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排序方式: 共有134条查询结果,搜索用时 15 毫秒
81.
82.
Torgerson DG Ampleford EJ Chiu GY Gauderman WJ Gignoux CR Graves PE Himes BE Levin AM Mathias RA Hancock DB Baurley JW Eng C Stern DA Celedón JC Rafaels N Capurso D Conti DV Roth LA Soto-Quiros M Togias A Li X Myers RA Romieu I Van Den Berg DJ Hu D Hansel NN Hernandez RD Israel E Salam MT Galanter J Avila PC Avila L Rodriquez-Santana JR Chapela R Rodriguez-Cintron W Diette GB Adkinson NF Abel RA Ross KD Shi M Faruque MU Dunston GM Watson HR Mantese VJ Ezurum SC Liang L Ruczinski I Ford JG 《Nature genetics》2011,43(9):887-892
Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10(-9)). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma. 相似文献
83.
Chi Chiu Wang Ellen Billett Astrid Borchert Hartmut Kuhn Christoph Ufer 《Cellular and molecular life sciences : CMLS》2013,70(4):599-630
Monoamine oxidases (MAOs) are flavoproteins of the outer mitochondrial membrane that catalyze the oxidative deamination of biogenic and xenobiotic amines. In mammals there are two isoforms (MAO-A and MAO-B) that can be distinguished on the basis of their substrate specificity and their sensitivity towards specific inhibitors. Both isoforms are expressed in most tissues, but their expression in the central nervous system and their ability to metabolize monoaminergic neurotransmitters have focused MAO research on the functionality of the mature brain. MAO activities have been related to neurodegenerative diseases as well as to neurological and psychiatric disorders. More recently evidence has been accumulating indicating that MAO isoforms are expressed not only in adult mammals, but also before birth, and that defective MAO expression induces developmental abnormalities in particular of the brain. This review is aimed at summarizing and critically evaluating the new findings on the developmental functions of MAO isoforms during embryogenesis. 相似文献
84.
Since the discovery of the trans-neptunian objects (TNOs) in 1992, nearly one thousand new members have been added to our Solar System, several of which are as big as--or even larger than--Pluto. The properties of the population of TNOs, such as the size distribution and the total number, are valuable information for understanding the formation of the Solar System, but direct observation is only possible for larger objects with diameters above several tens of kilometres. Smaller objects, which are expected to be more abundant, might be found when they occult background stars, but hitherto there have been no definite detections. Here we report the discovery of such occultation events at millisecond timescales in the X-ray light curve of Scorpius X-1. The estimated sizes of these occulting TNOs are < or =100 m. Their abundance is in line with an extrapolation of the distribution of sizes of larger TNOs. 相似文献
85.
Northcott PA Shih DJ Peacock J Garzia L Morrissy AS Zichner T Stütz AM Korshunov A Reimand J Schumacher SE Beroukhim R Ellison DW Marshall CR Lionel AC Mack S Dubuc A Yao Y Ramaswamy V Luu B Rolider A Cavalli FM Wang X Remke M Wu X Chiu RY Chu A Chuah E Corbett RD Hoad GR Jackman SD Li Y Lo A Mungall KL Nip KM Qian JQ Raymond AG Thiessen NT Varhol RJ Birol I Moore RA Mungall AJ Holt R Kawauchi D Roussel MF Kool M Jones DT Witt H Fernandez-L A Kenney AM Wechsler-Reya RJ Dirks P Aviv T 《Nature》2012,488(7409):49-56
Medulloblastoma, the most common malignant paediatric brain tumour, is currently treated with nonspecific cytotoxic therapies including surgery, whole-brain radiation, and aggressive chemotherapy. As medulloblastoma exhibits marked intertumoural heterogeneity, with at least four distinct molecular variants, previous attempts to identify targets for therapy have been underpowered because of small samples sizes. Here we report somatic copy number aberrations (SCNAs) in 1,087 unique medulloblastomas. SCNAs are common in medulloblastoma, and are predominantly subgroup-enriched. The most common region of focal copy number gain is a tandem duplication of SNCAIP, a gene associated with Parkinson's disease, which is exquisitely restricted to Group 4α. Recurrent translocations of PVT1, including PVT1-MYC and PVT1-NDRG1, that arise through chromothripsis are restricted to Group 3. Numerous targetable SCNAs, including recurrent events targeting TGF-β signalling in Group 3, and NF-κB signalling in Group 4, suggest future avenues for rational, targeted therapy. 相似文献
86.
Lin SM Tsai JY Hsiao CD Huang YT Chiu CL Liu MH Tung JY Liu TH Pan RL Sun YJ 《Nature》2012,484(7394):399-403
H(+)-translocating pyrophosphatases (H(+)-PPases) are active proton transporters that establish a proton gradient across the endomembrane by means of pyrophosphate (PP(i)) hydrolysis. H(+)-PPases are found primarily as homodimers in the vacuolar membrane of plants and the plasma membrane of several protozoa and prokaryotes. The three-dimensional structure and detailed mechanisms underlying the enzymatic and proton translocation reactions of H(+)-PPases are unclear. Here we report the crystal structure of a Vigna radiata H(+)-PPase (VrH(+)-PPase) in complex with a non-hydrolysable substrate analogue, imidodiphosphate (IDP), at 2.35?? resolution. Each VrH(+)-PPase subunit consists of an integral membrane domain formed by 16 transmembrane helices. IDP is bound in the cytosolic region of each subunit and trapped by numerous charged residues and five Mg(2+) ions. A previously undescribed proton translocation pathway is formed by six core transmembrane helices. Proton pumping can be initialized by PP(i) hydrolysis, and H(+) is then transported into the vacuolar lumen through a pathway consisting of Arg?242, Asp?294, Lys?742 and Glu?301. We propose a working model of the mechanism for the coupling between proton pumping and PP(i) hydrolysis by H(+)-PPases. 相似文献
87.
通过对17种氨基酸Rf值的测定,从中选择三组,每组五种氨基酸:1.赖氨酸、丝氨酸、脯氨酸、缬氨酸、亮氨酸;2.赖氨酸、苏氨酸、脯氨酸、缬氨酸、亮氨酸;3.赖氨酸、脯氨酸、酪氨酸、苯丙氨酸、亮氨酸。结果表明,所选择三组氨基酸分高效果明显好于实验教材中所选择的五种氨基酸的分离效果。 相似文献
88.
In viruses, as in eukaryotes, elaborate mechanisms have evolved to protect the genome and to ensure its timely replication and reliable transmission to progeny. Influenza A viruses are enveloped, spherical or filamentous structures, ranging from 80 to 120 nm in diameter. Inside each envelope is a viral genome consisting of eight single-stranded negative-sense RNA segments of 890 to 2,341 nucleotides each. These segments are associated with nucleoprotein and three polymerase subunits, designated PA, PB1 and PB2; the resultant ribonucleoprotein complexes (RNPs) resemble a twisted rod (10-15 nm in width and 30-120 nm in length) that is folded back and coiled on itself. Late in viral infection, newly synthesized RNPs are transported from the nucleus to the plasma membrane, where they are incorporated into progeny virions capable of infecting other cells. Here we show, by transmission electron microscopy of serially sectioned virions, that the RNPs of influenza A virus are organized in a distinct pattern (seven segments of different lengths surrounding a central segment). The individual RNPs are suspended from the interior of the viral envelope at the distal end of the budding virion and are oriented perpendicular to the budding tip. This finding argues against random incorporation of RNPs into virions, supporting instead a model in which each segment contains specific incorporation signals that enable the RNPs to be recruited and packaged as a complete set. A selective mechanism of RNP incorporation into virions and the unique organization of the eight RNP segments may be crucial to maintaining the integrity of the viral genome during repeated cycles of replication. 相似文献
89.
夫妻分别财产制是适应社会发展趋势的新型夫妻财产关系。在市场经济条件下,完善夫妻分别财产制、规范债务处理,使经济生活秩序化,使婚姻质量得到提高,这对维护夫妻双方及第三人的合法权益,都有十分重要的现实意义。 相似文献
90.
Chiaming Yen Wujeng Li 《厦门大学学报(自然科学版)》2002,(Z1)
In this paper, a Web-based Mechanical Design and A na lysis Framework (WMDAF) is proposed. This WMADF allows designers to develop web -based computer aided programs in a systematic way during the collaborative mec hanical system design and analysis process. This system is based on an emerg ing web-based Content Management System (CMS) called eXtended Object Oriented P ortal System (XOOPS). Due to the Open Source Status of the XOOPS CMS, programs d eveloped with this framework can be further customized to ... 相似文献