Bovine Feed Manipulation, Enhancement of Conjugated Linoleic Acid and Its Bioavailability

Diet is a pivotal contributing factor to the onset and progression of some chronic ailments nowadays. The conjugated linoleic acid (CLA), a bioactive component of ruminant fat, introduces more elucidates what we know polyunsaturated fats and diseases. CLA, a mixture of isomers c9, t11 and t10, c12, is the most abundant ranging from 80 to 90% of total CLA isomers and account for most known health benefits. Dairy milk and meat are the major dietary sources of CLA, and its concentration is of great interest to human health. The biofunctionalities of CLA from enriched dairy products are major attributes in the context of a substance present in our everyday diet. Thus, dietary modifications in animal feed, synthetic and microbial production have been made to increase CLA intake to enhance its clinical manifestations. However, the bioavailability and distribution of enriched or supplemented CLA has not been fully elucidated because of its response variation in different animal models. This chapter deals with different dietary sources, availability, enhancement of CLA in dairy products and its positive manifestation against different maladies. In conclusion, it is feasible to produce CLA-enriched dairy products with acceptable storage and sensory characteristics while deriving its nutritional benefits

Biology and Clinical Implications of the 19q13 Aggressive Prostate Cancer Susceptibility Locus

Genome-wide association studies (GWAS) have identified rs11672691 at 19q13 associated with aggressive prostate cancer (PCa). Here, we independently confirmed the finding in a cohort of 2,738 PCa patients and discovered the biological mechanism underlying this association. We found an association of the aggressive PCa-associated allele G of rs11672691 with elevated transcript levels of two biologically plausible candidate genes, PCAT19 and CEACAM21, implicated in PCa cell growth and tumor progression. Mechanistically, rs11672691 resides in an enhancer element and alters the binding site of HOXA2, a novel oncogenic transcription factor with prognostic potential in PCa. Remarkably, CRISPR/Cas9-mediated single-nucleotide editing showed the direct effect of rs11672691 on PCAT19 and CEACAM21 expression and PCa cellular aggressive phenotype. Clinical data demonstrated synergistic effects of rs11672691 genotype and PCAT19/CEACAM21 gene expression on PCa prognosis. These results provide a plausible mechanism for rs11672691 associated with aggressive PCa and thus lay the ground work for translating this finding to the clinic

Genome-Wide Association Study and Functional Characterization Identifies Candidate Genes for Insulin-Stimulated Glucose Uptake

Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in \u3e55,000 participants from three ancestry groups. We identified ten new loci (P \u3c 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits

Mobile Assisted Language Learning: Evaluation of Accessibility, Adoption, and Perceived Outcome among Students of Higher Education

The present study was aimed at analyzing students’ perceptions toward mobile assisted language learning (MALL), their use patterns, and their usefulness in their academic outcomes. The results indicated that students use widely different MALL software for different applications. In a survey of 581 students from Indian colleges and universities, the research identified five antecedent factors (namely, individual desire and motives, perceived ease of use, technological factors, social influence, and perceived usefulness) which influenced students in the areas of adopting MALL software, students’ readiness, students’ motivation, and the subsequent effect on student performances. The research further indicated that students’ readiness and their motivation level mediated the relationship between factors of adoption of MALL and perceived outcome. The relevance of positive language learning outcomes, theoretical contribution and managerial implications of the study are discussed

Trisk 95 as a novel skin mirror for normal and diabetic systemic glucose level

International audienceDeveloping trustworthy, cost effective, minimally or non-invasive glucose sensing strategies is of great need for diabetic patients. In this study, we used an experimental type I diabetic mouse model to examine whether the skin would provide novel means for identifying biomarkers associated with blood glucose level. We first showed that skin glucose levels are rapidly influenced by blood glucose concentrations. We then conducted a proteomic screen of murine skin using an experimental in vivo model of type I diabetes and wild-type controls. Among the proteins that increased expression in response to high blood glucose, Trisk 95 expression was significantly induced independently of insulin signalling. A luciferase reporter assay demonstrated that the induction of Trisk 95 expression occurs at a transcriptional level and is associated with a marked elevation in the Fluo-4AM signal, suggesting a role for intracellular calcium changes in the signalling cascade. Strikingly, these changes lead concurrently to fragmentation of the mitochondria. Moreover, Trisk 95 knockout abolishes both the calcium flux and the mitochondrial phenotype changes indicating dependency of glucose flux in the skin on Trisk 95 function. The data demonstrate that the skin reacts robustly to systemic blood changes, and that Trisk 95 is a promising biomarker for a glucose monitoring assembly

Trisk 95 as a novel skin mirror for normal and diabetic systemic glucose level

Abstract Developing trustworthy, cost effective, minimally or non-invasive glucose sensing strategies is of great need for diabetic patients. In this study, we used an experimental type I diabetic mouse model to examine whether the skin would provide novel means for identifying biomarkers associated with blood glucose level. We first showed that skin glucose levels are rapidly influenced by blood glucose concentrations. We then conducted a proteomic screen of murine skin using an experimental in vivo model of type I diabetes and wild-type controls. Among the proteins that increased expression in response to high blood glucose, Trisk 95 expression was significantly induced independently of insulin signalling. A luciferase reporter assay demonstrated that the induction of Trisk 95 expression occurs at a transcriptional level and is associated with a marked elevation in the Fluo-4AM signal, suggesting a role for intracellular calcium changes in the signalling cascade. Strikingly, these changes lead concurrently to fragmentation of the mitochondria. Moreover, Trisk 95 knockout abolishes both the calcium flux and the mitochondrial phenotype changes indicating dependency of glucose flux in the skin on Trisk 95 function. The data demonstrate that the skin reacts robustly to systemic blood changes, and that Trisk 95 is a promising biomarker for a glucose monitoring assembly

High-throughput screening of prostate cancer risk loci by single nucleotide polymorphisms sequencing

Abstract Functional characterization of disease-causing variants at risk loci has been a significant challenge. Here we report a high-throughput single-nucleotide polymorphisms sequencing (SNPs-seq) technology to simultaneously screen hundreds to thousands of SNPs for their allele-dependent protein-binding differences. This technology takes advantage of higher retention rate of protein-bound DNA oligos in protein purification column to quantitatively sequence these SNP-containing oligos. We apply this technology to test prostate cancer-risk loci and observe differential allelic protein binding in a significant number of selected SNPs. We also test a unique application of self-transcribing active regulatory region sequencing (STARR-seq) in characterizing allele-dependent transcriptional regulation and provide detailed functional analysis at two risk loci (RGS17 and ASCL2). Together, we introduce a powerful high-throughput pipeline for large-scale screening of functional SNPs at disease risk loci