Project description:<p>Traveler's diarrhea (TD) is caused by enterotoxigenic Escherichia coli (ETEC), other pathogenic gram-negative pathogens, norovirus and some parasites. Nevertheless, standard diagnostic methods fail to identify pathogens in more than 30% of TD patients, so it is predicted that new pathogens or groups of pathogens may be causative agents of disease. A comprehensive metagenomic study of the fecal microbiomes from 23 TD patients and seven healthy travelers was performed, all of which tested negative for the known etiologic agents of TD in standard tests. Metagenomic reads were assembled and the resulting contigs were subjected to semi-manual binning to assemble independent genomes from metagenomic pools. Taxonomic and functional annotations were conducted to assist identification of putative pathogens. We extracted 560 draft genomes, 320 of which were complete enough to be enough characterized as cellular genomes and 160 of which were bacteriophage genomes. We made predictions of the etiology of disease in individual subjects based on the properties and features of the recovered cellular genomes. Three subtypes of samples were observed. First were four patients with low diversity metagenomes that were predominated by one or more pathogenic E. coli strains. Annotation allowed prediction of pathogenic type in most cases. Second, five patients were co-infected with E. coli and other members of the Enterobacteriaceae, including antibiotic resistant Enterobacter, Klebsiella, and Citrobacter. Finally, several samples contained genomes that represented dark matter. In one of these samples we identified a TM7 genome that phylogenetically clustered with a strain isolated from wastewater and carries genes encoding potential virulence factors. We also observed a very high proportion of bacteriophage reads in some samples. The relative abundance of phage was significantly higher in healthy travelers when compared to TD patients. Our results highlight that assembly-based analysis revealed that diarrhea is often polymicrobial and includes members of the Enterobacteriaceae not normally associated with TD and have implicated a new member of the TM7 phylum as a potential player in diarrheal disease. </p>
Project description:Analysis of gene expression profiles is an attractive method for discovering how animals respond to environmental challenges in nature. Compared to low altitudes, high altitudes are characterized by reduced partial pressures of oxygen (hypoxia) and cooler ambient temperatures To better understand how mammals cope with high altitudes, we trapped wild house mice (Mus musculus domesticus) from 3 populations in La Paz, Bolivia (3000 - 3600 m) and 3 populations in Lima, Peru (0 – 200 m). Affymetrix GeneChip® Mouse Genome 430 2.0 Arrays were use to measure mRNA abundance in the livers of these mice.
Project description:This study seeks to assess the effects of prenatal exposure of female sheep to execessive testosterone in metabolically relevant liver and muscle tissue. The goals are to 1) determine noncoding RNA in the control animals and 2) assess the effects of prenatal T-treatment on non-coding RNA. 3) Finally identify putative ncRNA-totalRNA interactions.
Project description:We present a computational tool, FounderTracker, for discovering founder mutations in cancer, based on the detection of significantly conserved haplotypes in tumor SNP profiles. We demonstrate the relevance of the approach by identifying founder mutations in two different cancers, and we show with simulated data that FounderTracker can detect rare founder mutations with high power and negligible false discovery rate. FounderTracker is a powerful tool for discovering novel founder mutations that may explain part of the "missing" heritability in cancer. This SuperSeries is composed of the SubSeries listed below.
Project description:Severe sepsis leads to massive activation of coagulation and complement cascades that could contribute to multiple organ failure (MOF) and death. To investigate the role of the complement and its crosstalk with the hemostatic system in the pathophysiology and therapeutics of sepsis, we have used a potent inhibitor (compstatin) administered early or late post E. coli challenge in a baboon model of sepsis-induced MOF. Microarray was used to study the affect of complement pathway on global gene expression pattern in sepsis, aims on exploring and discovering the new target genes as potential drugs for the early treatment and prevention of sepsis. Lung and liver tissues were obtained from three normal healthy animals (as Ctl), three animals challenged with sublethal dose of E. coli as SLEC, three animals treated with Compstatin at different sepsis stages after E.coli challenge as SLEC-CST0 and SLEC-CST5. All the animals challenged with E. coli were sacrified at 24 hours post challenge. Total RNAs were isolated from these tissues, hybridized with Affymetrix Human Genome GeneChip U133A 2.0.
Project description:Here, we reveal that the Caenorhabditis elegans ADAR proteins promote survival of animals exposed to several opportunistic human pathogens. Our data indicate that ADARs help maintain proper levels of cuticular collagen genes, which in turn affects defense of the nematode to these bacteria.
Project description:In the present study, we investigated the effects of feeding Lactococcus lactis using Caenorhabditis elegans as a model animal. The survial of the adult C. elegans fed L. lactis was significantly better than that of unfed animals (control) upon infection with pathogens.
Project description:Bilirubin toxicity to the CNS has been widely studied for decades, and shown impacting potential toxic/adaptation mechanisms by a significant modulation of gene expression, suggesting that mechanisms having crucial role on the regulation of gene expression, such as epigenetic mechanisms, should have a strong impact in unconjugated bilirubin toxicity. In this work, we followed the levels of histone 3 acetylation (H3K14Ac) in the cerebellum (Cll) of the developing (2, 9, 17 days after the birth and in adult age) Gunn rat (the natural model for neonatal hyperbilirubinemia and kernicterus) by Western blot, discovering an age specific alteration of the H3K14Ac in the hyperbilirubinemic animals. Then, the H3K14Ac linked chromatin was immune-precipitated and submitted to sequencing (ChIP-Seq). The GeneOntology analysis revealed that almost the 45% of H3K14Ac ChiP-Seq TSS-promoter genes were involved in the CNS development.
Project description:To gain molecular insights on how NMUR-1 regulates C. elegans defense against pathogen infection, we used RNA-Seq to profile gene expression in nmur-1(ok1387) animals relative to wild-type animals with or without E. faecalis or S. enterica infection. We found that NMUR-1 modulates C. elegans transcription activity by regulating the expression of transcription factors, which, in turn, controls the expression of distinct immune genes in response to different pathogens.