Maternal Genistein Alters Coat Color and Protects A(vy) Mouse Offspring from Obesity by Modifying the Fetal Epigenome

Genistein, the major phytoestrogen in soy, is linked to diminished female reproductive performance and to cancer chemoprevention and decreased adipose deposition. Dietary genistein may also play a role in the decreased incidence of cancer in Asians compared with Westerners, as well as increased cancer incidence in Asians immigrating to the United States. Here, we report that maternal dietary genistein supplementation of mice during gestation, at levels comparable with humans consuming high-soy diets, shifted the coat color of heterozygous viable yellow agouti (A(vy)/a) offspring toward pseudoagouti. This marked phenotypic change was significantly associated with increased methylation of six cytosine–guanine sites in a retrotransposon upstream of the transcription start site of the Agouti gene. The extent of this DNA methylation was similar in endodermal, mesodermal, and ectodermal tissues, indicating that genistein acts during early embryonic development. Moreover, this genistein-induced hypermethylation persisted into adulthood, decreasing ectopic Agouti expression and protecting offspring from obesity. Thus, we provide the first evidence that in utero dietary genistein affects gene expression and alters susceptibility to obesity in adulthood by permanently altering the epigenome

Bone quality changes as measured by Raman and FTIR spectroscopy in primiparous cows with humeral fracture from New Zealand.

The occurrence of spontaneous humeral fractures in primiparous dairy cows from New Zealand prompted the study of bone material from affected cows to further characterize this condition and to outline a likely pathogenesis. Previous studies indicate that these cows developed osteoporosis due to periods of suboptimal bone formation followed by increased bone resorption during the period of lactation complicated by copper deficiency. We hypothesized that there are significant differences in the chemical composition/bone quality in bones from cows with spontaneous humeral fracture compared to cows without humeral fractures. In this study, Raman and Fourier transform infrared spectroscopy band ratios were, for the first time, measured, calculated, and compared in bone samples from 67 primiparous dairy cows that suffered a spontaneous fracture of the humerus and 14 age-matched post-calving cows without humeral fractures. Affected bone showed a significantly reduced mineral/matrix ratio, increased bone remodeling, newer bone tissue with lower mineralization and, lower carbonate substitution, and reduced crystallinity. As such, is likely that these have detrimentally impacted bone quality and strength in affected cows.Published onlin

Paternal obesity is associated with IGF2 hypomethylation in newborns: results from a Newborn Epigenetics Study (NEST) cohort

Data from epidemiological and animal model studies suggest that nutrition during pregnancy may affect the health status of subsequent generations. These transgenerational effects are now being explained by disruptions at the level of the epigenetic machinery. Besides in vitro environmental exposures, the possible impact on the reprogramming of methylation profiles at imprinted genes at a much earlier time point, such as during spermatogenesis or oogenesis, has not previously been considered. In this study, our aim was to determine associations between preconceptional obesity and DNA methylation profiles in the offspring, particularly at the differentially methylated regions (DMRs) of the imprinted Insulin-like Growth Factor 2 (IGF2) gene

Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications.

Analysis of DNA methylation patterns relies increasingly on sequencing-based profiling methods. The four most frequently used sequencing-based technologies are the bisulfite-based methods MethylC-seq and reduced representation bisulfite sequencing (RRBS), and the enrichment-based techniques methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylated DNA binding domain sequencing (MBD-seq). We applied all four methods to biological replicates of human embryonic stem cells to assess their genome-wide CpG coverage, resolution, cost, concordance and the influence of CpG density and genomic context. The methylation levels assessed by the two bisulfite methods were concordant (their difference did not exceed a given threshold) for 82% for CpGs and 99% of the non-CpG cytosines. Using binary methylation calls, the two enrichment methods were 99% concordant and regions assessed by all four methods were 97% concordant. We combined MeDIP-seq with methylation-sensitive restriction enzyme (MRE-seq) sequencing for comprehensive methylome coverage at lower cost. This, along with RNA-seq and ChIP-seq of the ES cells enabled us to detect regions with allele-specific epigenetic states, identifying most known imprinted regions and new loci with monoallelic epigenetic marks and monoallelic expression

GAS COFIRING FOR PERFORMANCE IMPROVEMENT AND EMISSIONS REDUCTION IN COAL AND WOOD-FIRED BOILERS

ABSTRACT Cofiring a small amount of gas in solid-fuel fired boilers is an efficient and economical way to resolve a variety of emissions and performance problems. Gas Research Institute has developed and demonstrated a specialized cofire retrofit package featuring dual, opposed high pressure drop gas burners to control the combustion over the solid fuel. Earlier demonstrations on coal-fired stokers have shown cofire to reduce emissions, enhance performance, increase efficiency and lower operating costs. In the present work, the cofire package has been applied to two coal and two wood-waste fired industrial boilers. At the first coal site, cofire reduced particulate up to 60 percent for 20 percent gas firing. At the second coal site, gas cofire was used to reduce NO x emissions by 20 percent for 20 percent cofire. For wood firing, the strongest driver for gas cofire is to correct for performance degradation caused by wet wood. At the two sites, gas cofire in the 10 to 15 percent range gave recovery of lost capacity derate and up to 90 percent reduction in carbon monoxide emissions

Ontogenic effects of early feeding of sea bass (Dicentrarchus labrax) larvae with a range of dietary n-3 HUFA levels on the functioning of PUFA desaturation pathways

Four replicated groups of sea bass (Dicentrarchus labrax) larvae were fed diets containing an extra-high level of highly unsaturated fatty acids (HUFA) (XH; 3·7% EPA + DHA), a high level of HUFA (HH; 1·7 %), a low level of HUFA (LH; 0·7%) or an extra-low level of HUFA (XLH; 0·5%) from day 6 to day 45 (experiment 1; XH1, HH1, LH1, XLH1). After a subsequent 1-month period feeding a commercial diet (2·7% EPA + DHA), the capacity of the four initial groups to adapt to an n-3 HUFA-restricted diet (0·3% EPA + DHA; R-groups: XH2R, HH2R, LH2R, XLH2R) was tested for 35 d. Larval dietary treatments had no effect on larval and juvenile survival rates. The wet weight of day 45 larvae was higher in XH1 and HH1 (P < 0·001), but the R-juvenile mass gains were similar in all treatments. D-6-desaturase (D6D) mRNA level was higher in LH1 and XLH1 at day 45 (

The structure of tris(chloromethyl)amine in the gas phase using quantum chemical calculations and gas electron diffraction and as a solid and melt using Raman spectroscopy

The equilibrium structure of tris(chloromethyl)amine, N(CH2Cl)3, has been determined in the gas phase using electron diffraction. Single-step distance corrections (representing the differences between the interatomic distances from the equilibrium structure and those from the vibrationally averaged structure) and amplitudes of vibration have been computed using semi-empirical molecular dynamics (SE-MD) simulations in order to treat accurately the description of the low-frequency, large-amplitude vibrational modes associated particularly with one CH2Cl group. A series of complementary theoretical calculations using the SOGGA11-X DFT functional with correlation-consistent basis sets of double-, triple-, and quadruple-ζ quality is also presented. The agreement between the experimental and theoretical equilibrium structural parameters attests to the accuracy of the applied theoretical calculations and of our gas-phase structural solution. Raman spectra have been recorded over a range of temperatures, allowing the solid and the melt to be studied, and the Raman-active intramolecular modes to be identified. Free from the influence of intermolecular interaction, the structure of tris(chloromethyl)amine in the gas phase is markedly different to that reported in the literature for the single crystal. This is discussed, and evidence for the anomeric effect in tris(chloromethyl)amine is evaluated

Season of conception in rural gambia affects DNA methylation at putative human metastable epialleles.

Throughout most of the mammalian genome, genetically regulated developmental programming establishes diverse yet predictable epigenetic states across differentiated cells and tissues. At metastable epialleles (MEs), conversely, epigenotype is established stochastically in the early embryo then maintained in differentiated lineages, resulting in dramatic and systemic interindividual variation in epigenetic regulation. In the mouse, maternal nutrition affects this process, with permanent phenotypic consequences for the offspring. MEs have not previously been identified in humans. Here, using an innovative 2-tissue parallel epigenomic screen, we identified putative MEs in the human genome. In autopsy samples, we showed that DNA methylation at these loci is highly correlated across tissues representing all 3 embryonic germ layer lineages. Monozygotic twin pairs exhibited substantial discordance in DNA methylation at these loci, suggesting that their epigenetic state is established stochastically. We then tested for persistent epigenetic effects of periconceptional nutrition in rural Gambians, who experience dramatic seasonal fluctuations in nutritional status. DNA methylation at MEs was elevated in individuals conceived during the nutritionally challenged rainy season, providing the first evidence of a permanent, systemic effect of periconceptional environment on human epigenotype. At MEs, epigenetic regulation in internal organs and tissues varies among individuals and can be deduced from peripheral blood DNA. MEs should therefore facilitate an improved understanding of the role of interindividual epigenetic variation in human disease

A Sustained Dietary Change Increases Epigenetic Variation in Isogenic Mice

Epigenetic changes can be induced by adverse environmental exposures, such as nutritional imbalance, but little is known about the nature or extent of these changes. Here we have explored the epigenomic effects of a sustained nutritional change, excess dietary methyl donors, by assessing genomic CpG methylation patterns in isogenic mice exposed for one or six generations. We find stochastic variation in methylation levels at many loci; exposure to methyl donors increases the magnitude of this variation and the number of variable loci. Several gene ontology categories are significantly overrepresented in genes proximal to these methylation-variable loci, suggesting that certain pathways are susceptible to environmental influence on their epigenetic states. Long-term exposure to the diet (six generations) results in a larger number of loci exhibiting epigenetic variability, suggesting that some of the induced changes are heritable. This finding presents the possibility that epigenetic variation within populations can be induced by environmental change, providing a vehicle for disease predisposition and possibly a substrate for natural selection