Assembly of hundreds of novel bacterial genomes from the chicken caecum, bioRxiv, 2019-07-12
AbstractChickens are a highly important source of protein for a large proportion of the human population. The caecal microbiota plays a crucial role in chicken nutrition through the production of short chain fatty acids, nitrogen recycling and amino acid production. In this study we sequenced DNA from caecal contents samples taken from 24 chickens belonging to either a fast or slower growing breed consuming either a vegetable-only diet or a diet containing fish meal. We utilised 1.6T of Illumina data to construct 469 draft metagenome-assembled bacterial genomes, including 460 novel strains, 283 novel species and 42 novel genera. We compared our genomes to data from eight EU countries and show that these genomes are abundant within European chicken flocks. We also compared the abundance of our genomes, and the carbohydrate active enzymes they produce, between our chicken groups and demonstrate that there are both breed- and diet-specific microbiomes, as well as an overlapping core microbiome. This data will form the basis for future studies examining the composition and function of the chicken caecal microbiota.
biorxiv microbiology 0-100-users 2019Microbiota supplementation with Bifidobacterium and Lactobacillus modifies the preterm infant gut microbiota and metabolome, bioRxiv, 2019-07-12
AbstractSupplementation with members of the early-life microbiota or ‘probiotics’ is becoming increasingly popular to attempt to beneficially manipulate the preterm gut microbiota. We performed a large longitudinal study comprising two preterm groups; 101 orally supplemented with Bifidobacterium and Lactobacillus (BifLacto) and 133 non-supplemented (Control) matched by age, sex, birth-mode, and diet. 16S rRNA metataxonomic profiling on stool samples (n = 592) indicated a predominance of Bifidobacterium, and a reduction of pathobionts in the BifLacto group. Metabolic phenotyping found a parallel increase in fecal acetate and lactate in the BifLacto group compared to the Control group, which positively correlated with Bifidobacterium abundance consistent with the ability of the supplemented Bifidobacterium strain to metabolize human milk oligosaccharides and reduced gut pH. This study demonstrates that microbiota supplementation can modify the preterm microbiome and the gastrointestinal environment to more closely resemble that of a full-term infant.
biorxiv microbiology 0-100-users 2019The place-cell representation of volumetric space in rats, bioRxiv, 2019-07-12
AbstractPlace cells are spatially modulated neurons found in the hippocampus that underlie spatial memory and navigation how these neurons represent 3D space is crucial for a full understanding of spatial cognition. We wirelessly recorded place cells in rats as they explored a cubic lattice climbing frame which could be aligned or tilted with respect to gravity. Place cells represented the entire volume of the mazes their activity tended to be aligned with the maze axes, and when it was more difficult for the animals to move vertically the cells represented space less accurately and less stably. These results demonstrate that even surface-dwelling animals represent 3D space and suggests there is a fundamental relationship between environment structure, gravity, movement and spatial memory.
biorxiv animal-behavior-and-cognition 0-100-users 2019Genome-wide association study provides new insights into the genetic architecture and pathogenesis of heart failure, bioRxiv, 2019-07-11
AbstractHeart failure (HF) is a leading cause of morbidity and mortality worldwide1. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained2–4. We report the largest GWAS meta-analysis of HF to-date, comprising 47,309 cases and 930,014 controls. We identify 12 independent variant associations with HF at 11 genomic loci, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function suggesting shared genetic aetiology. Expression quantitative trait analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homeostasis (BAG3), and cellular senescence (CDKN1A). Using Mendelian randomisation analysis we provide new evidence supporting previously equivocal causal roles for several HF risk factors identified in observational studies, and demonstrate CAD-independent effects for atrial fibrillation, body mass index, hypertension and triglycerides. These findings extend our knowledge of the genes and pathways underlying HF and may inform the development of new therapeutic approaches.
biorxiv genetics 0-100-users 2019CD44 regulates epigenetic plasticity by mediating iron endocytosis, bioRxiv, 2019-07-09
SUMMARYCD44 is a transmembrane glycoprotein that is linked to various biological processes reliant on the epigenetic plasticity of cells, including development, inflammation, immune responses, wound healing and cancer progression. While thoroughly studied, functional regulatory roles of this so-called ‘cell surface marker’ remain elusive. Here, we report the discovery that CD44 mediates endocytosis of iron interacting with hyaluronates in tumorigenic cell lines and primary cancer cells. We found that this glycan-mediated iron endocytosis mechanism is enhanced during epithelial-mesenchymal transition, unlike the canonical transferrin-dependent pathway. This transition is further characterized by molecular changes required for iron-catalyzed oxidative demethylation of the repressive histone mark H3K9me2 that governs the expression of mesenchymal genes. CD44 itself is transcriptionally regulated by nuclear iron, demonstrating a positive feedback loop, which is in contrast to the negative regulation of transferrin receptor by excess iron. Finally, we show that epigenetic plasticity can be altered by interfering with iron homeostasis using small molecules. This comprehensive study reveals an alternative iron uptake mechanism that prevails in the mesenchymal state of mammalian cells, illuminating a central role of iron as a rate-limiting regulator of epigenetic plasticity.
biorxiv cell-biology 0-100-users 2019Recent evolutionary history of tigers highlights contrasting roles of genetic drift and selection, bioRxiv, 2019-07-09
AbstractTigers are among the most charismatic of endangered species, yet little is known about their evolutionary history. We sequenced 65 individual genomes representing extant tiger geographic range. We found strong genetic differentiation between putative tiger subspecies, divergence within the last 10,000 years, and demographic histories dominated by population bottlenecks. Indian tigers have substantial genetic variation and substructure stemming from population isolation and intense recent bottlenecks here. Despite high genetic diversity across India, individual tigers host longer runs of homozygosity, potentially suggesting recent inbreeding here. Amur tiger genomes revealed the strongest signals of selection and over-representation of gene ontology categories potentially involved in metabolic adaptation to cold. Novel insights highlight the antiquity of northeast Indian tigers. Our results demonstrate recent evolution, with differential isolation, selection and drift in extant tiger populations, providing insights for conservation and future survival.
biorxiv genomics 0-100-users 2019