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

Single valley Dirac fermions in zero-gap HgTe quantum wells

Dirac fermions have been studied intensively in condensed matter physics in recent years. Many theoretical predictions critically depend on the number of valleys where the Dirac fermions are realized. In this work, we report the discovery of a two dimensional system with a single valley Dirac cone. We study the transport properties of HgTe quantum wells grown at the critical thickness separating between the topologically trivial and the quantum spin Hall phases. At high magnetic fields, the quantized Hall plateaus demonstrate the presence of a single valley Dirac point in this system. In addition, we clearly observe the linear dispersion of the zero mode spin levels. Also the conductivity at the Dirac point and its temperature dependence can be understood from single valley Dirac fermion physics.Comment: version 2: supplementary material adde

Serum Amyloid A in Stable COPD Patients is Associated with the Frequent Exacerbator Phenotype

Background: We sought to determine whether circulating inflammatory biomarkers were associated with the frequent exacerbator phenotype in stable COPD patients ie, those with two or more exacerbations in the previous year. Methods: Eighty-eight stable, severe, COPD patients (4 females) were assessed for exacerbation frequency, pulmonary function, fraction of expired nitric oxide (FENO); inflammatory variables were measured in venous blood. Logistic regression assessed associations between the frequent exacerbator phenotype and systemic inflammation. Results: Compared with infrequent exacerbators, frequent exacerbators (n=10; 11.4%) had greater serum concentration (median (25th-75th quartile)) of serum amyloid A (SAA; 134 (84– 178) vs 71 (38– 116) ng/mL; P=0.024), surfactant protein D (SP-D; 15.6 (9.0– 19.3) vs 8.5 (3.6– 14.9) ng/mL; P=0.049) and interleukin-4 (IL-4; 0.12 (0.08– 1.44) vs 0.03 (0.01– 0.10) pg/mL; P=0.001). SAA, SP-D and IL-4 were not significantly correlated with FEV1%predicted or FVC %predicted. After adjusting for sex, age, BMI, FEV1/FVC and smoking pack-years, only SAA remained independently associated with the frequent exacerbator phenotype (OR 1.49[1.09– 2.04]; P=0.012). The odds of being a frequent exacerbator was 18-times greater in the highest SAA quartile (≥ 124.1 ng/mL) than the lowest SAA quartile (≤ 44.1 ng/mL) (OR 18.34[1.30– 258.81]; P=0.031), and there was a significant positive trend of increasing OR with increasing SAA quartile (P=0.008). For SAA, the area under the receiver operating characteristic curve was 0.721 for identification of frequent exacerbators; an SAA cut-off of 87.0 ng/mL yielded an 80% sensitivity and 61.5% specificity. Conclusion: In stable COPD patients, SAA was independently associated with the frequent exacerbator phenotype, suggesting that SAA may be a useful serum biomarker to inform progression or management in COPD

Interval valued (\in,\ivq)-fuzzy filters of pseudo BLBL-algebras

We introduce the concept of quasi-coincidence of a fuzzy interval value with an interval valued fuzzy set. By using this new idea, we introduce the notions of interval valued (\in,\ivq)-fuzzy filters of pseudo $BL$-algebras and investigate some of their related properties. Some characterization theorems of these generalized interval valued fuzzy filters are derived. The relationship among these generalized interval valued fuzzy filters of pseudo $BL$-algebras is considered. Finally, we consider the concept of implication-based interval valued fuzzy implicative filters of pseudo $BL$-algebras, in particular, the implication operators in Lukasiewicz system of continuous-valued logic are discussed

Dual-gated bilayer graphene hot electron bolometer

Detection of infrared light is central to diverse applications in security, medicine, astronomy, materials science, and biology. Often different materials and detection mechanisms are employed to optimize performance in different spectral ranges. Graphene is a unique material with strong, nearly frequency-independent light-matter interaction from far infrared to ultraviolet, with potential for broadband photonics applications. Moreover, graphene's small electron-phonon coupling suggests that hot-electron effects may be exploited at relatively high temperatures for fast and highly sensitive detectors in which light energy heats only the small-specific-heat electronic system. Here we demonstrate such a hot-electron bolometer using bilayer graphene that is dual-gated to create a tunable bandgap and electron-temperature-dependent conductivity. The measured large electron-phonon heat resistance is in good agreement with theoretical estimates in magnitude and temperature dependence, and enables our graphene bolometer operating at a temperature of 5 K to have a low noise equivalent power (33 fW/Hz1/2). We employ a pump-probe technique to directly measure the intrinsic speed of our device, >1 GHz at 10 K.Comment: 5 figure

Genome-wide signatures of convergent evolution in echolocating mammals

Evolution is typically thought to proceed through divergence of genes, proteins, and ultimately phenotypes(1-3). However, similar traits might also evolve convergently in unrelated taxa due to similar selection pressures(4,5). Adaptive phenotypic convergence is widespread in nature, and recent results from a handful of genes have suggested that this phenomenon is powerful enough to also drive recurrent evolution at the sequence level(6-9). Where homoplasious substitutions do occur these have long been considered the result of neutral processes. However, recent studies have demonstrated that adaptive convergent sequence evolution can be detected in vertebrates using statistical methods that model parallel evolution(9,10) although the extent to which sequence convergence between genera occurs across genomes is unknown. Here we analyse genomic sequence data in mammals that have independently evolved echolocation and show for the first time that convergence is not a rare process restricted to a handful of loci but is instead widespread, continuously distributed and commonly driven by natural selection acting on a small number of sites per locus. Systematic analyses of convergent sequence evolution in 805,053 amino acids within 2,326 orthologous coding gene sequences compared across 22 mammals (including four new bat genomes) revealed signatures consistent with convergence in nearly 200 loci. Strong and significant support for convergence among bats and the dolphin was seen in numerous genes linked to hearing or deafness, consistent with an involvement in echolocation. Surprisingly we also found convergence in many genes linked to vision: the convergent signal of many sensory genes was robustly correlated with the strength of natural selection. This first attempt to detect genome-wide convergent sequence evolution across divergent taxa reveals the phenomenon to be much more pervasive than previously recognised

In situ epitaxial engineering of graphene and h-BN lateral heterostructure with a tunable morphology comprising h-BN domains

Graphene and hexagonal boron nitride (h-BN), as typical two-dimensional (2D) materials, have long attracted substantial attention due to their unique properties and promise in a wide range of applications. Although they have a rather large difference in their intrinsic bandgaps, they share a very similar atomic lattice; thus, there is great potential in constructing heterostructures by lateral stitching. Herein, we present the in situ growth of graphene and h-BN lateral heterostructures with tunable morphologies that range from a regular hexagon to highly symmetrical star-like structure on the surface of liquid Cu. The chemical vapor deposition (CVD) method is used, where the growth of the h-BN is demonstrated to be highly templated by the graphene. Furthermore, large-area production of lateral G-h-BN heterostructures at the centimeter scale with uniform orientation is realized by precisely tuning the CVD conditions. We found that the growth of h-BN is determined by the initial graphene and symmetrical features are produced that demonstrate heteroepitaxy. Simulations based on the phase field and density functional theories are carried out to elucidate the growth processes of G-h-BN flakes with various morphologies, and they have a striking consistency with experimental observations. The growth of a lateral G-h-BN heterostructure and an understanding of the growth mechanism can accelerate the construction of various heterostructures based on 2D materials

Upregulated sirtuin 1 by miRNA-34a is required for smooth muscle cell differentiation from pluripotent stem cells

© 2015 Macmillan Publishers Limited. All rights reserved. microRNA-34a (miR-34a) and sirtuin 1 (SirT1) have been extensively studied in tumour biology and longevityaging, but little is known about their functional roles in smooth muscle cell (SMC) differentiation from pluripotent stem cells. Using well-established SMC differentiation models, we have demonstrated that miR-34a has an important role in SMC differentiation from murine and human embryonic stem cells. Surprisingly, deacetylase sirtuin 1 (SirT1), one of the top predicted targets, was positively regulated by miR-34a during SMC differentiation. Mechanistically, we demonstrated that miR-34a promoted differentiating stem cells' arrest at G0G1 phase and observed a significantly decreased incorporation of miR-34a and SirT1 RNA into Ago2-RISC complex upon SMC differentiation. Importantly, we have identified SirT1 as a transcriptional activator in the regulation of SMC gene programme. Finally, our data showed that SirT1 modulated the enrichment of H3K9 tri-methylation around the SMC gene-promoter regions. Taken together, our data reveal a specific regulatory pathway that miR-34a positively regulates its target gene SirT1 in a cellular context-dependent and sequence-specific manner and suggest a functional role for this pathway in SMC differentiation from stem cells in vitro and in vivo

Origin of Shifts in the Surface Plasmon Resonance Frequencies for Au and Ag Nanoparticles

Origin of shifts in the surface plasmon resonance (SPR) frequency for noble metal (Au, Ag) nanoclusters are discussed in this book chapter. Spill out of electron from the Fermi surface is considered as the origin of red shift. On the other hand, both screening of electrons of the noble metal in porous media and quantum effect of screen surface electron are considered for the observed blue shift in the SPR peak position.Comment: 37 pages, 14 Figures in the submitted book chapter of The Annual Reviews in Plasmonics, edited by Professor Chris D. Geddes. Springer Scinec