A genome-wide association study of metabolic traits in human urine

We present a genome-wide association study of metabolic traits in human urine, designed to investigate the detoxification capacity of the human body. Using NMR spectroscopy, we tested for associations between 59 metabolites in urine from 862 male participants in the population-based SHIP study. We replicated the results using 1,039 additional samples of the same study, including a 5-year follow-up, and 992 samples from the independent KORA study. We report five loci with joint P values of association from 3.2 × 10(-19) to 2.1 × 10(-182). Variants at three of these loci have previously been linked with important clinical outcomes: SLC7A9 is a risk locus for chronic kidney disease, NAT2 for coronary artery disease and genotype-dependent response to drug toxicity, and SLC6A20 for iminoglycinuria. Moreover, we identify rs37369 in AGXT2 as the genetic basis of hyper-β-aminoisobutyric aciduria.     

Calcium oxalate urolithiasis in mice lacking anion transporter Slc26a6

Urolithiasis is one of the most common urologic diseases in industrialized societies. Calcium oxalate is the predominant component in 70-80% of kidney stones, and small changes in urinary oxalate concentration affect the risk of stone formation. SLC26A6 is an anion exchanger expressed on the apical membrane in many epithelial tissues, including kidney and intestine. Among its transport activities, SLC26A6 mediates Cl(-)-oxalate exchange. Here we show that mutant mice lacking Slc26a6 develop a high incidence of calcium oxalate urolithiasis. Slc26a6-null mice have significant hyperoxaluria and elevation in plasma oxalate concentration that is greatly attenuated by dietary oxalate restriction. In vitro flux studies indicated that mice lacking Slc26a6 have a defect in intestinal oxalate secretion resulting in enhanced net absorption of oxalate. We conclude that the anion exchanger SLC26A6 has a major constitutive role in limiting net intestinal absorption of oxalate, thereby preventing hyperoxaluria and calcium oxalate urolithiasis.     

Genome-wide association analysis identifies three psoriasis susceptibility loci

We carried out a meta-analysis of two recent psoriasis genome-wide association studies with a combined discovery sample of 1,831 affected individuals (cases) and 2,546 controls. One hundred and two loci selected based on P value rankings were followed up in a three-stage replication study including 4,064 cases and 4,685 controls from Michigan, Toronto, Newfoundland and Germany. In the combined meta-analysis, we identified three new susceptibility loci, including one at NOS2 (rs4795067, combined P = 4 × 10?11), one at FBXL19 (rs10782001, combined P = 9 × 10?1?) and one near PSMA6-NFKBIA (rs12586317, combined P = 2 × 10??). All three loci were also associated with psoriatic arthritis (rs4795067, combined P = 1 × 10??; rs10782001, combined P = 4 × 10??; and rs12586317, combined P = 6 × 1??) and purely cutaneous psoriasis (rs4795067, combined P = 1 × 10??; rs10782001, combined P = 2 × 10??; and rs12586317, combined P = 1 × 10??). We also replicated a recently identified association signal near RNF114 (rs495337, combined P = 2 × 10??).     

Electrical signals control wound healing through phosphatidylinositol-3-OH kinase-gamma and PTEN

Wound healing is essential for maintaining the integrity of multicellular organisms. In every species studied, disruption of an epithelial layer instantaneously generates endogenous electric fields, which have been proposed to be important in wound healing. The identity of signalling pathways that guide both cell migration to electric cues and electric-field-induced wound healing have not been elucidated at a genetic level. Here we show that electric fields, of a strength equal to those detected endogenously, direct cell migration during wound healing as a prime directional cue. Manipulation of endogenous wound electric fields affects wound healing in vivo. Electric stimulation triggers activation of Src and inositol-phospholipid signalling, which polarizes in the direction of cell migration. Notably, genetic disruption of phosphatidylinositol-3-OH kinase-gamma (PI(3)Kgamma) decreases electric-field-induced signalling and abolishes directed movements of healing epithelium in response to electric signals. Deletion of the tumour suppressor phosphatase and tensin homolog (PTEN) enhances signalling and electrotactic responses. These data identify genes essential for electrical-signal-induced wound healing and show that PI(3)Kgamma and PTEN control electrotaxis.     

高强混凝土柱抗震性能的足尺试验研究及理论分析

利用一套简单可靠的加载装置 ,对 6根 5 1 0mm× 5 1 0mm的高强混凝土柱足尺试件进行了固定轴力下的水平往复加载试验 .试验参数为塑性铰区的箍筋间隔、强度及轴压比等 .将试验结果与理论计算结果进行了对比 .研究表明高强混凝土柱的抗震延性受轴压比及配箍率影响较大 ,而现行的美国混凝土设计规范ACI3 1 8— 99抗震规范的箍筋设计公式对轴压比的影响考虑不足 .本文根据试验提出了一个以柱端相对位移或延性为性能指标的配箍设计公式     

Colour and size reveal hidden diversity of Necturus (Caudata: Proteidae) from the Gulf Coastal Plain of the United States

ABSTRACT

Recent data from the mitochondrial genome reveal six lineages of Gulf Coast Waterdogs traditionally classified as Necturus beyeri. Here, we use patterns of colour and body size, along with previously published data, to reveal a large, heavily spotted phenotype with an unstriped larva possessing numerous white spots; we re-describe N. beyeri to correspond to this phenotype. We also reveal a small, weakly spotted phenotype possessing an unstriped larva lacking numerous white spots. This phenotype characterises the Apalachicola and Escambia lineages, which current evidence suggests are paraphyletic. We reject taxonomies that place these two lineages in N. lodingi because the type specimen of this species appears to be a melanistic member of N. beyeri. Therefore, we describe the Apalachicola and Escambia lineages as independent new species.

http://ww.zoobank.org/urn:lsid:zoobank.org:act:C8508CCB-F54F-4DC8-B61D-56966A3F1CC8

http://www.zoobank.org/urn:lsid:zoobank.org:act:F044B2CC-55F0-4FFA-A312-9CAD9E73CD69