bluuebunny/crossref_metadata_2025_split huggingface dataset:
ViWrap: A modular pipeline to identify, bin, classify, and predict viral-host relationships for viruses from metagenomes
Authors: Zhou Zhichao , Martin Cody , Kosmopoulos James C. , Anantharaman Karthik 
Published: February 2023

AbstractViruses are increasingly being recognized as important components of human and environmental microbiomes. However, viruses in microbiomes remain difficult to study because of difficulty in culturing them and the lack of sufficient model systems. As a result, computational methods for identifying and analyzing uncultivated viral genomes from metagenomes have attracted significant attention. Such bioinformatics approaches facilitate screening of viruses from enormous sequencing datasets originating from various environments. Though many tools and databases have been developed for advancing the study of viruses from metagenomes, there is a lack of integrated tools enabling a comprehensive workflow and analyses platform encompassing all the diverse segments of virus studies. Here, we developed ViWrap, a modular pipeline written in Python. ViWrap combines the power of multiple tools into a single platform to enable various steps of virus analysis including identification, annotation, genome binning, species- and genus-level clustering, assignment of taxonomy, prediction of hosts, characterization of genome quality, comprehensive summaries, and intuitive visualization of results. Overall, ViWrap enables a standardized and reproducible pipeline for both extensive and stringent characterization of viruses from metagenomes, viromes, and microbial genomes. Our approach has flexibility in using various options for diverse applications and scenarios, and its modular structure can be easily amended with additional functions as necessary. ViWrap is designed to be easily and widely used to study viruses in human and environmental systems. ViWrap is publicly available via GitHub (https://github.com/AnantharamanLab/ViWrap). A detailed description of the software, its usage, and interpretation of results can be found on the website.HighlightsViWrap integrates state-of-the-art tools and databases for comprehensive characterization and study of viruses from metagenomes and genomes.ViWrap offers a highly flexible, modular, customizable, and easy-to-use pipeline with options for various applications and scenarios.ViWrap enables a standardized and reproducible pipeline for viral metagenomics, genomics, ecology, and evolution.
Metabolomics reveals nucleoside analogs for regulating mucosal-associated invariant T cell responses
Authors: Huang Shouxiong , Sharma Manju , Sallans Larry , Li Chunshun , Kh Zaman , Choubey Divaker , Newburg David , Huaman Moises A. , Hansen Ted , Cao Shugeng 
Published: February 2023

SummaryAlthough mucosal-associated invariant T (MAIT) cells recognize riboflavin-like metabolites from Gram-negative bacteria, MAIT cell stimulation by broad bacterial families and mammalian cells suggests the existence of novel ligands from different biological sources. Here we established a comparative platform of functional metabolomics and usedMycobacterium tuberculosisas a model to characterize novel metabolites for MAIT cell activation. We extracted and fractionated small metabolites ofM. tuberculosisusing high-performance liquid chromatography, showing a different MAIT cell stimulation pattern ofM. tuberculosismetabolite fractions in comparison withEscherichia colifractions. Mass profiling predicted multiple nucleoside analogs enriched in a biologically active fraction ofM. tuberculosis. Whereas the synthetic forms of these predictedM. tuberculosisnucleosides were unavailable, structural-based autodocking of analogous nucleosides conserved in mammals supported potential binding with MR1 protein. Indeed, functional assays of these conserved nucleosides demonstrated guanosine as a stimulator and deoxyformyluridine as an inhibitor of MAIT cell activation. Identification of bioactive nucleoside metabolites broadly conserved in bacterial and mammalian systems will facilitate an understanding of the regulatory roles of MAIT cells in infectious and inflammatory conditions.
Coevolution of the CDCA7-HELLS ICF-related nucleosome remodeling complex and DNA methyltransferases
Authors: Funabiki Hironori , Wassing Isabel E. , Jia Qingyuan , Luo Ji-Dung , Carroll Thomas 
Published: February 2023

Summary5-Methylcytosine (5mC) and DNA methyltransferases (DNMTs) are broadly conserved in eukaryotes but are also frequently lost during evolution. The mammalian SNF2 family ATPase HELLS and its plant ortholog DDM1 are critical for maintaining 5mC. Mutations in HELLS, its activator CDCA7, and thede novoDNA methyltransferase DNMT3B, cause immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome, a genetic disorder associated with the loss of DNA methylation. We here examine the coevolution of CDCA7, HELLS and DNMTs. While DNMT3, the maintenance DNA methyltransferase DNMT1, HELLS, and CDCA7 are all highly conserved in vertebrates and green plants, they are frequently co-lost in other evolutionary clades. The presence-absence patterns of these genes are not random; almost all CDCA7 harboring eukaryote species also have HELLS and DNMT1 (or another maintenance methyltransferase, DNMT5). Coevolution of presence-absence patterns (CoPAP) analysis in Ecdysozoa further indicates coevolutionary linkages among CDCA7, HELLS, DNMT1 and its activator UHRF1. We hypothesize that CDCA7 becomes dispensable in species that lost HELLS or DNA methylation, and/or the loss of CDCA7 triggers the replacement of DNA methylation by other chromatin regulation mechanisms. Our study suggests that a unique specialized role of CDCA7 in HELLS-dependent DNA methylation maintenance is broadly inherited from the last eukaryotic common ancestor.
Diagnostic performance of host protein signatures as a triage test for active pulmonary TB
Authors: Koeppel Lisa , Denkinger Claudia M , Wyss Romain , Broger Tobias , Chegou Novel N , Dunty Jill M , Scott Kerry , Cáceres Tatiana , Dutoit Elloise , Ugarte-Gil Cesar , Nicol Mark , Gotuzzo Eduardo , Corstjens Paul L A M , Geluk Annemieke , Sigal George B , Moreau Emmanuel , Albertini Audrey , Mantsoki Anna , Ongarello Stefano , Walzl Gerhard , Fernandez Suarez Marta 
Published: February 2023

AbstractThe current four symptom screen recommended by the WHO is widely used as screen to initiate diagnostic testing for active pulmonary tuberculosis (TB), yet the performance is poor especially when TB prevalence is low. In contrast, more sensitive molecular tests are less suitable for the placement at primary care level in low resource settings. In order to meet the WHO End TB targets new diagnostic approaches are urgently needed to find the missing undiagnosed cases. Proteomics-derived blood host biomarkers have been explored because protein detection technologies are suitable for the point-of-care setting and could meet cost targets.This study aims to find a biomarker signature that fulfills WHO’s target product profile (TPP) for a TB screening. 12 blood-based protein biomarkers from three sample populations (Vietnam, Peru, South Africa) are analyzed individually and in combinations via advanced statistical methods and machine learning algorithms. The combination of I-309, SYWC and kallistatin shows the most promising results for TB prediction throughout the datasets meeting the TPP for a triage test in adults from two countries (Peru and South Africa). The top performing individual markers identified at the global level (I-309 and SYWC) were also among the best performing markers at country level in South Africa and Vietnam.This analysis clearly shows that a host protein biomarker assay is feasible in adults for certain geographical regions based on one or two biomarkers with a performance that meets minimal WHO TPP criteria.Abstract ImportanceTuberculosis (TB) remains a serious worldwide health problem and diagnosis is hampered by the complexity of tests at primary care level in low resource settings or the low accuracy for screening settings. In order to meet the WHO End TB targets new diagnostic approaches are urgently needed to find the missing undiagnosed cases.This analysis clearly shows that a host protein biomarker assay is feasible in adults for certain geographical regions. We were able to construct an algorithm through statistical methods and machine learning algorithms whose performance meets the minimum of the WHO target product profile criteria. Thus, further work should be addressed at demonstrating that such as assay can be translated into a practical point-of-care test, and to better understand how to address regional differences in biomarker levels and responses.
Assessment of health-related quality of life in type 2 diabetes mellitus at Moi County referral hospital, Taita Taveta county
Authors: Mwadulo Dredah Wughanga , Madhavi Mbindu , Nkoroi Beatrice 
Published: February 2023

AbstractHealth-related quality of life is one’s perceived status of life in value systems and cultural settings where they dwell in and in relation to their aspirations, expectations, ideals and fears. Diabetes has always been seen as a disease of affluence but over the years it is increasingly becoming a problem in developing countries. Globally, approximately 1.5 million deaths that occurred in 2012 due to diabetes, 80% of the deaths occurred in the developing nations. There is an increasing problem of non-transmittable diseases in Sub-Saharan Africa region which has brought a change in lifestyles like smoking, physical inactivity and unhealthy diet. Such non-communicable diseases include cardiovascular diseases, neuropathies & renal disorders which are commonly associated as the complications for diabetes mellitus. Measuring the extent an illness has affected health is of significance to the care and management of those individuals with chronic diseases whose remedy is not likely and since they require long-term management and care. Quality of life has a multivariate approach as it highlights information on bodily health, emotional health, functional and social health spheres of an individual’s view of the extent their health has been affected. This measure, therefore, provides holistic care for an individual with diabetes mellitus. This study seeks to solely look at how the wellness of individuals with diabetes mellitus is affected. The research adopted a cross-sectional descriptive design. 165 respondents were selected through systematic random sampling. The researcher used logistic regression whereby patient’s characteristics like foot problem (aOR7.348; p=0.005) and numbness/pain in hands/legs/feet (aOR=0.155; p<0.001) were associated with low quality of life. Over half of the study participants 127 (77%) indicated that their health-related quality of life would be better without diabetes mellitus as depicted by a diabetes specific QoL mean score of-1.88 approximating to “much better” (−2). The overall mean ADDQoL AWI score (−4.48) indicated that the health-related quality of life of the patients was negatively impaired by type two diabetes mellitus. Among the 19 domain specific items, the study participants rated “sex life” as the most negatively impacted/ important (WI= -5.14). In conclusion, type two diabetes mellitus negatively affected the quality of life and diabetes neuropathy which featured as foot problem and numbness of hands/feet needs to be considered as a predisposing factor to low quality of life in diabetics. Care provided should go beyond the standard treatment that looks into how treatment, lifestyle & behavioral modifications affect daily functioning and well-being of patients thus focusing more on the individual patient’s context and ultimately improving the health-related quality of life of type two diabetes mellitus patients.
Investigation of HLA susceptibility alleles and genotypes with hematological disease among Chinese Han population
Authors: Li Ye-Mo , Li Yu-Xia , Li Dai-Yang , An Lin , Yuan Zhi-Yang , Liu Zhong-Liang , Du Ke-Ming , Zheng Zhong-Zheng 
Published: February 2023

ABSTRACTBackgroundServeral genes involved in the pathogenesis have been identified and a crucial role is known to be played by the human leukocyte antigen (HLA) system. However, the relationship between HLA and a cluster of hematological diseases has been rarely reported in China.MethodsBlood samples (n=123,913) from 43,568 patients and 80,345 individuals without known pathology were genotyped using sequence-based typing (SBT) for HLA class I and II.ResultsThe HLA-A*11:01, B*40:01, C*01:02, DQB1*03:01, and DRB1*09:01 were common in China. Additionally, compared to controls, in malignant hematologic diseases, 3 high-frequency alleles (DQB1*03:01, DQB1*06:02, and DRB1*15:01) were risky. And we observed 7 high-frequency risk alleles (A*01:01, B*46:01, C*01:02, DQB1*03:03, DQB1*05:02, DRB1*09:01, and DRB1*14:54) and 8 high-frequency susceptible genotypes (A*11:01-A*11:01, B*46:01-B*58:01, B*46:01-B*46:01, C*01:02-C*03:04, DQB1*03:01-DQB1*05:02, DQB1*03:03-DQB1*06:01, DRB1*09:01-DRB1*15:01, and DRB1*14:54-DRB1*15:01) for benign hematologic diseases.ConclusionOur results support the association between HLA alleles/genotypes and multiple hematological disorders, which is essential in disease surveillance.
Evolution of virus and virophage facilitates persistence in a tripartite microbial system
Authors: del Arco Ana , Fischer Matthias G. , Becks Lutz 
Published: February 2023

AbstractTripartite biotic interactions are inherently complex, and the strong interdependence of species and high levels of exploitation can make these systems short-lived and vulnerable to extinction. The persistence of species depends then on the balance between exploitation and avoidance of exploitation of the resource beyond the point where sustainable exploitation is no longer possible. We used this general prediction to test the potential for long-term persistence in a recently discovered tripartite microbial system in which a eukaryotic host is preyed upon by a giant virus that is in turn parasitized by a virophage. Host and virophage may benefit from this interaction because the virophage reduces the harmful effects of the giant virus on the host population over time and the virophage can survive integrated into the host genome when giant viruses are scarce. Here, we grew hosts in the presence and absence of the giant virus and virophage over ~280 host generations. We found that the three players persisted, but that the beneficial effect of the virophage for the host population diminished over time. We further tested whether the level of exploitation and replication evolved in the giant virus and/or virophage population over the course of the experiment and whether the changes were such that they avoid overexploitation. We found that the giant virus evolved towards lower replication levels and the virophage towards increased replication but decreased giant virus exploitation. These changes are predicted to facilitate persistence by lowering giant virus and host exploitation and consequently reducing the protective effect of the virophage.
Comparative genomics of novel Bacteroides acidifaciens isolates reveals candidates for adaptation to host subspecies in house mice
Authors: Fokt Hanna , Doms Shauni , Rühlemann Malte C. , Godfroid Maxime , Schmitz Ruth A. , Hermes Britt M. , Baines John F. 
Published: February 2023

AbstractThe breadth of phenotypes influenced by the gut microbiome in multicellular hosts has attracted the keen and renewed interest of evolutionary biologists.Comparative studies suggest that coevolutionary processes may occur as hosts and their associated microbes (i.e., holobionts) diverge. The majority of studies to date however lack information beyond that of 16S rRNA gene profiling, and thus fail to capture potential underlying genomic changes among microbes. In this study, we conducted a comparative genomic analysis of 19 newly sampledBacteroides acidifaciensisolates derived from the eastern and western house mouse subspecies,Mus musculus musculusandM. m. domesticus. Through a panel of genome-wide association (GWAS) analyses applied to pangenomic content, structural gene rearrangements, and SNPs, we reveal several candidates for adaptation to the host subspecies environment. The proportion of significant loci in each respective category is small, indicating low levels of differentiation according host subspecies. However, consistent signal is observed for genes involved in processes such as carbohydrate acquisition/utilization (SusD/RagB,amyAandamyS) and de novo purine nucleotide biosynthesis (purD), which serve as promising candidates for future experimental investigation in the house mouse as a model of holobiont evolution.
The source of microbial transmission influences niche colonization and microbiome development
Authors: Tanger Isabel S. , Stefanschitz Julia , Schwert Yannick , Roth Olivia 
Published: February 2023

AbstractEarly life microbial colonizers shape and support the immature vertebrate immune system. Microbial colonization relies on the vertical route via parental provisioning and the horizontal route via environmental contribution. Vertical transmission is mostly a maternal trait making it hard to determine the source of microbial colonization in order to gain insight in the establishment of the microbial community during crucial development stages. The evolution of unique male pregnancy in pipefishes and seahorses enables the disentanglement of both horizontal and vertical transmission, but also facilitates the differentiation of maternal vs. paternal provisioning ranging from egg development, to male pregnancy and early juvenile development. Using 16s rRNA amplicon sequencing and source-tracker analyses, we revealed how the distinct origins of transmission (maternal, paternal & horizontal) shaped the juvenile internal and external microbiome establishment in the broad-nosed pipefishSyngnathus typhle.Paternal provisioning mainly shaped the juvenile external microbiome, whereas maternal microbes were the main source of the internal juvenile microbiome, later developing into the gut microbiome. This suggests that stability of niche microbiomes may vary depending on the route and time point of colonization, the strength of environmental influences (i.e., horizontal transmission), and potentially the homeostatic function of the niche microbiome.
Colistin resistance and resistance determinants are mobile amongSalmonella entericaisolates from diseased and healthy pigs in Thailand
Authors: Prasertsee Teerarat , Pascoe Ben , Patchanee Prapas 
Published: February 2023

AbstractSalmonellais an important enteric pathogen that poses a threat to human and livestock animal health, with emerging multidrug resistance (MDR) a major public health issue globally. We investigated the prevalence ofSalmonellain healthy and diseased pigs from Thai pig farms and determined their phenotypic and genotypic antimicrobial resistance profiles. A total of 150 fecal samples were collected from pigs housed in pens from four separate pig farms in southern Thailand and tested for the presence ofSalmonella. ConfirmedSalmonellaisolates were tested for their susceptibility to 11 antimicrobials, and PCR used to detect known antimicrobial resistance genes (ARGs).Salmonellaisolates were cultured from 69% (103/150) of all fecal samples, with higher prevalence in disease pigs (12/15; 80%), compared with healthy pigs (91/135; 67%). Serotype Rissen was the most frequently identified serotype among theSalmonellaisolates. Resistance to ampicillin (AMP) (97%), sulfonamide-trimethoprim (SXT) (97%), and tetracycline (TET) (94%) were the most common phenotypes observed. The most common ARGs identified wereblaTEMgene (99.%),tetA(87%),sul1(77%), anddfrA1(74%), and more than 95% of theSalmonellaisolates tested were MDR - based on resistance to three or more antimicrobial classes. The most common antimicrobial resistance pattern exhibited was AMP-TET-SXT (76%), and resistance to colistin (via themcr-1gene) was observed in both healthy and diseased pigs. The clonal groups of PFGE analysis in serotype Typhimurium revealed the genetic relationship amongSalmonellaisolated from healthy and diseased pigs from different pig farms.
Interplay between PLEKHG3-regulated actin dynamics and lysosomal trafficking in cell motility
Authors: Ettelt Rainer , Vucak Georg , Didusch Sebastian , Riemelmoser Biljana , Ehrenreiter Karin , Hartl Markus , Huber Lukas A. , Baccarini Manuela 
Published: February 2023

AbstractLysosomes are highly dynamic organelles that regulate metabolic signaling pathways by recruiting cytosolic molecules to protein platforms on the lysosomal membrane. We performed a proximity-dependent labeling screen to identify novel proteins recruited to the LAMTOR complex, which regulates lysosome positioning and key signaling pathways such as mTORC1, AMPK, and MEK/ERK. We identified a network of proteins involved in actin remodelling, including Pleckstrin homology domain-containing family G member 3 (PLEKHG3), an actin-binding Rho guanine nucleotide exchange factor enriched in protrusions. We show that GFP-PLEKHG3 accumulates in focal adhesion sites, where it colocalizes with peripheral lysosomes. Peripheral accumulation of lysosomes concentrates PLEKHG3 below the plasma membrane, inhibits protrusion formation and limits cell motility. Thus, subcellular positioning of lysosomes impacts PLEKHG3 subcellular localization and the cell’s protrusion activity, shape, and motility. The results shed new light on the interplay between lysosomes and actin dynamics and provides insights into the mechanisms controlling cellular processes such as shape regulation and motility of the plasma membrane.
Gnotobiotic zebrafish microbiota display inter-individual variability affecting host physiology
Authors: Adade Emmanuel E. , Stevick Rebecca J. , Pérez-Pascual David , Ghigo Jean-Marc , Valm Alex M. 
Published: February 2023

AbstractGnotobiotic animal models reconventionalized under controlled laboratory conditions with multi-species bacterial communities are commonly used to study host-microbiota interactions under presumably more reproducible conditions than conventional animals. The usefulness of these models is however limited by inter-animal variability in bacterial colonization and our general lack of understanding of the inter-individual fluctuation and spatio-temporal dynamics of microbiota assemblies at the micron to millimeter scale. Here, we show underreported variability in gnotobiotic models by analyzing differences in gut colonization efficiency, bacterial composition, and host intestinal mucus production between conventional and gnotobiotic zebrafish larvae re-conventionalized with a mix of 9 bacteria isolated from conventional microbiota. Despite similar bacterial community composition, we observed high variability in the spatial distribution of bacteria along the intestinal tract in the reconventionalized model. We also observed that, whereas bacteria abundance and intestinal mucus per fish were not correlated, reconventionalized fish had lower intestinal mucus compared to conventional animals, indicating that the stimulation of mucus production depends on the microbiota composition. Our findings, therefore, suggest that variable colonization phenotypes affect host physiology and impact the reproducibility of experimental outcomes in studies that use gnotobiotic animals. This work provides insights into the heterogeneity of gnotobiotic models and the need to accurately assess re-conventionalization for reproducibility in host-microbiota studies.