33 research outputs found

    Anthrax Lethal Toxin-Induced Gene Expression Changes in Mouse Lung

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    A major virulence factor of Bacillus anthracis is the anthrax Lethal Toxin (LeTx), a bipartite toxin composed of Protective Antigen and Lethal Factor. Systemic administration of LeTx to laboratory animals leads to death associated with vascular leakage and pulmonary edema. In this study, we investigated whether systemic exposure of mice to LeTx would induce gene expression changes associated with vascular/capillary leakage in lung tissue. We observed enhanced susceptibility of A/J mice to death by systemic LeTx administration compared to the C57BL/6 strain. LeTx-induced groups of both up- and down-regulated genes were observed in mouse lungs 6 h after systemic administration of wild type toxin compared to lungs of mice exposed to an inactive mutant form of the toxin. Lungs of the less susceptible C57BL/6 strain showed 80% fewer differentially expressed genes compared to lungs of the more sensitive A/J strain. Expression of genes known to regulate vascular permeability was modulated by LeTx in the lungs of the more susceptible A/J strain. Unexpectedly, the largest set of genes with altered expression was immune specific, characterized by the up-regulation of lymphoid genes and the down-regulation of myeloid genes. Transcripts encoding neutrophil chemoattractants, modulators of tumor regulation and angiogenesis were also differentially expressed in both mouse strains. These studies provide new directions for the investigation of vascular leakage and pulmonary edema induced by anthrax LeTx

    Comparative Genomic Analysis of the Streptococcus dysgalactiae Species Group: Gene Content, Molecular Adaptation, and Promoter Evolution

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    Comparative genomics of closely related bacterial species with different pathogenesis and host preference can provide a means of identifying the specifics of adaptive differences. Streptococcus dysgalactiae (SD) is comprised of two subspecies: S. dysgalactiae subsp. equisimilis is both a human commensal organism and a human pathogen, and S. dysgalactiae subsp. dysgalactiae is strictly an animal pathogen. Here, we present complete genome sequences for both taxa, with analyses involving other species of Streptococcus but focusing on adaptation in the SD species group. We found little evidence for enrichment in biochemical categories of genes carried by each SD strain, however, differences in the virulence gene repertoire were apparent. Some of the differences could be ascribed to prophage and integrative conjugative elements. We identified approximately 9% of the nonrecombinant core genome to be under positive selection, some of which involved known virulence factors in other bacteria. Analyses of proteomes by pooling data across genes, by biochemical category, clade, or branch, provided evidence for increased rates of evolution in several gene categories, as well as external branches of the tree. Promoters were primarily evolving under purifying selection but with certain categories of genes evolving faster. Many of these fast-evolving categories were the same as those associated with rapid evolution in proteins. Overall, these results suggest that adaptation to changing environments and new hosts in the SD species group has involved the acquisition of key virulence genes along with selection of orthologous protein-coding loci and operon promoters

    Modelling anthelmintic resistance by extending eggCounts package to allow individual efficacy

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    The same anthelmintic treatment can have variable efficacy on individual animals even if the parasite population is homogenously susceptible. An extension of the R package eggCounts is proposed to take individual efficacy into account using a Bayesian hierarchical model. A simulation study is conducted to compare the performance of five different methods on estimating faecal egg count reduction and its uncertainty interval. Simulation results showed the individual efficacy model offered robust inference to two different data simulation procedures with low root mean squared error on the reduction estimate and appropriate uncertainty estimates. Different methods were used to evaluate the anthelmintic resistance in a dataset from USA with sheep and cattle faecal egg counts, where a strong anthelmintic resistance was detected. Open-source statistical tools were updated to include the proposed model. Keywords: Bayesian hierarchical model, Statistical analysis, Faecal egg count reduction test, Anthelmintic resistance, Simulation stud

    Modelling anthelmintic resistance by extending eggCounts package to allow individual efficacy

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    The same anthelmintic treatment can have variable efficacy on individual animals even if the parasite population is homogenously susceptible. An extension of the R package eggCounts is proposed to take individual efficacy into account using a Bayesian hierarchical model. A simulation study is conducted to compare the performance of five different methods on estimating faecal egg count reduction and its uncertainty interval. Simulation results showed the individual efficacy model offered robust inference to two different data simulation procedures with low root mean squared error on the reduction estimate and appropriate uncertainty estimates. Different methods were used to evaluate the anthelmintic resistance in a dataset from USA with sheep and cattle faecal egg counts, where a strong anthelmintic resistance was detected. Open-source statistical tools were updated to include the proposed model

    A Systematic Scoping Review on Recruiting and Retaining Seldom Heard Families in Longitudinal Qualitative Research

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    The aim of this scoping review was to systematically scope the existing literature on the best practice in how to design and conduct longitudinal qualitative research that works for, and is welcomed by two seldom heard kinds of families: (a) families in which a child has a learning disability of chromosomal or genetic origin (sub-review 1); and (b) families in which a parent has experienced violence or abuse from a partner in the last year (sub-review 2). Research questions RQ1 What challenges and elements of best practice can be found in the design and conduct of longitudinal and cross-sectional descriptive studies with hard to reach and hard to hear families? RQ 2. What evidence is there of successful strategies for overcoming these challenges
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