Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study

Prostate cancer (PrCa) is the most frequently diagnosed male cancer in developed countries. We conducted a multi-stage genome-wide association study for PrCa and previously reported the results of the first two stages, which identified 16 PrCa susceptibility loci. We report here the results of stage 3, in which we evaluated 1,536 SNPs in 4,574 individuals with prostate cancer (cases) and 4,164 controls. We followed up ten new association signals through genotyping in 51,311 samples in 30 studies from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. In addition to replicating previously reported loci, we identified seven new prostate cancer susceptibility loci on chromosomes 2p11, 3q23, 3q26, 5p12, 6p21, 12q13 and Xq12 (P = 4.0 × 10(-8) to P = 2.7 × 10(-24)). We also identified a SNP in TERT more strongly associated with PrCa than that previously reported. More than 40 PrCa susceptibility loci, explaining ～25% of the familial risk in this disease, have now been identified.     

低秩矩阵恢复模型改进及其在石油测井中的应用

传统的低秩矩阵恢复模型在去噪过程中通过将观测矩阵分解为低秩部分和稀疏部分达到噪声去除的目的,但该模型要求噪声矩阵必须是稀疏的。然而石油测井所获得的数据中噪声来源复杂,并不能完全保证噪声分布满足稀疏性的要求,使该模型在去噪时表现出一定的局限性,去噪效果不稳定,进而导致后续的数据处理准确率降低。为此,提出将加权范数的思想应用于传统的低秩矩阵恢复模型中,并在惩罚项中将F范数与待恢复矩阵的核范数相结合,构造改进的低秩矩阵恢复模型,使其能够在保证解的稳定性的同时,可以更好地挖掘观测矩阵的低秩性以及增强稀疏矩阵的稀疏性。通过非精确的拉格朗日乘子法分别对改进前后的模型进行求解,并对两种模型去噪后的测井数据分别采用支持向量机(SVM)和相关向量机(RVM)进行油气层识别,结果表明经改进的低秩矩阵恢复模型去噪后的测井数据在保证了油气层识别效率的同时,识别准确率上有了明显提升。     

Aluminium control of argon solubility in silicate melts under pressure

Understanding of the crystal chemistry of the Earth's deep mantle has evolved rapidly recently with the gradual acceptance of the importance of the effect of minor elements such as aluminium on the properties of major phases such as perovskite. In the early Earth, during its formation and segregation into rocky mantle and iron-rich core, it is likely that silicate liquids played a large part in the transport of volatiles to or from the deep interior. The importance of aluminium on solubility mechanisms at high pressure has so far received little attention, even though aluminium has long been recognized as exerting strong control on liquid structures at ambient conditions. Here we present constraints on the solubility of argon in aluminosilicate melt compositions up to 25 GPa and 3,000 K, using a laser-heated diamond-anvil cell. The argon contents reach a maximum that persists to pressures as high as 17 GPa (up to 500 km deep in an early magma ocean), well above that expected on the basis of Al-free melt experiments. A distinct drop in argon solubility observed over a narrow pressure range correlates well with the expected void loss in the melt structure predicted by recent molecular dynamics simulations. These results provide a process for noble gas sequestration in the mantle at various depths in a cooling magma ocean. The concept of shallow partial melting as a unique process for extracting noble gases from the early Earth, thereby defining the initial atmospheric abundance, may therefore be oversimplified.     

Atom-by-atom substitution of Mn in GaAs and visualization of their hole-mediated interactions

The discovery of ferromagnetism in Mn-doped GaAs has ignited interest in the development of semiconductor technologies based on electron spin and has led to several proof-of-concept spintronic devices. A major hurdle for realistic applications of Ga(1-x)Mn(x)As, or other dilute magnetic semiconductors, remains that their ferromagnetic transition temperature is below room temperature. Enhancing ferromagnetism in semiconductors requires us to understand the mechanisms for interaction between magnetic dopants, such as Mn, and identify the circumstances in which ferromagnetic interactions are maximized. Here we describe an atom-by-atom substitution technique using a scanning tunnelling microscope (STM) and apply it to perform a controlled study at the atomic scale of the interactions between isolated Mn acceptors, which are mediated by holes in GaAs. High-resolution STM measurements are used to visualize the GaAs electronic states that participate in the Mn-Mn interaction and to quantify the interaction strengths as a function of relative position and orientation. Our experimental findings, which can be explained using tight-binding model calculations, reveal a strong dependence of ferromagnetic interaction on crystallographic orientation. This anisotropic interaction can potentially be exploited by growing oriented Ga(1-x)Mn(x)As structures to enhance the ferromagnetic transition temperature beyond that achieved in randomly doped samples.     

Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed chaperone complex

Hsp90 (heat shock protein of 90 kDa) is a ubiquitous molecular chaperone responsible for the assembly and regulation of many eukaryotic signalling systems and is an emerging target for rational chemotherapy of many cancers. Although the structures of isolated domains of Hsp90 have been determined, the arrangement and ATP-dependent dynamics of these in the full Hsp90 dimer have been elusive and contentious. Here we present the crystal structure of full-length yeast Hsp90 in complex with an ATP analogue and the co-chaperone p23/Sba1. The structure reveals the complex architecture of the 'closed' state of the Hsp90 chaperone, the extensive interactions between domains and between protein chains, the detailed conformational changes in the amino-terminal domain that accompany ATP binding, and the structural basis for stabilization of the closed state by p23/Sba1. Contrary to expectations, the closed Hsp90 would not enclose its client proteins but provides a bipartite binding surface whose formation and disruption are coupled to the chaperone ATPase cycle.     

玉米抗大斑病菌单基因系的建立及其在Exserohilum turcicum生理小种鉴定中的应用

利用美国A632,B37,B73,B68,C103,Va26等30个Ht单基因鉴别寄主, 按美国伊利诺伊大学的大田接种方案与鉴定方法, 建立了适合中国的监测玉米
大斑病菌生理小种鉴定的21个Ht单基因系. 从吉林省15个地区的不同玉米品种中采集玉米大斑病样本, 采用单孢分离获得了32个玉米大斑病菌菌株, 利用已建立的上述21个Ht单基因鉴别寄主, 通过美国的大田鉴定方案进行生理小种鉴定. 结果表明, 这32个菌株均为0号小种, 并未出现生理小种分化现象.     

Landscape of transcription in human cells

Eukaryotic cells make many types of primary and processed RNAs that are found either in specific subcellular compartments or throughout the cells. A complete catalogue of these RNAs is not yet available and their characteristic subcellular localizations are also poorly understood. Because RNA represents the direct output of the genetic information encoded by genomes and a significant proportion of a cell's regulatory capabilities are focused on its synthesis, processing, transport, modification and translation, the generation of such a catalogue is crucial for understanding genome function. Here we report evidence that three-quarters of the human genome is capable of being transcribed, as well as observations about the range and levels of expression, localization, processing fates, regulatory regions and modifications of almost all currently annotated and thousands of previously unannotated RNAs. These observations, taken together, prompt a redefinition of the concept of a gene.     

High-mobility ultrathin semiconducting films prepared by spin coating

The ability to deposit and tailor reliable semiconducting films (with a particular recent emphasis on ultrathin systems) is indispensable for contemporary solid-state electronics. The search for thin-film semiconductors that provide simultaneously high carrier mobility and convenient solution-based deposition is also an important research direction, with the resulting expectations of new technologies (such as flexible or wearable computers, large-area high-resolution displays and electronic paper) and lower-cost device fabrication. Here we demonstrate a technique for spin coating ultrathin (approximately 50 A), crystalline and continuous metal chalcogenide films, based on the low-temperature decomposition of highly soluble hydrazinium precursors. We fabricate thin-film field-effect transistors (TFTs) based on semiconducting SnS(2-x)Se(x) films, which exhibit n-type transport, large current densities (>10(5) A cm(-2)) and mobilities greater than 10 cm2 V(-1) s(-1)--an order of magnitude higher than previously reported values for spin-coated semiconductors. The spin-coating technique is expected to be applicable to a range of metal chalcogenides, particularly those based on main group metals, as well as for the fabrication of a variety of thin-film-based devices (for example, solar cells, thermoelectrics and memory devices).     

Control of gene expression by a natural metabolite-responsive ribozyme

Most biological catalysts are made of protein; however, eight classes of natural ribozymes have been discovered that catalyse fundamental biochemical reactions. The central functions of ribozymes in modern organisms support the hypothesis that life passed through an 'RNA world' before the emergence of proteins and DNA. We have identified a new class of ribozymes that cleaves the messenger RNA of the glmS gene in Gram-positive bacteria. The ribozyme is activated by glucosamine-6-phosphate (GlcN6P), which is the metabolic product of the GlmS enzyme. Additional data indicate that the ribozyme serves as a metabolite-responsive genetic switch that represses the glmS gene in response to rising GlcN6P concentrations. These findings demonstrate that ribozyme switches may have functioned as metabolite sensors in primitive organisms, and further suggest that modern cells retain some of these ancient genetic control systems.