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排序方式: 共有105条查询结果,搜索用时 375 毫秒
61.
Jacobsen M Schweer D Ziegler A Gaber R Schock S Schwinzer R Wonigeit K Lindert RB Kantarci O Schaefer-Klein J Schipper HI Oertel WH Heidenreich F Weinshenker BG Sommer N Hemmer B 《Nature genetics》2000,26(4):495-499
Multiple sclerosis (MS) is the most common demyelinating disease of the central nervous system. It is widely accepted that a dysregulated immune response against brain resident antigens is central to its yet unknown pathogenesis. Although there is evidence that the development of MS has a genetic component, specific genetic factors are largely unknown. Here we investigated the role of a point mutation in the gene (PTPRC) encoding protein-tyrosine phosphatase, receptor-type C (also known as CD45) in the heterozygous state in the development of MS. The nucleotide transition in exon 4 of the gene locus interferes with mRNA splicing and results in altered expression of CD45 isoforms on immune cells. In three of four independent case-control studies, we demonstrated an association of the mutation with MS. We found the PTPRC mutation to be linked to and associated with the disease in three MS nuclear families. In one additional family, we found the same variant CD45 phenotype, with an as-yet-unknown origin, among the members affected with MS. Our findings suggest an association of the mutation in PTPRC with the development of MS in some families. 相似文献
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Kim BG Li C Qiao W Mamura M Kasprzak B Kasperczak B Anver M Wolfraim L Hong S Mushinski E Potter M Kim SJ Fu XY Deng C Letterio JJ 《Nature》2006,441(7096):1015-1019
SMAD4 (MAD homologue 4 (Drosophila)), also known as DPC4 (deleted in pancreatic cancer), is a tumour suppressor gene that encodes a central mediator of transforming growth factor-beta signalling. Germline mutations in SMAD4 are found in over 50% of patients with familial juvenile polyposis, an autosomal dominant disorder characterized by predisposition to hamartomatous polyps and gastrointestinal cancer. Dense inflammatory cell infiltrates underlay grossly normal appearing, non-polypoid colonic and gastric mucosa of patients with familial juvenile polyposis. This prominent stromal component suggests that loss of SMAD4-dependent signalling in cells within the epithelial microenvironment has an important role in the evolution of intestinal tumorigenesis in this syndrome. Here we show that selective loss of Smad4-dependent signalling in T cells leads to spontaneous epithelial cancers throughout the gastrointestinal tract in mice, whereas epithelial-specific deletion of the Smad4 gene does not. Tumours arising within the colon, rectum, duodenum, stomach and oral cavity are stroma-rich with dense plasma cell infiltrates. Smad4(-/-) T cells produce abundant T(H)2-type cytokines including interleukin (IL)-5, IL-6 and IL-13, known mediators of plasma cell and stromal expansion. The results support the concept that cancer, as an outcome, reflects the loss of the normal communication between the cellular constituents of a given organ, and indicate that Smad4-deficient T cells ultimately send the wrong message to their stromal and epithelial neighbours. 相似文献
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Massive gene decay in the leprosy bacillus 总被引:73,自引:0,他引:73
Cole ST Eiglmeier K Parkhill J James KD Thomson NR Wheeler PR Honoré N Garnier T Churcher C Harris D Mungall K Basham D Brown D Chillingworth T Connor R Davies RM Devlin K Duthoy S Feltwell T Fraser A Hamlin N Holroyd S Hornsby T Jagels K Lacroix C Maclean J Moule S Murphy L Oliver K Quail MA Rajandream MA Rutherford KM Rutter S Seeger K Simon S Simmonds M Skelton J Squares R Squares S Stevens K Taylor K Whitehead S Woodward JR Barrell BG 《Nature》2001,409(6823):1007-1011
Leprosy, a chronic human neurological disease, results from infection with the obligate intracellular pathogen Mycobacterium leprae, a close relative of the tubercle bacillus. Mycobacterium leprae has the longest doubling time of all known bacteria and has thwarted every effort at culture in the laboratory. Comparing the 3.27-megabase (Mb) genome sequence of an armadillo-derived Indian isolate of the leprosy bacillus with that of Mycobacterium tuberculosis (4.41 Mb) provides clear explanations for these properties and reveals an extreme case of reductive evolution. Less than half of the genome contains functional genes but pseudogenes, with intact counterparts in M. tuberculosis, abound. Genome downsizing and the current mosaic arrangement appear to have resulted from extensive recombination events between dispersed repetitive sequences. Gene deletion and decay have eliminated many important metabolic activities including siderophore production, part of the oxidative and most of the microaerophilic and anaerobic respiratory chains, and numerous catabolic systems and their regulatory circuits. 相似文献
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Veverka J Farquhar B Robinson M Thomas P Murchie S Harch A Antreasian PG Chesley SR Miller JK Owen WM Williams BG Yeomans D Dunham D Heyler G Holdridge M Nelson RL Whittenburg KE Ray JC Carcich B Cheng A Chapman C Bell JF Bell M Bussey B Clark B Domingue D Gaffey MJ Hawkins E Izenberg N Joseph J Kirk R Lucey P Malin M McFadden L Merline WJ Peterson C Prockter L Warren J Wellnitz D 《Nature》2001,413(6854):390-393
The NEAR-Shoemaker spacecraft was designed to provide a comprehensive characterization of the S-type asteroid 433 Eros (refs 1,2,3), an irregularly shaped body with approximate dimensions of 34 x 13 x 13 km. Following the completion of its year-long investigation, the mission was terminated with a controlled descent to its surface, in order to provide extremely high resolution images. Here we report the results of the descent on 12 February 2001, during which 70 images were obtained. The landing area is marked by a paucity of small craters and an abundance of 'ejecta blocks'. The properties and distribution of ejecta blocks are discussed in a companion paper. The last sequence of images reveals a transition from the blocky surface to a smooth area, which we interpret as a 'pond'. Properties of the 'ponds' are discussed in a second companion paper. The closest image, from an altitude of 129 m, shows the interior of a 100-m-diameter crater at 1-cm resolution. 相似文献
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Pose and structure estimation from a single image is a fundamental problem in machine vision and multiple sensor fusion and integration. In this paper we propose using rigid constraints described in different coordinate frames to iteratively estimate structural and camera pose parameters. Using geometric properties of reflected correspondences we put forward a new concept, the reflected pole of a rigid transformation. The reflected pole represents a general analysis of transformations that can be applied to both 2D and 3D transformations. We demonstrate how the concept is applied to calibration by proposing an iterative method to estimate the structural parameters of objects. The method is based on a coarse-to-fine strategy in which initial estimation is obtained through a classical linear algorithm which is then refined by iteration. For a comparative study of performance, we also implemented an extended motion estimation algorithm (from 2D-2D to 3D-2D case) based on epipolar geometry. 相似文献
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