Roux-En Y Gastric Bypass Surgery Induces Genome-Wide Promoter-Specific Changes in DNA Methylation in Whole Blood of Obese Patients

Context DNA methylation has been proposed to play a critical role in many cellular and biological processes. Objective To examine the influence of Roux-en-Y gastric bypass (RYGB) surgery on genome-wide promoter-specific DNA methylation in obese patients. Promoters are involved in the initiation and regulation of gene transcription. Methods Promoter-specific DNA methylation in whole blood was measured in 11 obese patients (presurgery BMI >35 kg/m2, 4 females), both before and 6 months after RYGB surgery, as well as once only in a control group of 16 normal-weight men. In addition, body weight and fasting plasma glucose were measured after an overnight fast. Results The mean genome-wide distance between promoter-specific DNA methylation of obese patients at six months after RYGB surgery and controls was shorter, as compared to that at baseline (p<0.001). Moreover, postsurgically, the DNA methylation of 51 promoters was significantly different from corresponding values that had been measured at baseline (28 upregulated and 23 downregulated, P<0.05 for all promoters, Bonferroni corrected). Among these promoters, an enrichment for genes involved in metabolic processes was found (n = 36, P<0.05). In addition, the mean DNA methylation of these 51 promoters was more similar after surgery to that of controls, than it had been at baseline (P<0.0001). When controlling for the RYGB surgery-induced drop in weight (-24% of respective baseline value) and fasting plasma glucose concentration (-16% of respective baseline value), the DNA methylation of only one out of 51 promoters (~2%) remained significantly different between the pre-and postsurgery time points. Conclusions Epigenetic modifications are proposed to play an important role in the development of and predisposition to metabolic diseases, including type II diabetes and obesity. Thus, our findings may form the basis for further investigations to unravel the molecular effects of gastric bypass surgery. Clinical Trial ClinicalTrials.gov NCT0173074

Longitudinal genome-wide methylation study of Roux-en-Y gastric bypass patients reveals novel CpG sites associated with essential hypertension

Background: Essential hypertension is a significant risk factor for cardiovascular diseases. Emerging research suggests a role of DNA methylation in blood pressure physiology. We aimed to investigate epigenetic associations of promoter related CpG sites to essential hypertension in a genome-wide methylation approach. Methods: The genome-wide methylation pattern in whole blood was measured in 11 obese patients before and six months after Roux-en-Y gastric bypass surgery using the Illumina 450 k beadchip. CpG sites located within 1500 bp of the transcriptional start site of adjacent genes were included in our study, resulting in 124 199 probes investigated in the subsequent analysis. Percent changes in methylation states and SBP measured before and six months after surgery were calculated. These parameters were correlated to each other using the Spearman's rank correlation method (Edgeworth series approximation). To further investigate the detected relationship between candidate CpG sites and systolic blood pressure levels, binary logistic regression analyses were performed in a larger and independent cohort of 539 individuals aged 19-101 years to elucidate a relationship between EH and the methylation state in candidate CpG sites. Results: We identified 24 promoter associated CpG sites that correlated with change in SBP after RYGB surgery (p < 10-16). Two of these CpG loci (cg00875989, cg09134341) were significantly hypomethylated in dependency of EH (p < 10-03). These results were independent of age, BMI, ethnicity and sex. Conclusions: The identification of these novel CpG sites may contribute to a further understanding of the epigenetic regulatory mechanisms underlying the development of essential hypertension

Large phenotype jumps in biomolecular evolution

By defining the phenotype of a biopolymer by its active three-dimensional shape, and its genotype by its primary sequence, we propose a model that predicts and characterizes the statistical distribution of a population of biopolymers with a specific phenotype, that originated from a given genotypic sequence by a single mutational event. Depending on the ratio g0 that characterizes the spread of potential energies of the mutated population with respect to temperature, three different statistical regimes have been identified. We suggest that biopolymers found in nature are in a critical regime with g0 in the range 1-6, corresponding to a broad, but not too broad, phenotypic distribution resembling a truncated Levy flight. Thus the biopolymer phenotype can be considerably modified in just a few mutations. The proposed model is in good agreement with the experimental distribution of activities determined for a population of single mutants of a group I ribozyme.Comment: to appear in Phys. Rev. E; 7 pages, 6 figures; longer discussion in VII, new fig.

Sonoluminescing air bubbles rectify argon

The dynamics of single bubble sonoluminescence (SBSL) strongly depends on the percentage of inert gas within the bubble. We propose a theory for this dependence, based on a combination of principles from sonochemistry and hydrodynamic stability. The nitrogen and oxygen dissociation and subsequent reaction to water soluble gases implies that strongly forced air bubbles eventually consist of pure argon. Thus it is the partial argon (or any other inert gas) pressure which is relevant for stability. The theory provides quantitative explanations for many aspects of SBSL.Comment: 4 page

Decomposition of 1,1-Dichloroethane and 1,1-Dichloroethene in an electron beam generated plasma reactor

An electron beam generated plasma reactor is used to decompose low concentrations (100–3000 ppm) of 1,1-dichloroethane and 1,1-dichloroethene in atmospheric pressure air streams. The energy requirements for 90% and 99% decomposition of each compound are reported as a function of inlet concentration. Dichloroethene decomposition is enhanced by a chlorine radical propagated chain reaction. The chain length of the dichloroethene reaction is estimated to increase with dichloroethene concentration from 10 at 100 ppm initial dichloroethene concentration to 30 at 3000 ppm. Both the dichloroethane and dichloroethene reactions seem to be inhibited by electron scavenging decomposition products. A simple analytic expression is proposed for fitting decomposition data where inhibition effects are important and simple first order kinetics are not observed