Investigation of MicroRNA and transcription factor mediated regulatory network for silicosis using systems biology approach

Silicosis is a major health issue among workers exposed to crystalline silica. Genetic susceptibility has been implicated in silicosis. The present research demonstrates key regulatory targets and propagated network of gene/miRNA/transcription factor (TF) with interactions responsible for silicosis by integrating publicly available microarray data using a systems biology approach. Array quality is assessed with the Quality Metrics package of Bioconductor, limma package, and the network is constructed using Cytoscape. We observed and enlist 235 differentially expressed genes (DEGs) having up-regulation expression (85 nos) and down-regulation expression (150 nos.) in silicosis; and 24 TFs for the regulation of these DEGs entangled with thousands of miRNAs. Functional enrichment analysis of the DEGs enlighten that, the maximum number of DEGs are responsible for biological process viz, Rab proteins signal transduction (11 nos.) and Cellular Senescence (20 nos.), whereas IL-17 signaling pathway (16 nos.) and Signalling by Nuclear Receptors (14 nos.) etc. are Biological Pathway involving more DEGs. From the identified 1100 high target microRNA (miRNA)s involved in silicosis, 1055 miRNAs are found to relate with down-regulated genes and 847 miRNAs with up-regulated genes. The CDK19 gene (Up-regulated) is associated with 617 miRNAs whereas down-regulated gene ARID5B is regulated by as high as 747 high target miRNAs. In Prediction of Small-molecule signatures, maximum scoring small-molecule combinations for the DEGs have shown that CGP-60774 (with 20 combinations), alvocidib (with 15 combinations) and with AZD-7762 (24 combinations) with few other drugs having the high probability of success.

155 Effects of sustained hyperprolactinemia in late gestation on the mammary parenchymal transcriptome of gilts

The study objective was to determine the effects of hyperprolactinemia on the mammary parenchymal transcriptome in late-pregnant gilts. Gilts were divided into 3 groups on day 90 of gestation to receive IM injections of 1) canola oil (CTL, n = 18) until day 109 of gestation, 2) domperidone (dopamine antagonist) until day 96 (T7, n = 17) or, 3) domperidone until day 109 (T20, n = 17). Mammary glands were collected on day 110 and parenchymal tissue was sampled for transcriptomic analyses. Total RNA was isolated from 6 CTL and 6 T20 gilts for microarray analysis. The GeneChip® Porcine Gene 1.0 ST Array (19,202 genes) was used for hybridization. Array quality control, data normalization and expression level analyses were performed with the Affymetrix Expression Console and Transcriptome Analysis Console (TAC) software. Using a threshold cut-off of 1.5 fold (P < 0.05), a total of 313 upregulated and 480 downregulated gene transcripts were identified in T20 vs CTL gilts. A qPCR validation analysis of selected upregulated (n = 13) and downregulated (n = 13) genes was conducted on all animals (CTL, T7, T20). The MIXED procedure of SAS was used for statistical analyses. All selected genes were validated for the CTL vs T20 comparison (P < 0.01). Only 4 selected genes (CAMK1G, COL9A1, P2RX7, TDRD1) were downregulated in the T7 treatment (vs CTL, P < 0.05). Functional analyses of differentially expressed genes were performed using the PANTHER classification system. The top upregulated Biological Process enriched GO terms were Inflammatory Response (GO:0006954) and Response to Lipid (GO:0033993). The Positive Regulation of Cell Population Proliferation (GO:0008284) and Regulation of Cellular Catabolic Process (GO:0031329) GO terms were identified for downregulated genes. Results suggest that a sustained hyperprolactinemia during late-pregnancy (T20 treatment) may increase mammary inflammatory response and reduce cell proliferation.

Medical consequences of pathogenic CNVs in adults: analysis of the UK Biobank

BackgroundGenomic CNVs increase the risk for early-onset neurodevelopmental disorders, but their impact on medical outcomes in later life is still poorly understood. The UK Biobank allows us to study the medical consequences of CNVs in middle and old age in half a million well-phenotyped adults.MethodsWe analysed all Biobank participants for the presence of 54 CNVs associated with genomic disorders or clinical phenotypes, including their reciprocal deletions or duplications. After array quality control and exclusion of first-degree relatives, we compared 381 452 participants of white British or Irish origin who carried no CNVs with carriers of each of the 54 CNVs (ranging from 5 to 2843 persons). We used logistic regression analysis to estimate the risk of developing 58 common medical phenotypes (3132 comparisons).Results and conclusionsMany of the CNVs have profound effects on medical health and mortality, even in people who have largely escaped early neurodevelopmental outcomes. Forty-six CNV–phenotype associations were significant at a false discovery rate threshold of 0.1, all in the direction of increased risk. Known medical consequences of CNVs were confirmed, but most identified associations are novel. Deletions at 16p11.2 and 16p12.1 had the largest numbers of significantly associated phenotypes (seven each). Diabetes, hypertension, obesity and renal failure were affected by the highest numbers of CNVs. Our work should inform clinicians in planning and managing the medical care of CNV carriers.

The Minnesota Center for Twin and Family Research Genome-Wide Association Study

As part of the Genes, Environment and Development Initiative, the Minnesota Center for Twin and Family Research (MCTFR) undertook a genome-wide association study, which we describe here. A total of 8,405 research participants, clustered in four-member families, have been successfully genotyped on 527,829 single nucleotide polymorphism (SNP) markers using Illumina's Human660W-Quad array. Quality control screening of samples and markers as well as SNP imputation procedures are described. We also describe methods for ancestry control and how the familial clustering of the MCTFR sample can be accounted for in the analysis using a Rapid Feasible Generalized Least Squares algorithm. The rich longitudinal MCTFR assessments provide numerous opportunities for collaboration.

New p-n Junction Photodetector Using Optimized ZnO Nanorod Array

In this research, nanoscale spatial resolution p-n junction photodetector arrays were developed using ZnO nanorod arrays grown on p-type silicon substrates. In order to optimize the nanorod array quality, an advanced combinatorial spreadsheet approach was used to optimize the Au catalyst thickness. The crystallinity of these as-grown ZnO nanorods’ was compared to that of bulk and thin film ZnO materials.