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141.
A physical map of the mouse genome 总被引:1,自引:0,他引:1
Gregory SG Sekhon M Schein J Zhao S Osoegawa K Scott CE Evans RS Burridge PW Cox TV Fox CA Hutton RD Mullenger IR Phillips KJ Smith J Stalker J Threadgold GJ Birney E Wylie K Chinwalla A Wallis J Hillier L Carter J Gaige T Jaeger S Kremitzki C Layman D Maas J McGrane R Mead K Walker R Jones S Smith M Asano J Bosdet I Chan S Chittaranjan S Chiu R Fjell C Fuhrmann D Girn N Gray C Guin R Hsiao L Krzywinski M Kutsche R Lee SS Mathewson C McLeavy C Messervier S Ness S Pandoh P Prabhu AL Saeedi P 《Nature》2002,418(6899):743-750
A physical map of a genome is an essential guide for navigation, allowing the location of any gene or other landmark in the chromosomal DNA. We have constructed a physical map of the mouse genome that contains 296 contigs of overlapping bacterial clones and 16,992 unique markers. The mouse contigs were aligned to the human genome sequence on the basis of 51,486 homology matches, thus enabling use of the conserved synteny (correspondence between chromosome blocks) of the two genomes to accelerate construction of the mouse map. The map provides a framework for assembly of whole-genome shotgun sequence data, and a tile path of clones for generation of the reference sequence. Definition of the human-mouse alignment at this level of resolution enables identification of a mouse clone that corresponds to almost any position in the human genome. The human sequence may be used to facilitate construction of other mammalian genome maps using the same strategy. 相似文献
142.
Mutant frizzled-4 disrupts retinal angiogenesis in familial exudative vitreoretinopathy 总被引:14,自引:0,他引:14
Robitaille J MacDonald ML Kaykas A Sheldahl LC Zeisler J Dubé MP Zhang LH Singaraja RR Guernsey DL Zheng B Siebert LF Hoskin-Mott A Trese MT Pimstone SN Shastry BS Moon RT Hayden MR Goldberg YP Samuels ME 《Nature genetics》2002,32(2):326-330
Familial exudative vitreoretinopathy (FEVR) is a hereditary ocular disorder characterized by a failure of peripheral retinal vascularization. Loci associated with FEVR map to 11q13-q23 (EVR1; OMIM 133780, ref. 1), Xp11.4 (EVR2; OMIM 305390, ref. 2) and 11p13-12 (EVR3; OMIM 605750, ref. 3). Here we have confirmed linkage to the 11q13-23 locus for autosomal dominant FEVR in one large multigenerational family and refined the disease locus to a genomic region spanning 1.55 Mb. Mutations in FZD4, encoding the putative Wnt receptor frizzled-4, segregated completely with affected individuals in the family and were detected in affected individuals from an additional unrelated family, but not in normal controls. FZD genes encode Wnt receptors, which are implicated in development and carcinogenesis. Injection of wildtype and mutated FZD4 into Xenopus laevis embryos revealed that wildtype, but not mutant, frizzled-4 activated calcium/calmodulin-dependent protein kinase II (CAMKII) and protein kinase C (PKC), components of the Wnt/Ca(2+) signaling pathway. In one of the mutants, altered subcellular trafficking led to defective signaling. These findings support a function for frizzled-4 in retinal angiogenesis and establish the first association between a Wnt receptor and human disease. 相似文献
143.
Apoptosis disables CD31-mediated cell detachment from phagocytes promoting binding and engulfment 总被引:19,自引:0,他引:19
Macrophage recognition and ingestion of 'self' cells undergoing apoptosis in vivo protects tissues from the toxic contents of dying cells and modulates macrophage regulation of inflammatory and immune responses. However, the complex molecular mechanisms mediating macrophage discrimination between viable and apoptotic cells are poorly understood. In particular, little is known of why viable nucleated cells are not engulfed by macrophages. To reveal active repulsion of viable cells and to seek specific capture or 'tethering' of apoptotic cells, we studied macrophage binding of viable and apoptotic leukocytes under conditions of flow. We found that homophilic ligation of CD31 (ref. 4) on viable leukocytes promoted their active, temperature-dependent detachment under low shear, whereas such CD31-mediated detachment was disabled in apoptotic leukocytes, promoting tight binding and macrophage ingestion of dying cells. Here we propose that CD31 (also known as platelet-endothelial cell adhesion molecule-1, PECAM-1) is an example of a cell-surface molecule that prevents phagocyte ingestion of closely apposed viable cells by transmitting 'detachment' signals, and which changes function on apoptosis, promoting tethering of dying cells to phagocytes. 相似文献
144.
The protein-protein interaction map of Helicobacter pylori 总被引:33,自引:0,他引:33
Rain JC Selig L De Reuse H Battaglia V Reverdy C Simon S Lenzen G Petel F Wojcik J Schächter V Chemama Y Labigne A Legrain P 《Nature》2001,409(6817):211-215
With the availability of complete DNA sequences for many prokaryotic and eukaryotic genomes, and soon for the human genome itself, it is important to develop reliable proteome-wide approaches for a better understanding of protein function. As elementary constituents of cellular protein complexes and pathways, protein-protein interactions are key determinants of protein function. Here we have built a large-scale protein-protein interaction map of the human gastric pathogen Helicobacter pylori. We have used a high-throughput strategy of the yeast two-hybrid assay to screen 261 H. pylori proteins against a highly complex library of genome-encoded polypeptides. Over 1,200 interactions were identified between H. pylori proteins, connecting 46.6% of the proteome. The determination of a reliability score for every single protein-protein interaction and the identification of the actual interacting domains permitted the assignment of unannotated proteins to biological pathways. 相似文献
145.
146.
Mouse models for Friedreich ataxia exhibit cardiomyopathy, sensory nerve defect and Fe-S enzyme deficiency followed by intramitochondrial iron deposits 总被引:15,自引:0,他引:15
Puccio H Simon D Cossée M Criqui-Filipe P Tiziano F Melki J Hindelang C Matyas R Rustin P Koenig M 《Nature genetics》2001,27(2):181-186
Friedreich ataxia (FRDA), the most common autosomal recessive ataxia, is characterized by degeneration of the large sensory neurons and spinocerebellar tracts, cardiomyopathy and increased incidence in diabetes. FRDA is caused by severely reduced levels of frataxin, a mitochondrial protein of unknown function. Yeast knockout models as well as histological and biochemical data from heart biopsies or autopsies of FRDA patients have shown that frataxin defects cause a specific iron-sulfur protein deficiency and intramitochondrial iron accumulation. We have recently shown that complete absence of frataxin in the mouse leads to early embryonic lethality, demonstrating an important role for frataxin during mouse development. Through a conditional gene-targeting approach, we have generated in parallel a striated muscle frataxin-deficient line and a neuron/cardiac muscle frataxin-deficient line, which together reproduce important progressive pathophysiological and biochemical features of the human disease: cardiac hypertrophy without skeletal muscle involvement, large sensory neuron dysfunction without alteration of the small sensory and motor neurons, and deficient activities of complexes I-III of the respiratory chain and of the aconitases. Our models demonstrate time-dependent intramitochondrial iron accumulation in a frataxin-deficient mammal, which occurs after onset of the pathology and after inactivation of the Fe-S-dependent enzymes. These mutant mice represent the first mammalian models to evaluate treatment strategies for the human disease. 相似文献
147.
148.
Serge M. Candéias Justyna Mika Paul Finnon Tom Verbiest Rosemary Finnon Natalie Brown Simon Bouffler Joanna Polanska Christophe Badie 《Cellular and molecular life sciences : CMLS》2017,74(23):4339-4351
While the biological effects of high-dose-ionizing radiation on human health are well characterized, the consequences of low-dose radiation exposure remain poorly defined, even though they are of major importance for radiological protection. Lymphocytes are very radiosensitive, and radiation-induced health effects may result from immune cell loss and/or immune system impairment. To decipher the mechanisms of effects of low doses, we analyzed the modulation of the T-cell receptor gene repertoire in mice exposed to a single low (0.1 Gy) or high (1 Gy) dose of radiation. High-throughput T-cell receptor gene profiling was used to visualize T-lymphocyte dynamics over time in control and irradiated mice. Radiation exposure induces “aging-like” effects on the T-cell receptor gene repertoire, detectable as early as 1 month post-exposure and for at least 6 months. Surprisingly, these effects are more pronounced in animals exposed to 0.1 Gy than to 1 Gy, where partial correction occurs over time. Importantly, we found that low-dose radiation effects are partially due to the hematopoietic stem cell impairment. Collectively, our findings show that acute low-dose radiation exposure specifically results in long-term alterations of the T-lymphocyte repertoire. 相似文献
149.
150.
Simon Schaffer 《Annals of science》2014,71(1):2-26
The celebrated Swedish natural philosopher and visionary theologian Emanuel Swedenborg (1688–1772) devoted major efforts to the establishment of a reliable method for the determination of longitude at sea. He first formulated a method, based on the astronomical observation of lunar position, while in London in 1710–12. He issued various versions of the method, both in Latin and in Swedish, throughout his career. In 1766, at the age of 78, he presented his scheme for judgment by the Board of Longitude in London. The rich archive of Swedenborg's career allows an unusually detailed historical analysis of his longitude project, an analysis rather better documented than that available for the host of contemporary projectors who launched longitude schemes, submitted their proposals to the Board of Longitude, and have too often been ignored or dismissed by historians. This analysis uses the longitude work to illuminate key aspects of Swedenborg's wider enterprises, including his scheme to set up an astronomical observatory in southern Sweden to be devoted to lunar and stellar observation, his complex attitude to astronomical and magnetic cosmology, and his attempt to fit the notion of longitude into his visionary world-view. Swedenborg's programme also helps make better sense of the metropolitan and international networks of diplomatic and natural philosophical communication in which the longitude schemes were developed and judged. It emerges that his longitude method owed much to the established principles of earlier Baroque and Jesuit natural philosophy while his mature cosmology sought a rational and enlightened model of the universe. 相似文献