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1,862 results for “Tuberculosis”
Whole genome sequence data of Mycobacterium tuberculosis and Mycolicibacterium smegmatis mutants of the riboflavin biosynthetic pathway- Part 2
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Outcomes and adverse events of pre- and extensively drug-resistant tuberculosis patients in Kinshasa, Democratique Republic of the Congo: retrospective cohort study
<p><strong>Abstract</strong></p> <p><strong>Background</strong>: Extensively drug-resistant tuberculosis (XDR TB) is a very serious form of tuberculosis that is burdened with a heavy mortality toll, especially before the advent of new TB drugs. The Democratic Republic of the Congo (DRC) is among the countries most affected by this new epidemic.</p> <p><strong>Methods:</strong> A retrospective analysis was performed of the records of all patients with pre- and extensively drug-resistant tuberculosis hospitalized from January 1, 2015 to December 31, 2017 and monitored for at least 6 months to one year after the end of their treatment in Kinshasa; an individualized therapeutic regimen with bedaquiline for 20 months was built for each patient. The adverse effects were systematically monitored.</p> <p><strong>Results:</strong> Of the 40 laboratory-confirmed patients, 32 (80%) patients started treatment, including 29 preXRB and 3 XDR TB patients. In the eligible group, 3 patients (9.4%) had HIV-TB coinfections. The therapeutic success rate was 53.2%, and the mortality rate was 46.8% (15/32); there were no relapses, failures or losses to follow-up. All coinfected HIV–TB patients died during treatment. The cumulative patient survival rate was 62.5% at 3 months, 53.1% at 6 months and 53.1% at 20 months. The most common adverse events were vomiting, Skin rash, anemia and peripheral neuropathy.</p> <p><strong>Conclusion: </strong>Bedaquiline based treatment improves patient survival in the DRC despite the still high mortality rate. The new anti-tuberculosis<br> drugs are a real hope for the management of Drug Resistant tuberculosis patient and other new therapeutic combinations may improve favorable outcomes.</p>
Data from: A natural gene drive system influences bovine tuberculosis susceptibility in African buffalo: possible implications for disease management
Bovine tuberculosis (BTB) is endemic to the African buffalo (Syncerus caffer) of Hluhluwe-iMfolozi Park (HiP) and Kruger National Park, South Africa. In HiP, the disease has been actively managed since 1999 through a test-and-cull procedure targeting BTB-positive buffalo. Prior studies in Kruger showed associations between microsatellite alleles, BTB and body condition. A sex chromosomal meiotic drive, a form of natural gene drive, was hypothesized to be ultimately responsible. These associations indicate high-frequency occurrence of two types of male-deleterious alleles (or multiple-allele haplotypes). One type negatively affects body condition and BTB resistance in both sexes. The other type has sexually antagonistic effects: negative in males but positive in females. Here, we investigate whether a similar gene drive system is present in HiP buffalo, using 17 autosomal microsatellites and microsatellite-derived Y-chromosomal haplotypes from 401 individuals, culled in 2002-2004. We show that the association between autosomal microsatellite alleles and BTB susceptibility detected in Kruger, is also present in HiP. Further, Y-haplotype frequency dynamics indicated that a sex chromosomal meiotic drive also occurred in HiP. BTB was associated with negative selection of male-deleterious alleles in HiP, unlike positive selection in Kruger. Birth sex ratios were female-biased. We attribute negative selection and female-biased sex ratios in HiP to the absence of a Y-chromosomal sex-ratio distorter. This distorter has been hypothesized to contribute to positive selection of male-deleterious alleles and male-biased birth sex ratios in Kruger. As previously shown in Kruger, microsatellite alleles were only associated with male-deleterious effects in individuals born after wet pre-birth years; a phenomenon attributed to epigenetic modification. We identified two additional allele types: male-specific deleterious and beneficial alleles, with no discernible effect on females. Finally, we discuss how our findings may be used for breeding disease-free buffalo and implementing BTB test-and-cull programs.
Data from: Dispersal patterns in a medium-density Irish badger population: implications for understanding the dynamics of tuberculosis transmission.
<p>European badgers (<i>Meles meles</i>) are group-living mustelids implicated in the spread of bovine tuberculosis (TB)<i> </i>to cattle and act as a wildlife reservoir for the disease. In badgers, only a minority of individuals disperse from their natal social group. However, dispersal may be extremely important for the spread of TB, as dispersers could act as hubs for disease transmission. We monitored a population of 139 wild badgers over seven years in a medium-density population (1.8 individuals/ km<sup>2</sup>). GPS-tracking collars were applied to 80 different individuals. Of these, we identified 25 dispersers, 14 of which were wearing collars as they dispersed. This allowed us to record the process of dispersal in much greater detail than ever before. We show that dispersal is an extremely complex process, and measurements of straight-line distance between old and new social groups can severely underestimate how far dispersers travel. Assumptions of straight-line travel can also underestimate direct and indirect interactions and the potential for disease transmission. For example, one female disperser which eventually settled 1.5 km from her natal territory travelled 308 km and passed through 22 different territories during dispersal. Knowledge of badgers'ranging behaviour during dispersal is crucial to understanding the dynamics of TB transmission, and for designing appropriate interventions, such as vaccination.</p>
Data from: Immune stability predicts tuberculosis infection risk in a wild mammal
Immunity is one of the most variable phenotypic traits in animals; however, some individuals may show less fluctuation in immune traits, resulting in stable patterns of immune variation over time. It is currently unknown whether immune variation has consequences for infectious disease risk. In this study, we identified moderately stable immune traits in wild African buffalo and asked whether the stability of these traits affected bovine tuberculosis (TB) infection risk. We found that adaptive immune traits such as the level of IFN-γ released after white blood cell stimulation, the number of circulating lymphocytes, and the level of antibodies against bovine adenovirus-3 were moderately repeatable (i.e. stable) over time, whereas parameters related to innate immunity either had low repeatability (circulating eosinophil numbers) or were not repeatable (e.g. neutrophil numbers, plasma bacteria killing capacity). Intriguingly, individuals with more repeatable IFN-γ and lymphocyte levels were at a significantly higher risk of acquiring TB infection. In stark contrast, average IFN-γ and lymphocyte levels were poor predictors of TB risk, indicating that immune variability rather than absolute response level better captured variation in disease susceptibility. This work highlights the important and under-appreciated role of immune variability as a predictor of infection risk.
Data from: Context-dependent costs and benefits of tuberculosis resistance traits in a wild mammalian host
Disease acts as a powerful driver of evolution in natural host populations, yet individuals in a population often vary in their susceptibility to infection. Energetic trade-offs between immune and reproductive investment lead to the evolution of distinct life-history strategies, driven by the relative fitness costs and benefits of resisting infection. However, examples quantifying the cost of resistance outside of the laboratory are rare. Here, we observe two distinct forms of resistance to bovine tuberculosis (bTB), an important zoonotic pathogen, in a free-ranging African buffalo (Syncerus caffer) population. We characterize these phenotypes as 'infection resistance', in which hosts delay or prevent infection, and 'proliferation resistance', in which the host limits the spread of lesions caused by the pathogen after infection has occurred. We found weak evidence that infection resistance to bTB may be heritable in this buffalo population (h2=0.10) and comes at the cost of reduced body condition and marginally reduced survival once infected, but also associates with an overall higher reproductive rate. Infection resistant animals thus appear to follow a 'fast' pace of life syndrome, in that they reproduce more quickly but die upon infection. In contrast, proliferation resistance had no apparent costs and was associated with measures of positive host health- such as having a higher body condition and reproductive rate. This study quantifies striking phenotypic variation in pathogen resistance and provides evidence for a link between life history variation and a disease resistance trait in a wild mammalian host population.
Data from: Risk alleles for tuberculosis infection associate with reduced immune reactivity in a wild mammalian host
Integrating biological processes across scales remains a central challenge in disease ecology. Genetic variation drives differences in host immune responses, which, along with environmental factors, generates temporal and spatial infection patterns in natural populations that epidemiologists seek to predict and control. However, genetics and immunology are typically studied in model systems, whereas population-level patterns of infection status and susceptibility are uniquely observable in nature. Despite obvious causal connections, organizational scales from genes to host outcomes to population patterns are rarely linked explicitly. Here we identify two loci near genes involved in macrophage (phagocyte) activation and pathogen degradation that additively increase risk of bovine tuberculosis infection by up to 9-fold in wild African buffalo. Furthermore, we observe genotype-specific variation in IL-12 production indicative of variation in macrophage activation. Here we provide measurable differences in infection resistance at multiple scales by characterizing the genetic and inflammatory variation driving patterns of infection in a wild mammal.
COMBAT TB Tuberculosis genome annotation database
<p>This is a Neo4j format *M. tuberculosis* reference annotation database. To view it you need a Neo4j (v 2.3) instance. There is a script (<strong>run_db.sh</strong>) that will start a Neo4j instance for you based on this data, using docker. Run that (<strong>bash run_db.sh</strong>) and connect to http://localhost:7474.</p> <p>The database was created by the COMBAT TB project (http://christoffels.sanbi.ac.za/index.php/projects/combat-tb) at the South African National Bioinformatics Institute (SANBI).<br /> <br /> Authors: Thoba Lose, Peter van Heusden, Ziphozakhe Mashologu, Alan Christoffels .</p> <p>The COMBAT TB project is funded by the South African Medical Research Council (MRC) and was supported by the South African<br /> Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa.</p>
Agent-based model predicts that layered structure and 3D movement work synergistically to reduce bacterial load in 3D in vitro models of tuberculosis granuloma - Location Data
<p>This dataset is meant to be used with "Agent-based model predicts that layered structure and 3D movement work synergistically to reduce bacterial load in 3D in vitro models of tuberculosis granuloma - Results and Data". It provides spatial output data for 4 different setups (spheroid, traditional, 3d gravity, and traditional floating) of an agent-based model of <i>in vitro </i>tuberculosis infection models. </p>
Population impact of fine particulate matter on tuberculosis risk in China: A causal inference
<p>Supplementary to "Population impact of fine particulate matter on tuberculosis risk in China: A causal inference"</p>
dataset- Tuberculosis detection using Squid Game Optimization with Deep Learning Model on Chest X-Ray Images
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ESAT-6 undergoes self-association at phagosomal pH and an ESAT-6 specific nanobody restricts M. tuberculosis growth in macrophages
<p><em>Mycobacterium tuberculosis</em> (Mtb) is known to survive within macrophages by compromising the integrity of the phagosomal compartment in which it resides. This activity primarily relies on the ESX-1 secretion system, predominantly involving the protein duo ESAT-6 and CFP-10. CFP-10 likely acts as a chaperone, while ESAT-6 likely disrupts phagosomal membrane stability via a largely unknown mechanism. we employ a series of biochemical analyses, protein modeling techniques, and a novel ESAT-6-specific nanobody to gain insight into the ESAT-6’s mode of action. First, we measure the binding kinetics of the tight 1:1 complex formed by ESAT-6 and CFP-10 at neutral pH. Subsequently, we demonstrate a rapid self-association of ESAT-6 into large complexes under acidic conditions, leading to the identification of a stable tetrameric ESAT-6 species. Using molecular dynamics simulations, we pinpoint the most probable interaction interface. Furthermore, we show that cytoplasmic expression of an anti-ESAT-6 nanobody blocks Mtb replication, thereby underlining the pivotal role of ESAT-6 in intracellular survival. Together, these data suggest that ESAT-6 acts by a pH dependent mechanism to establish two-way communication between the cytoplasm and the Mtb-containing phagosome.</p>
Data from: Use of the lung flute ECO to assist in sputum collection for tuberculosis testing: a randomized crossover trial
<p>The Lung Flute ECO, a self-powered, low cost, oscillatory positive expiratory pressure (OPEP) device, assisted people with presumptive tuberculosis to produce an adequate sputum volume for diagnostic testing and was well-tolerated.</p>
Electrochemical Biosensing of Tuberculosis using CRISPR-Cas12a and redox-probe modified oligonucleotide
<p>We have submitted the manuscript in HELIYON </p> <p><span>Manuscript. Number: HELIYON-D-24-20798R3 </span></p> <p>Title: An electrochemical biosensor for the detection of tuberculosis specific DNA with CRISPR-Cas12a and redox-probe modified oligonucleotide. </p> <p>The dataset used in that study is available here. </p>
GENOMIC INSIGHTS INTO THE GLOBAL EVOLUTION AND ANTIBIOTIC RESISTANCE OF THE MYCOBACTERIUM TUBERCULOSIS COMPLEX
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Genome of the inferred most recent common ancestor of the Mycobacterium tuberculosis complex
<p>Genome of the inferred most recent common ancestor of the <em>Mycobacterium tuberculosis</em> complex (MTBC) as described in <em>Human T cell epitopes of </em>Mycobacterium tuberculosis<em> are evolutionarily hyperconserved</em>. Comas et al 2010; Nature Genetics (doi:10.1038/ng.590).</p> <p>Mapping to the inferred MTBC ancestor instead of an extant, Lineage 4/LAM strain, allows to better distinguish between ancestral and derived mutations. This is exemplified by the number of single-nucleotide polymorphisms called for strains from different MTBC lineages (Figure 1).</p> <p>Figure 1 shows the number of fixed SNPs (fSNPs; allele frequency >= 90%), called for <em>Mycobacterium tuberculosis</em> isolates from different MTBC lineages when aligning to the reference strain H37Rv or to the MTBC ancestor. Each dot is an isolate. When aligning to the MTBC ancestor, some isolates appear as "outliers", with less fSNPs than the average. These are mixed infections.</p>
Drug sensitive and multidrug-resistant Mycobacterium tuberculosis genotypes from Bulgaria
<p>Dataset of drug sensitive and multidrug-resistant Mycobacteium tuberculosis spoligo- and MIRU-VNTR genotypes from Bulgaria collected between 2008 till 2019.</p>
Model-based analysis of tuberculosis genotype clusters in the United States reveals high degree of heterogeneity in transmission, and state-level differences across California, Florida, New York, and Texas.
<p>Data and codes for the publication</p>
Mycobacterium tuberculosis complex NGS made easy: data analysis step-by-step (datasets)
<p>Datasets used in the workshop "<em>Mycobacterium tuberculosis</em> complex NGS made easy: data analysis step-by-step". A capacity development initiative by TB-CAPT, PanACEA and Seq&Treat.</p>
Substrate recognition and cryo-EM structure of the ribosome-bound TAC toxin of Mycobacterium tuberculosis
<p>Datasets for the Figures 2 and S2 of the manuscript "Substrate recognition and cryo-EM structure of the ribosome-bound TAC toxin of Mycobacterium tuberculosis".</p> <p> </p> <p>The HTML files describe the analysis and the raw counts after nEMOTE-conv treatment.</p> <p>There are 5 files for each MMEMOTExx dataset:</p> <p>EmoteBarcodesReport.csv = summary<br> UnambNegTable.csv = counts of unique cuts on the reverse strand<br> UnambPosTable.csv = counts of unique cuts on the forward strand<br> AmbPosTable.csv = counts of all cuts on the forward strand<br> AmbNegTable.csv = counts of all cuts on the reverse strand</p> <p> </p>
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Allen Brain Atlas
Allen Brain Atlas is an Allen Institute collection of brain map atlases, datasets, APIs, and analysis tools covering mouse, human, and non-human primate brain resources.
Annotated Behaviour and Observability Dataset (ABODe)
ABODe is a University of Edinburgh DataShare dataset for behavior classification in group-housed mice using home-cage video, identities, bounding boxes, ground-plate positions, and annotator labels.
DANDI Archive for NWB datasets
DANDI is a BRAIN Initiative archive for publishing and sharing neurophysiology data, including electrophysiology, optophysiology, and behavioral data packaged as NWB and related standards.
International Brain Laboratory public data
The International Brain Laboratory public data releases expose standardized mouse decision-making experiments, including Neuropixels recordings, widefield calcium imaging, behavior, and session metadata accessed through the ONE API.
OpenNeuro
OpenNeuro is a free, open platform for sharing neuroimaging datasets, with public search, dataset pages, and download paths for web, S3, DataLad, and the OpenNeuro CLI.