The Total Western Diet and Vancomycin Increase Inflammation Mediated Colorectal Cancer

Total Western Diet (TWD) fed mice have increased azoxymethane/dextran sodium sulfate (AOM/DSS) induced colorectal cancer (CRC). Using the AOM/DSS model, another group found that vancomycin (VM) reduced CRC via changes to the microbiome. This study was done to determine interactions between diet and VM induced changes to the microbiome on CRC. C57BL/6J mice were allotted into 4 treatments in a 2X2 factorial design: 1)AIN93G diet+no VM (AN, n=33); 2)AIN93G+VM in drinking water (2g/L, AVM, n=30); 3)TWD+no VM (TN, n=35); 4)TWD+VM (TVM, n=29). Food and water was provided ad libitum with intakes measured weekly. Fecal samples were collected for microbiome analysis. After 14 days, mice were injected with AOM (10 mg/kg) to induce CRC, followed by 1% DSS added to drinking water for 10 days to induce inflammation. Mice were evaluated for colitis disease activity (CAD). After recovery (24 days post AOM), 48 mice (n=12 per group) were sacrificed and colons were examined by histopathology. Remaining mice were kept on treatments for 9 additional weeks, sacrificed, and colons were examined for tumor burden and histopathology. TWD increased CAD compared to AIN93G during active colitis (P\u3c0.001); the same effect was found when assessing mucosal injury (P=0.01). TWD and VM increased tumor burden (P=0.02 for diet, P=0.002 for VM treatment) and multiplicity (P\u3c0.001 for diet and VM treatment); there were significant interactions between these factors for tumor burden (P=0.03) and multiplicity (P=0.04). The greatest difference for tumor burden was between TVM mice (49.7510.06mm3, meanSEM) and AN mice (12.343.67mm3, P\u3c0.01). Tumor multiplicity showed similar results. Beta diversity analysis of the microbiome demonstrated that VM determined whether samples clustered together. The TWD increased CRC; contrary to a prior report, we demonstrate VM increases CRC. There are significant interactions between these factors. These results suggest that diet and the gut microbiome modulate CRC

Student Engagement in LDS Seminaries

This qualitative study examined student engagement in seminaries of The Church of Jesus Christ of Latter-day Saints (LDS). This study sought to answer the following question: What are seminary teachers, who have been identified by content experts as having high levels of student engagement, doing to generate high levels of student engagement in their classrooms? Ten LDS Seminary teachers were selected as participants for this study. The findings from this study were organized around the concepts of: competence, school membership, clarity of purpose, fairness, personal support, caring, authentic work, extrinsic reward, intrinsic interests, sense of ownership, connection to real-world application, and fun. The findings from this study suggest that there are 48 strategies that the 10 participants used to generate student engagement in their classrooms

The utility of DNA microarrays for characterizing genotoxicity.

Microarrays provide an unprecedented opportunity for comprehensive concurrent analysis of thousands of genes. The global analysis of the response of genes to a toxic insult (toxicogenomics), as opposed to the historical method of examining a few select genes, provides a more complete picture of toxicologically significant events. Here we examine the utility of microarrays for providing mechanistic insights into the response of cells to DNA damage. Our data indicate that the value of the technology is in its potential to provide mechanistic insight into the mode of action of a genotoxic compound. Array-based expression profiling may be useful for differentiating compounds that interact directly with DNA from those compounds that are genotoxic via a secondary mechanism. As such, genomic microarrays may serve as a valuable alternative methodology that helps discriminate between these two classes of compounds. Key words: biomarkers, gene expression profile, genetic toxicology, mechanism of action, toxicogenomics

Activity of Genes with Functions in Human Williams-Beuren Syndrome Is Impacted by Mobile Element Insertions in the Gray Wolf Genome.

In canines, transposon dynamics have been associated with a hyper-social behavioral syndrome, although the functional mechanism has yet to be described. We investigate the epigenetic and transcriptional consequences of these behavior-associated mobile element insertions (MEIs) in dogs and Yellowstone gray wolves. We posit that the transposons themselves may not be the causative feature; rather, their transcriptional regulation may exert the functional impact. We survey four outlier transposons associated with hyper-sociability, with the expectation that they are targeted for epigenetic silencing. We predict hyper-methylation of MEIs, suggestive that the epigenetic silencing of and not the MEIs themselves may be driving dysregulation of nearby genes. We found that transposon-derived sequences are significantly hyper-methylated, regardless of their copy number or species. Further, we have assessed transcriptome sequence data and found evidence that MEIs impact the expression levels of six genes (WBSCR17, LIMK1, GTF2I, WBSCR27, BAZ1B, and BCL7B), all of which have known roles in human Williams-Beuren syndrome due to changes in copy number, typically hemizygosity. Although further evidence is needed, our results suggest that a few insertions alter local expression at multiple genes, likely through a cis-regulatory mechanism that excludes proximal methylation