bluuebunny/crossref_metadata_2025_split huggingface dataset:
Haemolymphatic tissues of captive boa constrictor(Boa constrictor):morphological features in healthy individuals and with Boid Inclusion Body Disease
Authors: Dervas E. , Michalopoulou E. , Thiele T. , Baggio F. , Hetzel U. , Kipar A. 
Published: August 2024

AbstractKnowledge on the structure and composition of the haematopoietic tissue (HT) is essential to understand the basic immune functions of the immune system in any species. For reptiles, it is extremely limited, hence we undertook an in-depth in situ investigation of the HT (bone marrow, thymus, spleen, lymphatic tissue of the alimentary tract) in the common boa (Boa constrictor). We also assessed age- and disease-related changes, with a special focus on Boid Inclusion Body Disease, a highly relevant reptarenavirus-associated disease in boid snakes. The HT was subjected to gross, histological and ultrastructural examination, including special stains, immunohistochemistry, in situ hybridization and morphometric analyses. In general, the HT was dominated by T cells and lacked a clear structural organization, such as follicle formation. BIBD was associated with significantly higher cellularity and a granulomatous response in the spleen, and the presence of virus-infected haematopoietic cells in the bone marrow, suggesting the latter as a persistent source of viremia.HighlightsLymphatic tissues ofB. constrictorlack organization and are dominated by T cellsThe thymus ofB. constrictorshows slow age-related involutionBIBD-positiveboasshow a granulomatous response in the spleenReptarenaviruses infect haematopoietic cells in the bone marrowReptarenavirusinfectedbone marrow cells might represent a source of viremia
Plant-plant interactions in wheat mixtures modulate mean and variance of susceptibility to Septoria tritici blotch
Authors: Mathieu Laura , Ducasse Aurélie , Ballini Elsa , Morel Jean-Benoît 
Published: August 2024

AbstractVarietal mixtures are a promising agro-ecological approach to stabilizing yields by reducing diseases. The effects of mixtures stem from modifications of epidemiological processes and plant-plant interactions, which could explain some of the paradoxical observations made in the field. However, the role of plant-plant interactions in modifying bread wheat and durum wheat susceptibility to septoria tritici blotch remains to be elucidated. Our study aimed to determine the effect of such plant-plant interactions, by producing full matrices of binary mixtures in the absence of epidemics, on septoria symptoms—specifically necroses (lesions) and pycnidia (spore-containing structures). We employed statistical modeling to compare the mean and variance of focal plants’ phenotype in all mixturesversuspure conditions and in each mixtureversuspure condition. Our findings demonstrate significant effects of plant-plant interactions on wheat susceptibility to septoria. Notably, these interactions had specific rather than general effects, with some but not all genotypic combinations significantly influencing focal susceptibility to septoria. Furthermore, mixtures resulted in reduced necrosis with lower variance, but increased pycnidia formation. These results reinforce the need to consider specific plant-plant interactions for their contribution to trait means and variances. Better considering these interactions could improve crop management strategies that enhance disease control.HighlightWheat varietal mixtures modulate the mean and variance of septoria disease symptoms through specific plant-plant interactions. Mixtures reduce lesions and their variance but increase the formation of spore-containing bodies.
Local weakening of cell-ECM adhesion triggers basal tissue folding via changes in cell shape, actomyosin organization and E-cad levels
Authors: Valencia-Expósito Andrea , Khalilgharibi Nargess , Martínez-Abarca Millán Ana , Mao Yanlan , Martín-Bermudo María D. 
Published: August 2024

AbstractDuringdevelopment, epithelial sheets sculpt organs by folding, either apically or basally, into complex 3D structures. Given the presence of actomyosin networks and cell adhesion sites on both sides of cells, a common machinery mediating apical and basal epithelial tissue folding has been proposed. However, little is known about the mechanisms regulating epithelial folding towards the basal side. Here, using theDrosophilawing imaginal disc and a multidisciplinary approach, combining genetic perturbations and computational modelling, we demonstrate opposing roles for cell-cell and cell-ECM adhesion systems during epithelial folding. Thus, while cadherin-mediated adhesion, linked to actomyosin network, regulates apical folding, a reduction on integrin-dependent adhesion, followed by changes in cell shape, organization of the basal actomyosin cytoskeleton and E-Cad levels, is necessary and sufficient to trigger basal folding. These results suggest that modulation of the cell mechanical landscape through the crosstalk between integrins and cadherins is essential for correct epithelial folding.
Conjugation of dn-OPDA with amino acids inhibits its hormonal bioactivity inMarchantia polymorpha
Authors: Liang Wenting , Zamarreño Ángel M. , Torres-Montilla Salvador , de la Torre Antonio , Totozafy Jean Chrisologue , Kaji Takuya , Ueda Minoru , Corso Massimiliano , García-Mina José M. , Solano Roberto , Chini Andrea 
Published: August 2024

AbstractJasmonates are important phytohormones activating plant tolerance to biotic and abiotic stress, as well as different development processes. A conserved signalling pathway activated by distinct hormones in different plant species mediates these responses: dinor-12-oxo-phytodienoic acid (dn-OPDA) isomers in bryophytes and lycophytes, and JA-Ile in most vascular plants. The final responses depend, in many cases, on the accumulation of specialized metabolites. To identify novel compounds regulated by the dn-OPDA pathway in Marchantia, untargeted metabolomic analyses were carried out in response to dn-OPDA-regulated stress. A novel group of molecules were identified as dn-OPDA-amino acid conjugates (dn-OPDA-aas), and their accumulation after wounding and herbivory confirmed by targeted metabolic profiling in Marchantia and all species in which we previously found dn-iso-OPDA. Mutants inGRETCHEN-HAGEN 3A(MpGH3A) failed to accumulate dn-OPDA-aa conjugates, and showed a constitutive activation of the OPDA pathway and increased resistance to herbivory. Our results show that dn-iso-OPDA bioactivity is reduced by conjugation with amino acids. Therefore, a dichotomous role of jasmonate conjugation in land plants is highlighted: jasmonic acid (JA) conjugation with isoleucine (Ile) produce the bioactive JA-Ile in tracheophytes, whereas conjugation of dn-iso-OPDA with different amino acids disactivate the hormone in bryophytes and lycophytes.
Systematic deletion of symmetricalCFTRexons reveals new therapeutic targets for exon skipping antisense oligonucleotides
Authors: Pena-Rasgado Cecilia , Manriquez Elvia , Dundr Miroslav , Bridges Robert J. , Hastings Michelle L. , Michaels Wren E. 
Published: August 2024

AbstractThere is a major need for therapeutics that treat diseases caused by pathogenic gene variants that disrupt protein open-reading frames. Splice-switching antisense oligonucleotides (ASOs) offer a potential solution by inducing the skipping of exons containing these variants, removing them from the mRNA and correcting the open-reading frame. Cystic fibrosis (CF), caused by disruption of the CF transmembrane regulator (CFTR) gene, is one such disease that has many chain-terminating variants, which are untreatable with standard protein-targeted modulator therapies. UsingCFTRas a model, we demonstrate the utility of ASOs in engineering protein isoforms through exon skipping to rescue protein function disrupted by truncating variants. We functionally screened all CFTR isoforms generated by the deletion of symmetrical exons, which can be skipped without disrupting the open-reading frame. We identified exons that can be removed and produce CFTR isoforms that remain functionally responsive to modulators. We screened for ASOs that induce skipping of these exons and show that they recover CFTR function in airway cells derived from individuals with terminatingCFTRvariants. This study demonstrates that systematic functional analysis of in-frame exon-deleted protein isoforms can identify targets for ASO-based splice-switching therapies, a concept that can be broadly applied to any multi-exon protein-coding gene.
Reduced neural distinctiveness of speech representations in the middle-aged brain
Authors: Guo Zhe-chen , McHaney Jacie R. , Parthasarathy Aravindakshan , Chandrasekaran Bharath 
Published: August 2024

AbstractSpeech perception declines independent of hearing thresholds in middle-age, and the neurobiological reasons are unclear. In line with the age-related neural dedifferentiation hypothesis, we predicted that middle-aged adults show less distinct cortical representations of phonemes and acoustic-phonetic features relative to younger adults. In addition to an extensive audiological, auditory electrophysiological, and speech perceptual test battery, we measured electroencephalographic responses time-locked to phoneme instances (phoneme-related potential; PRP) in naturalistic, continuous speech and trained neural network classifiers to predict phonemes from these responses. Consistent with age-related neural dedifferentiation, phoneme predictions were less accurate, more uncertain, and involved a broader network for middle-aged adults compared with younger adults. Representational similarity analysis revealed that the featural relationship between phonemes was less robust in middle-age. Electrophysiological and behavioral measures revealed signatures of cochlear neural degeneration (CND) and speech perceptual deficits in middle-aged adults relative to younger adults. Consistent with prior work in animal models, signatures of CND were associated with greater cortical dedifferentiation, explaining nearly a third of the variance in PRP prediction accuracy together with measures of acoustic neural processing. Notably, even after controlling for CND signatures and acoustic processing abilities, age-group differences in PRP prediction accuracy remained. Overall, our results reveal “fuzzier” phonemic representations, suggesting that age-related cortical neural dedifferentiation can occur even in middle-age and may underlie speech perceptual challenges, despite a normal audiogram.
Development of ketobenzothiazole-based peptidomimetic TMPRSS13 inhibitors with low nanomolar potency
Authors: Joushomme Alexandre , Désilets Antoine , Champagne William , Hassanzadeh Malihe , Lemieux Gabriel , Gravel-Trudeau Alice , Lepage Matthieu , Lafrenière Sabrina , Froehlich Ulrike , List Karin , Boudreault Pierre-Luc , Leduc Richard 
Published: August 2024

AbstractTMPRSS13, a member of the Type II Transmembrane Serine Proteases (TTSP) family, is involved in cancer progression and in cell entry of respiratory viruses. To date, no inhibitors have been specifically developed toward this protease. In this study, a chemical library of 65 ketobenzothiazole-based peptidomimetic molecules was screened against a proteolytically active form of recombinant TMPRSS13 to identify novel inhibitors. Following an initial round of screening, subsequent synthesis of additional derivatives supported by molecular modelling, uncovered important molecular determinants involved in TMPRSS13 inhibition. One inhibitor, N-0430, achieved low nanomolar affinity towards TMPRSS13 activity in a cellular context. Using a SARS-CoV-2 pseudovirus cell entry model, we further show the ability of N-0430 to block TMPRSS13-dependent entry of the pseudovirus. The identified peptidomimetic inhibitors and the molecular insights of their potency gained from this study will aid in the development of specific TMPRSS13 inhibitors.
Immune aging impairs muscle regeneration via macrophage-derived anti-oxidant selenoprotein P
Authors: Hoang Dieu-Huong , Bouvière Jessica , Galvis Johanna , Moullé Pauline , Migliavacca Eugenia , Juban Gaëtan , Liot Sophie , Stuelsatz Pascal , Le Grand Fabien , Feige Jérôme N , Mounier Rémi , Chazaud Bénédicte 
Published: August 2024

AbstractMuscle regeneration is impaired in the aged organism, due to both intrinsic defects of muscle stem cells (MuSCs) and alterations of their environmental niche. However, the latter has still been poorly explored. Here, we compared and analyzed the time course of the various cell types constituting the MuSC niche during muscle generation in young and old mice. Aging altered the amplification of all niche cells with particularly prominent phenotypes in macrophages that impaired the resolution of inflammation in the old regenerating muscle. RNAsequencing of FACs-isolated MuSCs and non-myogenic niche cells during regeneration uncovered specific profiles and kinetics of genes and molecular pathways differentially regulated in old versus young regenerating muscle, indicating that each cell type responded to aging in a specific manner. Through this, we discovered that macrophages have a strong signature of aging with altered the activation of Selenoprotein P (Sepp1) expression in macrophages during the resolution of inflammation in regenerating muscle. Macrophage-specific deletion ofSepp1gene was sufficient to impair the acquisition of the repair inflammatory profile, perturbed the support of macrophages to MuSCsin vitroandin vivo, and to cause inefficient skeletal muscle regeneration. When transplanted in aged mice, bone marrow from young WT mice, but not Sepp1 KOs, restored muscle regeneration to youthful levels. Altogether this work provides a unique resource to study the aging of the MuSC niche, reveals that aging of niche cells is asynchronous and establishes impaired macrophage dynamics/polarization and the anti-oxidant Selenoprotein P expression as drivers of age-related decline of muscle regeneration.Teaser:Cell profiling reveals asynchronicity of aging in the muscle stem cell niche and age-dependent macrophage/stem cell interactions through anti-oxidant selenoprotein P
MINERVA FAIR assessment fosters open science & scientific crowd-sourcing in systems biomedicine
Authors: Balaur Irina , Welter Danielle , Rougny Adrien , Inau Esther Thea , Mazein Alexander , Ghosh Soumyabrata , Schneider Reinhard , Waltemath Dagmar , Ostaszewski Marek , Satagopam Venkata 
Published: August 2024

1AbstractThe Disease Maps Project (https://disease-maps.org) focuses on the development of diseasespecific comprehensive structured knowledge repositories supporting translational medicine research. These disease maps require continuous interdisciplinary collaboration and should be reusable and interoperable. Adhering to the Findable, Accessible, Interoperable and Reusable (FAIR) principles enhances the utility of such digital assets.We used the RDA FAIR Data Maturity Model and assessed the FAIRness of the Molecular Interaction NEtwoRk VisuAlization (MINERVA) Platform. MINERVA is a standalone webserver that allows users to manage, explore and analyse disease maps and their related data manually or programmatically. We exemplify the FAIR assessment on the Parkinson’s Disease Map (PD map) and the COVID-19 Disease Map, which are large-scale projects under the umbrella of the Disease Maps Project, aiming to investigate molecular mechanisms of the Parkinson’s disease and SARS-CoV-2 infection, respectively.We discuss the FAIR features supported by the MINERVA Platform and we outline steps to further improve the MINERVA FAIRness and to better connect this resource to other ongoing scientific initiatives supporting FAIR in computational systems biomedicine.
Ultrasound-activated microbubbles mediate F-actin disruptions and endothelial gap formation during sonoporation
Authors: Meijlink Bram , van der Kooij H. Rhodé , Wang Yuchen , Li Hongchen , Huveneers Stephan , Kooiman Klazina 
Published: August 2024

AbstractLocally opening up the endothelial barrier in a safe and controlled way is beneficial for drug delivery into the extravascular tissue. Although ultrasound-induced microbubble oscillations can affect endothelial barrier integrity, the mechanism remains unknown. Here we uncover a new role for F-actin in microbubble-mediated endothelial gap formation. Unique simultaneous high-resolution confocal microscopy and ultra-high-speed camera imaging (10 million frames per second) reveal that oscillating microbubbles (radius 1.3-3.8 µm) induce sonoporation in all cells in which F-actin remodeling occurred. F-actin disruption only mainly resulted in tunnel formation (75%) and F-actin stress fiber severing and recoil mainly resulted in cell-cell contact opening within 15 s upon treatment (54%) and tunnel formation (15%). Stress fiber severing occurred when fibers were within reach of the microbubble’s maximum radius during oscillation, requiring normal forces of ≥230 nN. Together, these findings reveal a novel mechanism of microbubble-mediated drug delivery, which associates with the underlying cytoskeletal organization.
Deciphering the coupling state-dependent transcription termination in theEscherichia coligalactose operon
Authors: N Monford Paul Abishek , Wang Xun , Jeon Heung Jin , Lim Heon M. 
Published: August 2024

ABSTRACTThe distance between the ribosome and the RNA polymerase active center, often referred to as the mRNA loop length, is a critical determinant of transcription-translation coupling. While structural biology studies have indicated the existence of multiple expressomes with varying mRNA loop lengths, theirin vivoroles and functional significance remain largely unexplored. This study delves into the mechanisms governing transcription termination within theEscherichia coligalactose operon, revealing a crucial role in the transcription and translation coupling state. The operon employs both Rho-independent and Rho-dependent terminators. Our findings demonstrate that long-loop coupled transcription-translation complexes preferentially terminate at the upstream Rho-independent terminator. In contrast, short-loop coupled complexes bypass the Rho-independent terminator and terminate at the downstream Rho-dependent terminator. The efficiency of the Rho-independent terminator is enhanced by an extended U-track, suggesting a novel mechanism for overcoming ribosome inhibition. These results challenge the traditional view of transcription termination as a random process, highlighting a predetermined mechanism contingent on the coupling state. This study emphasizes the intricate interactions between transcription and translation in prokaryotes. Understanding how these processes affect the RNA polymerase’s selection of transcriptional terminators is critical for developing strategies to regulate gene expression.
O-glycosylation contributes to mammalian glycoRNA biogenesis
Authors: Porat Jennifer , Watkins Christopher P. , Jin Chunsheng , Xie Xixuan , Tan Xiao , Lebedenko Charlotta G. , Hemberger Helena , Shin Woojung , Chai Peiyuan , Collins James J. , Garcia Benjamin A. , Bojar Daniel , Flynn Ryan A. 
Published: August 2024

AbstractThere is an increasing appreciation for the role of cell surface glycans in modulating interactions with extracellular ligands and participating in intercellular communication. We recently reported the existence of sialoglycoRNAs, where mammalian small RNAs are covalently linked to N-glycans through the modified base acp3U and trafficked to the cell surface. However, little is currently known about the role for O-glycosylation, another major class of carbohydrate polymer modifications. Here, we use parallel genetic, enzymatic, and mass spectrometry approaches to demonstrate that O-linked glycan biosynthesis is responsible for the majority of sialoglycoRNA levels. By examining the O-glycans associated with RNA from cell lines and colon organoids we find known and previously unreported O-linked glycan structures. Further, we find that O-linked glycans released from small RNA from organoids derived from ulcerative colitis patients exhibit higher levels of sialylation than glycans from healthy organoids. Together, our work provides flexible tools to interrogate O-linked glycoRNAs (O-glycoRNA) and suggests that they may be modulated in human disease.
The Role of Metabolic Strategies in Determining Microbial Community Diversity along Temperature Gradients
Authors: Duan Quqiming , Clegg Tom , Smith Thomas P. , Bell Thomas , Pawar Samraat 
Published: August 2024

AbstractBy conservative estimates, microbes make up about 17% of the world’s biomass and are essential for most ecosystem functions. However, the mechanisms driving the variation in microbial species diversity in response to both natural and anthropogenic temperature gradients remain unclear. In this study, we integrate ecological metabolic theory with a community assembly model to predict that microbial community diversity generally follows a unimodal pattern with temperature. The position and magnitude of peak diversity are determined by interaction-driven species sorting acting on variations in the temperature dependence of carbon use efficiency (CUE) and generalist-specialist tradeoff. Specifically, trait sorting across temperatures favours communities with high mean and low variance in species-level CUEs. We provide empirical evidence supporting our qualitative predictions of the unimodal temperature-diversity pattern along the global geological temperature gradient, which peaks at about 10-15°C. Our findings indicate that the response of diversity as well as CUE to temperature of microbial communities can be predicted from relatively feasible life-history trait measurements, paving the way for interlinking microbial community diversity and carbon cycling along spatial and temporal thermal gradients.
Phylogenomics of a genus of ‘Great Speciators’ reveals rampant incomplete lineage sorting, gene flow, and mitochondrial capture in island systems
Authors: McCullough Jenna M. , Eliason Chad M. , Hackett Shannon , Myers Corinne E. , Andersen Michael J. 
Published: August 2024

ABSTRACTThe flora and fauna of island systems, especially those in the Indo-Pacific, are renowned for their high diversification rates and outsized contribution to the development of evolutionary theories. The total diversity of geographic radiations of many Indo-Pacific fauna is often incompletely sampled in phylogenetic studies due to the difficulty in obtaining single island endemic forms across the Pacific and the relatively poor performance of degraded DNA when using museum specimens for inference of evolutionary relationships. New methods for production and analysis of genome-wide datasets sourced from degraded DNA are facilitating insights into the complex evolutionary histories of these influential island faunas. Here, we leverage whole genome resequencing (20X average coverage) and extensive sampling of all taxonomic diversity withinTodiramphuskingfishers, a rapid radiation of largely island endemic ‘Great Speciators.’ We find that whole genome datasets do not outright resolve the evolutionary relationships of this clade: four types of molecular markers (UCEs, BUSCOs, SNPs, and mtDNA) and tree building methods did not find a single well-supported and concordant species-level topology. We then uncover evidence of widespread incomplete lineage sorting and both ancient and contemporary gene flow and demonstrate how these factors contribute to conflicting evolutionary histories. Our complete taxonomic sampling allowed us to further identify a novel case of mitochondrial capture between two allopatric species, suggesting a potential historical (but since lost) hybrid zone as islands were successively colonized. Taken together, these results highlight how increased genomic and taxon sampling can reveal complex evolutionary patterns in rapid island radiations.