bluuebunny/crossref_metadata_2025_split huggingface dataset:
In silicosingle-cell metabolism analysis unravels a new transition stage of CD8 T cells 4 days post-infection
Authors: Christophe Arpin , Picard Franck , Gandrillon Olivier 
Published: September 2023

ABSTRACTCD8 T cell proper differentiation during antiviral responses relies on metabolic adaptations. Herein, we investigated global metabolic activity in single CD8 T cells along anin vivoresponse by estimating metabolic fluxes from single-cell RNA-sequencing data. The approach was validated by the observation of metabolic variations known from experimental studies on global cell populations, while adding temporally detailed information and unravelling yet undescribed sections of CD8 T cell metabolism that are affected by cellular differentiation. Furthermore, inter-cellular variability in gene expression level, highlighted by single cell data, and heterogeneity of metabolic activity 4 days post-infection, revealed a new transition stage accompanied by a metabolic switch in activated cells differentiating into full-blown effectors.
TIM-4 Identifies Effector B Cells Expressing a RORγt-Driven Proinflammatory Cytokine Module That Promotes Immune Responsiveness
Authors: Ding Qing , Wu Yufan , Triglia Elena Torlai , Gommerman Jennifer L. , Subramanian Ayshwarya , Kuchroo Vijay K. , Rothstein David M. 
Published: September 2023

ABSTRACTB cells can express pro-inflammatory cytokines that promote a wide variety of immune responses. Here we show that B cells expressing the phosphatidylserine receptor TIM-4, preferentially express IL-17A, as well as IL-22, IL-6, IL-1β, and GM-CSF - a collection of cytokines reminiscent of pathogenic Th17 cells. Expression of this proinflammatory module requires IL-23R signaling and selective expression of RORγt and IL-17A by TIM-4+B cells. TIM-4+B cell-derived-IL-17A not only enhances the severity of experimental autoimmune encephalomyelitis (EAE) and promotes allograft rejection, but also acts in an autocrine manner to prevent their conversion into IL-10-expressing B cells with regulatory function. Thus, IL-17A acts as an inflammatory mediator and also enforces the proinflammatory activity of TIM-4+B cells. Thus, TIM-4 serves as a broad marker for RORγt+effector B cells (Beff) and allows further study of the signals regulating Beff differentiation and effector molecule expression.
Genomic comparison of the temperate coralAstrangia poculatawith tropical corals yields insights into winter quiescence, innate immunity, and sexual reproduction
Authors: Stankiewicz Kathryn H. , Guiglielmoni Nadège , Kitchen Sheila A. , Flot Jean-François , Barott Katie L. , Davies Sarah W. , Finnerty John R. , Grace Sean P. , Kaufman Leslie S. , Putnam Hollie M. , Rotjan Randi D. , Sharp Koty H. , Baums Iliana B. 
Published: September 2023

AbstractFacultatively symbiotic corals provide important experimental models to explore the establishment, maintenance, and breakdown of the mutualism between corals and members of the algal family Symbiodiniaceae. The temperate coralAstrangia poculatais one such model as it is not only facultatively symbiotic, but also occurs across a broad temperature and latitudinal gradient. Here, we report thede novochromosome-scale assembly and annotation of theA. poculatagenome. Though widespread segmental/tandem duplications of genomic regions were detected, we did not find strong evidence of a whole genome duplication (WGD) event. Comparison of the gene arrangement betweenA. poculataand the tropical coralAcropora milleporarevealed 56.38% of the orthologous genes were conserved in syntenic blocks despite ∼415 million years of divergence. Gene families related to sperm hyperactivation and innate immunity, including lectins, were found to contain more genes inA. milleporarelative toA. poculata. Sperm hyperactivation inA. milleporais expected given the extreme requirements of gamete competition during mass spawning events in tropical corals, while lectins are important in the establishment of coral-algal symbiosis. By contrast, gene families involved in sleep promotion, feeding suppression, and circadian sleep/wake cycle processes were expanded inA. poculata. These expanded gene families may play a role inA. poculata’s ability to enter a dormancy-like state (“winter quiescence”) to survive freezing temperatures at the northern edges of the species’ range.
Predicting Long and Short Duration Beta Bursts from Subthalamic Nucleus Local Field Potential Activity in Parkinson’s Disease
Authors: Abdi-Sargezeh Bahman , Shirani Sepehr , Sharma Abhinav , Starr Philip A. , Little Simon , Oswal Ashwini 
Published: September 2023

AbstractNeural activities within the beta frequency range (13-30 Hz) are not stationary, but occur in transient packets known as beta bursts. Parkinson’s disease (PD) is characterized by the occurrence of beta bursts of increased duration and amplitude within the cortico-basal ganglia network. The pathophysiological importance of beta bursts is exemplified by the fact that they serve as a clinically useful feedback signal in beta amplitude triggered adaptive Deep Brain Stimulation (aDBS). Prolonged duration beta bursts are closely associated with motor impairments in PD, whilst bursts of shorter duration may have a physiological role. Consequently, we aimed to develop a deep learning-based pipeline capable of predicting long (>150ms) and short (<150ms) duration beta bursts from subthalamic nucleus local field potential (LFP) recordings. Our approach achieved promising accuracy values of 87% and 85.2% in two patients implanted with a DBS device that was capable of long-term wireless LFP sensing. Our findings highlight the feasibility of prolonged beta burst prediction and could inform the development of a new type of intelligent DBS approach with the capability of delivering stimulation only during the occurrence of prolonged bursts.
Massive detection of cryptic recessive genetic defects in cattle mining millions of life histories
Authors: Besnard Florian , Guintard Ana , Grohs Cécile , Guzylack-Piriou Laurence , Cano Margarita , Escouflaire Clémentine , Hozé Chris , Leclerc Hélène , Buronfosse Thierry , Dutheil Lucie , Jourdain Jeanlin , Barbat Anne , Fritz Sébastien , Deloche Marie-Christine , Remot Aude , Gaussères Blandine , Clément Adèle , Bouchier Marion , Contat Elise , Relun Anne , Plassard Vincent , Rivière Julie , Péchoux Christine , Vilotte Marthe , Eche Camille , Kuchly Claire , Charles Mathieu , Boulling Arnaud , Viard Guillaume , Minéry Stéphanie , Barbey Sarah , Birbes Clément , Danchin-Burge Coralie , Launay Frédéric , Mattalia Sophie , Allais-Bonnet Aurélie , Ravary Bérangère , Millemann Yves , Guatteo Raphaël , Klopp Christophe , Gaspin Christine , Iampietro Carole , Donnadieu Cécile , Milan Denis , Arcangioli Marie-Anne , Boussaha Mekki , Foucras Gilles , Boichard Didier , Capitan Aurélien 
Published: September 2023

AbstractWe present a data-mining framework designed to detect recessive defects in livestock that have been previously missed due to a lack of specific signs, incomplete penetrance, or incomplete linkage disequilibrium. This approach leverages the massive data generated by genomic selection. Its basic principle is to compare the observed and expected numbers of homozygotes for sliding haplotypes in animals with different life histories. Within three cattle breeds, we report 33 new loci responsible for increased risk of juvenile mortality and present a series of validations based on large-scale genotyping, clinical examination, and functional studies for candidate variants affecting theNOA1,RFC5,andITGB7genes. In particular, we describe disorders associated withNOA1andRFC5mutations for the first time in vertebrates. The discovery of these many new defects will help to characterize the genetic basis of inbreeding depression, while their management will improve animal welfare and reduce losses to the industry.
A Genetically Encoded Actuator Selectively Boosts L-type Calcium Channels in Diverse Physiological Settings
Authors: del Rivero Morfin Pedro J. , Chavez Diego Scala , Jayaraman Srinidhi , Yang Lin , Kochiss Audrey L. , Colecraft Henry M. , Liu X. Shawn , Marx Steven O. , Rajadhyaksha Anjali M. , Ben-Johny Manu 
Published: September 2023

AbstractL-type Ca2+channels (CaV1.2/1.3) convey influx of calcium ions (Ca2+) that orchestrate a bevy of biological responses including muscle contraction and gene transcription. Deficits in CaV1 function play a vital role in cardiac and neurodevelopmental disorders. Yet conventional pharmacological approaches to upregulate CaV1 are limited, as excessive Ca2+influx leads to cytotoxicity. Here, we develop a genetically encoded enhancer of CaV1.2/1.3 channels (GeeC) to manipulate Ca2+entry in distinct physiological settings. Specifically, we functionalized a nanobody that targets the CaVmacromolecular complex by attaching a minimal effector domain from a CaVenhancer—leucine rich repeat containing protein 10 (Lrrc10). In cardiomyocytes, GeeC evoked a 3-fold increase in L-type current amplitude. In neurons, GeeC augmented excitation-transcription (E-T) coupling. In all, GeeC represents a powerful strategy to boost CaV1.2/1.3 function in distinct physiological settings and, in so doing, lays the groundwork to illuminate new insights on neuronal and cardiac physiology and disease.
Immunohistochemical and ultrastructural characterization of the inner ear epithelial cells of splitnose rockfish (Sebastes diploproa)
Authors: Kwan Garfield T. , Andrade Leonardo R. , Prime Kaelan J. , Tresguerres Martin 
Published: September 2023

AbstractThe inner ear of teleost fish regulates the ionic and acid-base chemistry and secretes the protein matrix of the endolymph to facilitate otolith biomineralization, which are used to maintain vestibular and auditory functions. The otolith is biomineralized in a concentric ring pattern corresponding to seasonal growth, and this CaCO3polycrystal has become a vital aging and life-history tool for fishery managers, ecologists, and conservation biologists. Moreover, biomineralization patterns are sensitive to environmental variability including climate change, thereby threatening the accuracy and relevance of otolith-reliant toolkits. However, the cellular biology of the inner ear is poorly characterized, which is a hurdle for a mechanistic understanding of the underlying processes. This study provides a systematic characterization of the cell types in the inner ear of splitnose rockfish (Sebastes diploproa). Scanning electron microscopy revealed the apical morphologies of the six inner ear cell types. Additionally, immunostaining and confocal microscopy characterized the expression and subcellular localization of the proteins Na+/K+-ATPase, carbonic anhydrase, V-type H+-ATPase, Na+-K+-2Cl--Co-Transporter, Otolith Matrix Protein 1, and Otolin-1 in six inner ear cell types bordering the endolymph. This fundamental cytological characterization of the rockfish inner ear epithelium illustrates the intricate physiological processes involved in otolith biomineralization, and highlights how greater mechanistic understanding is necessary to predict their multi-stressor responses to future climate change.
Gene expression changes inDrosophila melanogasterfemales associated with the rescue of thebag of marbles(bam) hypomorph fertility defect byWolbachia pipientis
Authors: Kagemann Catherine H. , Colocho Gabriela M. , Aquadro Charles F. 
Published: September 2023

AbstractWolbachia pipientisare maternally transmitted endosymbiotic bacteria commonly found in arthropods and nematodes. These bacteria manipulate reproduction of the host to increase their transmission using mechanisms, such as cytoplasmic incompatibility, that favor infected female offspring. Interestingly,W. pipientisinfection partially rescues female fertility in flies containing hypomorph mutations ofbag of marbles(bam) inD. melanogaster, which functions in germline stem cell (GSC) maintenance and differentiation. Here we evaluated the effect ofW. pipientisvariant infection on host gene expression using RNA-seq. RNA-seq analysis using theW. pipientisinfected relative to uninfectedbamhypomorph genotype had differential expression for many ofbam’sgenetic and physical interactors. The highest magnitude of differential expression ofbam’sinteractors and other GSC genes involved in cystoblast differentiation occurred prior to peak fertility rescue. Our analysis showed that ubiquitination and histone lysine methylation could be important mechanisms involved in thebamhypomorph fertility rescue byW. pipientis.
Picoeukaryotic photosynthetic potential is functionally redundant but taxonomically structured at global scale
Authors: Schickele Alexandre , Debeljak Pavla , Ayata Sakina-Dorothée , Bittner Lucie , Pelletier Eric , Guidi Lionel , Irisson Jean-Olivier 
Published: September 2023

AbstractPrimary production, performed by RUBISCO, and often associated with carbon concentration mechanisms, is of major importance in the oceans. Thanks to growing metagenomic resources (e.g., eukaryotic Metagenome-Assembled-Genomes; MAGs), we provide the first reproducible machine-learning-based framework to derive the potential biogeography of a given function, through the multi-output regression of the standardized number of reads of the associated genes on environmental climatologies. We use it to study the genomic potential of C4-photosynthesis of picoeukaryotes, a diverse and abundant group of marine unicellular photosynthetic organisms. We show that the genomic potential supporting C4-enzymes and RUBISCO exhibit strong functional redundancy and an important affinity towards tropical oligotrophic waters. This redundancy is then structured taxonomically by the dominance of Mamiellophyceae and Prymnesiophyceae in mid and high latitudes. Finally, unlike the genomic potential related to most C4-enzymes, the one of RUBISCO showed a clear pattern affinity for temperate waters.
Exploring an EM-algorithm for banded regression in computational neuroscience
Authors: Fuglsang Søren A. , Madsen Kristoffer H. , Puonti Oula , Siebner Hartwig R. , Hjortkjær Jens 
Published: September 2023

AbstractRegression is a principal tool for relating brain responses to stimuli or tasks in computational neuroscience. This often involves fitting linear models with predictors that can be divided into groups, such as distinct stimulus feature subsets in encoding models or features of different neural response channels in decoding models. When fitting such models, it can be relevant to impose differential shrinkage of the different groups of regression weights. Here, we explore a framework that allow for straightforward definition and estimation of such models. We present an expectation-maximization algorithm for tuning hyperparameters that control shrinkage of groups of weights. We highlight properties, limitations, and potential use-cases of the model using simulated data. Next, we explore the model in the context of a BOLD fMRI encoding analysis and an EEG decoding analysis. Finally, we discuss cases where the model can be useful and scenarios where regularization procedures complicate model interpretation.
Structural Flexibility and Disassembly Kinetics of Single Ferritins Using Optical Nanotweezers
Authors: Yousefi Arman , Zheng Ze , Zargarbashi Saaman , Assadipapari Mahya , Hickman Graham J. , Parmenter Christopher D. J. , Bueno-Alejo Carlos J. , Sanderson Gabriel , Craske Dominic , Xu Lei , Rahmani Mohsen , Ying Cuifeng 
Published: September 2023

AbstractFerritin, a spherical protein shell assembled from 24 subunits, functions as an efficient iron storage and release system through its channels. Understanding how various chemicals affect the structural behaviour of ferritin is crucial for unravelling the origins of iron-related diseases in living organisms including humans. In particular, the influence of chemicals on ferritin’s dynamics and iron release is barely explored at the single-protein level. Here, by employing optical nanotweezers using double nanohole (DNH) structures, we examined the effect of ascorbic acid (reducing reagent) and pH on ferritin’s conformational dynamics. The dynamics of ferritin increased as the concentration of ascorbic acid approached saturation. At pH 2.0 ferritin exhibited significant structural fluctuations and eventually underwent a stepwise disassembly into fragments. This work, for the first time, tracked the disassembly pathway and kinetics of single ferritins in solution. We identified four critical fragments during its disassembly pathway, which are 22-mer, 12-mer, tetramer, and dimer subunits. Moreover, we presented the first single-molecule evidence of the cooperative disassembly of ferritin. Interrogating ferritin’s structural change in response to different chemicals holds importance for understanding their roles in iron metabolism, hence facilitating further development of medical treatments for the associated diseases.
Functional diversity ofNLRP3gain-of-function mutants associated with CAPS autoinflammation
Authors: Cosson Camille , Riou Romane , Patoli Danish , Niu Tingting , Rey Amaury , Groslambert Marine , Chatre Elodie , Allatif Omran , Henry Thomas , Venet Fabienne , Milhavet Florian , Boursier Guilaine , Belot Alexandre , Jamilloux Yvan , Merlin Etienne , Duquesne Agnès , Grateau Gilles , Savey Léa , Jacques Maria Alexandre Thibault , Pagnier Anne , Poutrel Solène , Lambotte Olivier , Mallebranche Coralie , Rieux-Laucat Frédéric , Bader-Meunier Brigitte , Amoura Zahir , Melki Isabelle , Touitou Isabelle , Geyer Matthias , Georgin-Lavialle Sophie , Py Bénédicte F. 
Published: September 2023

AbstractNLRP3-associated autoinflammatory disease (NLRP3-AID or CAPS) is an heterogenous group of monogenic autoinflammations associated withNLRP3gain-of-function mutations. The poor functional characterization of mostNLRP3variants is a barrier to diagnosis although patients can be efficiently treated with anti-IL-1 approaches. In addition, while NLRP3 inflammasome is controlled by coordinated priming and activation signals, gain-of-functions ofNLRP3variants have been only investigated in response to priming. Here, we functionally characterize 34NLRP3variantsin vitroby determining their activity in response to induction, priming and/or activation signals, and their sensitivity to inhibitors. We highlight the functional diversity of the gain-of-function mutants and describe four groups based on their profile of signals required for their activation, that correlate partly with the symptoms severities. We identify a new group ofNLRP3mutants responding to the activation signal without priming, with patients often misdiagnosed. Our results identify key NLRP3 residues controlling the inflammasome activity and sensitivity to inhibitors. The comparison of four inhibitors on the 34 variants identifies inhibitory mechanisms with broader efficiency for future drug design. Altogether, our results provide new insights on NLRP3 activation and an explanatory mechanism for NLRP3-AID heterogeneity, and original tools for NLRP3-AID diagnosis and anti-inflammatory disease drug development.eTOC SummaryFunctional characterization of 34 CAPS-associatedNLRP3variants identifies polymorphisms versus gain-of-function pathogenic mutants, and highlights diversities in the signals controlling their activation and in their sensitivity to inhibitors. This study provides tools for CAPS diagnosis and anti-inflammation drug development and insights on NLRP3 control mechanisms.
The evolution of environmentally mediated social interactions and posthumous spite under isolation by distance
Authors: Mullon Charles , Peña Jorge , Lehmann Laurent 
Published: September 2023

AbstractMany social interactions happen indirectly via modifications of the environment, e.g. through the secretion of functional compounds or the depletion of renewable resources. Here, we derive the selection gradient on a quantitative trait affecting dynamical environmental variables that feed back on reproduction and survival in a finite patch-structured population subject to isolation by distance. Our analysis shows that the selection gradient depends on how a focal individual influences the fitness of all future individuals in the population through modifications of the environmental variables they experience, weighted by the neutral relatedness between recipients and the focal. The evolutionarily relevant trait-driven environmental modifications are formalized as the extended phenotypic effects of an individual, quantifying how a trait change in an individual in the present affects the environmental variables in all patches at all future times. When the trait affects reproduction and survival through a payoff function, the selection gradient can be expressed in terms of extended phenotypic effects weighted by scaled-relatedness. We show how to compute extended phenotypic effects, relatedness, and scaled-relatedness using Fourier analysis, which allow us to investigate a broad class of environmentally mediated social interactions in a tractable way. We use our approach to study the evolution of a trait controlling the costly production of some lasting commons (e.g. a common-pool resource or a toxic compound) that can diffuse in space and persist in time. We show that indiscriminate posthumous spite readily evolves in this scenario. More generally whether selection favours environmentally mediated altruism or spite is determined by the spatial correlation between an individual’s lineage and the commons originating from its patch. The sign of this correlation depends on interactions between dispersal patterns and the commons’ renewal dynamics. More broadly, we suggest that selection can favour a wide range of social behaviours when these have carry-over effects in space and time.
Leishmaniinae: evolutionary inferences based on protein expression profiles (PhyloQuant) congruent with phylogenetic relationships amongLeishmania, Endotrypanum, Porcisia, Zelonia, Crithidia,andLeptomonas
Authors: Mule Simon Ngao , Alemán Evaristo Villalba , Fernandes Livia Rosa , Saad Joyce S. , de Oliveira Gilberto Santos , Martins Deivid , Angeli Claudia Blanes , Brandt-Almeida Deborah , Cortez Mauro , Larsen Martin Røssel , Shaw Jeffrey J. , Teixeira Marta M. G. , Palmisano Giuseppe 
Published: September 2023

AbstractEvolutionary relationships among parasites of the subfamily Leishmaniinae, which comprises pathogen agents of leishmaniasis, were inferred based on differential protein expression profiles from mass spectrometry-based quantitative data using the PhyloQuant method. Evolutionary distances following identification and quantification of protein and peptide abundances using Proteome Discoverer (PD) and MaxQuant (MQ) softwares were estimated for 11 species from 6 Leishmaniinae genera. Results clustered all dixenous species of the genusLeishmania, subgeneraL. (Leishmania), L. (Viannia)andL. (Mundinia),sister to the dixenous species of generaEndotrypanumandPorcisia.Positioned basal to the assemblage formed by all these parasites were the species of generaZelonia,CrithidiaandLeptomonas, so far described as monoxenous of insects although eventually reported from humans. Inferences based on protein expression profiles were congruent with currently established phylogeny using DNA sequences. Our results reinforce PhyloQuant as a valuable approach to infer evolutionary relationships consistent with genera, subgenera, and species-specific biological characteristics, able to resolve within Leishmaniinae, which is comprised of very tightly related trypanosomatids that are just beginning to be phylogenetically unravelled. In additional to evolutionary history, mapping of species-specific protein expression is paramount to understand differences in infection processes, disease presentations, tissue tropisms, potential to jump from insects to vertebrates including humans, and potential targets for species-specific diagnostic and drug development.