金属有机化合物化学气相淀积含钛硬质涂层的性能研究

在用文题淀积方法制备出氮化钛、碳氮化钛和碳氮氧化钛硬质涂层的基础上,用表面分析手段分别进行了成分、结构分析、形貌观察和硬度测定。结果表明:以二乙胺基钛为原料可分别在773K和973K淀积氮化钛和碳氮化钛涂层;用钛酸异丙酯和钛酸丁酯可分别在973K和1073K获得碳氮氧化钛涂层。所得的涂层表面光洁度高、与基体附着性好、硬度满足实用要求。相比于普通化学气相淀积方法,本法在制备硬质涂层上有两大优点:(1)淀积温度降低,扩大了基体的选用范围;(2)固溶体涂层的获得扩大了涂层的适用范围。     

Lysosomal chymotrypsin B potentiates apoptosis via cleavage of Bid

We have reported that chymotrypsin B (CtrB) is not just a digestive enzyme but is also stored in lysosomes. Herein, we demonstrated a broad distribution of CtrB and explored the involvement of CtrB in apoptosis. Exposure of RH-35 cells to H₂O₂ or palmitate induced the redistribution of lysosomal CtrB into the cytoplasm as a result of lysosomal membrane permeabilization (LMP). Suppression of CtrB significantly blocked apoptosis, while overexpression of CtrB sensitized apoptosis markedly. CtrB could cleave Bid under neutral conditions. In RH-35 cells with Bid silenced, apoptosis induced by CtrB protein was attenuated, suggesting that CtrB mediates apoptosis of RH-35 cells mainly through processing Bid. Our data also suggest that LMP occurs earlier than mitochondrial outer membrane permeabilization; Bid activation initiated by caspase-8 might be reinforced by CtrB in consequence of LMP, which causes a positive feedback loop leading to the accumulation of tBid, and results in lysosome- and mitochondrion-dependent apoptosis.     

Genome-wide association studies of 14 agronomic traits in rice landraces

Uncovering the genetic basis of agronomic traits in crop landraces that have adapted to various agro-climatic conditions is important to world food security. Here we have identified ～ 3.6 million SNPs by sequencing 517 rice landraces and constructed a high-density haplotype map of the rice genome using a novel data-imputation method. We performed genome-wide association studies (GWAS) for 14 agronomic traits in the population of Oryza sativa indica subspecies. The loci identified through GWAS explained ～ 36% of the phenotypic variance, on average. The peak signals at six loci were tied closely to previously identified genes. This study provides a fundamental resource for rice genetics research and breeding, and demonstrates that an approach integrating second-generation genome sequencing and GWAS can be used as a powerful complementary strategy to classical biparental cross-mapping for dissecting complex traits in rice.     

Genome-wide association study of flowering time and grain yield traits in a worldwide collection of rice germplasm

A high-density haplotype map recently enabled a genome-wide association study (GWAS) in a population of indica subspecies of Chinese rice landraces. Here we extend this methodology to a larger and more diverse sample of 950 worldwide rice varieties, including the Oryza sativa indica and Oryza sativa japonica subspecies, to perform an additional GWAS. We identified a total of 32 new loci associated with flowering time and with ten grain-related traits, indicating that the larger sample increased the power to detect trait-associated variants using GWAS. To characterize various alleles and complex genetic variation, we developed an analytical framework for haplotype-based de novo assembly of the low-coverage sequencing data in rice. We identified candidate genes for 18 associated loci through detailed annotation. This study shows that the integrated approach of sequence-based GWAS and functional genome annotation has the potential to match complex traits to their causal polymorphisms in rice.     

A genome-wide association study in Han Chinese identifies new susceptibility loci for ankylosing spondylitis

To identify susceptibility loci for ankylosing spondylitis, we performed a two-stage genome-wide association study in Han Chinese. In the discovery stage, we analyzed 1,356,350 autosomal SNPs in 1,837 individuals with ankylosing spondylitis and 4,231 controls; in the validation stage, we analyzed 30 suggestive SNPs in an additional 2,100 affected individuals and 3,496 controls. We identified two new susceptibility loci between EDIL3 and HAPLN1 at 5q14.3 (rs4552569; P = 8.77 × 10(-10)) and within ANO6 at 12q12 (rs17095830; P = 1.63 × 10(-8)). We also confirmed previously reported associations in Europeans within the major histocompatibility complex (MHC) region (top SNP, rs13202464; P < 5 × 10(-324)) and at 2p15 (rs10865331; P = 1.98 × 10(-8)). We show that rs13202464 within the MHC region mainly represents the risk effect of HLA-B*27 variants (including HLA-B*2704, HLA-B*2705 and HLA-B*2715) in Chinese. The two newly discovered loci implicate genes related to bone formation and cartilage development, suggesting their potential involvement in the etiology of ankylosing spondylitis.     

A genome-wide association study in Chinese men identifies three risk loci for non-obstructive azoospermia

Non-obstructive azoospermia (NOA) is one of the most severe forms of male infertility. Its pathophysiology is largely unknown, and few genetic influences have been defined. To identify common variants contributing to NOA in Han Chinese men, we performed a three-stage genome-wide association study of 2,927 individuals with NOA and 5,734 controls. The combined analyses identified significant (P < 5.0 × 10(-8)) associations between NOA risk and common variants near PRMT6 (rs12097821 at 1p13.3: odds ratio (OR) = 1.25, P = 5.7 × 10(-10)), PEX10 (rs2477686 at 1p36.32: OR = 1.39, P = 5.7 × 10(-12)) and SOX5 (rs10842262 at 12p12.1: OR = 1.23, P = 2.3 × 10(-9)). These findings implicate genetic variants at 1p13.3, 1p36.32 and 12p12.1 in the etiology of NOA in Han Chinese men.     

Exome sequencing of liver fluke-associated cholangiocarcinoma

Opisthorchis viverrini-related cholangiocarcinoma (CCA), a fatal bile duct cancer, is a major public health concern in areas endemic for this parasite. We report here whole-exome sequencing of eight O. viverrini-related tumors and matched normal tissue. We identified and validated 206 somatic mutations in 187 genes using Sanger sequencing and selected 15 genes for mutation prevalence screening in an additional 46 individuals with CCA (cases). In addition to the known cancer-related genes TP53 (mutated in 44.4% of cases), KRAS (16.7%) and SMAD4 (16.7%), we identified somatic mutations in 10 newly implicated genes in 14.8-3.7% of cases. These included inactivating mutations in MLL3 (in 14.8% of cases), ROBO2 (9.3%), RNF43 (9.3%) and PEG3 (5.6%), and activating mutations in the GNAS oncogene (9.3%). These genes have functions that can be broadly grouped into three biological classes: (i) deactivation of histone modifiers, (ii) activation of G protein signaling and (iii) loss of genome stability. This study provides insight into the mutational landscape contributing to O. viverrini-related CCA.     

Mutations in ISPD cause Walker-Warburg syndrome and defective glycosylation of α-dystroglycan

Walker-Warburg syndrome (WWS) is an autosomal recessive multisystem disorder characterized by complex eye and brain abnormalities with congenital muscular dystrophy (CMD) and aberrant a-dystroglycan glycosylation. Here we report mutations in the ISPD gene (encoding isoprenoid synthase domain containing) as the second most common cause of WWS. Bacterial IspD is a nucleotidyl transferase belonging to a large glycosyltransferase family, but the role of the orthologous protein in chordates is obscure to date, as this phylum does not have the corresponding non-mevalonate isoprenoid biosynthesis pathway. Knockdown of ispd in zebrafish recapitulates the human WWS phenotype with hydrocephalus, reduced eye size, muscle degeneration and hypoglycosylated a-dystroglycan. These results implicate ISPD in a-dystroglycan glycosylation in maintaining sarcolemma integrity in vertebrates.     

Frequent mutations of chromatin remodeling genes in transitional cell carcinoma of the bladder

Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Here we sequenced the exomes of nine individuals with TCC and screened all the somatically mutated genes in a prevalence set of 88 additional individuals with TCC with different tumor stages and grades. In our study, we discovered a variety of genes previously unknown to be mutated in TCC. Notably, we identified genetic aberrations of the chromatin remodeling genes (UTX, MLL-MLL3, CREBBP-EP300, NCOR1, ARID1A and CHD6) in 59% of our 97 subjects with TCC. Of these genes, we showed UTX to be altered substantially more frequently in tumors of low stages and grades, highlighting its potential role in the classification and diagnosis of bladder cancer. Our results provide an overview of the genetic basis of TCC and suggest that aberration of chromatin regulation might be a hallmark of bladder cancer.