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Stellat ganglion blockage within the treatment of continual refractory angina pectoris.
TMEM106B expression was upregulated by >2-fold in CAD coronary arteries. A significant association was found between variants in TMEM106B (but not in TMEM100) and CAD (P=1.9×10-8). Significant gene-gene interaction was detected between ANRIL variant rs2383207 and TMEM106B variant rs3807865 (P=0.009). A similar approach also identifies significant interaction between rs6903956 in ADTRP and rs17465637 in MIA3 (P=0.005). Conclusions We demonstrate 2 pairs of epistatic interactions between GWAS loci for CAD and offer important insights into the genetic architecture and molecular mechanisms for the pathogenesis of CAD. Our strategy has broad applicability to the identification of epistasis in other human diseases.Changes in whole blood DNA methylation levels at several CpG sites have been associated with circulating blood lipids, specifically high-density lipoprotein and triglycerides. This study performs a discovery and validation epigenome-wide association study (EWAS) for circulating lipoprotein(a) [Lp(a)], an independent risk factor for cardiovascular diseases. Whole-blood DNA methylation profiles were assessed in a cohort of 1020 elderly individuals using the Illumina EPIC array and independent validation in 359 elderly males using the Illumina 450 k array. Plasma Lp(a) was measured using an apolipoprotein(a)-size-independent ELISA. Epigenome-wide rank regression analysis identified and validated a single CpG site, cg17028067 located in intron 1 of the LPA gene, that was significantly associated with plasma Lp(a) levels after correction for multiple testing. Genotyping of the site identified a relatively uncommon SNP (rs76735376, MAF less then 0.02) at the CpG site that largely explained the observed methylation effect. Rs76735376 is an expression quantitative trait loci for the LPA gene and could affect expression by altering enhancer activity. This EWAS for plasma Lp(a) identified a single CpG site within LPA. This association is due to an uncommon, but highly effective genetic variant, which was not in significant linkage disequilibrium with other variants known to influence Lp(a) levels or apo(a) isoform size. This study highlights the utility of CpG site methylation to identify potentially important genetic associations that would not be readily apparent in a comparable size genetic association study.Theses reviewed in this issue include "Advanced Imaging Technologies for Combined Biomedical Ultrasound and Photoacoustic Imaging", "Engineering Bispecific Chimeric Antigen Receptors to Improve the Efficacy of Adoptive T-Cell Therapy", "Il-36 Gamma Promotes Anti-Tumor Immunity Through Therapeutic Induction of Tumor-Associated Tertiary Lymphoid Structures", "Investigating the Role of Matrix Vesicles During Aortic Valve Interstitial Cell Calcification", "Local Delivery of Cyclosporine and Erythropoietin Promote Functional Recovery in a Rodent Model of Stroke Injury by Endogenous Tissue Repair", and "Targeting Primary Cilia-mediated Mechanotransduction to Promote Whole Bone Formation".Along with Plasmopara destructor, Peronosopora belbahrii has arguably been the economically most important newly emerging downy mildew pathogen of the past two decades. Originating from Africa, it has started devastating basil production throughout the world, most likely due to the distribution of infested seed material. Here, we present the genome of this pathogen and results from comparisons of its genomic features to other oomycetes. The assembly of the nuclear genome was around 35.4 Mbp in length, with an N50 scaffold length of around 248 kbp and an L50 scaffold count of 46. The circular mitochondrial genome consisted of around 40.1 kbp. From the repeat-masked genome, 9,049 protein-coding genes were predicted, out of which 335 were predicted to have extracellular functions, representing the smallest secretome so far found in peronosporalean oomycetes. About 16% of the genome consists of repetitive sequences, and, based on simple sequence repeat regions, we provide a set of microsatellites that could be used for population genetic studies of P. belbahrii. P. belbahrii has undergone a high degree of convergent evolution with other obligate parasitic pathogen groups, reflecting its obligate biotrophic lifestyle. Features of its secretome, signaling networks, and promoters are presented, and some patterns are hypothesized to reflect the high degree of host specificity in Peronospora species. In addition, we suggest the presence of additional virulence factors apart from classical effector classes that are promising candidates for future functional studies.Peronospora destructor is an obligate biotrophic oomycete that causes downy mildew on onion (Allium cepa). Onion is an important crop worldwide, but its production is affected by this pathogen. We sequenced the genome of P. destructor using the PacBio sequencing platform, and de novo assembly resulted in 74 contigs with a total contig size of 29.3 Mb and 48.48% GC content. Here, we report the first high-quality genome sequence of P. destructor and its comparison with the genome assemblies of other oomycetes. The genome is a very useful resource to serve as a reference for analysis of P. read more destructor isolates and for comparative genomic studies of the biotrophic oomycetes.The present study investigated the relationship between local fat percentage (SKfat) and muscle quality (MQ) estimated by a new hand-held electrical impedance myography (hEIM) device or derived from ultrasound and strength assessments. The right anterior thigh of 90 healthy participants (mean ± SD; age=22.9 ± 2.9 years; 46 men BMI=23.9 ± 2.4 kgm-2; 46 women BMI=21.1 ± 1.9 kgm-2) was scanned by hEIM and ultrasound. Correlations between SKfat, local subcutaneous fat (SUBfat), and echo intensity (EIus) were explored. Correlations between MQ, EIus, quadriceps femoris anatomical cross-sectional area (ACSAQF), knee extensors maximum voluntary isometric torque (T), T/ACSAQF, EIus/SUBfat, and ACSAQF/SUBfat were also assessed. SKfat correlated with SUBfat (r=0.88; p less then 0.001) and EIus (r=0.64; p less then 0.001). MQ correlated with EIus (r=-0.66; p less then 0.001), ACSAQF (r=0.37; p less then 0.001), EIus/SUBfat (r=0.37; p less then 0.001), and ACSAQF/SUBfat (r=0.81; p less then 0.001). Multiple regression analysis showed that SUBfat, EIus, and sex explained 86% of SKfat variance, whereas ACSAQF/SUBfat, sex and EIus explained 75% of MQ variance.
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