bluuebunny/crossref_metadata_2025_split huggingface dataset:
<xhtml:span xmlns:xhtml="http://www.w3.org/1999/xhtml" xml:lang="en">The complete genome sequence of five pre-2013&#160;Escherichia coli sequence type (ST)1193 strains reveals insights into an emerging pathogen
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Authors: White Rhys T. , Ashcroft Melinda A. , Bauer Michelle J. , Bell Jan , Butkiewicz Dominika , Álvarez-Fraga Laura , Gibson Justine S. , Kidsley Amanda K. , Mollinger Joanne L. , Peters Kate M. , Phan Minh-Duy , Roberts Leah W. , Rogers Benjamin A. , Schembri Mark A. , Trott Darren J. , Turnidge John , Forde Brian M. , Beatson Scott A. 
Published: September 2024

Fluoroquinolone-resistant Escherichia coli sequence type (ST)1193 is a profound, emerging lineage associated with systemic, urinary tract, and neonatal infections. Humans, companion animals, and the environment are reservoirs for ST1193, which has been disseminated globally. Following its detection in 2007, ST1193 has been identified repeatedly amongst fluoroquinolone-resistant clones in Australia. However, despite the growing importance of ST1193, only three complete genomes are published in the literature, none of which are from Australia. Here we expand on the available ST1193 resources with the complete genomes of five ST1193 strains sequenced using Oxford Nanopore Technologies and Illumina. Using in silico genotyping, we found that all strains were multi-drug resistant, including resistances to fluoroquinolones and cephalosporins. In vitro antibiotic susceptibility testing mostly correlated with individual genotypes. The exception was MS8320, which had additional in vitro resistance to piperacillin/tazobactam, ampicillin/sulbactam, cefazolin and doripenem (carbapenem). Further investigation identified seven additional copies of an IS26 transposable unit carrying a blaTEM-1B beta-lactamase gene, suggesting this tandem amplification is associated with extended resistance phenotypes. Uropathogenicity factors, including three separate siderophore-encoding loci, were conserved in chromosomal and plasmid regions. Using all complete genomes, we further elucidated the recombination events surrounding the previously described K5/K1 capsular loci switch. Phenotypic confirmation of differing capsules in Australian ST1193 strains, coupled with genetic analysis revealing insertions downstream of the capsular locus, underscored the genetic distinctions between K5 and K1 capsule encoding strains. This study provides five new reference ST1193 genomes from Australia. These include the earliest complete K5-capsule ST1193 genomes on record (collected 2007), alongside our reference genome (MS10858); a clinical isolate obtained early during the ST1193 expansion and representative of the predominant K1-associated clade. These findings lay the foundations for further genomic and molecular analyses that may help understand the underlying reasons for the rapid global expansion of ST1193.
IL-23 tunes inflammatory functions of human mucosal-associated invariant T (MAIT) cells
Authors: Camard Laetitia , Stephen Tharshana , Yahia-Cherbal Hanane , Guillemot Vincent , Mella Sébastien , Baillet Victoire , Lopez-Maestre Hélène , Capocefalo Daniele , Cantini Laura , Leloup Claire , Marsande Julie , Sienes-Bailo Juan , Dangien Ambre , Pietrosemoli Natalia , Hasan Milena , Wang Huimeng , Eckle Sidonia B. G. , Fourie Anne M. , Greving Carrie , Shaikh Barbara Joyce , Parker Raphaelle , Cua Daniel J. , Bianchi Elisabetta , Rogge Lars 
Published: September 2024

SummaryIL-23 signaling plays a key role in the pathogenesis of chronic inflammatory and infectious diseases, yet the cellular targets and signaling pathways affected by this cytokine remain poorly understood. We show that IL-23 receptors are expressed on the large majority of human MAIT, but not of conventional T cells. Protein and transcriptional profiling at the population and single cell level demonstrates that stimulation with IL-23 or the structurally related cytokine IL-12 drives distinct functional profiles, revealing a high level of plasticity of MAIT cells. IL-23, in particular, affects key molecules and pathways related to autoimmunity and cytotoxic functions. Integrated analysis of transcriptomic and chromatin accessibility, supported by CRISPR/Cas9 mediated deletion, shows that AP-1 transcription factors constitute a key regulatory node of the IL-23 pathway in MAIT cells. In conclusion, our findings indicate that MAIT cells are key mediators of IL-23 functions in immunity to infections and chronic inflammatory diseases.
Bone mechano-response is driven by locomotion transitions during vertebrate evolution
Authors: Shimochi Saeka , Brunet Clara , Fontcuberta-Rigo Margalida , Hrovat Katja , Puigbò Pere , Nakamura Miho 
Published: September 2024

AbstractThe skeleton supports the muscles in keeping the body upright against gravity while enduring thousands of daily loads. In this study, we investigated non-collagenous bone matrix proteins using osteoblast cell cultures and phylogenetic analyses to identify the molecular mechanisms involved in mechanical loading. The results indicate that the bone mechano-response is an evolutionary-driven process and that several non-collagenous proteins may significantly regulate the bone’s response to mechanical stress. According to our results, two significant evolutionary transitions in vertebrate locomotion shaped the roles of non-collagenous proteins in humans: the water-to-land transition, which increased mechanical stress on the limbs, and the evolution to bipedalism in humans, which altered the distribution of stress on the lower and upper limbs. Fetuin A, positively selected in both evolutionary transitions, showed the most significant expression change during mechanical stimulation.
The lincRNAPantr1is a FOXG1 target gene conferring site-specific chromatin binding of FOXG1
Authors: Gather Fabian , Rauleac Tudor , Akol Ipek , Arumugam Ganeshkumar , Fullio Camila L. , Müller Teresa , Kleidonas Dimitrios , Fischer Andre , Vlachos Andreas , Backofen Rolf , Vogel Tanja 
Published: September 2024

ABSTRACTDerailed gene expression programs within the developing nervous system, encompassing both transcriptional and posttranscriptional processes, can cause diverse neurodevelopmental diseases (NDD). The NDD FOXG1-syndrome lacks full understanding of the mechanistic role of its eponymous gene product. While it is known that FOXG1 acts in part at the chromatin by binding to regulative regions, it is unclear what factors control its presence at specific sites. Long non-coding RNAs (lncRNAs) can mediate site-directed transcription factor binding, but their potential role in FOXG1-syndrome has not been described. Here, we show that FOXG1 localisation is regulated at selected loci through the lncRNAPantr1.We identified FOXG1 as an upstream transcriptional activator ofPantr1in human and mice. Further, we discovered that FOXG1 has the ability to associate with RNAs. Both, transcriptional regulation ofPantr1by FOXG1 and association of both partners, build up a regulative network that impacts the localisation of FOXG1 at selected genomic loci. Specifically,Pantr1facilitates cooperative presence of FOXG1/NEUROD1 at specific sites, andPantr1reduction leads to redistribution of FOXG1 to comparably more generic binding sites. The rescue of impaired dendritic outgrowth upon FOXG1 reduction by simultaneous overexpression ofPantr1underlines the importance of the FOXG1/Pantr1regulative network.GRAPHICAL ABSTRACT
Robustness Revisited: On the Neutral Evolution of Centrality and Localization
Authors: Sella Yehonatan , Bergman Aviv 
Published: September 2024

AbstractThis study investigates the intricate interplay among neutral landscape structure, mutation rate, recombination rate, and population dynamics in shaping evolutionary robustness. We provide a comprehensive framework that elucidates how different evolutionary forces interact to influence genotypic robustness and localization within haploid and diploid populations. We demonstrate that in haploid populations, high mutation rates relative to recombination typically drive the population toward regions of increased eigencentrality, a graphtheoretic measure of centrality which is correlated while not identical to mutational robustness. On the other hand, recombination increases the localization of the population to a smaller region of genotypic space, while high values of recombination relative to mutation can introduce shifts in distribution away from eigencentrality and toward attractors of the recombination dynamics. Diploid dynamics further complicate these interactions, showing reduced alignment with eigencentrality under both high mutation and recombination rates, with the exception of structured diploid landscapes where dynamics are still aligned with increasing eigencentrality. Our findings underscore the nuanced dependencies of evolutionary outcomes on both local and global landscape structures as well as evolutionary parameters.Significance StatementOur work advances the theory of neutral evolution, paying particular attention to the question of how the holistic fitness landscape structure shapes the process of evolution and gives rise to emergent evolutionary phenomena. Since neutral evolution does not depend on direct selection, its ramifications can be both subtle, as they depend on network-wide properties, and ubiquitous, as they are not tied to context-specific adaptations. Our study provides a theoretical framework that connects the structure of neutral fitness landscapes with the dynamics of mutation and recombination rates, and the distinct behaviors of haploid and diploid populations. We establish general heuristic principles regarding the way evolutionary outcomes, such as robustness and localization, are influenced by the interplay of these factors.
A hepatocyte-specific cytochromecoxidase deficiency in mice leads to a lymphopenia owing to deficiencies in bone marrow progenitors
Authors: Pioli KimAnh T. , Ghosh Sampurna , Boulet Aren , Leary Scot C. , Pioli Peter D. 
Published: September 2024

SummaryMutations that negatively impact mitochondrial function are highly prevalent in humans and lead to disorders with a wide spectrum of disease phenotypes, including deficiencies in immune cell development and/or function. Previous analyses of mice with a hepatocyte-specific cytochromecoxidase (COX) deficiency revealed an unexpected peripheral blood leukopenia associated with splenic and thymic atrophy. Here, we use mice with a hepatocyte-specific deletion of the COX assembly factorSco1to show that metabolic defects extrinsic to the hematopoietic compartment lead to a pan-lymphopenia represented by severe losses in both B and T cells. We further demonstrate that immune defects in these mice are associated with the loss of bone marrow lymphoid progenitors common to both lineages and early signs of autoantibody-mediated autoimmunity. Our findings collectively point to a significant role for hepatocyte dysfunction as an instigator of immunodeficiency in patients with congenital mitochondrial defects who suffer from chronic or recurrent infections.
Novel method to assess group dynamics in rats reveals deficits in behavioral contagion in KM rats
Authors: Smirnov K. , Starkov I. , Sysoeva O. , Midzyanovskaya I. 
Published: September 2024

AbstractBehavioral copying is a key process in group actions, but it is challenging for individuals with Autism Spectrum Disorder (ASD). We investigated behavioral contagion, or instinctual replication of behaviors, in Krushinky-Molodkina (KM) rats (n=16), a new rodent model for ASD, compared to control Wistar rats (n=15). A randomly chosen healthy Wistar male (“demonstrator rat”) was introduced to the homecage of experimental rats (“observers”) 10-14 days before the experiments to become a member of the group. For the implementation of the behavioral contagion experiment, we used the IntelliCage system, where rats can live in a group of 5-6 rats and their water visits can be fully controlled. During the experiment, the demonstrator was taken out of IntelliCage for 24 hours of water deprivation and then placed back. As a result, a drinking behavior of the water-deprived demonstrator rat prompted activated behaviors in the whole group. Unlike the Wistar controls, KM observers showed fewer visits to the drinking bottles, particularly lacking inspection visits. The control group, in contrast, exhibited a dynamic, cascade-like visiting of the water corners. The proportion of activated observers in KM rats was significantly lower, as compared to Wistar ones, and they did not mimic other observer rats. KM rats, therefore, displayed an attenuated pattern of behavioral contagion, highlighting social deficits in this ASD model. This study suggests that measuring group dynamics of behavioral contagion in an automated, non-invasive setup offers valuable insights into social behavior in rodents, particularly for studying social deficits in ASD models.HighlightsThirsty demonstrators triggered an avalanche of observers’ visits to the water cornersThe contaged behavior was attenuated in observer KM ratsBehavioral contagion test provides a new tool for objective, automated phenotyping in rodent models of social deficits
Application of cryo-FIB-SEM for investigating organelle ultrastructure in guard cells of higher plants
Authors: Franzisky Bastian Leander , Zhang Xudong , Burkhardt Claus Jakob , Majorovits Endre , Hummel Eric , Schertel Andreas , Geilfus Christoph-Martin , Zörb Christian 
Published: September 2024

AbstractStomata are vital for CO2 and water vapor exchange, with guard cells’ aperture and ultrastructure highly responsive to environmental cues. However, traditional methods for studying guard cell ultrastructure, which rely on chemical fixation and embedding, often distort cell morphology and compromise membrane integrity, leaving no suitable methodology until now. In contrast, plunge-freezing in liquid ethane rapidly preserves cells in a near-native vitreous state for cryogenic electron microscopy. Using this approach, we applied Cryo-Focused Ion Beam-Scanning Electron Microscopy (cryo- FIB-SEM) to study the guard cell ultrastructure ofVicia faba, a higher plant model chosen for its sensitivity to external factors and ease of epidermis isolation, advancing beyond previous cryo-FIB-SEM applications in lower plant algae. The results firstly introduced cryo-FIB-SEM volume imaging, enabling subcellular ultrastructure visualization of higher plants likeV. fabain a vitrified, unaltered state. 3D models of organelles such as stromules, chloroplast protrusions, chloroplasts, starch granules, mitochondria, and vacuoles were reconstructed from cryo-FIB-SEM volumetric data, with their surface area and volume initially determined using manual segmentation. Future studies using this near-native volume imaging technique hold promise for investigating how environmental factors like drought or salinity influence stomatal behavior and the morphology of guard cells and their organelles.
Full-season spring migration counts reveal seasonal contrasts in raptor migration through the eastern Black Sea flyway
Authors: Tal Tohar , Jansen Diego , Jansen Erik , Green Arthur W. , Hoekstra Elien , Heetkamp Marc , T’jollyn Filiep , Engelen Dries , Hoekstra Bart , Kaasiku Triin , Vansteelant Wouter M.G. 
Published: September 2024

AbstractThe extent to which geographical features like coastlines and mountain ranges funnel migrating birds depends on the seasonal context and direction of migration. Near Batumi, in the Republic of Georgia, the eastern Black Sea coast and Lesser Caucasus funnel over one million raptors through a 10-20 km wide coastal strip every autumn. The funnelling effect of the Lesser Caucasus appears much less evident for northbound migrants. Yet historical data suggest tens of thousands of raptors pass through the region in spring. To elucidate the composition and timing of spring raptor migration we conducted full-season migration surveys near Batumi in 2019, 2020 and 2022. In total, we recorded 33 species and, on average, counted 542,161 raptors (min. 455,799 - max. 618,848) annually. The bulk of the spring passage consisted of Black KiteMilvus migrans(239,649 ± 22,547) and Steppe BuzzardButeo buteo vulpinus(194,029 ± 102,702). The most diverse and intense spring migration occurred from late March through mid-April, when the median passage date of 12 of 15 common species (>100 ind. y-1) occurred. Species with longer autumn migration periods tended to have longer spring migration periods, and most species had a longer migration period in spring than in autumn, likely due to larger age differences in timing during spring. Species’ abundance was up to an order of magnitude lower in spring than in autumn, consistent with a weaker bottleneck-effect in spring. Nevertheless, our results confirm the eastern Black Sea coast as a principal spring flyway and help redraw the map of East African-Eurasian migration for several Palearctic raptors. While we will not continue annual spring migration surveys, our data provides a baseline for detecting changes in raptor migration through short-term surveys and can help plan migration-based conservation and research at Batumi in spring.
Selective killing of plasma cell clones using splice-switching oligonucleotides targeting immunoglobulin variable exons
Authors: Lambert Jean-Marie , Praité Antoine , Contini Marion , Ashi Mohamad Omar , Marchalot Anne , Pennec Soazig Le , Sirac Christophe , Al Hayek Sandy , Delpy Laurent 
Published: September 2024

ABSTRACTDeregulated proliferation of a plasma cell (PC) clone is accompanied by an excess production of a monoclonal immunoglobulin (mo-Ig) component with unique V(D)J rearrangement features. In systemic Ig light chain (AL) amyloidosis, organ dysfunction is due to the deposition of amyloid fibrils composed of mo-Ig light chains in target tissues. Recent advances in exon skipping therapy using splice-switching antisense oligonucleotides (ASO) prompted us to examine a new antisense strategy targeting the variable (V) exon in myeloma cells. Indeed, we previously observed that the production of truncated Ig light chains, encoded by alternatively spliced mRNAs lacking V exon, heightened endoplasmic reticulum (ER) stress and triggered apoptosis of antibody-secreting plasma cells. We designed ASO hybridizing donor or acceptor V exon splice sites on mo-Ig pre-mRNAs. These compounds were very potent alternative splicing inducers and increased the production of V-domain-less truncated Ig chains. Remarkably,in vitroexperiments and tumor xenograft models revealed that myeloma cells were highly sensitive to specific ASO treatment, compared to an irrelevant control-ASO. RNA-seq experiments further confirmed that the production of truncated Ig induced upon ASO treatment provoked a massive myeloma cell death through ER stress-associated apoptosis. In addition, high throughput sequencing of Ig repertoire demonstrated that ASO targeting JH2 or Jκ1 donor splice site induced massive elimination of VDJH2- or VJκ1-rearranged clones respectively, while sparing the others. Collectively, these data provide evidence that ASO targeting V exon on mo-Ig pre-mRNAs can emerge as new weapons to induce selective killing of plasma cell clones.
Richness and composition of phyllosphereMethylobacteriumcommunities cause variation inArabidopsis thalianagrowth
Authors: Lauzon Jocelyn , Pelletier Jérémie , Favron Élanore , Wang Zihui , Kembel Steven W. 
Published: September 2024

ABSTRACTThe phyllosphere – the aerial parts of plants – forms a vast microbial habitat that harbors diverse bacterial communities playing key roles in ecosystem function. The foliar surface is thus a promising study system to investigate biodiversity-ecosystem function relationships. Researchers have found a positive correlation between leaf bacterial diversity and ecosystem productivity, but the causality of this relationship has yet to be demonstrated. To understand how the diversity and composition of phyllosphere bacterial communities could cause variation in the growth of their host plants, we assembled synthetic communities composed of different diversity and compositions ofMethylobacteriumstrains – a plant growth-promoting bacterial genus ubiquitous in the phyllosphere – that we inoculated onArabidopsis thalianagrown in gnotobiotic conditions. We hypothesized that (1) increasingMethylobacteriumdiversity should cause an increase in host growth; (2) strains should differ in their impact on host growth; and (3) the relationship between bacterial diversity and plant productivity should be strain-dependent. Our results supported our three hypotheses but revealed unpredicted patterns in howA. thalianaleaf biomass varied according to inoculatedMethylobacteriumstrain richness and identity. Increasing bacterial richness induced a higher host leaf biomass, but only after an initial reduction in biomass, suggesting competition alleviation by multispecies interactions. TwoMethylobacteriumstrains showed beneficial effects onA. thalianagrowth, and one strain was detrimental for the plant. Community composition shaped the relationship between diversity and productivity, highlighting the importance of community mutualistic and antagonistic interactions. Furthermore, niche complementarity was likely the main ecological mechanism driving the diversity-productivity relationship in our study system. By demonstrating the causal effects ofMethylobacteriumcommunity diversity and composition on host plant growth, our experiment shed light on the importance of phyllosphere bacteria in terrestrial ecosystem functioning.
The over-activated peritoneal immune environment in endometriosis is characterised by a lack of PD-1 inhibition
Authors: Tresso Anna , Thota Niharika , James Chloe , Borash Natasha , Brennan Emily , Bayat Shima , Vollenhoven Beverley , Tapmeier Thomas 
Published: September 2024

AbstractBackgroundEndometriosis is characterised by chronic inflammation in the peritoneal cavity causing acute and chronic pelvic pain, largely explained by dysregulation in the immune environment within peritoneal fluid. The activation status of the peritoneal immune cells is unclear. In addition, a comparison with the status of the systemic immune system is desirable to explore avenues of diagnosis and treatment of endometriosis-related inflammation and pain.Objective(s)To investigate the immune environment in endometriosis in peritoneal fluid and blood by full-spectrum flow cytometry with a focus on activation and inhibition of immune cells.Study DesignThis was an observational study in patients undergoing laparoscopy for diagnosis or treatment of peritoneal endometriosis or for unrelated conditions; PF was collected from n=5 endometriosis patients and n=4 controls, blood from n=4 endometriosis patients and n=3 controls. Data were analysed for statistical significance using ANOVA, the Kruskal-Wallis or Mann-Whitney U test, with a p-value below 0.05 considered significant.ResultsWe observed a prevailing of myeloid immune cells in the peritoneal fluid as opposed to lymphoid cells in the blood. The main differences between endometriosis and control samples, however, were found in the smaller compartments, i.e., in lymphoid populations in peritoneal fluid and myeloid populations in blood. PD-1 levels in peritoneal fluid endometriosis samples were significantly lower than in controls (p<0.05).Conclusion(s)The immune checkpoint PD-1 could be a new angle of treating endometriosis-related inflammation and pain in women suffering from this chronic and intractable condition.TweetableLack of PD-1 plays a role in endometriosis-related inflammation.AJOG at a glanceThe inflammatoru immune environment in endometriosis needs investigating as it iis causative of the pain, i.e., the predominant symptom.We found a lack of PD-1 expression on peritoneal fluid cells in endometriosis compared to controls.This could explain the persistent inflammation and open avenues of treatment.