miRNAs from Inflamed Gingiva Link Gene Signaling to Increased MET Expression.

Several array-based microRNA (miRNA) expression studies independently showed increased expression of miRNAs hsa-miR-130a-3p, -142-3p, -144-3p, -144-5p, -223-3p, -17-5p, and -30e-5p in gingiva affected by periodontal inflammation. We aimed to determine direct target genes and signaling pathways regulated by these miRNAs to identify processes relevant to gingival inflammatory responses and tissue homeostasis. We transfected miRNA mimics (mirVana) for each of the 7 miRNAs separately into human primary gingival fibroblasts cultured from 3 different donors. Following RNA sequencing, differential gene expression and second-generation gene set enrichment analyses were performed. miRNA inhibition and upregulation was validated at the transcript and protein levels using quantitative reverse transcriptase polymerase chain reaction, Western blotting, and reporter gene assays. All 7 miRNAs significantly increased expression of the gene MET proto-oncogene, receptor tyrosine kinase (MET). Expression of known periodontitis risk genes CPEB1, ABCA1, and ATP6V1C1 was significantly repressed by hsa-miR-130a-3p, -144-3p, and -144-5p, respectively. The genes WASL, ENPP5, ARL6IP1, and IDH1 showed the most significant and strongest downregulation after hsa-miR-142-3p, -17-5p, -223-3p, and -30e-5p transfection, respectively. The most significantly regulated gene set of each miRNA related to cell cycle (hsa-miRNA-144-3p and -5p [Padj = 4 × 10-40 and Padj = 4 × 10-6], -miR-17-5p [Padj = 9.5 × 10-23], -miR-30e-5p [Padj = 8.2 × 10-18], -miR-130a-3p [Padj = 5 × 10-15]), integrin cell surface interaction (-miR-223-3p [Padj = 2.4 × 10-7]), and interferon signaling (-miR-142-3p [Padj = 5 × 10-11]). At the end of acute inflammation, gingival miRNAs bring together complex regulatory networks that lead to increased expression of the gene MET. This underscores the importance of mesenchymal cell migration and invasion during gingival tissue remodeling and proliferation in restoring periodontal tissue homeostasis after active inflammation. MET, a receptor of the mitogenic hepatocyte growth factor fibroblast secreted, is a core gene of this process.

Maternal immune activation results in complex microglial transcriptome signature in the adult offspring that is reversed by minocycline treatment.

Maternal immune activation (MIA) during pregnancy has been linked to an increased risk of developing psychiatric pathologies in later life. This link may be bridged by a defective microglial phenotype in the offspring induced by MIA, as microglia have key roles in the development and maintenance of neuronal signaling in the central nervous system. The beneficial effects of the immunomodulatory treatment with minocycline on schizophrenic patients are consistent with this hypothesis. Using the MIA mouse model, we found an altered microglial transcriptome and phagocytic function in the adult offspring accompanied by behavioral abnormalities. The changes in microglial phagocytosis on a functional and transcriptional level were similar to those observed in a mouse model of Alzheimer's disease hinting to a related microglial phenotype in neurodegenerative and psychiatric disorders. Minocycline treatment of adult MIA offspring reverted completely the transcriptional, functional and behavioral deficits, highlighting the potential benefits of therapeutic targeting of microglia in psychiatric disorders.

Combining frequency and positional information to predict transcription factor binding sites.

MOTIVATION: Even though a number of genome projects have been finished on the sequence level, still only a small proportion of DNA regulatory elements have been identified. Growing amounts of gene expression data provide the possibility of finding coregulated genes by clustering methods. By analysis of the promoter regions of those genes, rather weak signals of transcription factor binding sites may be detected. RESULTS: We introduce the new algorithm ITB, an Integrated Tool for Box finding, which combines frequency and positional information to predict transcription factor binding sites in upstream regions of coregulated genes. Motifs are extracted by exhaustive analysis of regular expression-like patterns and by estimating probabilities of positional clusters of motifs. ITB detects consensus sequences of experimentally verified transcription factor binding sites of the yeast Saccharomyces cerevisiae. Moreover, a number of new binding site candidates with significant scores are predicted. Besides applying ITB on yeast upstream regions, the program is run on human promoter sequences. AVAILABILITY: ITB is available upon request.

Isentropes and Hugoniot curves for dense hydrogen and deuterium.

Multiple-shock experiments with fluid hydrogen have shown that a transition from semiconducting behavior to metal-like conductivity occurs at pressures (p) of about 140 GPa and temperatures (T) near 3000 K. We model the p-T pathway by Hugoniot curves (initial shock) and isentropes (subsequent shocks). For the calculation of these curves we apply an expression for the free energy developed recently for dense hydrogen and deuterium plasma in the regions of partial dissociation and partial ionization. Furthermore, we discuss the relations between Hugoniot curves, isentropes and the coexistence line of the plasma phase transition.

Normalization strategies for cDNA microarrays.

Multiple Arabidopsis thaliana clones from an experimental series of cDNA microarrays are evaluated in order to identify essential sources of noise in the spotting and hybridization process. Theoretical and experimental strategies for an improved quantitative evaluation of cDNA microarrays are proposed and tested on a series of differently diluted control clones. Several sources of noise are identified from the data. Systematic and stochastic fluctuations in the spotting process are reduced by control spots and statistical techniques. The reliability of slide to slide comparison is critically assessed within the statistical framework of pattern matching and classification.