Transcriptome profiling of the small intestinal epithelium in germfree versus conventional piglets

<p>Abstract</p> <p>Background</p> <p>To gain insight into host-microbe interactions in a piglet model, a functional genomics approach was used to address the working hypothesis that transcriptionally regulated genes associated with promoting epithelial barrier function are activated as a defensive response to the intestinal microbiota. Cesarean-derived germfree (GF) newborn piglets were colonized with adult swine feces, and villus and crypt epithelial cell transcriptomes from colonized and GF neonatal piglets were compared using laser-capture microdissection and high-density porcine oligonucleotide microarray technology.</p> <p>Results</p> <p>Consistent with our hypothesis, resident microbiota induced the expression of genes contributing to intestinal epithelial cell turnover, mucus biosynthesis, and priming of the immune system. Furthermore, differential expression of genes associated with antigen presentation (pan SLA class I, <it>B2M</it>, <it>TAP1 </it>and <it>TAPBP</it>) demonstrated that microbiota induced immune responses using a distinct regulatory mechanism common for these genes. Specifically, gene network analysis revealed that microbial colonization activated both type I (IFNAR) and type II (IFNGR) interferon receptor mediated signaling cascades leading to enhanced expression of signal transducer and activator of transcription 1 (STAT1), STAT2 and IFN regulatory factor 7 (IRF7) transcription factors and the induction of IFN-inducible genes as a reflection of intestinal epithelial inflammation. In addition, activated RNA expression of NF-kappa-B inhibitor alpha (<it>NFκBIA</it>; a.k.a I-kappa-B-alpha, IKBα) and toll interacting protein (<it>TOLLIP</it>), both inhibitors of inflammation, along with downregulated expression of the immunoregulatory transcription factor GATA binding protein-1 (<it>GATA1</it>) is consistent with the maintenance of intestinal homeostasis.</p> <p>Conclusion</p> <p>This study supports the concept that the intestinal epithelium has evolved to maintain a physiological state of inflammation with respect to continuous microbial exposure, which serves to sustain a tight intestinal barrier while preventing overt inflammatory responses that would compromise barrier function.</p

Sugar-Sweetened Beverages and Adverse Human Health Outcomes: An Umbrella Review of Meta-Analyses of Observational Studies

Our aim was to conduct an umbrella review of evidence from meta-analyses of observational studies investigating the link between sugar-sweetened beverage consumption and human health outcomes. Using predefined evidence classification criteria, we evaluated evidence from 47 meta-analyses encompassing 22,055,269 individuals. Overall, 79% of these analyses indicated direct associations between greater sugar-sweetened beverage consumption and higher risks of adverse health outcomes. Convincing evidence (class I) supported direct associations between sugar-sweetened beverage consumption and risks of depression, cardiovascular disease, nephrolithiasis, type 2 diabetes mellitus, and higher uric acid concentrations. Highly suggestive evidence (class II) supported associations with risks of nonalcoholic fatty liver disease and dental caries. Out of the remaining 40 meta-analyses, 29 were graded as suggestive or weak in the strength of evidence (classes III and IV), and 11 showed no evidence (class V). These findings inform and provide support for population-based and public health strategies aimed at reducing sugary drink consumption for improved health.</p

Speech Communication

Contains table of contents for Part V, table of contents for Section 1, reports on six research projects and a list of publications.C.J. Lebel FellowshipDennis Klatt Memorial FundNational Institutes of Health Grant R01-DC00075National Institutes of Health Grant R01-DC01291National Institutes of Health Grant R01-DC01925National Institutes of Health Grant R01-DC02125National Institutes of Health Grant R01-DC02978National Institutes of Health Grant R01-DC03007National Institutes of Health Grant R29-DC02525National Institutes of Health Grant F32-DC00194National Institutes of Health Grant F32-DC00205National Institutes of Health Grant T32-DC00038National Science Foundation Grant IRI 89-05249National Science Foundation Grant IRI 93-14967National Science Foundation Grant INT 94-2114

Transcriptome profiling of the small intestinal epithelium in germfree versus conventional piglets-0

<p><b>Copyright information:</b></p><p>Taken from "Transcriptome profiling of the small intestinal epithelium in germfree versus conventional piglets"</p><p>http://www.biomedcentral.com/1471-2164/8/215</p><p>BMC Genomics 2007;8():215-215.</p><p>Published online 5 Jul 2007</p><p>PMCID:PMC1949829.</p><p></p>ted in red while those in black are non-enriched. GOTM analysis demonstrated that more specific biological processes such as immune response, regulation of hydrolase activity, peptide transport and JAK-STAT cascade were significantly modulated by the microbiota. Number of observed genes in a particular biological process is indicated by "n"

Transcriptome profiling of the small intestinal epithelium in germfree versus conventional piglets-1

<p><b>Copyright information:</b></p><p>Taken from "Transcriptome profiling of the small intestinal epithelium in germfree versus conventional piglets"</p><p>http://www.biomedcentral.com/1471-2164/8/215</p><p>BMC Genomics 2007;8():215-215.</p><p>Published online 5 Jul 2007</p><p>PMCID:PMC1949829.</p><p></p>. Red and green colors indicate up- and downregulation in CONV versus GF epithelia, respectively, whereas no color indicates that nodes were not differentially expressed on the array. The network is showing direct literature-supported relationships and confirms the interferon-mediated activation of transcription factors STAT1 and STAT2, which are involved in the expression of IFN-inducible target genes such as class I (in figure; pan SLA I on array and by qRT-PCR), , , , and in CONV compared with GF piglets

Predicting Positive Education Outcomes for Emerging Adults in Mental Health Systems of Care

Emerging adults who receive services based on positive youth development models have shown an ability to shape their own life course to achieve positive goals. This paper reports secondary data analysis from the Longitudinal Child and Family Outcome Study including 248 culturally-diverse youth ages 17 through 22 receiving mental health services in systems of care. After 12 months of services, school performance was positively related to youth ratings of school functioning, and service participation and satisfaction. Regression analysis revealed ratings of young peoples’ perceptions of school functioning and their experience in services added to the significant prediction of satisfactory school performance, even controlling for sex and attendance. Finally, in addition to expected predictors, participation in planning their own services significantly predicted enrollment in higher education for those who finished high school. Findings suggest that programs and practices based on positive youth development approaches can improve educational outcomes for emerging adults

Whole genome sequencing identifies structural variants contributing to hematologic traits in the NHLBI TOPMed program

Genome-wide association studies have identified thousands of single nucleotide variants and small indels that contribute to variation in hematologic traits. While structural variants are known to cause rare blood or hematopoietic disorders, the genome-wide contribution of structural variants to quantitative blood cell trait variation is unknown. Here we utilized whole genome sequencing data in ancestrally diverse participants of the NHLBI Trans Omics for Precision Medicine program (N = 50,675) to detect structural variants associated with hematologic traits. Using single variant tests, we assessed the association of common and rare structural variants with red cell-, white cell-, and platelet-related quantitative traits and observed 21 independent signals (12 common and 9 rare) reaching genome-wide significance. The majority of these associations (N = 18) replicated in independent datasets. In genome-editing experiments, we provide evidence that a deletion associated with lower monocyte counts leads to disruption of an S1PR3 monocyte enhancer and decreased S1PR3 expression