The fecal microbiome and metabolome differs between dogs fed Bones and Raw Food (BARF) diets and dogs fed commercial diets

Introduction: Feeding a Bones and Raw Food (BARF) diet has become an increasing trend in canine nutrition. Bones and Raw Food diets contain a high amount of animal components like meat, offal, and raw meaty bones, combined with comparatively small amounts of plant ingredients like vegetables and fruits as well as different sorts of oil and supplements. While many studies have focused on transmission of pathogens via contaminated meat and on nutritional imbalances, only few studies have evaluated the effect of BARF diets on the fecal microbiome and metabolome. The aim of the study was to investigate differences in the fecal microbiome and the metabolome between dogs on a BARF diet and dogs on a commercial diet (canned and dry dog food). Methods: Naturally passed fecal samples were obtained from 27 BARF and 19 commercially fed dogs. Differences in crude protein, fat, fiber, and NFE (Nitrogen-Free Extract) between diets were calculated with a scientific nutrient database. The fecal microbiota was analyzed by 16S rRNA gene sequencing and quantitative PCR assays. The fecal metabolome was analyzed in 10 BARF and 9 commercially fed dogs via untargeted metabolomics approach. Results: Dogs in the BARF group were fed a significantly higher amount of protein and fat and significantly lower amount of NFE and fiber. There was no significant difference in alpha-diversity measures between diet groups. Analysis of similarity (ANOSIM) revealed a significant difference in beta-diversity (p < 0.01) between both groups. Linear discriminant analysis effect size (LefSe) showed a higher abundance of Lactobacillales, Enterobacteriaceae, Fusobacterium and, Clostridium in the BARF group while conventionally fed dogs had a higher abundance of Clostridiaceae, Erysipelotrichaceae, Ruminococcaceae, and Lachnospiraceae. The qPCR assays revealed significantly higher abundance of Escherichia coli (E. coli) and Clostridium (C.). perfringens and an increased Dysbiosis Index in the BARF group. Principal component analysis (PCA) plots of metabolomics data showed clustering between diet groups. Random forest analysis showed differences in the abundance of various components, including increased 4-hydroxybutryric acid (GBH) and 4-aminobutyric acid (GABA) in the BARF group. Based on univariate statistics, several metabolites were significantly different between diet groups, but lost significance after adjusting for multiple comparison. No differences were found in fecal bile acid concentrations, but the BARF group had a higher fecal concentration of cholesterol in their feces compared to conventionally fed dogs. Conclusion: Microbial communities and metabolome vary significantly between BARF and commercially fed dogs

Five challenges in modelling interacting strain dynamics

Population epidemiological models where hosts can be infected sequentially by different strains have the potential to help us understand many important diseases. Researchers have in recent years started to develop and use such models, but the extra layer of complexity from multiple strains brings with it many technical challenges. It is therefore hard to build models which have realistic assumptions yet are tractable. Here we outline some of the main challenges in this area. First we begin with the fundamental question of how to translate from complex small-scale dynamics within a host to useful population models. Next we consider the nature of so-called "strain space". We describe two key types of host heterogeneities, and explain how models could help generate a better understanding of their effects. Finally, for diseases with many strains, we consider the challenge of modelling how immunity accumulates over multiple exposures

Regulated on Activation, Normal T cell Expressed and Secreted (RANTES) drives the resolution of allergic asthma

RANTES is implicated in allergic asthma and in T cell-dependent clearance of infection. RANTES receptor family comprises CCR1, CCR3, and CCR5, which are G-protein-coupled receptors consisting of seven transmembrane helices. Infections with respiratory viruses like Rhinovirus cause induction of RANTES production by epithelial cells. Here, we studied the role of RANTES in the peripheral blood mononuclear cells in cohorts of children with and without asthma and validated and extended this study to the airways of adults with and without asthma. We further translated these studies to a murine model of asthma induced by house dust mite allergen in wild-type RANTES and CCR5-deficient mice. Here we show an unpredicted therapeutic role of RANTES in the resolution of allergen-induced asthma by orchestrating the transition of effector GATA-3+CD4+ T cells into immune-regulatory-type T cells and inflammatory eosinophils into resident eosinophils as well as increased IL-10 production in the lung

TLR 7/8 regulates Type I and Type III Interferon Signalling in RV1b induced Allergic Asthma

QUESTION Interferon responses have been reported to be defective in rhinovirus (RV) induced asthma. The heterodimeric receptor of type I Interferon (IFN) (IFN-α/-β) is composed by IFNαR-1 and IFNαR-2. Ligand binding to the IFN-α/-β receptor complex activates STAT1 and STAT2 intracellularly. Although type III Interferon (IFN-λ) binds to a different receptor containing IFNλRA and IL-10R2, its triggering leads to activation of the same downstream transcription factors. Here we analysed the effects of Rhinovirus to Interferon type I and III receptors and asked about possible Toll-like receptor 7/8 agonist R848 mediated IFNαR1 and IFNλRα regulation. METHODS We measured IFN-α, -β, -λ and their receptor levels in PBMCs supernatants and cell pellets stimulated with RV1b and the Toll-like Receptor 7/8 (TLR7/8) agonist (R848), in two cohorts of children with and without asthma recruited at preschool age (PreDicta) and at primary school age (AGENDAS) as well as in cell supernatants from total lung cells isolated from mice. RESULTS We observed that R848 induced IFNλR mRNA expression in PBMCs of healthy and asthmatic children, but suppressed the IFNαR mRNA levels. In murine lung cells, RV1balone and together with R848 suppressed IFNαR protein in T cells compared to controls and in total lung IFNλR mRNA compared to RV1b infection alone. ANSWER In PBMCs from pre-school children, IFNαR mRNA was reduced and IFNλRα mRNA was induced upon treatment with TLR7/8 agonist thus suggesting new avenues for induction of anti-viral immune responses in pediatric asthma

Regulated on Activation, Normal T cell Expressed and Secreted (RANTES) drives the resolution of allergic asthma

RANTES is implicated in allergic asthma and in T cell-dependent clearance of infection. RANTES receptor family comprises CCR1, CCR3, and CCR5, which are G-protein-coupled receptors consisting of seven transmembrane helices. Infections with respiratory viruses like Rhinovirus cause induction of RANTES production by epithelial cells. Here, we studied the role of RANTES in the peripheral blood mononuclear cells in cohorts of children with and without asthma and validated and extended this study to the airways of adults with and without asthma. We further translated these studies to a murine model of asthma induced by house dust mite allergen in wild-type RANTES and CCR5-deficient mice. Here we show an unpredicted therapeutic role of RANTES in the resolution of allergen-induced asthma by orchestrating the transition of effector GATA-3+CD4+ T cells into immune-regulatory-type T cells and inflammatory eosinophils into resident eosinophils as well as increased IL-10 production in the lung

Regulated on Activation, Normal T cell Expressed and Secreted (RANTES) drives the resolution of allergic asthma

RANTES is implicated in allergic asthma and in T cell-dependent clearance of infection. RANTES receptor family comprises CCR1, CCR3, and CCR5, which are G-protein-coupled receptors consisting of seven transmembrane helices. Infections with respiratory viruses like Rhinovirus cause induction of RANTES production by epithelial cells. Here, we studied the role of RANTES in the peripheral blood mononuclear cells in cohorts of children with and without asthma and validated and extended this study to the airways of adults with and without asthma. We further translated these studies to a murine model of asthma induced by house dust mite allergen in wild-type RANTES and CCR5-deficient mice. Here we show an unpredicted therapeutic role of RANTES in the resolution of allergen-induced asthma by orchestrating the transition of effector GATA-3+CD4+ T cells into immune-regulatory-type T cells and inflammatory eosinophils into resident eosinophils as well as increased IL-10 production in the lung

Regulated on Activation, Normal T cell Expressed and Secreted (RANTES) drives the resolution of allergic asthma

Abstract RANTES is implicated in allergic asthma and in T cell-dependent clearance of infection. RANTES receptor family comprises CCR1, CCR3, and CCR5, which are G-protein-coupled receptors consisting of seven transmembrane helices. Infections with respiratory viruses like Rhinovirus cause induction of RANTES production by epithelial cells. Here, we studied the role of RANTES in the peripheral blood mononuclear cells in cohorts of children with and without asthma and validated and extended this study to the airways of adults with and without asthma. We further translated these studies to a murine model of asthma induced by house dust mite allergen in wild-type RANTES and CCR5-deficient mice. Here we show an unpredicted therapeutic role of RANTES in the resolution of allergen-induced asthma by orchestrating the transition of effector GATA-3+CD4+ T cells into immune-regulatory-type T cells and inflammatory eosinophils into resident eosinophils as well as increased IL-10 production in the lung

Convection permitting regional climate change simulations for understanding future climate and informing decision making in Africa

Pan-Africa convection-permitting regional climate model simulations have been performed to study the impact of high resolution and the explicit representation of atmospheric moist convection on the present and future climate of Africa. These unique simulations have allowed European and African climate scientists to understand the critical role that the representation of convection plays in the ability of a contemporary climate model to capture climate and climate change, including many impact relevant aspects such as rainfall variability and extremes. There are significant improvements in not only the small-scale characteristics of rainfall such as its intensity and diurnal cycle, but also in the large-scale circulation. Similarly effects of explicit convection affect not only projected changes in rainfall extremes, dry-spells and high winds, but also continental-scale circulation and regional rainfall accumulations. The physics underlying such differences are in many cases expected to be relevant to all models that use parameterized convection. In some cases physical understanding of small-scale change mean that we can provide regional decision makers with new scales of information across a range of sectors. We demonstrate the potential value of these simulations both as scientific tools to increase climate process understanding and, when used with other models, for direct user applications. We describe how these ground-breaking simulations have been achieved under the UK Government’s Future Climate for Africa Programme. We anticipate a growing number of such simulations, which we advocate should become a routine component of climate projection, and encourage international co-ordination of such computationally, and human-resource expensive simulations as effectively as possible