Evaluation of genetic susceptibility of common variants in CACNA1D with schizophrenia in Han Chinese

The heritability of schizophrenia (SCZ) has been estimated to be as high as 80%, suggesting that genetic factors may play an important role in the etiology of SCZ. Cav1.2 encoded by CACNA1C and Cav1.3 encoded by CACNA1D are dominant calcium channel-forming subunits of L-type Voltage-dependent Ca(2+) channels, expressed in many types of neurons. The CACNA1C has been consistently found to be a risk gene for SCZ, but it is unknown for CACNA1D. To investigate the association of CACNA1D with SCZ, we designed a two-stage case-control study, including a testing set with 1117 cases and 1815 controls and a validation set with 1430 cases and 4295 controls in Han Chinese. A total of selected 97 tag single nucleotide polymorphisms (SNPs) in CACNA1D were genotyped, and single-SNP association, imputation analysis and gender-specific association analyses were performed in the two independent datasets. None was found to associate with SCZ. Further genotype and haplotype association analyses indicated a similar pattern in the two-stage study. Our findings suggested CACNA1D might not be a risk gene for SCZ in Han Chinese population, which add to the current state of knowledge regarding the susceptibility of CACNA1D to SCZ

A study of two bispectral features from envelope signals for bearing fault diagnosis

: To accurately detect and diagnose bearing faults, bispectral analysis has received more attention recently because of its unique property of noise reduction and nonlinearity extraction. Particularly this study investigates two typical bispectra: conventional bispectrum (CB) and modulation signal bispectrum (MSB) for suppressing noise influences in envelope signals and hence obtaining more accurate diagnostic features. The first component from the diagonal slice of CB results and that of the subdiagonal slices of MSB results are taken as the diagnostic features considering effective inclusion of information and easy of computations. Simulative and experimental studies show that both MSB and CB features result in good diagnostic performances but MSB may outperform CB slightly in that it shows smaller variance in attaining the feature and more sensitive to weak fault signatures. This merit of MSB may be due to that the MSB feature has more diagnostic information as it is the combination of first three harmonics, whereas the CB feature is combined from just the first two harmonics

Approaches for integrating heterogeneous RNA-seq data reveal cross-talk between microbes and genes in asthmatic patients.

Sputum induction is a non-invasive method to evaluate the airway environment, particularly for asthma. RNA sequencing (RNA-seq) of sputum samples can be challenging to interpret due to the complex and heterogeneous mixtures of human cells and exogenous (microbial) material. In this study, we develop a pipeline that integrates dimensionality reduction and statistical modeling to grapple with the heterogeneity. LDA(Latent Dirichlet allocation)-link connects microbes to genes using reduced-dimensionality LDA topics. We validate our method with single-cell RNA-seq and microscopy and then apply it to the sputum of asthmatic patients to find known and novel relationships between microbes and genes

Whole blood DNA methylation signatures of diet are associated with cardiovascular disease risk factors and all-cause mortality

Background: DNA methylation patterns associated with habitual diet have not been well studied. Methods: Diet quality was characterized using a Mediterranean-style diet score and the Alternative Healthy Eating Index score. We conducted ethnicity-specific and trans-ethnic epigenome-wide association analyses for diet quality and leukocyte-derived DNA methylation at over 400 000 CpGs (cytosine-guanine dinucleotides) in 5 population-based cohorts including 6662 European ancestry, 2702 African ancestry, and 360 Hispanic ancestry participants. For diet-associated CpGs identified in epigenome-wide analyses, we conducted Mendelian randomization (MR) analysis to examine their relations to cardiovascular disease risk factors and examined their longitudinal associations with all-cause mortality. Results: We identified 30 CpGs associated with either Mediterranean-style diet score or Alternative Healthy Eating Index, or both, in European ancestry participants. Among these CpGs, 12 CpGs were significantly associated with all-cause mortality (Bonferroni correctedP<1.6x10(-3)). Hypermethylation of cg18181703 (SOCS3) was associated with higher scores of both Mediterranean-style diet score and Alternative Healthy Eating Index and lower risk for all-cause mortality (P=5.7x10(-15)). Ten additional diet-associated CpGs were nominally associated with all-cause mortality (P<0.05). MR analysis revealed 8 putatively causal associations for 6 CpGs with 4 cardiovascular disease risk factors (body mass index, triglycerides, high-density lipoprotein cholesterol concentrations, and type 2 diabetes mellitus; Bonferroni corrected MRP<4.5x10(-4)). For example, hypermethylation of cg11250194 (FADS2) was associated with lower triglyceride concentrations (MR,P=1.5x10(-14)).and hypermethylation of cg02079413 (SNORA54;NAP1L4) was associated with body mass index (corrected MR,P=1x10(-6)). Conclusions: Habitual diet quality was associated with differential peripheral leukocyte DNA methylation levels of 30 CpGs, most of which were also associated with multiple health outcomes, in European ancestry individuals. These findings demonstrate that integrative genomic analysis of dietary information may reveal molecular targets for disease prevention and treatment

A Meta-analysis of Gene Expression Signatures of Blood Pressure and Hypertension

Genome-wide association studies (GWAS) have uncovered numerous genetic variants (SNPs) that are associated with blood pressure (BP). Genetic variants may lead to BP changes by acting on intermediate molecular phenotypes such as coded protein sequence or gene expression, which in turn affect BP variability. Therefore, characterizing genes whose expression is associated with BP may reveal cellular processes involved in BP regulation and uncover how transcripts mediate genetic and environmental effects on BP variability. A meta-analysis of results from six studies of global gene expression profiles of BP and hypertension in whole blood was performed in 7017 individuals who were not receiving antihypertensive drug treatment. We identified 34 genes that were differentially expressed in relation to BP (Bonferroni-corrected p<0.05). Among these genes, FOS and PTGS2 have been previously reported to be involved in BP-related processes; the others are novel. The top BP signature genes in aggregate explain 5%–9% of inter-individual variance in BP. Of note, rs3184504 in SH2B3, which was also reported in GWAS to be associated with BP, was found to be a trans regulator of the expression of 6 of the transcripts we found to be associated with BP (FOS, MYADM, PP1R15A, TAGAP, S100A10, and FGBP2). Gene set enrichment analysis suggested that the BP-related global gene expression changes include genes involved in inflammatory response and apoptosis pathways. Our study provides new insights into molecular mechanisms underlying BP regulation, and suggests novel transcriptomic markers for the treatment and prevention of hypertension

Multi-tissue integrative analysis of personal epigenomes

Evaluating the impact of genetic variants on transcriptional regulation is a central goal in biological science that has been constrained by reliance on a single reference genome. To address this, we constructed phased, diploid genomes for four cadaveric donors (using long-read sequencing) and systematically charted noncoding regulatory elements and transcriptional activity across more than 25 tissues from these donors. Integrative analysis revealed over a million variants with allele-specific activity, coordinated, locus-scale allelic imbalances, and structural variants impacting proximal chromatin structure. We relate the personal genome analysis to the ENCODE encyclopedia, annotating allele- and tissue-specific elements that are strongly enriched for variants impacting expression and disease phenotypes. These experimental and statistical approaches, and the corresponding EN-TEx resource, provide a framework for personalized functional genomics

Methods on scheduling of hydro-photovoltaic complementary system

The hydro-photovoltaic complementarity is an important operation mode to promote the grid-connected absorption, and one of the main directions of solar energy development and utilization in the future. The paper expounds the principle of hydro-photovoltaic complementarity and the influence of the installed ratio on economy, also summarizes and analyzes the research results of hydro-photovoltaic complementary system operation scheduling methods. In view of the uncertainty of hydro-photovoltaic complementary generation, the paper proposes several suggestions and expectations for the study of hydro-photovoltaic complementarity, to provide ideas for improve the economy and reliability of short-term and large-scale hydro-photovoltaic complementary operation

Key Parameters of Gob-Side Entry Retaining in A Gassy and Thin Coal Seam with Hard Roof

Gob-side entry retaining (GER) employed in a thin coal seam (TCS) can increase economic benefits and coal recovery, as well as mitigate gas concentration in the gob. In accordance with the caving style of a limestone roof, the gas concentration and air pressure in the gob were analyzed, and a roof-cutting mechanical model of GER with a roadside backfill body (RBB) was proposed, to determine the key parameters of the GER-TCS, including the roof-cutting resistance and the width of the RBB. The results show that if the immediate roof height is greater than the seam height, the roof-cutting resistance and width of the RBB should meet the requirement of the immediate roof being totally cut along the gob, for which the optimal roof-cutting resistance and width of RBB were determined by analytical and numerical methods. The greater the RBB width, the greater its roof-cutting resistance. The relationship between the supporting strength of the RBB and the width of the RBB can be derived as a composite curve. The floor heave of GER increases with increasing RBB width. When the width of the RBB increased from 0.8 m to 1.2 m, the floor heave increased two-fold to 146.2 mm. GER was applied in a TCS with a limestone roof of 5 m thickness; the field-measured data verified the conclusions of the numerical model

The Critical Depth of Freeze-Thaw Soil under Different Types of Snow Cover

Snow cover is the most common upper boundary condition influencing the soil freeze-thaw process in the black soil farming area of northern China. Snow is a porous dielectric cover, and its unique physical properties affect the soil moisture diffusion, heat conduction, freezing rate and other variables. To understand the spatial distribution of the soil water-heat and the variable characteristics of the critical depth of the soil water and heat, we used field data to analyze the freezing rate of soil and the extent of variation in soil water-heat in a unit soil layer under bare land (BL), natural snow (NS), compacted snow (CS) and thick snow (TS) treatments. The critical depth of the soil water and heat activity under different snow covers were determined based on the results of the analysis, and the variation fitting curve of the difference sequences on the soil temperature and water content between different soil layers and the surface 5-cm soil layer were used to verify the critical depth. The results were as follows: snow cover slowed the rate of soil freezing, and the soil freezing rate under the NS, CS and TS treatments decreased by 0.099 cm/day, 0.147 cm/day and 0.307 cm/day, respectively, compared with that under BL. In addition, the soil thawing time was delayed, and the effect was more significant with increased snow cover. During freeze-thaw cycles, the extent of variation in the water and heat time series in the shallow soil was relatively large, while there was less variation in the deep layer. There was a critical stratum in the vertical surface during hydrothermal migration, wherein the critical depth of soil water and heat change gradually increased with increasing snow cover. The variance in differences between the surface layer and both the soil water and heat in the different layers exhibited “steady-rising-steady” behavior, and the inflection point of the curve is the critical depth of soil freezing and thawing. This critical layer is a demarcation point between frozen soil and non-frozen soil, delineating the boundary between soil water and heat migration and non-migration. Furthermore, with increasing snow cover thickness and increasing density, the critical depth gradually increased