{"messages":[{"status":"ok","category":"all","interval":"2024-08-01:2024-08-31","funder":"all","cursor":"201","count":30,"count_new_papers":"3469","total":"4881"}], "collection":[{"title":"Withania somnifera root extract (LongeFera-TM) confers beneficial effects on health and lifespan of the model worm Caenorhabditis elegans","authors":"Thakkar, N.; Gajera, G.; Mehta, D.; Nair, S.; Kothari, V.","author_corresponding":"Vijay Kothari","author_corresponding_institution":"Nirma University","doi":"10.1101\/2024.08.01.606126","date":"2024-08-02","version":"1","type":"new results","license":"cc_by_nc_nd","category":"molecular biology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2024\/08\/02\/2024.08.01.606126.source.xml","abstract":"Withania somnifera is among the most widely prescribed medicinal plants in traditional Indian medicine. Hydroalcoholic extract of the roots of this plant was investigated for its effects on the overall health and lifespan of the model worm Caenorhabditis elegans. Extract-exposed worms registered longer lifespan, higher fertility, better motility and metabolic activity. Whole transcriptome analysis of the extract-treated worms revealed the differential expression of the genes associated with lifespan extension, eggshell assembly and integrity, progeny formation, yolk lipoproteins, collagen synthesis, cuticle molting, etc. This extract seems to exert its beneficial effect on C. elegans partly by triggering remodeling of the developmentally programmed apical extracellular matrix (aECM). Differential expression of certain important genes (cpg-2, cpg-3, sqt- 1, dpy-4, dpy-13, and col-17) was confirmed through PCR assay too. Some of the differently expressed genes (gfat-2, unc-68, dpy-4, dpy-13, col-109, col-169, and rmd-1) in worms experiencing pro-health effect of the extract were found through cooccurrence analysis to have their homologous counterpart in humans. Our results validate the potential of W. somnifera extract as a phytopharmaceutical.","funder":"NA","published":"10.33393\/dti.2025.3368","server":"bioRxiv"},{"title":"Identification of Disease-relevant, Sex-based Proteomic Differences in iPSC-derived Vascular Smooth Muscle","authors":"Ariyasinghe, N. R.; Gupta, D.; Escopete, S.; Stotland, A. B.; Sundararaman, N.; Ngu, B.; Dabke, K.; Rai, D.; McCarthy, L.; de Souza Santos, R.; McCain, M. L.; Sareen, D.; Parker, S. J.","author_corresponding":"Sarah J Parker","author_corresponding_institution":"Advanced Clinical Biosystems Research Institute, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA","doi":"10.1101\/2024.07.30.605659","date":"2024-08-02","version":"1","type":"new results","license":"cc_no","category":"molecular biology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2024\/08\/02\/2024.07.30.605659.source.xml","abstract":"The prevalence of cardiovascular disease varies with sex, and the impact of intrinsic sex-based differences on vasculature is not well understood. Animal models can provide important insight into some aspects of human biology, however not all discoveries in animal systems translate well to humans. To explore the impact of chromosomal sex on proteomic phenotypes, we used iPSC-derived vascular smooth muscle cells from healthy donors of both sexes to identify sex-based proteomic differences and their possible effects on cardiovascular pathophysiology. Our analysis confirmed that differentiated cells have a proteomic profile more similar to healthy primary aortic smooth muscle than iPSCs. We also identified sex-based differences in iPSC- derived vascular smooth muscle in pathways related to ATP binding, glycogen metabolic process, and cadherin binding as well as multiple proteins relevant to cardiovascular pathophysiology and disease. Additionally, we explored the role of autosomal and sex chromosomes in protein regulation, identifying that proteins on autosomal chromosomes also show sex-based regulation that may affect the protein expression of proteins from autosomal chromosomes. This work supports the biological relevance of iPSC-derived vascular smooth muscle cells as a model for disease, and further exploration of the pathways identified here can lead to the discovery of sex-specific pharmacological targets for cardiovascular disease.\n\nSignificanceIn this work, we have differentiated 4 male and 4 female iPSC lines into vascular smooth muscle cells, giving us the ability to identify statistically-significant sex-specific proteomic markers that are relevant to cardiovascular disease risk (such as PCK2, MTOR, IGFBP2, PTGR2, and SULTE1).","funder":"NA","published":"NA","server":"bioRxiv"},{"title":"Perceived and observed biases within scientific communities: a case study in movement ecology","authors":"Shaw, A. K.; Fouda, L.; Mezzini, S.; Kim, D.; Chatterjee, N.; Wolfson, D.; Abrahms, B.; Attias, N.; Beardsworth, C. E.; Beltran, R.; Binning, S. A.; Blincow, K. M.; Chan, Y.-C.; Fronhofer, E. A.; Hegemann, A.; Hurme, E. R.; Iannarilli, F.; Kellner, J. B.; McCoy, K. D.; Rafiq, K.; Saastamoinen, M.; Sequeira, A. M. M.; Serota, M. W.; Sumasgutner, P.; Tao, Y.; Torstenson, M.; Yanco, S. W.; Beck, K. B.; Bertram, M. G.; Beumer, L. T.; Bradaric, M.; Clermont, J.; Ellis-Soto, D.; Faltusova, M.; Fieberg, J.; Hall, R. J.; Kolzsch, A.; Lai, S.; Lee-Cruz, L.; Loretto, M.-C.; Loveridge, A.; Michelangeli, ","author_corresponding":"Allison K. Shaw","author_corresponding_institution":"Department of Ecology, Evolution, and Behavior, University of Minnesota, St. Paul, Minnesota, USA","doi":"10.1101\/2024.07.29.605602","date":"2024-08-02","version":"1","type":"new results","license":"cc_by_nc_nd","category":"ecology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2024\/08\/02\/2024.07.29.605602.source.xml","abstract":"Who conducts biological research, where, and how the results are disseminated varies among geographies and identities. Identifying and documenting these forms of bias by research communities is a critical first step towards addressing them. We documented perceived and observed biases in movement ecology. Movement ecology is a rapidly expanding sub-discipline of biology, which is strongly underpinned by fieldwork and technology use. First, we surveyed attendees of an international conference, and discussed the results at the conference (comparing uninformed vs informed perceived bias). Although most researchers identified as bias-aware, only a subset of biases were discussed in conversation. Next, by considering author affiliations from publications in the journal Movement Ecology, we found among-country discrepancies between the country of the authors affiliation and study site location related to national economics. At the within-country scale, we found that race-gender identities of postgraduate biology researchers in the USA differed from national demographics. We discuss the role of potential specific causes for the emergence of bias in the sub-discipline, e.g. parachute-science or accessibility to fieldwork. Undertaking data-driven analysis of bias within research sub-disciplines can help identify specific barriers and first steps towards the inclusion of a greater diversity of participants in the scientific process.","funder":"NA","published":"10.1098\/rspb.2025.0679","server":"bioRxiv"},{"title":"Ecology and abundant occurrence of Genea (Pyronemataceae) in western Oregon, U.S.A.","authors":"Dawson, H. R.; Dawson, H. A.","author_corresponding":"Hilary Rose Dawson","author_corresponding_institution":"Australian National University","doi":"10.1101\/2024.07.29.604843","date":"2024-08-02","version":"1","type":"new results","license":"cc_by","category":"ecology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2024\/08\/02\/2024.07.29.604843.source.xml","abstract":"Hypogeous fungi (\"truffles\") are challenging to study because they produce underground sporocarps that may not be found during traditional fungal surveys. Commercially valuable truffles are located using scent-detection dogs trained on truffles. However, the dogs are not necessarily limited to commercial truffle species when trained on other truffle taxa of interest. For example, Genea (Pyronemataceae, Ascomycota) is a genus of common but difficult to find truffles that develops small and often soil-colored hypogeous ascomata (truffles).. We used a truffle dog trained to locate Genea truffles in the southern Willamette Valley and associated mountains in western Oregon, U.S.A, recording when the sporocarps were present at a wide range of elevations (113 to 1879 m). We found Genea was present in half of our surveys, and noted that it rarely fruited in areas that had experienced wildfire. This study demonstrates the value of using truffle dogs in documenting truffle diversity, particularly those that are difficult to locate visually, and provides further evidence for the abundance of Genea.","funder":"NA","published":"NA","server":"bioRxiv"},{"title":"Variable prevalence of protective Spiroplasma infection over time in two natural populations of Drosophila hydei","authors":"Jones, J. E.; Court, R.; Kageyama, D.; Obbard, D. J.; Hurst, G. D. D.","author_corresponding":"Jordan Elouise Jones","author_corresponding_institution":"University of Liverpool","doi":"10.1101\/2024.07.31.606006","date":"2024-08-02","version":"1","type":"new results","license":"cc_by_nc_nd","category":"ecology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2024\/08\/02\/2024.07.31.606006.source.xml","abstract":"The temporal dynamics of protective symbionts have rarely been characterized outside of aphid hosts. Here, we determine the prevalence of Spiroplasma in two populations of D. hydei where Spiroplasma infection had been previously recorded (UK and Japan). We observe that infection in both populations is variable over time and confirm the persistence of Spiroplasma in the UK population for 9 years. Thus, variable prevalence over time appears to be a common feature of these symbioses.","funder":"NA","published":"NA","server":"bioRxiv"},{"title":"Inferring polygenic negative selection underlying an individual trait as a distribution of fitness effects (DFEs) from GWAS summary statistics","authors":"Xue, A. T.; Huang, Y.-f.; Siepel, A.","author_corresponding":"Alexander T. Xue","author_corresponding_institution":"Cold Spring Harbor Laboratory","doi":"10.1101\/2024.07.29.601707","date":"2024-08-02","version":"1","type":"new results","license":"cc_by_nc_nd","category":"evolutionary biology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2024\/08\/02\/2024.07.29.601707.source.xml","abstract":"There has been rising interest in exploiting data from genome-wide association studies (GWAS) to detect a genetic signature of natural selection acting on a given phenotype. However, current approaches are unable to directly estimate the distribution of fitness effects (DFE), an established property in population genetics that can elucidate genomic architecture pertaining to a particular focal trait. To this end, we introduce ASSESS, an inferential method that exploits the Poisson Random Field (PRF) to model selection coefficients from genome-wide allele count data, while jointly conditioning GWAS summary statistics on a latent distribution of phenotypic effect sizes. This probabilistic model is unified under the assumption of an explicit relationship between fitness and trait effect to yield a DFE. To gauge the performance of ASSESS, we enlisted various simulation experiments that covered a range of usage cases and model misspecifications, which revealed accurate recovery of the underlying selection signal. As a further proof-of-concept, ASSESS was applied to an array of publicly available human trait data, whereby we replicated previously published empirical findings from an alternative methodology. These demonstrations illustrate the potential of ASSESS to satisfy an increasing need for powerful yet convenient population genomic inference from GWAS summary statistics.\n\nAuthor SummaryThe growth of genome-wide association studies (GWAS) over the past decade has provided a wealth of resources for uncovering the genomic architecture underlying complex traits, including the footprint of selection. Currently, there are computational tools for inferring natural selection whereby GWAS results are leveraged to conduct a binary test for overall presence, estimate a correlated property, or summarize polygenic selection strength with a single statistic. However, a methodology that exploits GWAS data to estimate the distribution of fitness effects (DFE), which is the most direct measurement for the genetic impact of natural selection acting on a complex trait, does not currently exist. To this end, we constructed an approach to directly infer the DFE, wherein per-site selection coefficients specifically associated with a focal trait are aggregated across the genome. This implementation is designed to explicitly model an entire genome-wide set of summary statistics output from a GWAS rather than the individual-level input data, which offers computational efficiency and convenience as well as alleviates privacy concerns. We expect this to be a promising development given the further accumulation of GWAS results and investigators seeking more sophisticated analyses into the relationship between genetics and traits.","funder":"NA","published":"NA","server":"bioRxiv"},{"title":"Genome-Wide Analysis of TCP Family Genes and Their Constitutive Expression Pattern Analysis in the Melon (Cucumis melo)","authors":"Jone, M. J. H.; Siddique, M. N. A.; Biswas, M. K.; Hossain, M. R.","author_corresponding":"Mohammad Rashed Hossain","author_corresponding_institution":"Plant Molecular Breeding and Bioinformatics Laboratory, Department of Genetics and Plant Breeding, Bangladesh Agricultural University, Mymensingh - 2202, Bangla","doi":"10.1101\/2024.07.30.605410","date":"2024-08-02","version":"1","type":"new results","license":"cc_by","category":"bioinformatics","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2024\/08\/02\/2024.07.30.605410.source.xml","abstract":"TCP proteins are plant-specific transcription factors that play essential roles in various developmental processes, including leaf morphogenesis and senescence, flowering, lateral branching, hormone crosstalk, and stress responses. However, the specific functions of TCP genes in melon remain largely unknown. This study identified and characterized 29 putative TCP genes in melon. These genes were classified into two classes: Class-I (13 genes) and Class-II (16 genes). The chromosomal location, gene structure, conserved motifs, structural homology, cis-regulating elements, transcript expression patterns, and potential protein-protein interactions were further analyzed. The results revealed that the putative CmTCP genes are distributed across nine of the twelve melon chromosomes and exhibit diverse expression patterns in different tissues and during floral organ development. Phylogenetic analysis suggests that some CmTCP genes may have similar functions to their homologs in other plant species, while others may have undergone functional diversification. This study provides a valuable resource for future investigations into the specific roles of individual CmTCP genes in melon development and paves the way for elucidating the mechanisms by which TCP proteins regulate leaf elongation, floral development, and lateral branching.","funder":"NA","published":"NA","server":"bioRxiv"},{"title":"Assessing the ability of ChatGPT to extract natural product bioactivity and biosynthesis data from publications","authors":"Kalmer, T. L.; Ancajas, C. M. F.; Cheng, Z.; Oyedele, A. S.; Davis, H. L.; Walker, A.","author_corresponding":"Allison Walker","author_corresponding_institution":"Vanderbilt Unviersity","doi":"10.1101\/2024.08.01.606186","date":"2024-08-02","version":"1","type":"new results","license":"cc_by","category":"bioinformatics","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2024\/08\/02\/2024.08.01.606186.source.xml","abstract":"Natural products are an excellent source of therapeutics and are often discovered through the process of genome mining, where genomes are analyzed by bioinformatic tools to determine if they have the biosynthetic capacity to produce novel or active compounds. Recently, several tools have been reported for predicting natural product bioactivities from the sequence of the biosynthetic gene clusters that produce them. These tools have the potential to accelerate the rate of natural product drug discovery by enabling the prioritization of novel biosynthetic gene clusters that are more likely to produce compounds with therapeutically relevant bioactivities. However, these tools are severely limited by a lack of training data, specifically data pairing biosynthetic gene clusters with activity labels for their products. There are many reports of natural product biosynthetic gene clusters and bioactivities in the literature that are not included in existing databases. Manual curation of these data is time consuming and inefficient. Recent developments in large language models and the chatbot interfaces built on top of them have enabled automatic data extraction from text, including scientific publications. We investigated how accurate ChatGPT is at extracting the necessary data for training models that predict natural product activity from biosynthetic gene clusters. We found that ChatGPT did well at determining if a paper described discovery of a natural product and extracting information about the products bioactivity. ChatGPT did not perform as well at extracting accession numbers for the biosynthetic gene cluster or producers genome although using an altered prompt improved accuracy.","funder":"NA","published":"NA","server":"bioRxiv"},{"title":"Integrative analysis of patient-derived tumoroids and ex vivo organoid modeling of ARID1A loss in bladder cancer reveals therapeutic molecular targets","authors":"Scholtes, M. P.; Akbarzadeh, M.; Nakauma-Gonzales, J. A.; Galaras, A.; Bazrafshan, A.; Torenvliet, B.; Beikmohammadi, L.; Lozovanu, V.; Romal, S.; Moulos, P.; Kan, T. W.; Algoe, M.; van Royen, M. E.; Sachetti, A.; van den Bosch, T. P. P.; Eussen, B.; de Klein, A.; van Leenders, G. J. L. H.; Boormans, J. L.; Hatzis, P.; Palstra, R.-J.; Zuiverloon, T. C. M.; Mahmoudi, T.","author_corresponding":"Tokameh Mahmoudi","author_corresponding_institution":"Erasmus MC Cancer Institute","doi":"10.1101\/2024.07.29.601702","date":"2024-08-02","version":"1","type":"new results","license":"cc_by_nc_nd","category":"cancer biology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2024\/08\/02\/2024.07.29.601702.source.xml","abstract":"Somatic mutations in ARID1A (AT-rich interactive domain-containing protein 1A) are present in approximately 25% of bladder cancers (BC) and are associated with poor prognosis. With a view to discover effective treatment options for ARID1A-deficient BC patients, we set out to identify targetable effectors dysregulated consequent to ARID1A deficiency. Integrative analyses of ARID1A depletion in normal organoids and data mining in publicly available datasets revealed upregulation of DNA repair and cell cycle-associated genes consequent to loss of ARID1A and identified CHEK1 (Checkpoint kinase 1) and chromosomal passenger complex member BIRC5 (Baculoviral IAP Repeat Containing 5) as therapeutically drug-able candidate molecular effectors. Ex vivo treatment of patient-derived BC tumoroids with clinically advanced small molecule inhibitors targeting CHEK1 or BIRC5 was associated with increased DNA damage signalling and apoptosis, and selectively induced cell death in tumoroids lacking ARID1A protein expression. Thus, integrating public datasets with patient-derived organoid modelling and ex-vivo drug testing can uncover key molecular effectors and mechanisms of oncogenic transformation, potentially leading to novel therapeutic strategies. Our data point to ARID1A protein expression as a suitable candidate biomarker for the selection of BC patients responsive to therapies targeting BIRC5 and CHEK1.","funder":"NA","published":"10.1016\/j.canlet.2025.217506","server":"bioRxiv"},{"title":"Development and application of species ID and insecticide resistance assays, for monitoring sand fly Leishmania vectors in the Mediterranean basin and in the Middle East","authors":"Balaska, S.; Khajehali, J.; Mavridis, K.; Akiner, M.; Papapostolou, K. M.; Remadi, L.; Kioulos, I.; Miaoulis, M.; Fotakis, E. A.; Chaskopoulou, A.; Vontas, J.","author_corresponding":"John Vontas","author_corresponding_institution":"Institute of Molecular Biology and Biotechnology","doi":"10.1101\/2024.07.30.605769","date":"2024-08-02","version":"1","type":"new results","license":"cc_by","category":"pharmacology and toxicology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2024\/08\/02\/2024.07.30.605769.source.xml","abstract":"AbstractsO_ST_ABSBackgroundC_ST_ABSDevelopment of insecticide resistance (IR) in sand fly populations is an upcoming issue of public health concern, threatening leishmaniasis mitigation efforts by insecticide- based vector control. There is a major knowledge gap in the IR status of wild populations worldwide, possibly attributed to the unavailability of specialized tools, such as bioassay protocols, species baseline susceptibility to insecticides and molecular markers, to monitor such phenomena in sand flies.\n\nMethodology\/ Principal findingsSeveral sand fly populations from (semi-)rural regions of Greece, Turkey and Iran were sampled and identified to species, showing populations structure in accordance with previously reported data. Genotyping of known pyrethroid resistance-associated loci revealed the occurrence of voltage-gated sodium channel (vgsc) mutations in all surveyed countries. Knock-down resistance (kdr) mutation L1014F was prevalent in Turkish regions and L1014F and L1014S were recorded for the first time in Iran and in Turkey and Greece, respectively, yet in low frequencies. Moreover, CDC bottle bioassays against pyrethroids in mixed species populations from Greece indicated full susceptibility, using though the mosquito discriminating doses. In parallel, we established a novel individual bioassay protocol and applied it comparatively among distinct Phlebotomus species populations, to detect any possible divergent species-specific response to insecticides. Indeed, a significantly different knock-down rate between P. simici and P. perfiliewi was observed upon exposure to deltamethrin.\n\nConclusions\/SignificanceIR in sand flies is increasingly reported in leishmaniasis endemic regions, highlighting the necessity to generate additional monitoring tools, that could be implemented in relevant eco-epidemiological settings, in the context of IR management. Our molecular and phenotypic data add to the IR map in a macroarea with otherwise limited data coverage.\n\nAuthor SummaryPhlebotomine sand flies vector leishmaniasis to human and animals, a neglected tropical disease of the (sub-)tropics, displaying an expanding epidemiological tendency towards previously non-endemic regions. As leishmaniasis eradication largely relies on vectors insecticidal control, regular monitoring of insecticide resistance (IR) is a core element of integrated vector management. IR data are limited in sand fly populations worldwide though, among others due to the unavailability of robust molecular diagnostic and phenotyping tools. Here, we aim to characterise the pyrethroid resistance (PyR) status of populations originating from countries of the Mediterranean basin and the Middle East; i.e. Greece, Turkey and Iran. PyR-associated mutations were detected in all three countries, while the populations from Greece exhibited susceptibility upon exposure to deltamethrin in CDC bioassays. We established an individual bioassay protocol to enable IR monitoring in settings with multi- species population structure, and applied it comparatively among three distinct Phlebotomus species, revealing that they respond differently to insecticide treatment. Our study will facilitate systematic surveillance and evidence-based sand fly control in the endemic regions.","funder":"NA","published":"NA","server":"bioRxiv"},{"title":"Resveratrol targets G-quadruplexes to exert its pharmacological effects","authors":"Soriano-Lerma, A.; Sanchez-Martin, V.; Murciano-Calles, J.; Ortiz-Gonzalez, M.; Tello-Lopez, M. J.; Perez-Carrasco, V.; Linde-Rodriguez, A.; Ramirez-Macias, I.; Gomez-Pinto, I.; Lopez-Aliaga, I.; Soriano, M.; Garcia-Salcedo, J. A.","author_corresponding":"Jose A Garcia-Salcedo","author_corresponding_institution":"University Hospital Virgen de las Nieves","doi":"10.1101\/2024.07.29.605564","date":"2024-08-02","version":"1","type":"new results","license":"cc_by_nd","category":"physiology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2024\/08\/02\/2024.07.29.605564.source.xml","abstract":"Resveratrol (RSV) is one of the most studied and used biomolecules, for which many pharmacological effects targeting multiple tissues have been described. However, a common underlying mechanism driving its full pharmacological activity has not been elucidated to date. G-quadruplexes (G4s) are non-canonical nucleic acid structures found in promoters and involved in controlling gene transcription. This study demonstrates a G4-dependent mode of action for RSV, explaining its multi-target traits. RSV was shown to stabilise cellular G4s, which accumulate around double strand breaks (DSBs) in the promoters of differentially expressed genes (DEGs). G4 targeting triggers DNA damage and controls gene expression. Unravelling the main mode of action of RSV will be helpful to improve its therapeutic potential in a wide variety of health scenarios.","funder":"NA","published":"NA","server":"bioRxiv"},{"title":"Unraveling the Neural Landscape of Mental Disorders using Double Functional Independent Primitives (dFIPs)","authors":"Soleimani, N.; Iraji, A.; Pearlson, G. D.; Preda, A.; Calhoun, V.","author_corresponding":"Najme Soleimani","author_corresponding_institution":"Georgia State University","doi":"10.1101\/2024.08.01.606076","date":"2024-08-02","version":"1","type":"new results","license":"cc_by","category":"neuroscience","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2024\/08\/02\/2024.08.01.606076.source.xml","abstract":"Mental illnesses extract a high personal and societal cost, and thus explorations of the links between mental illness and functional connectivity in the brain are critical. Investigating major mental illnesses, believed to arise from disruptions in sophisticated neural connections, allows us to comprehend how these neural network disruptions may be linked to altered cognition, emotional regulation, and social interactions. Although neuroimaging has opened new avenues to explore neural alterations linked to mental illnesses, the field still requires precise and sensitive methodologies to inspect these neural substrates of various psychological disorders. In this study, we employ a hierarchical methodology to derive double functionally independent primitives (dFIPs) from resting state functional magnetic resonance neuroimaging data (rs-fMRI). These dFIPs encapsulate canonical overlapping patterns of functional network connectivity (FNC) within the brain. Our investigation focuses on the examination of how combinations of these dFIPs relate to different mental disorder diagnoses. The central aim is to unravel the complex patterns of FNC that correspond to the diverse manifestations of mental illnesses. To achieve this objective, we used a large brain imaging dataset from multiple sites, comprising 5805 total individuals diagnosed with schizophrenia (SCZ), autism spectrum disorder (ASD), bipolar disorder (BPD), major depressive disorder (MDD), and controls. The key revelations of our study unveil distinct patterns associated with each mental disorder through the combination of dFIPs. Notably, certain individual dFIPs exhibit disorder-specific characteristics, while others demonstrate commonalities across disorders. This approach offers a novel, data-driven synthesis of intricate neuroimaging data, thereby illuminating the functional changes intertwined with various mental illnesses. Our results show distinct signatures associated with psychiatric disorders, revealing unique connectivity patterns such as heightened cerebellar connectivity in SCZ and sensory domain hyperconnectivity in ASD, both contrasted with reduced cerebellar-subcortical connectivity. Utilizing the dFIP concept, we pinpoint specific functional connections that differentiate healthy controls from individuals with mental illness, underscoring its utility in identifying neurobiological markers. In summary, our findings delineate how dFIPs serve as unique fingerprints for different mental disorders.","funder":"NA","published":"10.1016\/j.bpsc.2025.03.015","server":"bioRxiv"},{"title":"The Body Mirroring Thought: The Relationship Between Thought Transitions and Fluctuations in Autonomic Nervous Activity Mediated by Interoception","authors":"Sakuragi, M.; Shinagawa, K.; Terasawa, Y.; Umeda, S.","author_corresponding":"Mai Sakuragi","author_corresponding_institution":"Keio University","doi":"10.1101\/2024.07.30.605929","date":"2024-08-02","version":"1","type":"new results","license":"cc_by_nd","category":"neuroscience","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2024\/08\/02\/2024.07.30.605929.source.xml","abstract":"Our thought states change unconsciously. This study verified that the transference of thought states varies with fluctuations in autonomic nervous activity, and that this effect is modulated by interoceptive accuracy. The participants completed the heartbeat counting task (HCT) and vigilance task (VT). We assessed the participants interoceptive accuracy based on their performance on the HCT. The VT is a simple attention task, and during this task, we asked the participants to report the content and contemplation of their thoughts. Consequently, participants with accurate interoception were more likely to remain in a highly contemplative thought state when sympathetic activity was activated. In contrast, the dominance of parasympathetic activity facilitated transitions to different thought states or experiences of less contemplative thought states in them. The results suggest that even subtle changes in bodily responses at rest can affect thought transitions in people with accurate interoception.","funder":"NA","published":"10.1016\/j.concog.2024.103770","server":"bioRxiv"},{"title":"Bovine H5N1 influenza virus binds poorly to human-type sialic acid receptors","authors":"Santos, J. J. S.; Wang, S.; McBride, R.; Zhao, Y.; Paulson, J. C.; Hensley, S. E.","author_corresponding":"Scott E. Hensley","author_corresponding_institution":"University of Pennsylvania","doi":"10.1101\/2024.08.01.606177","date":"2024-08-02","version":"1","type":"new results","license":"cc_by_nc_nd","category":"microbiology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2024\/08\/02\/2024.08.01.606177.source.xml","abstract":"Clade 2.3.4.4b highly pathogenic H5N1 avian influenza (HPAI) viruses started circulating widely in lactating dairy cattle in the United States at the end of 2023. Avian influenza viruses enter cells after binding to glycan receptors with terminally linked 2-3 sialic acid, whereas human influenza viruses typically bind to glycan receptors terminally linked 2-6 sialic acid in the upper respiratory tract. Here, we evaluated the receptor binding properties of hemagglutinin (HA) trimers from a clade 2.3.4.4b avian isolate (A\/American Wigeon\/South Carolina\/22-000345-001\/2021) and a cattle isolate (A\/dairy cattle\/Texas\/24-008749-002-v\/2024). Using two different methods, we found that both of the 2.3.4.4b H5s bound efficiently to glycan receptors with terminally linked 2-3 sialic acid with no detectable binding to glycan receptors with terminally linked 2-6 sialic acid. Our data suggest that clade 2.3.4.4b H5N1 viruses bind poorly to human receptors. It will be important to continue evaluating receptor binding properties of these viruses as they evolve in cattle.","funder":"NA","published":"NA","server":"bioRxiv"},{"title":"Genetic diversity and antimicrobial resistance of Campylobacter jejuni isolates from Gambian children under five with moderate-to-severe diarrhoea and healthy Controls","authors":"Betts, M.; Dione, M.; Ikumapayi, U. N.; Senghore, M.; Lamin, M.; Foster-Nyarko, E.; Jaffali, J.; Panchalingam, S.; Nataro, J. P.; Kotloff, K. L.; Levine, M. M.; Saha, D.; Hossain, J. M.; Kwambana-Adams, B.; Antonio, M.","author_corresponding":"Modupeh Betts","author_corresponding_institution":"Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, UK","doi":"10.1101\/2024.07.30.605890","date":"2024-08-02","version":"1","type":"new results","license":"cc_by_nc","category":"microbiology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2024\/08\/02\/2024.07.30.605890.source.xml","abstract":"IntroductionCampylobacter is a leading cause of bacterial gastroenteritis globally, but its molecular epidemiology remains poorly understood in sub-Saharan Africa. This study investigates the genotypic population structure of Campylobacter jejuni isolates from children with moderate-to-severe diarrhoea (MSD) and healthy controls in The Gambia. Additionally, we determined the antimicrobial susceptibility levels of the isolates.\n\nMethodsAs part of the Global Enteric Multicenter Study (GEMS) in The Gambia, a total of 49 C. jejuni isolates were collected from the stools of children under 5 years old, including 22 with MSD and 27 healthy controls. These isolates were subjected to multilocus sequence typing (MLST) and antimicrobial susceptibility testing using the disc-diffusion method.\n\nResultsThe C. jejuni isolates belonged to 22 sequence types (STs), ten of which were novel. The most common STs were ST-353 (19.1%, 9\/47), ST-7784 (12.7%, 6\/47), and ST-1038 (10.6%, 5\/47). All isolates were fully susceptible to erythromycin, tetracycline, gentamicin and chloramphenicol, with two isolates (4.4%, 2\/45) resistant to ciprofloxacin and nalidixic acid. Antimicrobial resistance or intermediate susceptibility to trimethoprim-sulfamethoxazole, cefotaxime and ampicillin was observed in 91.1% (41\/45), 90.9% (40\/44), and 44.4% (20\/45) of the isolates, respectively. There was no strong evidence linking C. jejuni antimicrobial susceptibility or MLST genotype to MSD status.\n\nConclusionThis study provides the first overview of the high genotypic diversity of human C. jejuni isolates in The Gambia and reveals low-level resistance among the isolates to antibiotics commonly used to treat campylobacteriosis. The study contributes to understanding the epidemiology and resistance patterns of C. jejuni in this region.","funder":"NA","published":"NA","server":"bioRxiv"},{"title":"Nanopore-based analysis unravels the genetic landscape and phylogenetic placement of human-infecting Trichuris species in Cote d'Ivoire, Tanzania, Uganda, and Laos","authors":"Rahman, N.; Ba\u0308r, M. A.; Dommann, J.; Hu\u0308rlimann, E.; Coulibaly, J. T.; Ali, S.; Sayasone, S.; Beinamaryo, P.; Keiser, J.; Schneeberger, P. H. H.","author_corresponding":"Pierre H.H. Schneeberger","author_corresponding_institution":"Swiss TPH","doi":"10.1101\/2024.07.31.605962","date":"2024-08-02","version":"1","type":"new results","license":"cc_by_nc_nd","category":"genomics","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2024\/08\/02\/2024.07.31.605962.source.xml","abstract":"Soil-transmitted helminthiases, particularly trichuriasis, affect over 500 million people, mostly in low- and middle-income countries. Traditional diagnostics fail to distinguish between Trichuris species, obscuring transmission patterns and treatment outcomes. Using nanopore-based full-length ITS2 rDNA sequencing, we analyzed 687 samples from Cote dIvoire, Laos, Tanzania, and Uganda, confirming the phylogenetic placement of Trichuris trichiura and the recently described Trichuris incognita. We identified two genetically distinct Trichuris species infecting humans, with divergent geographic patterns and presence in non-human primates, suggesting complex host-parasite dynamics. Within-country genetic variation indicated local adaptation and cryptic population structure. Importantly, we demonstrated that ITS2 fragment length is a robust, cost-effective diagnostic marker for differentiating T. incognita and T. trichiura, offering a practical alternative to sequencing for resource-limited settings. These findings expose the hidden complexity of Trichuris infections and highlight the urgent need to update diagnostic and control strategies to account for overlooked species diversity in endemic regions.","funder":[{"name":"European Research Council","id":"https:\/\/ror.org\/0472cxd90","id-type":"ROR","award":""}],"published":"NA","server":"bioRxiv"},{"title":"WITHDRAWN: Multimolecular feature-based machine learning: system biology enhanced RF-QSAR modeling for the efficient prediction of the inhibitory potential of diverse SARS CoV-2 3CL Protease inhibitors","authors":"Manaithiya, A.; Bhowmik, R.; Ray, R.; Kumar, S.; Sharma, S.; Mathew, B.; Gong, W.; Parkkila, S.; Aspatwar, A.","author_corresponding":"Ashok Aspatwar","author_corresponding_institution":"Tampere University","doi":"10.1101\/2024.04.30.591922","date":"2024-08-02","version":"2","type":"withdrawn","license":"cc_by_nc_nd","category":"bioinformatics","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2024\/08\/02\/2024.04.30.591922.source.xml","abstract":"Withdrawal StatementThe authors have withdrawn their manuscript owing to the inability to complete the revisions or follow up on the manuscript at this time, due to personal circumstances. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.","funder":"NA","published":"NA","server":"bioRxiv"},{"title":"Sulfoglycodendron Antivirals with Scalable Architectures and Activities","authors":"KRAL, P.; Coppola, F.; Jafari, R.; McReynolds, K. D.","author_corresponding":"PETR KRAL","author_corresponding_institution":"University of Illinois at Chicago","doi":"10.1101\/2024.08.01.606251","date":"2024-08-02","version":"1","type":"new results","license":"cc_by_nd","category":"pharmacology and toxicology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2024\/08\/02\/2024.08.01.606251.source.xml","abstract":"Many viruses initiate their cell-entry by binding their multi-protein receptors to human heparan sulfate proteoglycans (HSPG) and other molecular components present on cellular membranes. These viral interactions could be blocked and the whole viruses could be eliminated by suitable HSPG-mimetics providing multivalent binding to viral protein receptors. Here, large sulfoglycodendron HSPG-mimetics of different topologies, structures, and sizes were designed to this purpose. Atomistic molecular dynamics simulations were used to examine the ability of these broad-spectrum antivirals to block multi-protein HSPG-receptors in HIV, SARS-CoV-2, HPV, and dengue viruses. To characterize the inhibitory potential of these mimetics, their binding to individual and multiple protein receptors was examined. In particular, vectorial distributions of binding energies between the mimetics and viral protein receptors were introduced and calculated along the simulated trajectories. Space-dependent residual analysis of the mimetic-receptor binding was also performed. This analysis revealed detail nature of binding between these antivirals and viral protein receptors, and provided evidence that large inhibitors with multivalent binding might act like a molecular glue initiating the self-assembly of protein receptors in enveloped viruses.\n\nTOC FIGURE\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=103 SRC=\"FIGDIR\/small\/606251v2_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (51K):\norg.highwire.dtl.DTLVardef@55801borg.highwire.dtl.DTLVardef@14dac62org.highwire.dtl.DTLVardef@707fa1org.highwire.dtl.DTLVardef@1cb451a_HPS_FORMAT_FIGEXP  M_FIG C_FIG","funder":"NA","published":"10.1021\/acs.jcim.4c00541","server":"bioRxiv"},{"title":"Using virtual patient cohorts to uncover immune response differences in cancer and immunosuppressed COVID-19 patients","authors":"Gazeau, S.; Deng, X.; Brunet-Ratnasingham, E.; Kaufmann, D. E.; Larochelle, C.; Morel, P. A.; Heffernan, J. M.; Davis, C. L.; Smith, A. M.; Jenner, A. L.; Craig, M.","author_corresponding":"Morgan Craig","author_corresponding_institution":"Sainte-Justine University Hospital Research Centre, Montr\u00e9al, Canada; Department of Mathematics and Statistics, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, Canada","doi":"10.1101\/2024.08.01.605860","date":"2024-08-02","version":"1","type":"new results","license":"cc_by_nc","category":"immunology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2024\/08\/02\/2024.08.01.605860.source.xml","abstract":"The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) resulted in millions of deaths globally. Adults with immunosuppression (e.g., solid organ transplant recipients) and those undergoing active cancer treatments experience worse infections and more severe COVID-19. It is difficult to conduct clinical studies in these populations, resulting in a restricted amount of data that can be used to relate mechanisms of immune dysfunction to COVID-19 outcomes in these vulnerable groups. To study immune dynamics after infection with SARS-CoV-2 and to investigate drivers of COVID-19 severity in individuals with cancer and immunosuppression, we adapted our mathematical model of the immune response during COVID-19 and generated virtual patient cohorts of cancer and immunosuppressed patients. The cohorts of plausible patients recapitulated available longitudinal clinical data collected from patients in Montreal, Canada area hospitals. Our model predicted that both cancer and immunosuppressed virtual patients with severe COVID-19 had decreased CD8+ T cells, elevated interleukin-6 concentrations, and delayed type I interferon peaks compared to those with mild COVID-19 outcomes. Additionally, our results suggest that cancer patients experience higher viral loads (however, with no direct relation with severity), likely because of decreased initial neutrophil counts (i.e., neutropenia), a frequent toxic side effect of anti-cancer therapy. Furthermore, severe cancer and immunosuppressed virtual patients suffered a high degree of tissue damage associated with elevated neutrophils. Lastly, parameter values associated with monocyte recruitment by infected cells were found to be elevated in severe cancer and immunosuppressed patients with respect to the COVID-19 reference group. Together, our study highlights that dysfunction in type I interferon and CD8+ T cells are key drivers of immune dysregulation in COVID-19, particularly in cancer patients and immunosuppressed individuals.","funder":"NA","published":"10.1371\/journal.pcbi.1013170","server":"bioRxiv"},{"title":"Microplastics as a novel substrate for antimicrobial resistance: Effects of concentration, composition, and size on E. coli multidrug resistance","authors":"Gross, N.; Muhvich, J.; Ching, C.; Gomez, B.; Nahum, Y.; Zaman, M. H.","author_corresponding":"Neila Gross","author_corresponding_institution":"Boston University","doi":"10.1101\/2024.08.01.606221","date":"2024-08-02","version":"1","type":"new results","license":"cc_by_nc_nd","category":"microbiology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2024\/08\/02\/2024.08.01.606221.source.xml","abstract":"Microplastics (MPs) have emerged as a significant environmental pollutant with profound implications for public health, particularly as substrates to facilitate bacterial antimicrobial resistance (AMR). Recently, studies have shown that MPs may accommodate microbial communities, chemical contaminants and genetic material containing AMR genes. This study investigated the effects of MP concentration, composition, and size on the development of multidrug resistance in Escherichia coli. Specifically, we exposed E. coli to varying concentrations of different MP types, including polyethylene (PE), polystyrene (PS), and polypropylene (PP), across a range of sizes (3-10 {micro}m, 10-50 {micro}m, and 500 {micro}m). Results indicated a direct correlation between MP presence and elevated multidrug-resistant (MDR) in E. coli.\n\nNotably, MPs exhibited a higher propensity for facilitating resistance than control substrates such as glass, likely due to their hydrophobicity, greater adsorption capacities, and surface chemistries. Furthermore, we observed that co-culture with MPs resulted in biofilm formation. Notably, we found that the bacteria from passaged MPs formed stronger biofilms once the MPs were removed, associated with changes in motility. Thus, we find that MPs also select for cells that are better at forming biofilms, which can lead to recalcitrant infections in the environment and healthcare setting. Our study highlights the immediate need for comprehensive environmental management strategies to mitigate the risk posed by MPs.\n\nImportanceAntimicrobial resistance is one of the worlds most pressing global health crises, with an estimated 10 million deaths per year forecasted by 2050. With the pipeline of antibiotics running dry, it is imperative that mitigation strategies understand the mechanisms that drive the genesis of antimicrobial resistance. One emerging dimension of antimicrobial resistance is the environment. This study highlights the relationship between a widespread environmental pollutant, (MPs), and the rise of drug-resistant bacteria. While it is known that MPs facilitate resistance through several modes (biofilm formation, plastic adsorption rates, etc.), this study fills the knowledge gap on how different types of MPs are contributing to antimicrobial resistance.","funder":"NA","published":"NA","server":"bioRxiv"},{"title":"Recycling of trans-Golgi SNAREs is essential for apoplastic effector secretion and effective pathogenicity of Magnaporthe oryzae","authors":"Lin, L.; Wu, Q.; Wang, S.; Gong, Q.; Huang, X.; Abubakar, Y. S.; Liu, Y.; Cao, J.; Hu, J.; Wang, Z.; Lu, G.; Zheng, W.","author_corresponding":"Wenhui Zheng","author_corresponding_institution":"Fujian Agriculture and Forestry University","doi":"10.1101\/2024.08.02.606313","date":"2024-08-02","version":"1","type":"new results","license":"cc_no","category":"microbiology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2024\/08\/02\/2024.08.02.606313.source.xml","abstract":"Vesicle transport is an essential process that mediates the growth, development and virulence of pathogenic fungi. However, the intricate mechanisms underlying how vesicle transport regulates the secretion of effector proteins remain to be fully elucidated. Here, we unveiled a novel pathway in which retromer and trans-Golgi (TGN) SNARE proteins co-regulate the proper secretion of apoplastic effectors in the rice blast fungus Magnaporthe oryzae. A TGN-associated SNARE complex consisting of MoSnc1, MoTlg1, MoTlg2, and MoVti1 was found to be essential for growth, development and pathogenicity in the fungus. Moreover, the TGN-associated SNARE complex is indispensable for accurate secretion of apoplastic effectors. Furthermore, we have elucidated that the dynamin-like protein MoVps1, an upstream regulator of the retromer complex, regulates the fission of MoVps35-coated vesicle and the proper localization of the TGN-associated SNARE complex. Additionally, we employed prochlorperazine, which identified as a potent dynamin inhibitor, elicits a developmental response in M. oryzae akin to MoVPS1 disruption, highlighting the pivotal regulatory role of dynamin and its potential as a therapeutic target for rice blast disease management. In conclusion, the study uncovered a specific mechanism by which MoVps1 and the retromer complex regulate the positioning of TGN-associated SNARE proteins to effectively promote effector secretion. It provides a deeper understanding of the molecular mechanisms of effector secretion in fungi and underscores the importance of vesicle transport in fungal pathogenesis.\n\nImportanceVesicle transport is essential for pathogenic fungi as it controls the secretion of effectors that modulate interactions with the host and infection processes. The detailed mechanisms of effector secretion via vesicular pathways in these fungi are not yet fully understood. In this study, we have discovered a new regulatory pathway involving the retromer complex and trans-Golgi SNARE proteins that is critical for the proper secretion of apoplast effectors in M. oryzae. We have identified an important TGN-associated SNARE complex, consisting of MoSnc1, MoTlg1, MoTlg2 and MoVti1, which is required for the development and pathogenicity of M. oryzae. Our results emphasize the importance of this SNARE complex for the precise secretion of effectors into the apoplast, a key step in pathogenesis. Additionally, we demonstrated that the dynamin-like protein MoVps1, a protein acting upstream of the retromer complex, is vital for the correct localization of the TGN-associated SNARE complex. Furthermore, our research underscores the critical regulatory role of dynamin in M. oryzae pathogenesis, with prochlorperazine serving as an inhibitor that mimics the phenotypic effects of MoVps1 disruption, thereby highlighting its potential as a biopesticide candidate for rice blast disease management. Our study has uncovered a specific regulatory mechanism in which MoVps1 and the retromer complex control the positioning and function of TGN-associated SNARE proteins, thereby facilitating effector secretion. This work not only advances our understanding of the molecular basis of effector secretion in fungi, but also has implications for the development of novel strategies to control fungal diseases.","funder":"NA","published":"NA","server":"bioRxiv"},{"title":"SIP2 functions as the master transcription factor of the Plasmodium merozoite formation","authors":"Nishi, T.; Kaneko, I.; Yuda, M.","author_corresponding":"Masao Yuda","author_corresponding_institution":"Mie University: Mie Daigaku","doi":"10.1101\/2024.08.02.606280","date":"2024-08-02","version":"1","type":"new results","license":"cc_by","category":"microbiology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2024\/08\/02\/2024.08.02.606280.source.xml","abstract":"Malaria, one of the most serious infectious diseases worldwide, is caused by the proliferation of Plasmodium parasites through repeated cycles of intraerythrocytic development. The parasite replicates via schizogony in host erythrocytes, producing multiple progeny merozoites that invade new erythrocytes to continue the intraerythrocytic developmental cycle. Although merozoite formation is the most crucial step in parasite proliferation and malaria pathogenesis, the molecular mechanism regulating merozoite formation remains unclear. SIP2 is an AP2 transcription factor expressed during schizogony and is particularly conserved among erythrocyte-infecting apicomplexan parasites. Here, we reveal that SIP2 in P. berghei (PbSIP2) functions as a transcriptional activator that regulates merozoite formation. Disruption of pbsip2 using a dimerizable Cre recombinase system resulted in developmental arrest before merozoite formation and significant downregulation of merozoite-related genes. ChIP-seq of PbSIP2 showed that it comprehensively activated merozoite-related genes by binding to previously reported cis-regulatory elements of merozoite invasion-related genes, including the bipartite motif (TGCAN4-6GTGCA). Collectively, our results indicate that SIP2 is a transcription factor that establishes erythrocyte infectivity and may have an evolutionary origin from the common ancestor of erythrocyte-infecting apicomplexan parasites.","funder":"NA","published":"10.1126\/sciadv.ads5458","server":"bioRxiv"},{"title":"Impact of commercial gut health interventions on caecal metagenome and broiler performance","authors":"Pangga, G. M. V.; Star-Shirko, B.; Psifidi, A.; Xia, D.; Corcionivoschi, N.; Kelly, C.; Hughes, C.; Lavery, U.; Richmond, A.; Ijaz, U. Z.; Gundogdu, O.","author_corresponding":"Ozan Gundogdu","author_corresponding_institution":"London School of Hygiene & Tropical Medicine","doi":"10.1101\/2024.08.02.606333","date":"2024-08-02","version":"1","type":"new results","license":"cc_by_nc","category":"microbiology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2024\/08\/02\/2024.08.02.606333.source.xml","abstract":"BackgroundMaintaining gut health is a persistent and unresolved challenge in the poultry industry. Given the critical role of gut health in chicken performance and welfare, there is a pressing need to identify effective gut health intervention (GHI) strategies to ensure optimal outcomes in poultry farming. In this study, across three broiler production cycles, we compared the metagenomes and performance of broilers provided with ionophores as control against birds subjected to five different GHI combinations involving vaccination, probiotics, prebiotics, essential oils, and reduction of ionophore use.\n\nResultsUsing a binning strategy, 84 ([≥]75% completeness, [≤] 5% contamination) metagenome-assembled genomes (MAGs) from 118 caecal samples were recovered and annotated for their metabolic potential. The majority of these (n = 52, 61%) had a differential response across all cohorts and are associated with the performance parameter - European Poultry Efficiency Factor (EPEF). The control group exhibited the highest EPEF, followed closely by the cohort where probiotics are used in conjunction with vaccination. The use of Probiotics B, a commercial Bacillus strain-based formulation, was determined to contribute to the superior performance of birds. GHI supplementation generally affected abundance of microbial enzymes relating to carbohydrate and protein digestion, and metabolic pathways relating to energy, nucleotide synthesis, short-chain fatty acid synthesis, and drug-transport systems. These shifts are hypothesised to differentiate performance among groups and cycles, highlighting the beneficial role of several bacteria including Rikenella microfusus and UBA7160 species.\n\nConclusionsAll GHIs are shown to be effective methods for gut microbial modulation, with varying influences on MAG diversity, composition and microbial functions. These metagenomic insights greatly enhance our understanding of microbiota-related metabolic pathways, enabling us to devise strategies against enteric pathogens related to poultry products and presenting new opportunities to improve overall poultry performance and health.","funder":"NA","published":"10.1186\/s40168-024-02012-7","server":"bioRxiv"},{"title":"A genome-wide genetic screen identified targets for destabilizing the parasitophorous vacuole of Chlamydia trachomatis","authors":"Babu Sait, M. R.; Jachmann, L. H.; Milivojevic, M.; Llorente-Saez, C.; Dhanjal, S.; Schumacher, F.; Henriksson, S.; Gayathri Vegesna, N. V.; Chaban, A.; Mohanty, P.; O\u0308lander, M.; Muraleedharan, S.; Farmand Azadeh, S.; Kleuser, B.; Schmierer, B.; Sixt, B. S.","author_corresponding":"Barbara Susanne Sixt","author_corresponding_institution":"Department of Molecular Biology, Ume\u00e5 University, Ume\u00e5, Sweden","doi":"10.1101\/2024.08.02.606337","date":"2024-08-02","version":"1","type":"new results","license":"cc_no","category":"microbiology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2024\/08\/02\/2024.08.02.606337.source.xml","abstract":"The bacterial pathogen Chlamydia trachomatis employs the effector CpoS to suppress a host defense response that aborts intracellular bacterial growth by inducing host cell death. While conducting a CRISPR knock-out screen for genes contributing to this response, we uncovered a mutant deficient for CpoS to display a markedly increased reliance on host cellular ceramide synthesis, compensating for its diminished ability to acquire sphingolipids via modulating membrane trafficking. Employing the power of the just recently established molecular genetic toolbox for Chlamydia, we developed an innovative microscopic reporter system that revealed the mutant to thrive in unstable parasitophorous vacuoles (inclusions), characterized initially by the release of individual bacteria from otherwise intact-appearing vacuoles. CpoS-deficient inclusions were further destabilized by disruptions in ceramide synthesis, while supplementation of sphingoid bases stabilized them, also preventing the defensive host cell death response. Notably, early inclusion destabilization, achieved by simultaneous disruption of two transport routes, caused infection clearance without damaging the host cells. Overall, this study highlights the inclusions role as a refuge, demonstrates CpoS to maintain inclusion integrity by ensuring sphingolipid supply, and provides directions for a future therapeutic exploitation.\n\nSIGNIFICANCEA wide range of clinically significant microbes evolved to hide from the intrinsic defenses of their host cells by thriving within membrane-enclosed pathogen-containing vacuoles. This raises the intriguing possibility that such vacuoles could be targeted therapeutically. The bacterial pathogen Chlamydia trachomatis could be an exceptionally well-suited target for such innovative medicines given its medical importance and strict dependence on host cells. However, progress has been stalled by the lack of sensitive tools for detecting inclusion damage. Here, we resolved this major technical roadblock and uncovered the pathogen to employ the secreted effector CpoS, a modulator of membrane trafficking, to stabilize its vacuole by ensuring adequate sphingolipid supply. These methodological advances and mechanistic insights should promote the development of vacuole-destabilizing therapeutics.","funder":"NA","published":"10.1371\/journal.pbio.3003297","server":"bioRxiv"},{"title":"Endocytic dynamin deficiency impairs the host colonization of phytopathogenic fungi","authors":"Chen, X.; Chen, X.; Long, Y.; Fang, Z.; Abubakar, Y. S.; Zheng, H.; Wang, Z.; Zheng, W.","author_corresponding":"Wenhui Zheng","author_corresponding_institution":"Fujian Agriculture and Forestry University","doi":"10.1101\/2024.08.02.606287","date":"2024-08-02","version":"1","type":"new results","license":"cc_no","category":"microbiology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2024\/08\/02\/2024.08.02.606287.source.xml","abstract":"During host-pathogen interactions, fungal pathogens exploit the endolysosomal trafficking network to fine-tune their responses to host and environmental stimuli, thereby facilitating disease progression. However, the molecular mechanisms underlying the fungal-specific functions of the endolysosomal network require further investigation. Here, we systematically characterized the endolysosomal network in Fusarium graminearum using the dynamin-like GTPase FgVps1 as an entry point. Functional analysis revealed that FgVps1 is essential for the release of retromer- and sorting nexin-associated vesicles from endosomes, thereby facilitating the trafficking of v-SNARE protein FgSnc1 and promoting fungal development and pathogenicity. Building on this, we further discovered that the retromer core subunit FgVps35 interacts with sorting nexin FgSnx4 and identified the corresponding interaction interface, which involves residues FgVps35N383 and FgSnx4E373. In addition, the ESCRT-II component FgVps36 bridges ESCRT-I and -III and interacts with both FgVps35 and FgSnx4, thereby preventing their mislocalization to the vacuole and maintaining endolysosomal trafficking. Notably, we demonstrated that inhibition of FgVps1 function, either by blocking its GTPase activity or by disrupting actin polymerization, effectively impaired endosomal trafficking and attenuates fungal pathogenicity. Altogether, our results uncover key mechanisms underlying the function of fungal endolysosomal network and providing a promising broad-spectrum strategy for controlling phytopathogenic fungi.","funder":[{"name":"National Natural Science Foundation of China","id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","award":"32272481;32122071;"},{"name":"Postdoctoral Fellowship Program of CPSF","id":"","id-type":"ROR","award":"GZC20230448;"}],"published":"NA","server":"bioRxiv"},{"title":"The Streptococcus agalactiae LytSR two-component regulatory system promotes vaginal colonisation and virulence in vivo","authors":"AlQadeeb, H.; Baltazar, M.; Cazares, A.; Poonpanichakul, T.; Kjos, M.; French, N.; Kadioglu, A.; O'Brien, M.","author_corresponding":"Marie O'Brien","author_corresponding_institution":"Department of Clinical Infection, Microbiology and Immunology, University of Liverpool, UK; ReNewVax Ltd.","doi":"10.1101\/2024.08.02.606384","date":"2024-08-02","version":"1","type":"new results","license":"cc_no","category":"microbiology","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2024\/08\/02\/2024.08.02.606384.source.xml","abstract":"Streptococcus agalactiae (or Group B Streptococcus, GBS) is a leading cause of neonatal sepsis and meningitis globally. To sense and respond to variations in its environment, GBS possesses multiple two-component regulatory systems (TCSs) such as LytSR. Here, we aimed to investigate the role of LytSR in GBS pathogenicity. We generated an isogenic lytS knockout mutant in a clinical GBS isolate and used a combination of phenotypic in vitro assays and in vivo murine models to investigate the contribution of lytS to the colonisation and invasive properties of GBS. Deletion of the lytS gene in the GBS chromosome resulted in significantly higher survival rates in mice during sepsis, accompanied by reduced bacterial loads in blood, lung, spleen, kidney and brain tissue compared to infection with the wild-type strain. In a mouse model of GBS vaginal colonisation, we also observed that the lytS knockout mutant was cleared more readily from the vaginal tract compared to its wild-type counterpart. Interestingly, lower levels of proinflammatory cytokines were found in the serum of mice infected with the lytS mutant. Our results demonstrate that the LytSR TCS plays a key role in GBS tissue invasion and pathogenesis, and persistence of mucosal colonisation.\n\nImportanceStreptococcus agalactiae (Group B strep, or GBS) is a common commensal of the female urogenital tract and one of WHOs priority pathogens. The bacterium has evolved mechanisms to adapt and survive in its host, many of which are regulated via two-component signal transduction systems (TCSs), however, the exact contributions of TCSs towards GBS pathogenicity remain largely obscure.\n\nWe have constructed a TCS lytS-deficient mutant in a CC-17 hypervirulent GBS clinical isolate. Using murine models, we showed that LytSR regulatory system is essential for vaginal colonisation via promoting biofilm production. We also observed that lytS deficiency led to significantly attenuated virulence properties and lower levels of proinflammatory cytokines in blood. Our findings are of significant importance in that they unveil a previously unreported role for LytSR in GBS and pave the way towards a better understanding of its ability to transition from an innocuous commensal to a deadly pathogen.","funder":"NA","published":"10.1128\/spectrum.01970-24","server":"bioRxiv"},{"title":"Evaluation of vectors for gene expression in Pseudovibrio bacteria and their application in Aplysina marine sponge studies","authors":"Dai, Y.; Pita, L.; Eustaquio, A. S.","author_corresponding":"Alessandra S Eustaquio","author_corresponding_institution":"University of Illinois Chicago","doi":"10.1101\/2024.08.01.606211","date":"2024-08-02","version":"1","type":"new results","license":"cc_by_nc_nd","category":"genetics","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2024\/08\/02\/2024.08.01.606211.source.xml","abstract":"-Proteobacteria belonging to the Pseudovibrio genus have been isolated from different marine organisms including marine sponges, corals and algae. This genus was first described in 2004 and has since garnered attention due to the potential ecological relevance and biotechnological application of its metabolites. For instance, we recently reported specialized metabolites we named pseudovibriamides from Pseudovibrio brasiliensis Ab134. The pseudovibriamide encoding ppp gene cluster is found in two thirds of Pseudovibrio genomes. Pseudovibriamides coordinate motility and biofilm formation, behaviors that are known to be important for host colonization. Although we previously established reverse genetics methods to delete genes via homologous recombination, no self-replicative vectors have been reported for Pseudovibrio. We show that plasmid vectors containing two different broad-host-range replicons, RSF1010 and pBBR1, can be used in P. brasiliensis. The efficiency of vector transfer by electroporation averaged [~] 3 x 103 CFU\/{micro}g plasmid DNA whereas the conjugation frequency from E. coli ranged from 10-3 to 10-6. We then tested the vectors for fluorescent protein expression and consequent labeling, which allowed us to observe their effects on swarming motility and to compare plasmid stability. This study expands the genetic toolbox available for Pseudovibrio which is expected to enable future ecological and biotechnological studies.\n\nImportanceThe genus Pseudovibrio of -Proteobacteria has consistently been isolated from marine sponges and other marine organisms such as corals and algae. Pseudovibrio bacteria are a source of antibiotics and other secondary metabolites with the potential to be developed into pharmaceuticals. Moreover, the secondary metabolites they produce are important for their physiology and for interactions with other organisms. Here we expand the genetic tool box available for Pseudovibrio bacteria by establishing self-replicative vectors that can be used for the expression of e.g., fluorescent proteins. The availability of genetic tools is important to enable us to explore the emerging ecological and biotechnological potential of Pseudovibrio bacteria.","funder":"NA","published":"10.1128\/aem.00207-25","server":"bioRxiv"},{"title":"Ordering molecular diversity in untargeted metabolomics via molecular community networking","authors":"Coler, E. A.; Melnik, A.; Lotfi, A.; Moradi, D.; Ahiadu, B.; Portal Gomes, P. W.; Patan, A.; Dorrestein, P. C.; Barnes, S.; Boginski, V.; Semenov, A.; Aksenov, A. A.","author_corresponding":"Alexander A Aksenov","author_corresponding_institution":"University of Connecticut","doi":"10.1101\/2024.08.02.606356","date":"2024-08-02","version":"1","type":"new results","license":"cc_by_nd","category":"biochemistry","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2024\/08\/02\/2024.08.02.606356.source.xml","abstract":"Natures molecular diversity is not random but displays intricate organization stemming from biological necessity. Molecular networking connects metabolites with structural similarity, enabling molecular discoveries from mass spectrometry data using arbitrary similarity thresholds that can fracture natural metabolite families. We present molecular community networking (MCN), that optimizes connectivity for each metabolite, rescuing lost relationships and capturing otherwise \"hidden\" metabolite connections. Using MCN, we demonstrate the discovery of novel dipeptide-conjugated bile acids.","funder":"NA","published":"NA","server":"bioRxiv"},{"title":"The phage protein paratox is a multifunctional metabolic regulator of Streptococcus","authors":"Muna, T. H.; Rutbeek, N. R.; Horne, J.; Lao, Y. W.; Krokhin, O. V.; Prehna, G.","author_corresponding":"Gerd Prehna","author_corresponding_institution":"University of Manitoba","doi":"10.1101\/2024.08.02.605684","date":"2024-08-02","version":"1","type":"new results","license":"cc_by_nc_nd","category":"biochemistry","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2024\/08\/02\/2024.08.02.605684.source.xml","abstract":"Streptococcus pyogenes, or Group A Streptococcus (GAS), is a commensal bacteria and human pathogen. Central to GAS pathogenesis is the presence of prophage encoded virulence genes. The conserved phage gene for the protein paratox (Prx) is genetically linked to virulence genes, but the reason for this linkage is unknown. Prx inhibits GAS quorum sensing and natural competence by binding the transcription factor ComR. However, inhibiting ComR does not explain the virulence gene linkage. To address this, we took a mass-spectrometry approach to search for other Prx interaction partners. The data demonstrates that Prx binds numerous DNA binding proteins and transcriptional regulators. We show binding of Prx in vitro with the GAS protein EndoS1 (SpyM3_0890) and the phage protein JM3 (SpyM3_1246). An EndoS1:Prx complex X-ray crystal structure reveals that EndoS1 and ComR possess a conserved Prx binding helix. Computational modelling predicts that the Prx binding helix is present in several, but not all, binding partners. Namely, JM3 lacks the Prx binding helix. As Prx is conformationally dynamic, this suggests partner-dependent binding modes. Overall, Prx acts as a metabolic regulator of GAS to maintain the phage genome. As such, Prx maybe a direct contributor to the pathogenic conversion of GAS.","funder":"NA","published":"10.1093\/nar\/gkae1200","server":"bioRxiv"},{"title":"Structural mechanism of MUC5AC mucin net-like polymer formation and its SNP variability that affect risk of the lung diseases COPD and IPF","authors":"Trillo-Muyo, S.; Anna, E.; Magnusson, J. M.; Hansson, G. C.","author_corresponding":"Gunnar C Hansson","author_corresponding_institution":"Univ. Gothenburg","doi":"10.1101\/2024.08.02.606332","date":"2024-08-02","version":"1","type":"new results","license":"cc_no","category":"biochemistry","jatsxml":"https:\/\/www.biorxiv.org\/content\/early\/2024\/08\/02\/2024.08.02.606332.source.xml","abstract":"Gel-forming mucins MUC5AC and MUC5B constitute the main structural component of the mucus in the respiratory system. Secreted mucins interact specifically with each other and other molecules giving mucus specific properties. We determined the cryoEM structures of the wild type MUC5AC-D3 assembly and the structural SNP variants R996Q and R1201W. Our structures explain the basis of MUC5AC N-terminal non-covalent oligomerization upon secretion. The MUC5AC-D3 assembly forms covalent dimers in two alternative conformations, open and closed. The closed conformation dimers interact through an arginine rich loop in the TIL3 domain forming tetramers. Moreover, we found a positive disease correlation between the SNP (R996Q, rs878913005), Chronic Obstructive Pulmonary Disease (COPD), and Idiopathic Pulmonary Fibrosis (IPF). The well-known MUC5B promotor SNP (rs35705950) association with IPF is much stronger when combined with the MUC5AC SNP. Our study provides a model to explain the formation of MUC5AC net-like structures and how both SNPs will affect mucus organization and increase risk of lung disease.","funder":"NA","published":"NA","server":"bioRxiv"}]}