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We performed a genome-wide association study of melanoma in a discovery cohort of 2,168 Australian individuals with melanoma and 4,387 control individuals. In this discovery phase, we confirm several previously characterized melanoma-associated loci at MC1R, ASIP and MTAP-CDKN2A. We selected variants at nine loci for replication in three independent case-control studies (Europe: 2,804 subjects with melanoma, 7,618 control subjects; United States 1: 1,804 subjects with melanoma, 1,026 control subjects; United States 2: 585 subjects with melanoma, 6,500 control subjects). The combined meta-analysis of all case-control studies identified a new susceptibility locus at 1q21.3 (rs7412746, P = 9.0 × 10(-11), OR in combined replication cohorts of 0.89 (95% CI 0.85-0.95)). We also show evidence suggesting that melanoma associates with 1q42.12 (rs3219090, P = 9.3 × 10(-8)). The associated variants at the 1q21.3 locus span a region with ten genes, and plausible candidate genes for melanoma susceptibility include ARNT and SETDB1. Variants at the 1q21.3 locus do not seem to be associated with human pigmentation or measures of nevus density.  相似文献   
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Smoking marijuana or administration of its main active constituent, delta9-tetrahydrocannabinol (delta9-THC), may exert potent dilating effects on human airways. But the physiological significance of this observation and its potential therapeutic value are obscured by the fact that some asthmatic patients respond to these compounds with a paradoxical bronchospasm. The mechanisms underlying these contrasting responses remain unresolved. Here we show that the endogenous cannabinoid anandamide exerts dual effects on bronchial responsiveness in rodents: it strongly inhibits bronchospasm and cough evoked by the chemical irritant, capsaicin, but causes bronchospasm when the constricting tone exerted by the vagus nerve is removed. Both effects are mediated through peripheral CB1 cannabinoid receptors found on axon terminals of airway nerves. Biochemical analyses indicate that anandamide is synthesized in lung tissue on calcium-ion stimulation, suggesting that locally generated anandamide participates in the intrinsic control of airway responsiveness. In support of this conclusion, the CB1 antagonist SR141716A enhances capsaicin-evoked bronchospasm and cough. Our results may account for the contrasting bronchial actions of cannabis-like drugs in humans, and provide a framework for the development of more selective cannabinoid-based agents for the treatment of respiratory pathologies.  相似文献   
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【目的】研究丛枝菌根(Arbuscular mycorrhiza,AM)真菌在喀斯特自然土壤条件下对喀斯特先锋草本植物根系的影响。【方法】通过自然土接种AM真菌(N)、灭菌土接种AM真菌(M)及灭菌土壤对照(S)共3种土壤处理,种植喀斯特先锋植物狗尾草(Setaria viridis)、荩草(Arthraxon hispidus)、鬼针草(Bidens pilosa)及狼杷草(Bidens tripartita),并测定它们的根系生物量、根长、根表面积、根体积、根平均直径、根尖数及根分枝数。【结果】荩草、鬼针草及狼杷草在N处理及M处理下具有较高的菌根侵染率,狗尾草的菌根侵染率较低。与S处理相比,M处理下AM真菌明显提高了荩草、鬼针草及狼杷草的根系生物量、根长、根表面积、根体积、根尖数、根分枝数及组织密度,降低了根平均直径、比根长、比根面积及比根体积;与M处理相比,N处理明显降低了荩草、鬼针草及狼杷草的根系生物量、根长、根表面积、根体积、根尖数、根分枝数及组织密度,提高了比根长、比根面积及比根体积,但对根平均直径无明显影响。【结论】荩草、鬼针草及狼杷草具有较高菌根侵染率,能与AM真菌共生获得更加发达的根系,而自然土壤削弱了AM真菌对荩草、鬼针草及狼杷草根系生长的促进作用。  相似文献   
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Separate sodium and calcium spikes in the same axon   总被引:2,自引:0,他引:2  
G O Mackie  R W Meech 《Nature》1985,313(6005):791-793
Aglantha digitale is a jellyfish (order Hydromedusae) capable of two distinct kinds of locomotion; 'slow' swimming which is generated endogenously and is used in fishing behaviour, and 'fast' swimming which is evoked by predators and serves for escape. Both forms of swimming are produced by contraction of the bell-shaped body wall and expulsion of a jet of water from an opening at the base of the animal. During slow swimming, the contractions are weak and the animal moves about 15 mm, roughly one body length, but during a fast swim there is a more violent contraction which can propel the animal five times as far. Both forms of contraction depend on impulses in the eight giant motor axons that synapse directly with the muscle sheet making up the inner surface of the body wall. We report here that the giant motor axons are able to mediate both kinds of activity because they can conduct two different sorts of impulse. Fast swimming requires a rapidly conducted Na+-dependent action potential whereas slow swimming depends on a low amplitude Ca2+ 'spike'. This is the first report of an axon capable of two kinds of impulse propagation and it provides a physiological function for low potential Ca2+ activation.  相似文献   
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Evans RL  Hirth G  Baba K  Forsyth D  Chave A  Mackie R 《Nature》2005,437(7056):249-252
Magnetotelluric and seismic data, collected during the MELT experiment at the southern East Pacific Rise, constrain the distribution of melt beneath this mid-ocean-ridge spreading centre and also the evolution of the oceanic lithosphere during its early cooling history. Here we focus on structures imaged at distances approximately 100 to 350 km east of the ridge crest, corresponding to seafloor ages of approximately 1.3 to 4.5 million years (Myr), where the seismic and electrical conductivity structure is nearly constant and independent of age. Beginning at a depth of about 60 km, we image a large increase in electrical conductivity and a change from isotropic to transversely anisotropic electrical structure, with higher conductivity in the direction of fast propagation for seismic waves. Conductive cooling models predict structure that increases in depth with age, extending to about 30 km at 4.5 Myr ago. We infer, however, that the structure of young oceanic plates is instead controlled by a decrease in water content above a depth of 60 km induced by the melting process beneath the spreading centre.  相似文献   
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基于并行工程的产品开发过程管理的研究   总被引:1,自引:0,他引:1  
并行工程采用集成化与并行化的思想来开发产品,强调在信息集成基础上的过程集成,运用工作流管理技术能够很好地达到此目的。在分析工作流管理技术的基础上,以冲压模具的开发过程为例来说明用工作流管理技术实现产品开发过程管理的  相似文献   
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研究了合金中M_6C,M_(23)C_6及MC的晶体结构、化学组成、形态、分布及数量,它们的溶解析出规律及互相转化。  相似文献   
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