排序方式: 共有66条查询结果,搜索用时 15 毫秒
21.
Coucke PJ Willaert A Wessels MW Callewaert B Zoppi N De Backer J Fox JE Mancini GM Kambouris M Gardella R Facchetti F Willems PJ Forsyth R Dietz HC Barlati S Colombi M Loeys B De Paepe A 《Nature genetics》2006,38(4):452-457
Arterial tortuosity syndrome (ATS) is an autosomal recessive disorder characterized by tortuosity, elongation, stenosis and aneurysm formation in the major arteries owing to disruption of elastic fibers in the medial layer of the arterial wall. Previously, we used homozygosity mapping to map a candidate locus in a 4.1-Mb region on chromosome 20q13.1 (ref. 2). Here, we narrowed the candidate region to 1.2 Mb containing seven genes. Mutations in one of these genes, SLC2A10, encoding the facilitative glucose transporter GLUT10, were identified in six ATS families. GLUT10 deficiency is associated with upregulation of the TGFbeta pathway in the arterial wall, a finding also observed in Loeys-Dietz syndrome, in which aortic aneurysms associate with arterial tortuosity. The identification of a glucose transporter gene responsible for altered arterial morphogenesis is notable in light of the previously suggested link between GLUT10 and type 2 diabetes. Our data could provide new insight on the mechanisms causing microangiopathic changes associated with diabetes and suggest that therapeutic compounds intervening with TGFbeta signaling represent a new treatment strategy. 相似文献
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Kraft B Johswich A Kauczor G Scharenberg M Gerardy-Schahn R Bakker H 《Cellular and molecular life sciences : CMLS》2011,68(24):4091-4100
The glycolipid specific Drosophila melanogaster β1,4-N-acetylgalactosaminyltransferase B (β4GalNAcTB) depends on a zinc finger DHHC protein family member named GalNAcTB pilot (GABPI)
for activity and translocation to the Golgi. The six-membrane spanning protein actually lacks the cysteine in the cytoplasmic
DHHC motif, displaying DHHS instead. Here we show that the whole conserved region around the DHHS sequence, which is essential
for palmitoylation in DHHC proteins, is not required for GABPI to interact with β4GalNAcTB. In contrast, the two luminal loops
between transmembrane domain 3–4 and 5–6 contain conserved amino acids, which are crucial for activity. Besides the dependence
on GABPI, β4GalNAcTB requires its exceptional short stem region for activity. A few hydrophobic amino acids positioned close
to the transmembrane domain are essential for the interaction with GABPI. Along with its catalytic domain, β4GalNAcTB, thus,
requires an area in its own stem region and two small luminal loops of GABPI as "add-on" domains. Moreover, some inactive
GABPI mutants could be rescued by fusion with β4GalNAcTB, indicating their importance in direct GABPI-β4GalNAcTB interaction. 相似文献
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The fine-scale distribution of meiotic recombination events in the human genome can be inferred from patterns of haplotype diversity in human populations but directly studied only by high-resolution sperm typing. Both approaches indicate that crossovers are heavily clustered into narrow recombination hot spots. But our direct understanding of hot-spot properties and distributions is largely limited to sperm typing in the major histocompatibility complex (MHC). We now describe the analysis of an unremarkable 206-kb region on human chromosome 1, which identified localized regions of linkage disequilibrium breakdown that mark the locations of sperm crossover hot spots. The distribution, intensity and morphology of these hot spots are markedly similar to those in the MHC. But we also accidentally detected additional hot spots in regions of strong association. Coalescent analysis of genotype data detected most of the hot spots but showed significant differences between sperm crossover frequencies and historical recombination rates. This raises the possibility that some hot spots, particularly those in regions of strong association, may have evolved very recently and not left their full imprint on haplotype diversity. These results suggest that hot spots could be very abundant and possibly fluid features of the human genome. 相似文献
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Influence of the Indonesian Throughflow on the upwelling off the east coast of South Java 总被引:3,自引:0,他引:3
A wave-tide-circulation coupled model is used to simulate upwelling off the south coast of Java, Indone- sia. The results show that the vertical velocity off East Java is stronger than other parts in this area. The strongest vertical velocity is located approximately at 80 m depth. The annual averaged values of upwelling are 2.3 × 10-6 and 1.06 × 10-5 m/s for south of West Java and south of East Java, respectively. The vertical velocity from the model shows that upwelling off West Java has seasonal variability, while it is quite steady and strong off East Java. Additional numerical experiments show that the wind is not the dominant factor for the steady upwelling off the southern part of East Java. It is then hypothesized that the Indonesian Throughflow (ITF) may be responsible for the upwelling. To test this hypothesis, two scenarios are implemented, both of which block the outflow of the ITF. Sensitive study shows that the ITF plays a key role in the formation of East Java upwelling. The effect of the ITF can account for about 55 %-65 % of the upwelling. 相似文献
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Pounds et al. argue that global warming contributes to amphibian declines by encouraging outbreaks of the chytrid fungus Batrachochytrium dendrobatidis. Although our findings agree with the climate-linked epidemic hypothesis, this pathogen is probably not the only proximate factor in such cases: in the Trasimeno Lake area of Umbria in central Italy, for example, the water frog Rana lessonae first declined in the late 1990s, yet chytridiomycosis was not observed until 2003 (refs 5, 6). Here we show that the chytrid was common there throughout 1999-2002, in a previously unknown form that did not cause disease. We therefore think that the focus by Pounds et al. on a single pathogen is hard to justify because the host-parasite ecology is at present so poorly understood. 相似文献
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Hu L Crawford SE Czako R Cortes-Penfield NW Smith DF Le Pendu J Estes MK Prasad BV 《Nature》2012,485(7397):256-259
As with many other viruses, the initial cell attachment of rotaviruses, which are the major causative agent of infantile gastroenteritis, is mediated by interactions with specific cellular glycans. The distally located VP8* domain of the rotavirus spike protein VP4 (ref. 5) mediates such interactions. The existing paradigm is that 'sialidase-sensitive' animal rotavirus strains bind to glycans with terminal sialic acid (Sia), whereas 'sialidase-insensitive' human rotavirus strains bind to glycans with internal Sia such as GM1 (ref. 3). Although the involvement of Sia in the animal strains is firmly supported by crystallographic studies, it is not yet known how VP8* of human rotaviruses interacts with Sia and whether their cell attachment necessarily involves sialoglycans. Here we show that VP8* of a human rotavirus strain specifically recognizes A-type histo-blood group antigen (HBGA) using a glycan array screen comprised of 511 glycans, and that virus infectivity in HT-29 cells is abrogated by anti-A-type antibodies as well as significantly enhanced in Chinese hamster ovary cells genetically modified to express the A-type HBGA, providing a novel paradigm for initial cell attachment of human rotavirus. HBGAs are genetically determined glycoconjugates present in mucosal secretions, epithelia and on red blood cells, and are recognized as susceptibility and cell attachment factors for gastric pathogens like Helicobacter pylori and noroviruses. Our crystallographic studies show that the A-type HBGA binds to the human rotavirus VP8* at the same location as the Sia in the VP8* of animal rotavirus, and suggest how subtle changes within the same structural framework allow for such receptor switching. These results raise the possibility that host susceptibility to specific human rotavirus strains and pathogenesis are influenced by genetically controlled expression of different HBGAs among the world's population. 相似文献