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

Influence of antihypertensive drugs on aortic and coronary effects of Ang-(1-7) in pressure-overloaded rats

This study investigated the influence of antihypertensive drugs, such as angiotensin-converting enzyme inhibitors (ACEIs), AT1 receptor blockers (ARBs), voltage-gated L-type calcium channel blockers, and mineralocorticoid receptor antagonists (MRAs), on the effects of angiotensin-(1-7) [Ang-(1-7)] on aorta and coronary arteries from pressure-overloaded rats. Pressure overload was induced by abdominal aortic banding (AB). To evaluate the role of antihypertensive drugs on the effect of Ang-(1-7), AB male Wistar rats weighing 250–300 g were treated with vehicle or low doses (5 mg·kg-1·day-1, gavage) of losartan, captopril, amlodipine, or spironolactone. Isolated aortic rings and isolated perfused hearts under constant flow were used to evaluate the effect of Ang-(1-7) in thoracic aorta and coronary arteries, respectively. Ang-(1-7) induced a significant relaxation in the aorta of sham animals, but this effect was reduced in the aortas of AB rats. Chronic treatments with losartan, captopril or amlodipine, but not with spironolactone, restored the Ang-(1-7)-induced aorta relaxation in AB rats. The coronary vasodilatation evoked by Ang-(1-7) in sham rats was blunted in hypertrophic rats. Only the treatment with losartan restored the coronary vasodilatory effect of Ang-(1-7) in AB rat hearts. These data support a beneficial vascular effect of an association of Ang-(1-7) and some antihypertensive drugs. Thus, this association may have potential as a new therapeutic strategy for cardiovascular diseases

Drain current modulation in a nanoscale field-effect-transistor channel by single dopant implantation

We demonstrate single dopant implantation into the channel of a silicon nanoscale metal-oxide-semiconductor field-effect-transistor. This is achieved by monitoring the drain current modulation during ion irradiation. Deterministic doping is crucial for overcoming dopant number variability in present nanoscale devices and for exploiting single atom degrees of freedom. The two main ion stopping processes that induce drain current modulation are examined. We employ 500 keV He ions, in which electronic stopping is dominant, leading to discrete increases in drain current and 14 keV P dopants for which nuclear stopping is dominant leading to discrete decreases in drain current.Kavli Institute of NanoscienceApplied Science

Single Ion Implantation into Si-Based Devices

Deterministic doping is crucial for overcoming dopant number variability in present nano-scale devices and for exploiting single atom degrees of freedom. The development of determinisitic doping schemes is required. Here, two approaches to the detection of single ion impact events in Si-based devices are reviewed. The first is via specialized PiN structures where ions are directed onto a target area around which a field effect transistor can be formed. The second approach involves monitoring the drain current modulation during ion irradiation. We investigate the detection of both high energy He+ and 14 keV P+ dopants. The stopping of these ions is dominated by ionization and nuclear collisions, respectively. The optimization of the implant energy for a particular device and post-implantation processing are also briefly considered.QN/Quantum NanoscienceApplied Science