Over-expression of Arabidopsis AtCHR23 chromatin remodeling ATPase results in increased variability of growth and gene expression

Plants are sessile organisms that deal with their -sometimes adverse- environment in well-regulated ways. Chromatin remodeling involving SWI/SNF2-type ATPases is thought to be an important epigenetic mechanism for the regulation of gene expression in different developmental programs and for integrating these programs with the response to environmental signals. In this study, we report on the role of chromatin remodeling in Arabidopsis with respect to the variability of growth and gene expression in relationship to environmental conditions

Blood transcriptional and microRNA responses to short-term exposure to disinfection by-products in a swimming pool.

BACKGROUND: Swimming in a chlorinated pool results in high exposure levels to disinfection by-products (DBPs), which have been associated with an increased risk of bladder cancer. OBJECTIVES: By studying molecular responses at the blood transcriptome level we examined the biological processes associated with exposure to these compounds. METHODS: Whole-genome gene expression and microRNA analysis was performed on blood samples collected from 43 volunteers before and 2h after 40min swimming in an indoor chlorinated pool (PISCINAII study). Exposure to THMs was measured in exhaled breath. Heart rate and kcal expenditure were measured as proxies for physical activity. Associations between exposure levels and gene expression were assessed using multivariate normal models (MVN), correcting for age, body mass index and sex. A Bonferroni threshold at 5% was applied. RESULTS: MVN-models for the individual exposures identified 1778 genes and 23 microRNAs that were significantly associated with exposure to at least one DBP. Due to co-linearity it was not possible to statistically disentangle responses to DBP exposure from those related to physical activity. However, after eliminating previously reported transcripts associated with physical activity a large number of hits remained associated with DBP exposure. Among those, 9 were linked with bladder and 31 with colon cancer. Concordant microRNA/mRNA expressions were identified in association with DBP exposure for hsa-mir-22-3p and hsa-miR-146a-5p and their targets RCOR1 and TLR4, both related to colon cancer in association with DBP exposure. CONCLUSIONS: Short-term exposure to low levels of DBPs shows genomics responses that may be indicative of increased cancer risk

Short-term transcriptome and microRNAs responses to exposure to different air pollutants in two population studies.

Diesel vehicle emissions are the major source of genotoxic compounds in ambient air from urban areas. These pollutants are linked to risks of cardiovascular diseases, lung cancer, respiratory infections and adverse neurological effects. Biological events associated with exposure to some air pollutants are widely unknown but applying omics techniques may help to identify the molecular processes that link exposure to disease risk. Most data on health risks are related to long-term exposure, so the aim of this study is to investigate the impact of short-term exposure (two hours) to air pollutants on the blood transcriptome and microRNA expression levels. We analyzed transcriptomics and microRNA expression using microarray technology on blood samples from volunteers participating in studies in London, the Oxford Street cohort, and, in Barcelona, the TAPAS cohort. Personal exposure levels measurements of particulate matter (PM10, PM2.5), ultrafine particles (UFPC), nitrogen oxides (NO2, NO and NOx), black carbon (BC) and carbon oxides (CO and CO2) were registered for each volunteer. Associations between air pollutant levels and gene/microRNA expression were evaluated using multivariate normal models (MVN). MVN-models identified compound-specific expression of blood cell genes and microRNAs associated with air pollution despite the low exposure levels, the short exposure periods and the relatively small-sized cohorts. Hsa-miR-197-3p, hsa-miR-29a-3p, hsa-miR-15a-5p, hsa-miR-16-5p and hsa-miR-92a-3p are found significantly expressed in association with exposures. These microRNAs target also relevant transcripts, indicating their potential relevance in the research of omics-biomarkers responding to air pollution. Furthermore, these microRNAs are also known to be associated with diseases previously linked to air pollution exposure including several cancers such lung cancer and Alzheimer's disease. In conclusion, we identified in this study promising compound-specific mRNA and microRNA biomarkers after two hours of exposure to low levels of air pollutants during two hours that suggest increased cancer risks

Circulating MicroRNAs as novel biomarkers of drug-induced liver injury in humans

MicroRNAs have become a promising candidate for responding to the need for more specific and sensitive biomarkers for drug-induced liver injury (DILI). These small noncoding RNA molecules exert a regulatory function on biological processes by fine tuning gene expression levels. MicroRNAs are the most abundant and stable class of small RNAs in the cell and they are expressed in a cell type- and organ-specific manner. The expression of miRNAs changes with disease state and cells are actively and/or passively secreting miRNAs into the peripheral circulation. These extracellular, circulating miRNAs have been found to reflect the condition of distant organs. Numerous studies have shown elevated serum levels of miR-122, a liver-enriched miRNA, upon drug-induced hepatotoxicity and as a consequence of other liver injuries. These studies demonstrate the potential use of blood samples as minimally invasive, miRNA based “liquid biopsies,” able to interrogate hepatotoxic mechanisms and liver pathology. The purpose of this review is to summarize the recent advances on miRNA-based biomarker research for drug-induced liver injury

Over-expression of Arabidopsis AtCHR23 chromatin remodeling ATPase results in increased variability of growth and gene expression

Plants are sessile organisms that deal with their -sometimes adverse- environment in well-regulated ways. Chromatin remodeling involving SWI/SNF2-type ATPases is thought to be an important epigenetic mechanism for the regulation of gene expression in different developmental programs and for integrating these programs with the response to environmental signals. In this study, we report on the role of chromatin remodeling in Arabidopsis with respect to the variability of growth and gene expression in relationship to environmental conditions

Global microRNA analysis in primary hepatocyte cultures

MicroRNAs are small non-coding molecules that regulate gene expression and in return affect diverse biological functions, including those involved in toxicity and development of disease. Recent evidence suggests that microRNAs play an important role in liver pathologies, like viral hepatitis, alcoholic liver, hepatocellular carcinoma, or drug-induced liver injury. Furthermore, numerous studies demonstrated the high potential of microRNAs as promising non-invasive biomarkers of liver disease or as relevant targets for therapeutic treatment. This chapter describes a method for global microRNA analysis of primary hepatocytes by high-throughput sequencing. The method comprises the isolation of high-quality total RNA, analysis of microRNA sequencing data, and the validation of the findings by reverse transcriptase quantitative polymerase chain reaction analysis