The role of developmental plasticity and epigenetics in human health.
ABSTRACT Considerable epidemiological, experimental and clinical data have amassed showing that the risk of developing disease in later life is dependent on early life conditions, mainly operating within the normative range of developmental exposures. This relationship reflects plastic responses made by the developing organism as an evolved strategy to cope with immediate or predicted circumstances, to maximize fitness in the context of the range of environments potentially faced. There is now increasing evidence, both in animals and humans, that such developmental plasticity is mediated in part by epigenetic mechanisms. However, recognition of the importance of developmental plasticity as an important factor in influencing later life health-particularly within the medical and public health communities-is low, and we argue that this indifference cannot be sustained in light of the growing understanding of developmental processes and the rapid rise in the prevalence of obesity and metabolic disease globally.
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ABSTRACT: Epigenetic dysregulation in disease is increasingly studied as a potential mediator of pathophysiology. The epigenetic events are believed to occur in somatic cells, but the limited changes of DNA methylation in studies to date indicate that only subsets of the cells tested undergo epigenetic dysregulation. The recognition of this subpopulation effect indicates the need for care in design and execution of epigenome-wide association studies (EWASs), paying particular attention to confounding sources of variability. To maximize the sensitivity of the EWASs, ideally, the cell type mediating the disease should be tested, which is not always practical or ethical in human subjects. The value of using accessible cells as surrogates for the target, disease-mediating cell type has not been rigorously tested to date. In this review, participants in a workshop convened by the National Institutes of Health update EWAS design and execution guidelines to reflect new insights in the field.
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ABSTRACT: Lactoferrin (LF) content in infant milk powder has been strictly regulated by many governments and there is a need for convenient and reliable assays. Using hybridoma techniques, fourteen monoclonal antibodies (mAbs) active against LF were prepared. Two antibodies (mAb2 and mAb3), recognizing spatially distant epitopes of LF, were selected to establish a sandwich enzyme-linked immunosorbent assay (ELISA). A solution of mAb3 (1 μg mL−1) was coated onto micro-titer plates for LF capture while mAb2 labeled with horseradish peroxidase (2.2 μg mL−1) was used as a detection antibody. Under optimized conditions, the proposed sandwich ELISA was evaluated, and linearly responded to LF standards in a range of 5-600 ng mL−1 and the limit of detection was 3.23 ng mL−1. Lactoferrin samples were able to be determined after simple dilution, and the recovery in fortified milk powder averaged between 98% and 109%. The developed assay showed both high specificity (with no obvious cross-reactivity with related proteins) and reproducibility (the coefficient of variation ranged from 4.5% to 7.1%), indicating the utility of this sandwich ELISA in LF monitoring.Analytical methods 01/2014; 6(13):4742. DOI:10.1039/c4ay00321g · 1.94 Impact Factor
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ABSTRACT: Over recent years, studies have demonstrated links between risk of cardiovascular disease in adulthood and adverse events that occurred very early in life during fetal development. The concept that there are embryonic and fetal adaptive responses to a sub-optimal intrauterine environment often brought about by poor maternal diet that result in permanent adverse consequences to life-long health is consistent with the definition of "programming". The purpose of this review is to provide an overview of the current knowledge of the effects of intrauterine growth restriction (IUGR) on long-term cardiac structure and function, with particular emphasis on the effects of maternal protein restriction. Much of our recent knowledge has been derived from animal models. We review the current literature of one of the most commonly used models of IUGR (maternal protein restriction in rats), in relation to birth weight and postnatal growth, blood pressure and cardiac structure and function. In doing so, we highlight the complexity of developmental programming, with regards to timing, degree of severity of the insult, genotype and the subsequent postnatal phenotype.Nutrients 01/2014; 7(1):119-152. DOI:10.3390/nu7010119 · 3.15 Impact Factor