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Weng, S.

Publications and source records attributed to Weng, S..

At least 19 recordsLinked to original sources
bioRxiv2026

Veillonella dispar triggers dual-hits in the pathogenesis of autoimmune hepatitis and primary biliary cholangitis via testosterone depletion-BAFF-B cell axis and Th17 cell activation

Objective: Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) frequently present as overlap syndromes, characterized by shared sexual dimorphism and elevated intestinal Veillonella dispar (V. dispar) abundance, yet exhibiting distinct hallmark pathological manifestations. This study aimed to elucidate the shared pathogenesis, phenotypic differentiation mechanisms and sex-specific predisposition of AIH and PBC induced by V. dispar. Methods: Clean-grade and germ-free (GF) mice were employed to establish AIH and PBC models. Model induction involved oral gavage of V. dispar and intraperitoneal injection of either liver-specific antigen S100 (for AIH) or a pyruvate dehydrogenase complex E2 subunit (PDC-E2) mimetic peptide (for PBC). Single-cell RNA sequencing, metabolomics, transmission electron microscopy, western blotting, and flow cytometry were utilized to elucidate the underlying mechanisms. Results: V. dispar successfully induced autoimmune liver disease-like features in mice, characterized by significant intrahepatic B cell infiltration. Mechanistically, V. dispar caused systemic arginine reduction, leading to intrinsic apoptosis of gonadal stromal cells and a subsequent reduction in testosterone. This decreased testosterone weakened its inhibitory effect on B cell activating factor (BAFF) secretion, thereby amplifying B cell-mediated immune responses. Furthermore, in the presence of S100 or PDC-E2 mimetic peptide, V. dispar also facilitated Th17 cell activation, which guided the phenotypic differentiation into AIH or PBC, respectively. Consistent with these findings, our clinical observations revealed that patients with AIH and PBC tended to harbor enriched V. dispar, along with lower serum arginine and testosterone. In addition, elevated serum levels of BAFF and IL-17 were also observed in these patients. Conclusion: V. dispar induces reduced testosterone levels and upregulation of BAFF, leading to intrahepatic B cell expansion, which serves as the common pathogenic basis for AIH and PBC. The presence of S100 and PDC-E2 subsequently drives further maturation of these expanded B cells and promotes Th17 cell activation, thereby determining the phenotypic divergence between AIH and PBC.

immunology↗
bioRxiv2026

The Candida Genome Database: New Interface and New Tools

The Candida Genome Database (CGD; www.candidagenome.org) is both a model organism database and a fungal pathogen database. As a model organism database, CGD stores data for Candida albicans, which serves as a model species both for other Candida spp. and for non-Candida fungi that form biofilms and undergo routine morphogenic switching. As a fungal pathogen database, CGD now hosts locus pages for six species of the best-studied pathogenic fungi in the Candida group. Pathogenic Candida species have become increasingly drug resistant and there is thus a pressing need for research into basic Candida biology, epidemiology, phylogeny, and potential new antifungals, as well as a single location where all of the available data are collected, curated, and made easily searchable. CGD curates the gene-based Candida experimental literature in real time, extracting, organizing and standardizing gene annotations. CGD also links clinical data on disease to relevant Literature Topics to improve searchability for clinical researchers. Because CGD curates the literature for multiple species and most research focuses on aspects related to pathogenicity, we focus our curation efforts on assigning Literature Topic tags, collecting detailed mutant phenotype data, and assigning controlled Gene Ontology terms with accompanying evidence codes. Our Summary pages for each locus include the primary name and all aliases for that locus, a description of the gene and/or gene product, detailed ortholog information with links, a synteny view, a JBrowse window with a visual view of the gene on its chromosome, links to Phenotype, Gene Ontology, Interactions, and Expression pages, as well as sequence information, references cited on the summary page itself, and any locus notes. The database also serves as a community hub, where we link to various types of reference material of relevance to Candida researchers, including colleague information, news, and notice of upcoming meetings. We routinely survey the community to learn how the field is evolving and how needs may have changed. Here we describe CGDs new modern web interface and multiple new tools that have been added in the last 6 months, allowing, among other things, users to better understand the available expression data for a locus and seamlessly switch between species for a given locus.

genetics↗
bioRxiv2026

Gn1a rice promotes symbiotic fish growth via reprogramming soil microbiome

Rice-fish symbiotic ecosystems significantly contribute to world food supply. Mutation in rice (Oryza sativa) quantitative trait locus Gn1a, encoding a cytokinin oxidase/dehydrogenase (OsCKX2), leads to cytokinin accumulation in plant, which promotes tillering and panicle branching to achieved higher yield and also shows a selective effect on soil microbial composition. Given that the growth of aquatic animals can be shaped by their surrounding microbial communities, we asked whether adjusting rice cytokinin levels might synergistically boosts both rice yield and fish growth. Herein, we co-cultured common carp (Cyprinus carpio) with ckx2 rice plants to determine the effect of cytokinins on fish. Surprisingly, compared to wild-type plants, the ckx2 plants enhanced nearly 10% fish growth and improved fish antibacterial capacity against Aeromonas hydrophila and Edwardsiella tarda. In fact, the growth-promoting effect on fish requires mediation by the soil microbiota. Mechanistically, ckx2 plants secreted more cytokinins into soil to reprogram the microbial composition, which subsequently translocated to fish gut and modulated the keystone microbes in gut to facilitate short-chain fatty acid production and carbohydrate degradation. These findings provide the first evidence that rice-derived cytokinins exert a cross-kingdom growth-promoting effect on fish, providing a boosting dual-production strategy for advancing rice-fish symbiotic ecosystem.

plant biology↗
bioRxiv2025

ISKNV-pORF71 hijacks outer mitochondrial membrane-localized VDAC2 to the nucleus, enhancing apoptosis by disrupting mitochondrial membrane permeability

Infectious spleen and kidney necrosis virus (ISKNV), the type species of the genus Megalocytivirus within the family Iridoviridae, is one of the most devastating pathogens affecting global teleost populations. Our previous study confirmed that ISKNV-pORF71 (p71/VP71) is a viral virulence factor by constructing a recombinant virus with ISKNV orf071 deletion (ISKNV-{Delta}71). In the present study, we further found that compared with ISKNV-WT, the ISKNV-{Delta}71 mutant is more capable of maintaining mitochondrial membrane potential, alleviating mitochondrial membrane permeabilization, preserving mitochondrial membrane integrity, sustaining lower cytochrome c release, and thereby reducing the apoptosis rate of infected cells. Further investigations demonstrated a strong interaction between p71 and the outer mitochondrial membrane (OMM)-localized voltage-dependent anion channel 2 (VDAC2). At the subcellular level, p71 and mandarin fish VDAC2 (mfVDAC2) are originally localized to the nucleus and mitochondria, respectively. However, in cells co-transfected with p71 and mfVDAC2, robust nuclear translocation of mfVDAC2 was verified. Endogenous mfVDAC2 was also confirmed to undergo nuclear translocation upon ISKNV-WT infection. In the zebrafish infection model, zebrafish VDAC2 (zfVDAC2)--but not zfVDAC-1 or zfVDAC-3--was observed to translocate into the nucleus through interaction with p71. Using CRISPR/Cas9 technology, VDAC2-knockout zebrafish were successfully constructed. Infection experiments showed that ISKNV-{Delta}71 exhibits significantly reduced lethality to both wild-type zebrafish and zfVDAC2-knockout zebrafish. In conclusion, our findings reveal that p71 exerts its function during ISKNV infection by hijacking VDAC2 into the nucleus, which alters mitochondrial membrane permeability and enhances ISKNV-induced apoptosis. The phenotypic characteristics of VDAC2 knockout (vdac-/-) zebrafish were also thoroughly analyzed and discussed. Author summaryVDAC2, a well-characterized cellular protein localized to the outer mitochondrial membrane (OMM), plays critical roles in viral pathogenesis and antiviral immune escape. Previous studies have shown that VDAC2 interacts directly or indirectly with viral proteins or functions as a functional receptor to modulate viral pathogenesis; however, few studies have demonstrated that VDAC2 is hijacked from its native OMM to other organelles. Our study here provides robust evidence that cellular VDAC2 is rerouted from its original OMM to the nucleus through interaction with ISKNV p71, thereby altering viral pathogenesis. This work offers novel insights into the role of VDAC2 in pathogen virulence. As far as we know, this is the first report demonstrating that host VDAC2 is hijacked into the nucleus by a viral protein to subsequently modulate the viral life cycle. Collectively, these findings advance our understanding of the active regulation of host functional proteins by iridoviruses.

microbiology↗
bioRxiv2025

RNA viruses in water shape the viromes of shrimp and fish in aquaculture systems

Aquatic environments host immense RNA viral diversity, yet the extent to which waterborne viruses influence the virome of aquatic animals remains unclear. Here, we conducted a comprehensive longitudinal metatranscriptomic analysis of water, shrimp, and fish across multiple culture stages in aquaculture systems. We identified 3,211 RNA viruses spanning 21 viral supergroups, with 97.4% representing novel species. Water exhibited the greatest viral diversity (3,093 species), followed by shrimp (1,280) and fish (398), with most viruses detected in shrimp and fish also detected in water. Diversity analyses revealed increasing richness and significant compositional shifts in 92 high-abundance viruses (>1,000 RPM) across culture stages. Viral abundance in aquatic animals was strongly correlated with that in water, and the temporal trajectories of the 16 most abundant viruses were closely synchronized between water and shrimp. Furthermore, 337 virus species were shared among shrimp and two fish species, of which 309 were present in water. These findings demonstrated that RNA viruses in water shape the composition and dynamics of aquatic animal viromes, underscoring the importance of water virome surveillance and management for disease prevention in shrimp aquaculture.

microbiology↗
bioRxiv2025

Transferrin receptor 1 (TfR1) functions as an entry receptor for scale drop disease virus to invade host cell via clathrin-mediated endocytosis

Scale drop disease virus (SDDV), a distinct member of the genus Megalocytivirus within the Iridoviridae family, has emerged as a novel threat to global teleost aquaculture. Despite its importance, the pathogenic mechanism of SDDV remains largely elusive. In this study, we identified mandarin fish transferrin receptor 1 (mfTfR1) as an entry receptor for SDDV to invade host cells. Firstly, mfTfR1 was detected in high abundance in purified SDDV virions and exhibited dynamic responses to SDDV infection, showing distinct regulatory patterns both in vivo and in vitro. Overexpression of mfTfR1 in low-permissive fathead minnow (FHM) cells significantly enhanced SDDV replication, particularly during the early stages of viral binding and entry. Conversely, antibody-blocking experiments and treatment with the TfR1 inhibitor ferristatin II significantly suppressed SDDV entry. Further investigation revealed that mfTfR1 directly interacted with the major capsid protein (MCP) of SDDV, and the helical domain of mfTfR1 was identified as the crucial docking site. The binding site within the helical domain was determined, and disrupting this interaction significantly reduced viral entry and host mortality. Finally, we demonstrated that SDDV could activate Src kinase-mediated tyrosine phosphorylation of mfTfR1. This phosphorylation event enhanced the internalization of mfTfR1 and facilitated clathrin-mediated endocytosis. Collectively, our study provides compelling evidence to confirm that mfTfR1 functions as an entry receptor that mediates SDDV entry into host cells via clathrin-mediated endocytosis, leading to a lethal infection outcome. Our work lays the ground work for the development of targeted therapeutic strategies to mitigate the impact of SDDV in aquaculture. IMPORTANCETfR1, a dimeric glycoprotein classified as a type II transmembrane receptor, facilitates the cellular internalization of holo-transferrin. In several mammalian and avian RNA viruses, TfR1 serves as a crucial receptor to mediate the entry of viruses into host cells. As an emerging large DNA virus, SDDV poses an emerging threat to teleosts globally, however, its underlying pathogenic mechanisms remain poorly understood. In this study, we are the first to identify mfTfR1 as a crucial receptor for SDDV entry. We demonstrated a specific interaction between mfTfR1 and the major capsid protein (MCP) of SDDV, with the helical domain of mfTfR1 acting as the binding site. Moreover, we confirmed that SDDV enters cells through mfTfR1-mediated clathrin-dependent endocytosis. This work highlights the essential role of TfR1 in aquatic DNA viral infections and establishes the theoretical foundation for developing targeted therapeutic strategies against SDDV.

microbiology↗
bioRxiv2025

Scale drop disease virus (SDDV) triggering ferroptosis both in vivo and in vitro facilitates virus infection via targeting transferrin receptor 1 (TfR1)

Scale drop disease virus (SDDV) is a distinct member in genus Megalocytivirus of family Iridoviridae, garnering increasing attention due to its significant threat to teleost. Ferroptosis is a new type of cell death discovered recently and involved in various viral infections. Knowledges on SDDV induced ferroptosis remains unclear. Here, we demonstrated that SDDV infection triggers ferroptosis, as evidenced by hallmark features such as iron overload, massive lipid peroxides accumulation, glutathione depletion and glutathione peroxidase 4 downregulation. SDDV-infected MFF-1 cells exhibited increased reactive oxygen species production and mitochondrial shrinkage. Treatment with Ferrostatin-1, a potent ferroptosis inhibitor, significantly attenuated SDDV replication in MFF-1 cells and could improve the survival of mandarin fish upon SDDV challenge. Treatment with an iron chelator mitigated ferroptosis and reduced the mortality of mandarin fish following SDDV infection, suggesting that SDDV-induced ferroptosis is iron-dependent. Finally, we demonstrated that SDDV infection could upregulate the expression of transferrin receptor protein 1 (TfR1), a critical iron transporter, to disrupt cellular iron homeostasis, induce ferroptosis, and then facilitate viral infection. Collectively, our findings provide compelling evidence that SDDV infection induces ferroptosis by targeting TfR1 to facilitate virus infection. Inhibiting ferroptosis represents a promising immunotherapeutic strategy for combating SDDV infection in aquaculture.

microbiology↗
bioRxiv2025

Dissection of the Global Responses of Mandarin Fish Pyloric Caecum to An Acute Ranavirus (MRV) Infection Reveals the Formation of Serositis and Then Ascites

Mandarin fish ranavirus (MRV), a variant of largemouth bass virus (LMBV), is a distinct member of the genus Ranavirus within the family Iridoviridae. Acute MRV infection predominantly affects the pyloric caecum, a critical visceral organ in mandarin fish, and is hypothesized to drive the characteristic external clinical sign of severe ascites. In this study, we reveal that acute MRV infection initially targets the serosal layer of the pyloric caecum of mandarin fish, leading to rapid progression into fibrinous serositis characterized by serosal hypertrophy, fibrosis, hyperemia, edema, and tissue adhesions. Using single-cell RNA sequencing, we dissect the cellular composition of epithelial, immune, and stromal populations, identifying significant enrichment of macrophages and granulocytes, alongside T and natural killer cells, as key mediators of acute cytokine and inflammatory responses. Then, robust experimental evidence demonstrates that MRV attacks specific immune cell subsets of T and B cells and stromal cells of fibroblasts, myofibroblasts, endothelial cells, and pericytes, resulting in upregulation of genes and pathways associated with extracellular matrix (ECM) formation, collagen biosynthesis, and vascular remodeling in the hyperplastic serosal zone. Additionally, both host-derived type V collagens and MRV-encoded collagens are implicated in ECM formation in the hypertrophic serosa. Collectively, this study provides a comprehensive single-cell resolution analysis of the pyloric caecums response to acute MRV infection and highlights virus- driven serositis as the underlying cause of severe ascites in mandarin fish. ImportanceThe pyloric caecum is a vital digestive and immune organ in many bony fish species, including the mandarin fish, a carnivorous species with an exceptionally developed pyloric caecum comprising 207-326 caeca per individual. While MRV/LMBV infects various fish species, severe ascites is uniquely observed in infected mandarin fish. This study demonstrates that acute MRV infection induces fibrinous serositis in the pyloric caecum, characterized by hyperemia, edema, and hyperplasia, ultimately resulting in ascites and mortality. Leveraging single-cell RNA sequencing, we provide a detailed landscape of the cell types affected or involved in the inflammatory response, revealing their roles in the pathogenesis of serositis. These findings advance our understanding of MRV-induced pathology and its species-specific manifestations.

microbiology↗
bioRxiv2024

Saccharomyces Genome Database: Advances in Genome Annotation, Expanded Biochemical Pathways, and Other Key Enhancements

Budding yeast (Saccharomyces cerevisiae) is the most extensively characterized eukaryotic model organism and has long been used to gain insight into the fundamentals of genetics, cellular biology, and the functions of specific genes and proteins. The Saccharomyces Genome Database (SGD) is a scientific resource that provides information about the genome and biology of S. cerevisiae. For more than 30 years, SGD has maintained the genetic nomenclature, chromosome maps, and functional annotation for budding yeast along with search and analysis tools to explore these data. Here we describe recent updates at SGD, including the two most recent reference genome annotation updates, expanded biochemical pathways representation, changes to SGD search and data files, and other enhancements to the SGD website and user interface. These activities are part of our continuing effort to promote insights gained from yeast to enable the discovery of functional relationships between sequence and gene products in fungi and higher eukaryotes.

genetics↗
bioRxiv2024

Discovery and binding site identification of a single-stranded DNA-binding protein that interacts with double-stranded DNA

Scientists have conducted in-depth studies on single-stranded DNA (ssDNA) binding and protein interaction network of single-stranded DNA binding proteins (SSBs). SSBs are widely present in cells from lower prokaryotes to higher mammals and are important proteins for ssDNA protection. In-depth studies in recent years have revealed a wide range of interactions between SSBs and other proteins. Studies have shown that in addition to playing the role of ssDNA protector, SSBs are also important members of biochemical pathways such as DNA replication and recombination. In this study, a single-stranded DNA binding protein SSF encoded by E. coli F plasmid with highly conserved N-terminal region was demonstrated to have ssDNA binding ability similar to E. coli SSB through gel migration experiments. At the same time, the dsDNA binding ability of SSF was also demonstrated, and the dissociation constant of this interaction (in the range of microliters) was determined by Micro-scale Thermophoresis (MST). Through the above experiments, a previously unreported SSB with dsDNA binding ability was revealed, and the region interacting with dsDNA was determined to be the C-terminal unstructured region. This study lays a foundation for further understanding of the mechanism of bacterial conjugation conducted by F plasmid, as well as the potential dsDNA binding ability and biological significance of other SSBs.

biochemistry↗
bioRxiv2024

A noncanonical GTPase signaling mechanism controls exit from mitosis in budding yeast

In the budding yeast Saccharomyces cerevisiae, exit from mitosis is coupled to spindle position to ensure successful genome partitioning between mother and daughter cell. This coupling occurs through a GTPase signaling cascade known as the mitotic exit network (MEN). The MEN senses spindle position via a Ras-like GTPase Tem1 which localizes to the spindle pole bodies (SPBs, yeast equivalent of centrosomes) during anaphase and signals to its effector protein kinase Cdc15. How Tem1 couples the status of spindle position to MEN activation is not fully understood. Here, we show that Cdc15 has a relatively weak preference for Tem1GTP and Tem1s nucleotide state does not change upon MEN activation. Instead, we find that Tem1s nucleotide cycle establishes a localization-based concentration difference in the cell where only Tem1GTP is recruited to the SPB, and spindle position regulates the MEN by controlling Tem1 localization. SPB localization of Tem1 primarily functions to promote Tem1-Cdc15 interaction for MEN activation by increasing the effective concentration of Tem1. Consistent with this model, we demonstrate that artificially tethering Tem1 to the SPB or concentrating Tem1 in the cytoplasm with genetically encoded multimeric nanoparticles could bypass the requirement of Tem1GTP and correct spindle position for MEN activation. This localization/concentration-based GTPase signaling mechanism for Tem1 differs from the canonical Ras-like GTPase signaling paradigm and is likely relevant to other localization-based signaling scenarios.

cell biology↗
bioRxiv2024

Peripheral B Lymphocyte Serves as A Reservoir for The Persistently Covert Infection of Mandarinfish Siniperca chuatsi Ranavirus

Genus Ranavirus in family Iridoviridae is composed of large members with various genomic sizes and viral gene contents, infecting a variety of ectothermic vertebrates including reptile, amphibians and bony fish worldwide. Mandarinfish ranavirus (MRV) is a very distinctive member among genus Ranavirus. Persistently convert infection of MRV were previously observed in natural outbreak of MRV, but the underlying mechanism remains unclear. We here evidenced that mandarinfish peripheral B lymphocytes are implemented as viral reservoirs to maintain persistent and covert infection. When mandarinfish were infected with sublethal dosage of MRV under nonpermissive temperature (19 {o}C) and permissive temperature (26 {o}C), respectively, all fish in 19 {o}C group survived and entered persistent phase of infection characterized with very low viral load in white blood cell, whereas partial fish died of MRV infection in 26 {o}C group, and the survivals then initiated persistent status. Gradually raising temperature, vaccination and dexamethasone treatment can reactivate the quiescent MRV to replicate and result in partial mortality. The viral reservoir investigates showed that IgM+-labelled B lymphocytes but not CD3{Delta}+-labelled T lymphocytes and MRC-1+-labelled macrophages are target cells for the persistent infection of MRV. Moreover, the quiescent MRV could not be reactivated by heat-killed Escherichia coli, indicating a very different reactivation mechanism from that of other known rannaviral member. Collectively, we are the first to confirm the presence of B cell-dependent persistent and covert infection of ranavirus, and provide a new clue for better understanding the complex infection mechanism of vertebrate iridovirus, especially regarding ranavirus. IMPORTANCEViruses known as HIV, HBV and EBV etc. evade host immune clearance by establishing long-term even lifelong persistent or latent infection. In vertebrate iridovirus, FV3, the type species of genus Ranavirus was evidenced to establish persistent infection by using Xenopus peritoneal macrophages as reservoirs. MRV is a very distinctive ranavirus from FV3 with very different genomic content and host species. We here uncovered MRV establishes persistent and covert infection by using peripheral B lymphocytes as virus reservoirs. During persistent infection, very low copies of quiescent MRV were harbored in peripheral B lymphocytes. Water temperature stress, vaccination stimulation, and dexamethasone treatment can reactivate quiescent MRV to replicate in abundance via a non-TLR5-mediated manner, and results in recurrence of MRV disease. Our finding suggests the diversity and complexity of the pathogenic mechanisms among ranaviruses, and also has important scientific significance for in-depth understanding of the infection and immunity interaction of vertebrate iridoviruses.

microbiology↗
bioRxiv2023

New tools reveal PCP-dependent polarized mechanics in the cortex and cytoplasm of single cells during convergent extension

Understanding biomechanics of biological systems is crucial for unraveling complex processes like tissue morphogenesis. However, current methods for studying cellular mechanics in vivo are limited by the need for specialized equipment and often provide limited spatiotemporal resolution. Here we introduce two new techniques, Tension by Transverse Fluctuation (TFlux) and in vivo microrheology, that overcome these limitations. They both offer time-resolved, subcellular biomechanical analysis using only fluorescent reporters and widely available microscopes. Employing these two techniques, we have revealed a planar cell polarity (PCP)-dependent mechanical gradient both in the cell cortex and the cytoplasm of individual cells engaged in convergent extension. Importantly, the non-invasive nature of these methods holds great promise for its application for uncovering subcellular mechanical variations across a wide array of biological contexts. SummaryNon-invasive imaging-based techniques providing time-resolved biomechanical analysis at subcellular scales in developing vertebrate embryos.

developmental biology↗
bioRxiv2023

Lung cancer-intrinsic SOX2 expression mediates resistance to checkpoint blockade therapy by inducing Treg-dependent CD8+ T cell exclusion

Tumor-intrinsic signaling pathways can drastically affect the tumor immune microenvironment (TME), promoting tumor progression and resistance to immunotherapy by excluding immune cell populations from the tumor. Several tumor-cell intrinsic pathways have been reported to affect myeloid cell infiltration and downstream T cell infiltration. Clinical evidence suggests that the exclusion of cytotoxic T cells from the tumor core likewise mediates resistance. Here, we find that tumor cell-intrinsic SOX2 expression induces the exclusion of cytotoxic T cells from the tumor core and promotes resistance to checkpoint blockade therapy. CD8+ T cell exclusion was dependent on regulatory T cell-mediated suppression of tumor vasculature. Depleting tumor-infiltrating regulatory T cells via Glucocorticoid-Induced TNFR-Related (GITR) restored CD8+ T cell infiltration and reduced tumor growth in combination with checkpoint blockade therapy. SignificanceWe identified tumor cell-intrinsic SOX2 expression in lung cancer as a mechanism of resistance to immunotherapy. SOX2 expression increases regulatory T cell populations in the TME, negatively affecting the tumor vasculature and blunting CD8+ T cell infiltration into the tumor core. This effect could be reverted by targeting regulatory T cells with anti-GITR therapy.

immunology↗
bioRxiv2023

Host and transmission route of Enterocytozoon hepatopenaei (EHP) from dragonfly to shrimp

Enterocytozoon hepatopenaei (EHP) is a shrimp pathogen that causes huge economic losses. In the present study, the hosts of EHP were investigated using polymerase chain reaction (PCR) in an aquaculture farm located in Maoming, China. EHP was detected in Litopenaeus vannamei, Penaeus monodon, crab, false mussel, and three dragonfly species (Anax parthenope, Pantala flavescens, and Ischnura senegalensis). In the histopathological examination using hematoxylin-eosin staining, EHP spores were found in nymphs and adult dragonflies naturally infected with EHP that were collected from the shrimp farm. Fluorescence in situ hybridization results showed a positive signal for EHP infection in the fat body of dragonfly nymphs. Immature and mature microsporidian spores and late sporogonial plasmodium were observed in the cytoplasm of dragonfly nymphs using transmission electron microscopy. The transmission of EHP from shrimp to dragonfly nymphs was confirmed via cohabitation challenge experiments in which EHP-free dragonfly nymphs were cohabited with EHP-infected shrimp, and the transmission of EHP from dragonfly nymphs to shrimp was demonstrated via the cohabitation of EHP-infected dragonfly nymphs with EHP-free shrimp and oral administration challenge experiments. This study confirms that dragonflies can act as natural EHP hosts, and a novel EHP horizontal transmission route exists between dragonflies and shrimp. Author summaryTo the authors knowledge, this study presents the first report of microsporidia (EHP) infecting both crustaceans and insects (A. parthenope, P. flavescens, and I. senegalensis). The horizontal transmission of EHP between dragonfly nymphs and shrimp was confirmed through cohabitation and oral administration challenge experiments. EHP has become a globally significant threat to shrimp aquaculture. The findings of the present study will help to design prevention strategies, such as the use of nets to prevent dragonflies from entering shrimp ponds.

microbiology↗
bioRxiv2022

SurvivalML: an integrative platform for the discovery and exploration of prognostic models in multi-center cancer cohorts

Advances in multi-omics and big-data technologies have led to numerous prognostic signatures aimed at improving current clinicopathological staging systems. Due to the lack of reproducibility and independent confirmation, few signatures have been translated into clinical routine. As high-quality datasets accumulate, identifying robust signatures across multiple independent cohorts becomes possible. Nonetheless, inaccurate data retrieval, different versions of genome annotations, disparate expression distributions, difficult data cleaning, inconsistent clinical information, algorithm selection, and parameter tuning have impeded model development and validation in multi-center datasets. Hence, for the first time, we introduced SurvivalML (https://rookieutopia.com/app_direct/SurvivalML/), a web application for helping develop and validate prognostic models across multi-center datasets. SurvivalML included 37,325 samples (253 eligible datasets) with both transcriptome data and survival information from 21 cancer types, which were renewedly and uniformly re-annotated, normalized, and cleaned. This application provided 10 survival machine-learning algorithms for flexibly training models via tuning essential parameters online and delivered four aspects for model evaluation, including Kaplan-Meier survival analysis, time-dependent ROC, calibration curve, and decision curve analysis. Overall, we believe that SurvivalML can serve as an attractive platform for model discovery from multi-center datasets.

bioinformatics↗
bioRxiv2022

BEST: a web application for comprehensive biomarker exploration on large-scale data in solid tumors

SummaryData mining from RNA-seq or microarray data has become an essential part of cancer biomarker exploration. Certain existing web servers are valuable and broadly utilized, but the meta-analysis of multiple datasets is absent. Most web servers only contain tumor samples from the TCGA database with only one cohort for each cancer type, which also means that the analysis results mainly derived from a single cohort are thin and unstable. Indeed, consistent performance across multiple independent cohorts is the foundation for an excellent biomarker. Moreover, many analytical functions researchers require remain adequately unmet by these tools. Thus, we introduce BEST (Biomarker Exploration for Solid Tumors), a web application for comprehensive biomarker exploration on large-scale data in solid tumors. BEST includes more than 50,000 samples of 27 cancer types. To ensure the comparability of genes between different sequencing technologies and the legibility of clinical traits, we re-annotated transcriptome data based on the GRCh38 patch 13 sequences and unified the nomenclature of clinical traits. BEST delivers fast and customizable functions, including clinical association, survival analysis, enrichment analysis, cell infiltration, immunomodulator, immunotherapy, candidate agents, and genomic alteration. Together, our web server provides multiple cleaned-up independent datasets and diverse analysis functionalities, helping unleash the value of current data resources. It is freely available at https://rookieutopia.com/. The bigger pictureBioinformatics web servers enable researchers without computational programming skills to conduct various bioinformatics analyses. However, most web servers only contain tumor samples from the TCGA database with only one cohort for each cancer type, which also means that the analysis results mainly derived from a single cohort are thin and unstable. Thus, we introduce BEST (Biomarker Exploration for Solid Tumors), a web application for comprehensive biomarker exploration on large-scale data in solid tumors. BEST includes more than 50,000 samples of 27 cancer types that have been uniformly re-annotated based on the GRCh38 patch 13 sequences, which ensures the comparability of genes between different sequencing technologies. BEST also offers prevalent functions including clinical association, survival analysis, enrichment analysis, cell infiltration, immunomodulator, immunotherapy, candidate agents, and genomic alteration. Together, BEST provides a curated database and innovative analytical pipelines to explore cancer biomarkers at high resolution.

genomics↗
bioRxiv2022

Hypodermal ribosome synthesis inhibition induces a nutrition-uncoupled organism-wide growth quiescence

Inter-organ communication is a key aspect of multicellular organismal growth, development, and homeostasis. Importantly, cell-non-autonomous inhibitory cues that limit tissue specific growth alterations are poorly characterized due to limitations of cell ablation approaches. Here, we report a robust system to investigate nutrition-independent organism-wide growth coordination by modulating ribosome biogenesis at distinct steps in a tissue-specific and reversible fashion in Caenorhabditis elegans. We find an organism-wide growth quiescence response upon suppression of ribosome synthesis either by depletion of an RNA polymerase I (Pol I) subunit or either of two critical ribosome biogenesis factors, RRB-1 and TSR-2, which are the chaperone proteins required for assembly of ribosomal proteins, RPL-3 and RPS-26, respectively. The observed organism-wide growth checkpoint is independent of the nutrition-dependent insulin signaling pathways and is not rescued by daf-16(mu86), a bypass mutation that suppresses the starvation-induced quiescence response. Upon systematically exploring tissues involved in this process, we find that inhibition of hypodermal ribosome synthesis is sufficient to trigger an organism-wide growth quiescence response and leads to organism-wide gene expression changes. At the RNA level, we observe over- and under-expression of several tissue-restricted genes in a wide range of cell types, including touch receptor neurons suggesting inter-organ communication upon hypodermis driven ribosome inhibition. At the protein level, we observed over-expression of secreted proteins (CPR-4, TTR family proteins) as well as an organism-wide reduction both in cytosolic and mitochondrial ribosomal proteins in response to hypodermis RNA Pol I depletion. Finally, we find that dense core vesicle secretion specifically from the hypodermis tissue by the unc-31 gene plays a significant role in mediating the quiescence phenotype. Taken together, these results suggest the presence of a nutrition-independent multicellular growth coordination initiated from the hypodermis tissue.

developmental biology↗