Environ Mol Mutagen

Epigenetic changes such as DNA methylation may be a molecular mechanism through which environmental exposures affect health. Methylation of Alu and long interspersed nucleotide elements (LINE-1) is a well-established measure of DNA methylation often used in epidemiologic studies. Yet, few studies have examined the effects of host factors on LINE-1 and Alu methylation in children. We characterized the relationship of age, sex, and prenatal exposure to persistent organic pollutants (POPs), dichlorodiphenyl trichloroethane (DDT), dichlorodiphenyldichloroethylene (DDE), and polybrominated diphenyl ethers (PBDEs), with DNA methylation in a birth cohort of Mexican-American children participating in the CHAMACOS study. We measured Alu and LINE-1 methylation by pyrosequencing bisulfite-treated DNA isolated from whole blood samples collected from newborns and nine-year old children (n\ue2\u20ac\u2030=\ue2\u20ac\u2030358). POPs were measured in maternal serum during late pregnancy. Levels of DNA methylation were lower in nine-year olds compared to newborns and were higher in boys compared to girls. Higher prenatal DDT/E exposure was associated with lower Alu methylation at birth, particularly after adjusting for cell type composition (P\ue2\u20ac\u2030=\ue2\u20ac\u20300.02 for o,p' -DDT). Associations of POPs with LINE-1 methylation were only identified after examining the co-exposure of DDT/E with PBDEs simultaneously. Our data suggest that repeat element methylation can be an informative marker of epigenetic differences by age and sex and that prenatal exposure to POPs may be linked to hypomethylation in fetal blood. Accounting for co-exposure to different types of chemicals and adjusting for blood cell types may increase sensitivity of epigenetic analyses for epidemiological studies.P01 ES009605/ES/NIEHS NIH HHS/United StatesP01 ES009605/ES/NIEHS NIH HHS/United StatesR01 ES015572/ES/NIEHS NIH HHS/United StatesR01 OH007400/OH/NIOSH CDC HHS/United States2015-04-27T00:00:00

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

MTF chip performance assessment.

<p>Results from this study were used to compare the MTF chip based model to <i>in vivo/ex vivo</i> and other <i>in vitro</i> tissue model studies. Many models only examine certain features of pathology, this MTF chip based model mimics ventricular tissue architecture and generates multiscale readouts and can be used to compare healthy and diseased tissues.</p

ANG II treatment leads to decreased contractile function.

<p>(A,) MTF Chip. (A,i) Photograph of experimental setup (Scale bar: 1 cm). (A ii-iii) Schematic of the MTF chip in diastole (ii) and systole positions (iii). Microcontact printing was used to pattern cells to resemble the structure of heart tissue architecture mimicked on the MTF chip (Scale bar: 20 μm). (A,iv) Fibronectin patterns on surface of thin film drive tissue architecture (Scale bar: 20 μm). (A,v) Brightfield image of engineered cardiac tissues on the MTF. (B-D) (i) Diastole and (ii) peak systole of muscular thin films. Blue outline represents the original film length, red line represents the x-projection of the radius of curvature of the film (Scale bar: 500 μm). (E) Representative stress traces generated from x-projections of films (F) ANG II treatment leads to a decrease in contractile stress generation. Control n = 85 tissues, 5 nM n = 15 tissues, 100 nM n = 69 tissues, 3 harvests. Tissues were paced at 2Hz (mean ± SEM, * indicates p < 0.05 vs control, # indicates p < 0.05 vs. 100 nM).</p

ANG II increases the occurrence of early after depolarizations (EADs) and arrhythmias.

<p>(A) Normalized fluorescence intensity of Rohd 2 dye (top panel) over time (<i>x</i>-axis) along a line crossing the 2D field of view (<i>y</i>-axis). Average fluorescence intensity traces (Bottom), red markers indicate the applied electrical pacing at 2Hz (Scale bar: 500 ms). Traces were normalized relative to the maximum peak intensity, F_N<b>=</b> F_{instantaneous}/ F_max. (B) Percentage EAD events relative to total paced events. (C) Percentage of EADs which evolved into sustained arrhythmia. (D) Time to peak for each condition. Control n = 8 tissues, 5 nM n = 8 tissues, 100 nM n = 10 tissues (mean ± SEM; * indicates p < 0.05 vs. control).</p