Genome-wide association study identifies a new melanoma susceptibility locus at 1q21.3

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.     

Thiyl radicals in biosystems: effects on lipid structures and metabolisms

Thiyl radicals are intermediates of enzyme- and radical-driven biochemical processes, and their potential as reactive species in the biological environment has been somehow underestimated. From organic chemistry, however, it is known that thiyl radicals isomerize the double bonds of unsaturated fatty acids to a mixture with very dominating trans isomers. Recently, this reaction has been particularly studied for biosystems, focusing on the effect of thiyl radicals on the natural all-cis double bonds of unsaturated phospholipids, which undergo a conversion to the unnatural trans form. In this paper we report briefly the role of thiyl radicals in biosystems, describe the main features of the radical-induced cis-trans isomerization process under both in vitro and in vivo conditions, and reflect on some consequences for membrane structures, lipid metabolism and enzymatic reactions.Received 29 October 2004; received after revision 3 December 2004; accepted 4 January 2005     

Folic acid and biotin on the metabolism of one carbon unit: Utilization of β- carbon of serine for the synthesis of methionine

Riassunto La sintesi di metionina da serina e omocisteina risulta notevolmente diminuita nel fegato di ratti carenti di acido folico e biotina, non solo rispetto ad animali controllo, ma anche a quelli carenti solo di acido folico. La biotina pertanto sembra influenzare l'utilizzazione del-carbonio della serina per la sintesi del metile della metionina probabilmente attraverso il suo effetto sulla disponibilità dei coenzimi dell'acido folico nel fegato.     

An electrochemical and microstructural characterization of steel-mortar admixed with corrosion inhibitors

The present research brings new insights on the role of admixed corrosion inhibitors in the processes of cement hydration and rebar corrosion.The admixing of NaCl and the corrosion inhibitors in fresh mortar was found to alter the morphology and microstructure of the hardened mortar at the steel-mortar interfacial region.The admixing of the inhibitors increased the risk of carbonation of cement hydrates at the steel-mortar interfacial region,but partially displaced chloride ions. Chloride and the admixed in...     

阻尼器对高速铁路连续梁桥易损性的影响研究

中等跨径的预应混凝土连续梁广泛运用于高速铁路,以往震害及实验都表明该类桥型在地震下的破坏集中在桥墩和支座位置。为研究阻尼器对高速铁路连续梁桥地震易损性的影响,以某典型高速铁路连续梁桥为例,采用IDA方法,利用有限元软件OpenSees建立了地震易损性分析模型,定义四种破坏极限状态,并应用基于可靠度理论的概率解析易损性函数表达式获得地震易损性曲线,探讨阻尼器对桥梁地震易损性的影响。结果表明:设置阻尼器使桥梁受力更为合理,可进一步提高桥梁抗震性能。     

Studies on relationships between riboflavin and folate

Résumé Des rats carencés en riboflavine, comparés aux contrôles, ont présenté une remarquable augmentation de la quantité de FIGlu éliminé. Une augmentation moins évidente a été observée dans l'élimination de AIC. Aucune variation, au contraire, en ce qui concerne les enzymes FIGlu transferase et AICR trànsformylase.     

Selective absorption processes as the origin of puzzling spectral line polarization from the Sun.

Magnetic fields play a key role in most astrophysical systems, from the Sun to active galactic nuclei. They can be studied through their effects on atomic energy levels, which produce polarized spectral lines. In particular, anisotropic radiation 'pumping' processes (which send electrons to higher atomic levels) induce population imbalances that are modified by weak magnetic fields. Here we report peculiarly polarized light in the He I 10,830-A multiplet observed in a coronal filament located at the centre of the solar disk. We show that the polarized light arises from selective absorption from the ground level of the triplet system of helium, and that it implies the presence of magnetic fields of the order of a few gauss that are highly inclined with respect to the solar radius vector. This disproves the common belief that population imbalances in long-lived atomic levels are insignificant in the presence of inclined fields of the order of a few gauss, and opens up a new diagnostic window for the investigation of solar magnetic fields.     

Detectable clonal mosaicism from birth to old age and its relationship to cancer

We detected clonal mosaicism for large chromosomal anomalies (duplications, deletions and uniparental disomy) using SNP microarray data from over 50,000 subjects recruited for genome-wide association studies. This detection method requires a relatively high frequency of cells with the same abnormal karyotype (>5-10%; presumably of clonal origin) in the presence of normal cells. The frequency of detectable clonal mosaicism in peripheral blood is low (<0.5%) from birth until 50 years of age, after which it rapidly rises to 2-3% in the elderly. Many of the mosaic anomalies are characteristic of those found in hematological cancers and identify common deleted regions with genes previously associated with these cancers. Although only 3% of subjects with detectable clonal mosaicism had any record of hematological cancer before DNA sampling, those without a previous diagnosis have an estimated tenfold higher risk of a subsequent hematological cancer (95% confidence interval = 6-18).