Evidence for Positive Selection in the C-terminal Domain of the Cholesterol Metabolism Gene PCSK9 Based on Phylogenetic Analysis in 14 Primate Species

Cholesterol homeostasis is maintained through finely tuned mechanisms regulating intestinal absorption, hepatic biosynthesis and secretion as well as plasma clearance. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted enzyme of the serine protease family that reduces cellular uptake of plasma low-density lipoprotein (LDL) cholesterol by promoting LDL receptor (LDL-R) degradation. Species-specific positive selection has been noted in the LDLR promoter, leading to differential expression of LDLR among primates. Whether PCSK9 experienced significant selective pressure to maintain a functional relationship with its target protein, LDL-R, is unknown.We compiled the sequences of the coding regions of PCSK9 from 14 primate species in the clade of Hominoids, Old World monkeys and New World monkeys. To detect selective pressure at the protein level, the ratios of nonsynonymous/synonymous substitution rate (d(N)/d(S)) under different evolutionary models were calculated across the phylogeny of PCSK9. Maximum likelihood analyses of d(N)/d(S) ratios for the aligned coding region sequences among 14 primate species indicated that PCSK9 was subject to a strong functional constraint (i.e., purifying selection). However, positive selection was noted in the functional carboxyl-terminal (C-terminal) domain in many branches across the phylogeny, especially in the lineage leading to the orangutan. Furthermore, at least five positively selected amino acids were detected in this lineage using the branch-site model A. In a sliding-window analysis, several d(N)/d(S) peaks in the C-terminal domain in both the human and the orangutan branches were noted.These results suggest that among primates, differential selective pressure has shaped evolutionary patterns in the functional domains of PCSK9, an important regulator of cholesterol homeostasis

htSNPer1.0: software for haplotype block partition and htSNPs selection

BACKGROUND: There is recently great interest in haplotype block structure and haplotype tagging SNPs (htSNPs) in the human genome for its implication on htSNPs-based association mapping strategy for complex disease. Different definitions have been used to characterize the haplotype block structure in the human genome, and several different performance criteria and algorithms have been suggested on htSNPs selection. RESULTS: A heuristic algorithm, generalized branch-and-bound algorithm, is applied to the searching of minimal set of haplotype tagging SNPs (htSNPs) according to different htSNPs performance criteria. We develop a software htSNPer1.0 to implement the algorithm, and integrate three htSNPs performance criteria and four haplotype block definitions for haplotype block partitioning. It is a software with powerful Graphical User Interface (GUI), which can be used to characterize the haplotype block structure and select htSNPs in the candidate gene or interested genomic regions. It can find the global optimization with only a fraction of the computing time consumed by exhaustive searching algorithm. CONCLUSION: htSNPer1.0 allows molecular geneticists to perform haplotype block analysis and htSNPs selection using different definitions and performance criteria. The software is a powerful tool for those focusing on association mapping based on strategy of haplotype block and htSNPs

A survey of electromagnetic influence on uavs from an ehv power converter stations and possible countermeasures

National Natural Science Foundation of China (Grant Nos. 11872148, U1908217, 61801034).It is inevitable that high-intensity, wide-spectrum electromagnetic emissions are generated by the power electronic equipment of the Extra High Voltage (EHV) power converter station. The surveillance flight of Unmanned Aerial Vehicles (UAVs) is thus, situated in a complex electromagnetic environment. The ubiquitous electromagnetic interference demands higher electromagnetic protection requirements from the UAV construction and operation. This article is related to the UAVs patrol inspections of the power line in the vicinity of the EHV converter station. The article analyzes the electromagnetic interference characteristics of the converter station equipment in the surrounding space and the impact of the electromagnetic emission on the communication circuits of the UAV. The anti-electromagnetic interference countermeasures strive to eliminate or reduce the threats of electromagnetic emissions on the UAV’s hardware and its communication network.publishersversionpublishe

A Genome-Wide Association Study of Red Blood Cell Traits Using the Electronic Medical Record

The Electronic Medical Record (EMR) is a potential source for high throughput phenotyping to conduct genome-wide association studies (GWAS), including those of medically relevant quantitative traits. We describe use of the Mayo Clinic EMR to conduct a GWAS of red blood cell (RBC) traits in a cohort of patients with peripheral arterial disease (PAD) and controls without PAD.Results for hemoglobin level, hematocrit, RBC count, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration were extracted from the EMR from January 1994 to September 2009. Out of 35,159 RBC trait values in 3,411 patients, we excluded 12,864 values in 1,165 patients that had been measured during hospitalization or in the setting of hematological disease, malignancy, or use of drugs that affect RBC traits, leaving a final genotyped sample of 3,012, 80% of whom had ≥2 measurements. The median of each RBC trait was used in the genetic analyses, which were conducted using an additive model that adjusted for age, sex, and PAD status. We identified four genomic loci that were associated (P<5 × 10(-8)) with one or more of the RBC traits (HBLS1/MYB on 6q23.3, TMPRSS6 on 22q12.3, HFE on 6p22.1, and SLC17A1 on 6p22.2). Three of these loci (HBLS1/MYB, TMPRSS6, and HFE) had been identified in recent GWAS and the allele frequencies, effect sizes, and the directions of effects of the replicated SNPs were similar to the prior studies.Our results demonstrate feasibility of using the EMR to conduct high throughput genomic studies of medically relevant quantitative traits

Covert Communications in STAR-RIS Assisted NOMA IoT Networks over Nakagami-m Fading Channels

The combination of simultaneously transmitting and reflecting-reconfigurable intelligent surface (STAR-RIS) and non-orthogonal multiple (NOMA) brings the necessary full-space degrees of freedom and spatial multiplexing gains for the Internet of Things (IoT) networks. The inherent network heterogeneity and sharing of wireless channels may however increase the exposure of the information interactions to the third party. To address this issue, we propose a covert communication scheme in STAR-RIS assisted NOMA networks over Nakagami-m fading channels, where both downlink and uplink IoT scenarios are considered. Under the NOMA protocol with imperfect successive interference cancellation (SIC), an IoT access point interacts with two IoT users aided by a STAR-RIS without being detected by two wardens. In this scenario, the two IoT users are located on both sides of the STAR-RIS which adopts coherent phase shifting and operates according to the mode switching protocol. To evaluate the wardens&#x2019; detection performance, the Kullback-Leibler (KL) divergence is used. Furthermore, the cascaded channel gains of IoT users and wardens are respectively characterized as Gamma and complex Gaussian random variables. The closed-form expressions of the expectations of KL divergence and the interruption probabilities for downlink and uplink are derived. To further improve the performance, we formulate the effective covert rate maximization as the joint optimization problems of the transmit power and power allocation coefficient for downlink and uplink, subject to the constraints for covertness, reliability and power budget, which are respectively resolved analytically. Extensive simulation results indicate that the proposed scheme improves covertness compared with the benchmarks

Geographic differences in allele frequencies of susceptibility SNPs for cardiovascular disease

<p>Abstract</p> <p>Background</p> <p>We hypothesized that the frequencies of risk alleles of SNPs mediating susceptibility to cardiovascular diseases differ among populations of varying geographic origin and that population-specific selection has operated on some of these variants.</p> <p>Methods</p> <p>From the database of genome-wide association studies (GWAS), we selected 36 cardiovascular phenotypes including coronary heart disease, hypertension, and stroke, as well as related quantitative traits (eg, body mass index and plasma lipid levels). We identified 292 SNPs in 270 genes associated with a disease or trait at <it>P </it>< 5 × 10^-8. As part of the Human Genome-Diversity Project (HGDP), 158 (54.1%) of these SNPs have been genotyped in 938 individuals belonging to 52 populations from seven geographic areas. A measure of population differentiation, <it>F</it>_ST, was calculated to quantify differences in risk allele frequencies (RAFs) among populations and geographic areas.</p> <p>Results</p> <p>Large differences in RAFs were noted in populations of Africa, East Asia, America and Oceania, when compared with other geographic regions. The mean global <it>F</it>_ST(0.1042) for 158 SNPs among the populations was not significantly higher than the mean global <it>F</it>_STof 158 autosomal SNPs randomly sampled from the HGDP database. Significantly higher global <it>F</it>_ST(<it>P </it>< 0.05) was noted in eight SNPs, based on an empirical distribution of global <it>F</it>_STof 2036 putatively neutral SNPs. For four of these SNPs, additional evidence of selection was noted based on the integrated Haplotype Score.</p> <p>Conclusion</p> <p>Large differences in RAFs for a set of common SNPs that influence risk of cardiovascular disease were noted between the major world populations. Pairwise comparisons revealed RAF differences for at least eight SNPs that might be due to population-specific selection or demographic factors. These findings are relevant to a better understanding of geographic variation in the prevalence of cardiovascular disease.</p