeling data was analyzed using FluxPyt, our previously developed Python-based tool. Threefold differences in the growth rates of these strains were observed when growing anaerobically on glucose in M9 medium, withE. coliW being the fastest (μ = 0.62 ± 0.01 h-1) andE. coliC the slowest (μ = 0.22 ± 0.01 h-1). The strain’s growth rates correlate with glucose uptake and flux through the oxidative pentose phosphate pathway. Interestingly, succinate was a major product inE. coliC only.13C-MFA revealed that under these conditions, Entner–Doudoroff (ED) pathway was active inE. coliC andE. coliW but not inE. coliK-12 MG1655. InE. coliK-12 MG1655 andE. coliC, the Tricarboxylic Acid (TCA) cycle ran incompletely. Also, the glyoxylate shunt was inactive in all three strains. Growth, xylose intake rates, and product profiles on xylose mirrored those of glucose. Thus, this study has highlighted significant differences in the growth and metabolism of theE. colistrains on glucose and xylose. This will form a basis for identifying the best strain for a particular application.
Increased TRPV4 channel expression enhances and impairs blood vessel function in hypertension
Authors: Zhang Xun , Buckley Charlotte , Lee Matthew D , MacDonald Margaret , Wilson Calum , McCarron John G 
Published: March 2024

AbstractBackgroundEndothelial cell TRPV4 channels provide a control point that is pivotal in regulating blood vessel diameter by mediating the Ca2+-dependent release of endothelial-derived vasoactive factors. In hypertension, TRPV4-mediated control of vascular function is disrupted but the underlying mechanisms, and precise physiological consequences remain controversial.MethodsHere, using a comprehensive array of methodologies, endothelial TRPV4 channel function was examined in intact arteries from normotensive WKY and hypertensive SHR rats.ResultsOur results show there is a notable shift in vascular reactivity in hypertension, characterized by enhanced endothelium-dependent vasodilation at low levels of TRPV4 channel activation. However, at higher levels of TRPV4 activity, this vasodilatory response is reversed, contributing to the aberrant vascular tone observed in hypertension. The change in response, from dilation to constriction, was accompanied by a shift in intracellular Ca2+signaling modalities arising from TRPV4 activity. Oscillatory TRPV4-evoked IP3-mediated Ca2+release, which underlies dilation, decreased, while the contraction inducing sustained Ca2+rise, arising from TRPV4-mediated Ca2+influx, increased. Our findings also reveal that while the sensitivity of endothelial cell TRPV4 to activation was unchanged, expression of the channel is upregulated and IP3receptors are downregulated in hypertension.ConclusionsThese data highlight the intricate interplay between endothelial TRPV4 channel expression, intracellular Ca2+signaling dynamics, and vascular reactivity. Moreover, the data support a new unifying hypothesis for the vascular impairment that accompanies hypertension. Specifically, that endothelial cell TRPV4 channels play a dual role in modulating blood vessel function in hypertension.