Project description:Transcription profiling of brains from mice fed with or without creatine supplementation to study the molecular mechanism of creatine improving health and life span in mice
Project description:Approximately 15% of US adults have circulating levels of uric acid above its solubility limit, which is causally linked to the inflammatory disease gout. In most mammals, uric acid elimination is facilitated by the enzyme uricase. However, human uricase is a pseudogene, having been inactivated early in hominid evolution. Though it has long been known that a substantial amount of uric acid is eliminated in the gut, the role of the gut microbiota in hyperuricemia has not been studied. Here we identify a gene cluster, widely distributed in the gut microbiome, that encodes a pathway for uric acid degradation. Stable isotope tracing demonstrates that gut bacteria metabolize uric acid to xanthine or short chain fatty acids such as acetate, lactate and butyrate. Ablation of the microbiota in uricase-deficient mice causes profound hyperuricemia, and anaerobe-targeted antibiotics increase the risk of gout in humans. These data reveal a role for the gut microbiota in uric acid excretion and highlight the potential for microbiome-targeted therapeutics in hyperuricemia.
Project description:To investigate the polyadenylated transcriptomes of the Wistar Han rat SON in EH from 3-month old euhydrated and dehydrated rats and from 18-month old euhydrated and dehydrated rats. We then performed gene expression profiling analysis using data obtained from adult and aged rat in EH and Dh conditions
Project description:E. histolytica of strains HM1:IMSS (virulent) and Rahman (avirulent) were examined for response to oxidative and nitrosative stress. Response to oxidative stress in E. histolytica was assayed by treating Eh (HM1:IMSS) and Eh (Rahman) with 1mM H2O2 for 60 minutes or 90 minutes and comparing transcription to parasites grown in TYI. In addition, response to nitosative stress was assayed in Eh (HM1:IMSS) by treatment for 60 minutes with 200 µM DPTA-NONOate.
Project description:Little is known about the extent of genetic variability among Entamoeba strains and potential genotypic associations with virulence. Variable phenotypes have been identified for Entamoeba strains. E. histolytica is invasive and causes colitis and liver abscesses, but only in 10% of infected individuals; 90% of subjects remain asymptomatically colonized. E. dispar, a closely related species, appears to be incapable of causing invasive disease. In order to determine the extent of genetic diversity among Entamoeba strains we have developed an E. histolytica genomic DNA microarray and used it to genotype strains of E. dispar and E. histolytica. Based on the identification of divergent genetic loci, all six strains (four EH and two ED) had unique genetic fingerprints. Genomic regions with unusually high levels of divergence were identified indicating that structural or evolutionary pressures are molding selective regions of the Entamoeba genome. Comparison of divergent genetic regions allowed us to readily distinguish between EH and ED, identify novel genetic regions that may be used for strain and species typing, and identity a number of novel potential virulence determinants. Among these are Androgen Inducible Gene1, a CXXC receptor kinase, a peroxiredoxin 1-related gene, a Ras family member gene, a Rab geranylgeranyltransferase, and a gene with a UPF0034 domain. Among the four EH strains, an avirulent strain EH (Rahman) was the most divergent and phylogenetically distinct raising the intriguing possibility that genetic subtypes of E. histolytica may be at least partially responsible for the observed variability in clinical outcomes. Our approach shows the utility of a microarray-based genotyping assay to identify genetic variability between Entamoeba isolates and can readily be applied to the study of clinical isolates. A genotyping experiment design type classifies an individual or group of individuals on the basis of alleles, haplotypes, SNP's. Keywords: genotyping_design