Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10-11 to 5.0 × 10-21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10-6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)

Helium trapping in carbide precipitates in a tempered F82H ferritic–martensitic steel

The microstructural changes of a tempered F82H ferritic–martensitic steel following He implantation at 60 and 500 °C have been examined by transmission electron microscopy (TEM) and atom probe tomography (APT). After irradiation at 500 °C, numerous He bubbles were formed throughout the matrix, whereas after irradiation at 60 °C, no bubbles were seen to form in the matrix. In both irradiations, He bubbles were observed to have formed within large carbide precipitates, determined by APT compositional analysis to be M23C6. The observed preferential He bubble formation in carbides during low temperature He irradiation occurs as a result of the diffusing He being trapped in the carbide due to the strong He–C bond. As the He concentration increases in the carbide due to trapping, He bubbles are formed

Energy dependence of He-ion-induced tungsten nanofuzz formation at non-normal incidence angles

We report measurements of He-ion-beam induced tungsten nanofuzz formation for normal and non-normal incidence angles in the energy range 218eV–10keV. At 218eV, the fuzz tendrils are fine and grow randomly away from the interface in the direction of the surface normal. Above 480eV, the fuzz tendrils become increasingly coarser, and their growth direction is in the direction of the incident beam. This change is attributed to the ion-induced displacement damage which becomes effective once the displacement damage threshold energy is exceeded, and produces additional near-surface trapping sites in those portions of the surface that are in direct line of sight of the incident beam which can nucleate He clusters and initiate bubble growth. Once the surface morphology roughens sufficiently for shadowing to occur, the subsequent fuzz growth occurs preferentially toward the incident ion beam. Molecular dynamics (MD) simulations were carried out to determine the displacement damage threshold energies in the near-surface region along the three major crystallographic directions. It was found that the tungsten bulk values are established within the first 2–4 atomic layers below the tungsten surface. SRIM simulations based on the MD energy thresholds indicate that vacancy damage production in the near-surface region quickly dominates over sputtering in near-surface lattice modification effects as the energy above the damage threshold increases

Characterization of polysulfides in Saccharomyces cerevisiae cells and finished wine from a cysteine-supplemented model grape medium

Polysulfide degradation in wine can result in hydrogen sulfide (H2S) release, imparting a rotten-egg smell that is detrimental to wine quality. Although the presence of wine polysulfides has been demonstrated, their biogenesis remains unclear. This study investigated the role of Saccharomyces cerevisiae in polysulfide formation during fermentation, with and without 5 mM cysteine supplementation as an H2S source. Using an established liquid chromatography-tandem mass spectrometry method, monobromobimane derivatives of hydropolysulfides, including CysSSSH, CysSSSSH and GSSSSH, and two oxidized polysulfides, GSSG and GSSSSG, were detected in yeast cells at the end of fermentation in a grape juice-like medium. Polysulfide production by four S. cerevisiae single deletion mutants (BY4743 Δcys3, Δcys4, Δmet17 and Δtum1) showed no significant differences compared to BY4743, suggesting that uncharacterized pathways maintain cellular polysulfide homeostasis. Five mM cysteine addition increased the formation of shorter sulfur chain species, including GSS-bimane and GSSG, but did not elevate levels of longer sulfur chain species. Additionally, polysulfides with even numbers of sulfur atoms tended to predominate in cellular lysates. Oxidized polysulfides and longer chain hydropolysulfides were not detected in finished wines. This evidence suggests that these polysulfides are unstable in wine-like environments or not transported extracellularly. Collectively, our data illustrate the complexity of yeast polysulfide metabolism under fermentation conditions.Chien-Wei Huang, Rebecca C. Deed, Katie Parish-Virtue, Lisa I. Pilkington, Michelle E. Walker, Vladimir Jiranek, Bruno Fedrizz