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Abstract: Many herpesviruses, including Marek''s disease viruses (MDV1 and MDV2), encode microRNAs. In this study, we report microRNAs of two related herpesviruses, infectious laryngotracheitis virus (ILTV) and herpesvirus of turkeys (HVT), as well as additional MDV2 microRNAs. The genome locations, but not microRNA sequences, are conserved among all four of these avian herpesviruses. Most are clustered in the repeats flanking the unique long region (I/TRL), except in ILTV which lacks these repeats. Two abundant ILTV microRNAs are antisense to the immediate early gene ICP4. A homologue of host microRNA, gga-miR-221, was found among the HVT microRNAs. Additionally, a cluster of HVT microRNAs was found in a region containing two locally duplicated segments, resulting in paralogous HVT microRNAs with 96–100% identity. The prevalence of microRNAs in the genomic repeat regions as well as in local repeats suggests the importance of genetic plasticity in herpesviruses for microRNA evolution and preservation of function. [Copyright &y& Elsevier]

Abstract: Chronic drinking water exposure to inorganic arsenic and its metabolites increases tumor frequency in the skin of K6/ODC transgenic mice. To identify potential biomarkers and modes of action for this skin tumorigenicity, we characterized gene expression profiles from analysis of K6/ODC mice administered 0, 0.05, 0.25, 1.0 and 10 ppm sodium arsenite in their drinking water for 4 weeks. Following exposure, total RNA was isolated from mouse skin and processed to biotin-labeled cRNA for microarray analyses. Skin gene expression was analyzed with Affymetrix Mouse Genome 430A 2.0 GeneChips®, and pathway analysis was conducted with DAVID (NIH), Ingenuity® Systems and MetaCore''s GeneGo. Differential expression of several key genes was verified through qPCR. Only the highest dose (10 ppm) resulted in significantly altered KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, including MAPK, regulation of actin cytoskeleton, Wnt, Jak–Stat, Tight junction, Toll-like, phosphatidylinositol and insulin signaling pathways. Approximately 20 genes exhibited a dose response, including several genes known to be associated with carcinogenesis or tumor progression including cyclin D1, CLIC4, Ephrin A1, STAT3 and DNA methyltransferase 3a. Although transcription changes in all identified genes have not previously been linked to arsenic carcinogenesis, their association with carcinogenesis in other systems suggests that these genes may play a role in the early stages of arsenic-induced skin carcinogenesis and can be considered potential biomarkers. [Copyright &y& Elsevier]

Abstract: Intermedin (IMD) is a novel member of the calcitonin/calcitonin gene-related peptide (CT/CGRP) family identified from human and other vertebrate tissues. Preprointermedin (preproIMD) can generate a 47 amino acid mature peptide (IMD1–47) and a shorter 40 amino acid one (IMD8–47) by proteolytic cleavage. Amino acid sequence analysis showed that cleavage sites are located between two basic amino acids at Arg93-Arg94, resulting in the production of preproIMD95–147, namely IMD1–53. The present study was designed to observe the effects of IMD1–53 on cardiac function in ischemia/reperfusion (I/R) injury in isolated rat hearts. Perfusion with high-dose IMD1–53 gave higher left ventricular systolic pressure (LVSP) and maximal rate of increase and decrease of left ventricle pressure (±LVdP/dtmax), and coronary perfusion flow (CPF) than those of controls. Cardiac I/R induced a marked inhibition of cardiac function and myocardial injury. Reperfusion with IMD1–53 significantly ameliorated the inhibited cardiac function and bradycardia induced by I/R. Compared with the I/R-treatment alone, IMD1–53 reperfusion augmented CPF, LVSP, and maximal rate of increase and decrease of left ventricle pressure (±LVdP/dtmax) and decreased LVDP. In addition, reperfusion with IMD1–53markedly attenuated the leakage of lactate dehydrogenase and malondialdehyde content in myocardia compared with I/R alone. Reperfusion with IMD1–53increased the content of cyclic adenosine monophosphate in comparison with I/R alone. Interestingly, the above IMD1–53 effects are similar to those of adrenomedullin. These results suggest that IMD1–53, like adrenomedullin, has cardioprotective effects against myocardial I/R injury. [Copyright &y& Elsevier]