Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations

Chronic kidney disease (CKD), impairment of kidney function, is a serious public health problem, and the assessment of genetic factors influencing kidney function has substantial clinical relevance. Here, we report a meta-analysis of genome-wide association studies for kidney function-related traits, including 71,149 east Asian individuals from 18 studies in 11 population-, hospital- or family-based cohorts, conducted as part of the Asian Genetic Epidemiology Network (AGEN). Our meta-analysis identified 17 loci newly associated with kidney function-related traits, including the concentrations of blood urea nitrogen, uric acid and serum creatinine and estimated glomerular filtration rate based on serum creatinine levels (eGFRcrea) (P < 5.0 × 10(-8)). We further examined these loci with in silico replication in individuals of European ancestry from the KidneyGen, CKDGen and GUGC consortia, including a combined total of ～110,347 individuals. We identify pleiotropic associations among these loci with kidney function-related traits and risk of CKD. These findings provide new insights into the genetics of kidney function.     

The malaria parasite Plasmodium vivax exhibits greater genetic diversity than Plasmodium falciparum

We sequenced and annotated the genomes of four P. vivax strains collected from disparate geographic locations, tripling the number of genome sequences available for this understudied parasite and providing the first genome-wide perspective of global variability in this species. We observe approximately twice as much SNP diversity among these isolates as we do among a comparable collection of isolates of P. falciparum, a malaria-causing parasite that results in higher mortality. This indicates a distinct history of global colonization and/or a more stable demographic history for P. vivax relative to P. falciparum, which is thought to have undergone a recent population bottleneck. The SNP diversity, as well as additional microsatellite and gene family variability, suggests a capacity for greater functional variation in the global population of P. vivax. These findings warrant a deeper survey of variation in P. vivax to equip disease interventions targeting the distinctive biology of this neglected but major pathogen.     

Large-scale genome-wide association studies in East Asians identify new genetic loci influencing metabolic traits

To identify the genetic bases for nine metabolic traits, we conducted a meta-analysis combining Korean genome-wide association results from the KARE project (n = 8,842) and the HEXA shared control study (n = 3,703). We verified the associations of the loci selected from the discovery meta-analysis in the replication stage (30,395 individuals from the BioBank Japan genome-wide association study and individuals comprising the Health2 and Shanghai Jiao Tong University Diabetes cohorts). We identified ten genome-wide significant signals newly associated with traits from an overall meta-analysis. The most compelling associations involved 12q24.11 (near MYL2) and 12q24.13 (in C12orf51) for high-density lipoprotein cholesterol, 2p21 (near SIX2-SIX3) for fasting plasma glucose, 19q13.33 (in RPS11) and 6q22.33 (in RSPO3) for renal traits, and 12q24.11 (near MYL2), 12q24.13 (in C12orf51 and near OAS1), 4q31.22 (in ZNF827) and 7q11.23 (near TBL2-BCL7B) for hepatic traits. These findings highlight previously unknown biological pathways for metabolic traits investigated in this study.     

Prevention of cisplatin-induced ototoxicity by the inhibition of gap junctional intercellular communication in auditory cells

Cis-diamminedichloroplatinum (cisplatin) is an effective chemotherapeutic drug for cancer therapy. However, most patients treated with cisplatin are at a high risk of ototoxicity, which causes severe hearing loss. Inspired by the “Good Samaritan effect” or “bystander effect” from gap junction coupling, we investigated the role of gap junctions in cisplatin-induced ototoxicity as a potential therapeutic method. We showed that connexin 43 (Cx43) was highly expressed in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells, mediating cell–cell communication. The viability of HEI-OC1 cells was greatly decreased by cisplatin treatment, and cisplatin-treated HEI-OC1 cells showed lower Cx43 expression compared to that of untreated HEI-OC1 cells. In particular, high accumulation of Cx43 was observed around the nucleus of cisplatin-treated cells, whereas scattered punctuate expression of Cx43 was observed in the cytoplasm and membrane in normal cells, suggesting that cisplatin may interrupt the normal gap junction communication by inhibiting the trafficking of Cx43 to cell membranes in HEI-OC1 cells. Interestingly, we found that the inhibition of gap junction activity reduced cisplatin-induced apoptosis of auditory hair cells. Cx43 siRNA- or 18α-GA-treated HEI-OC1 cells showed higher cell viability compared to control HEI-OC1 cells during cisplatin treatment; this was also supported by fluorescence recovery after photobleaching studies. Inhibition of gap junction activity reduced recovery of calcein acetoxymethyl ester fluorescence compared to control cells. Additionally, analysis of the mechanisms involved demonstrated that highly activate extracellular signal-regulated kinase and protein kinase B, combined with inhibition of gap junctions may promote cell viability during cisplatin treatment.     

Cold tolerance of two Antarctic terrestrial arthropods

Summary Two Antarctic arthropods,Alaskozetes antarcticus (Acari) andCryptopygus antarcticus (Collembola) possess the ability to supercool to –30°C, but the realisation of this potential is dependent on starvation. The mite contains glycerol in a concentration of about 1% fresh weight.Acknowledgments. We thank the British Antarctic Survey, Cambridge and the Zoological Institute. University of Oslo for support and reasearch facilities, and the Natural Environment Research Council for a research grant (GR. 3/2797). We are grateful to Ms I. Tambs-Lyche for technical assistance.     

应用PRO/ENGINEER开发机床夹具设计库

应用PRO／Engineer强大的功能模块，用成组技术的分类方法，创建机床标准组合夹具，建立和开发相应的标准件、通用件元件库，成形机夹具设计库，进行机床夹具应用设计。这种机床夹具设计库开发应用简单，拓展容易。     

用原噬菌体诱导法检测30种化学物质的潜在遗传毒性

应用原噬菌体诱导法检测了包括农药、食品添加剂和化妆品等30种不同化学物质的遗传毒性,并用S9和S14模拟代谢系统.在S9存在时,有17种化学物质能诱导原噬菌体的释放;在S14存在时,只有10种化学物质能诱导原噬菌体的释放;如果不加S9和S14,有15种化学物质有这种作用.测得结果为阳性的化学物质中有些是已知的潜在诱变剂和致癌剂(NTG、黄曲霉毒素B_1)或抗癌药(丝裂霉素C、阿糖胞苷和消瘤芥).     

Forecasting with an econometric model: The issue of judgemental adjustment

The paper outlines the current state of forecasting with an econometric model. After briefly distinguishing econometric techniques from other statistical approaches and arguing the advantages of this approach the paper concentrates on the issue of judgemental adjustments to models for forecasting purposes. Two types of adjustment are distinguished and the conditions under which each is justified are stated. Guidance in the use of adjustment is offered through a review of considerations in an actual forecasting situation.