InsPR-RyR Ca channel crosstalk facilitates arrhythmias in the failing human ventricle.

Dysregulated intracellular Ca handling involving altered Ca release from intracellular stores via RyR channels underlies both arrhythmias and reduced function in heart failure (HF). Mechanisms linking RyR dysregulation and disease are not fully established. Studies in animals support a role for InsP receptor Ca channels (InsPR) in pathological alterations in cardiomyocyte Ca handling but whether these findings translate to the divergent physiology of human cardiomyocytes during heart failure is not determined.

Effect of maternal preconceptional and pregnancy micronutrient interventions on children's DNA methylation: Findings from the EMPHASIS study.

Background: Maternal nutrition in pregnancy has been linked to offspring health in early and later life, with changes to DNA methylation (DNAm) proposed as a mediating mechanism.

Objective: We investigated intervention-associated DNAm changes in children whose mothers participated in 2 randomized controlled trials of micronutrient supplementation before and during pregnancy, as part of the EMPHASIS (Epigenetic Mechanisms linking Preconceptional nutrition and Health Assessed in India and sub-Saharan Africa) study (ISRCTN14266771).

Design: We conducted epigenome-wide association studies with blood samples from Indian (n = 698) and Gambian (n = 293) children using the Illumina EPIC array and a targeted study of selected loci not on the array.

Transcriptional co-expression regulatory network analysis for Snail and Slug identifies , an inflammatory cytokine receptor, to be preferentially expressed in ST-EPN- and PF-EPN-A molecular subgroups of intracranial ependymomas.

Recent molecular subgrouping of ependymomas (EPN) by DNA methylation profiling has identified ST-EPN- and PF-EPN-A subgroups to be associated with poor outcome. Snail/Slug are cardinal epithelial-to-mesenchymal transcription factors (EMT-TFs) and are overexpressed in several CNS tumors, including EPNs. A systematic analysis of gene-sets/modules co-expressed with and genes using published expression microarray dataset (GSE27279)identified 634 genes for with enriched TGF-β, PPAR and PI3K signaling pathways, and 757 genes for with enriched focal adhesion, ECM-receptor interaction and regulation of actin cytoskeleton related pathways.

Candidate genes linking maternal nutrient exposure to offspring health via DNA methylation: a review of existing evidence in humans with specific focus on one-carbon metabolism.

Background: Mounting evidence suggests that nutritional exposures during pregnancy influence the fetal epigenome, and that these epigenetic changes can persist postnatally, with implications for disease risk across the life course.

Methods: We review human intergenerational studies using a three-part search strategy. Search 1 investigates associations between preconceptional or pregnancy nutritional exposures, focusing on one-carbon metabolism, and offspring DNA methylation.

Protocol for the EMPHASIS study; epigenetic mechanisms linking maternal pre-conceptional nutrition and children's health in India and Sub-Saharan Africa.

Background: Animal studies have shown that nutritional exposures during pregnancy can modify epigenetic marks regulating fetal development and susceptibility to later disease, providing a plausible mechanism to explain the developmental origins of health and disease. Human observational studies have shown that maternal peri-conceptional diet predicts DNA methylation in offspring. However, a causal pathway from maternal diet, through changes in DNA methylation, to later health outcomes has yet to be established.

Intrauterine Programming of Diabetes and Adiposity.

The prevalence of diabetes and adiposity has increased at an alarming rate and together they contribute to the rise in morbidity and mortality worldwide. Genetic studies till date have succeeded in explaining only a proportion of heritability, while a major component remains unexplained. Early life determinants of future risk of these diseases are likely contributors to the missing heritability and thus have a significant potential in disease prevention.