Meta-analysis of differentially expressed genes in autism based on gene expression data.

The purpose of this study was to identify differentially expressed (DE) genes and biological processes associated with changes in gene expression in autism. We performed a meta-analysis using new publicly available Gene Expression Omnibus (GEO) datasets of autism. We performed Gene Ontology (GO) enrichment analyses and pathway analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG). Ten GEO datasets, including 364 cases and 248 controls, were available for the meta-analysis. We identified 3105 genes that were consistently DE in autism (1425 upregulated and 1680 downregulated genes). We also found that 7 genes were associated with phospholipase A2 (PLA2), including LYPLA2P1, PLA2G4D, PNPLA2, LYPLA2, PLA2G6, PLA2G7, and PLA2G5. We found GO terms for molecular functions significantly enriched in structural constituent of ribosome (GO: 0003735, P = 1.87-E06) and transcription regulator activity (GO: 0030528, P = 8.86E-04), while for biological processes, the enriched GO terms were involved in translational elongation (GO: 0006414, P = 1.74E-12) and the response to cytokine stimuli (GO: 0034097, P = 2.76E-05). The most significant pathway in our KEGG analysis was the ribosome pathway (P = 7.90E-12). Our meta-analysis identified genes that were consistently DE and biological pathways associated with gene expression changes in autism.

The miR-181d-regulated metalloproteinase Adamts1 enzymatically impairs adipogenesis via ECM remodeling.

The extracellular matrix (ECM) maintenance is crucial to the structural integrity of adipocytes and whole adipose tissue formation. However, the potential impact of the ECM on adipocyte lineage commitment is unclear. Herein, we demonstrate that forced expression of matrix-associated metalloproteinase Adamts1 (a disintegrin and metalloproteinase with thrombospondin motifs 1), which we show is targeted by microRNA-181d (miR-181d) during BMP4-induced adipocytic lineage commitment, markedly impairs adipocyte commitment. Conversely, siRNA-induced inhibition of Adamts1 promotes adipocyte commitment. Adamst1 metalloprotease activity is required for this inhibition and is determined to function via remodeling ECM components followed by activating FAK-ERK signaling pathway during the commitment process. Furthermore, ablation of Adamts1 in adipose tissue increases adipose tissue mass, reduces insulin sensitivity, and disrupts lipid homeostasis. This finding is consistent with Adamts1 decreased expression in the adipose tissue of obese mice and an inverse correlation of Adamts1 expression with body mass index in humans. Collectively, our results indicate that Adamts1 acts as an ECM 'modifier', with miR-181d-induced downregulation, that regulates adipocyte lineage commitment and obesity.

Expression of Bradyrhizobium japonicum nodulation gene in Rhizobium fredii nod mutants.

The B. japonicum USDA 110 pLAFR1 gene library was transferred to Tn5-induced Rhizobium fredii USDA 191-4 Nod- mutants with helper plasmid pRK2013. SmR TcR transconjugants occurred with a frequency of 5 x 10(-4). The transconjugants were purified and used to inoculate germinated soybean seeds. Seven nodules were obtained in the nodulation experiment. The fast-growing Nod+ SmR TcR Rhizobium fredii strain was isolated from all nodules. Each isolate had acquired a new plasmid with a molecular mass of approximately 51 kb. This recombinant plasmid was transferred to E. coli HB101 by helper pRK2013 at a frequency of 1 x 10(-4). In addition to the vector fragment, all the recombinant plasmids gave 23 kb and 6.5 kb fragments on EcoRI digestion. A DNA-DNA hybridization test with a 32P-labelled nod gene probe (prepared from pRmSL26) confirmed that the 20 kb EcoRI-BamHI DNA fragment of the plasmids exhibited sequence homology with an R. meliloti nod gene probe.