排序方式: 共有43条查询结果,搜索用时 15 毫秒
21.
Simpson MA Irving MD Asilmaz E Gray MJ Dafou D Elmslie FV Mansour S Holder SE Brain CE Burton BK Kim KH Pauli RM Aftimos S Stewart H Kim CA Holder-Espinasse M Robertson SP Drake WM Trembath RC 《Nature genetics》2011,43(4):303-305
We used an exome-sequencing strategy and identified an allelic series of NOTCH2 mutations in Hajdu-Cheney syndrome, an autosomal dominant multisystem disorder characterized by severe and progressive bone loss. The Hajdu-Cheney syndrome mutations are predicted to lead to the premature truncation of NOTCH2 with either disruption or loss of the C-terminal proline-glutamate-serine-threonine-rich proteolytic recognition sequence, the absence of which has previously been shown to increase Notch signaling. 相似文献
22.
Crow YJ Hayward BE Parmar R Robins P Leitch A Ali M Black DN van Bokhoven H Brunner HG Hamel BC Corry PC Cowan FM Frints SG Klepper J Livingston JH Lynch SA Massey RF Meritet JF Michaud JL Ponsot G Voit T Lebon P Bonthron DT Jackson AP Barnes DE Lindahl T 《Nature genetics》2006,38(8):917-920
Aicardi-Goutières syndrome (AGS) presents as a severe neurological brain disease and is a genetic mimic of the sequelae of transplacentally acquired viral infection. Evidence exists for a perturbation of innate immunity as a primary pathogenic event in the disease phenotype. Here, we show that TREX1, encoding the major mammalian 3' --> 5' DNA exonuclease, is the AGS1 gene, and AGS-causing mutations result in abrogation of TREX1 enzyme activity. Similar loss of function in the Trex1(-/-) mouse leads to an inflammatory phenotype. Our findings suggest an unanticipated role for TREX1 in processing or clearing anomalous DNA structures, failure of which results in the triggering of an abnormal innate immune response. 相似文献
23.
D'Angelo G Polishchuk E Di Tullio G Santoro M Di Campli A Godi A West G Bielawski J Chuang CC van der Spoel AC Platt FM Hannun YA Polishchuk R Mattjus P De Matteis MA 《Nature》2007,449(7158):62-67
The molecular machinery responsible for the generation of transport carriers moving from the Golgi complex to the plasma membrane relies on a tight interplay between proteins and lipids. Among the lipid-binding proteins of this machinery, we previously identified the four-phosphate adaptor protein FAPP2, the pleckstrin homology domain of which binds phosphatidylinositol 4-phosphate and the small GTPase ARF1. FAPP2 also possesses a glycolipid-transfer-protein homology domain. Here we show that human FAPP2 is a glucosylceramide-transfer protein that has a pivotal role in the synthesis of complex glycosphingolipids, key structural and signalling components of the plasma membrane. The requirement for FAPP2 makes the whole glycosphingolipid synthetic pathway sensitive to regulation by phosphatidylinositol 4-phosphate and ARF1. Thus, by coupling the synthesis of glycosphingolipids with their export to the cell surface, FAPP2 emerges as crucial in determining the lipid identity and composition of the plasma membrane. 相似文献
24.
This paper reviews the visioning literature along five key dimensions: analysis of an organization's current situation, assessment of the external environment, identification of desired future vision, connection of the future to the present state, and testing the vision. It then describes one particular participative visioning methodology, which has largely been used in the public sector, the CHOICES approach. The paper then analyzes the CHOICES approach along the five key dimensions identified earlier. Gaps in the approach are identified and a revised methodology is outlined. The paper ends with a summary of results from a pilot study which tested the revised methodology. 相似文献
25.
Frances Egan 《Studies in history and philosophy of science》2010,41(3):253-259
The computational theory of mind construes the mind as an information-processor and cognitive capacities as essentially representational capacities. Proponents of the view (hereafter, ‘computationalists’) claim a central role for representational content in computational models of these capacities. In this paper I argue that the standard view of the role of representational content in computational models is mistaken; I argue that representational content is to be understood as a gloss on the computational characterization of a cognitive process. 相似文献
26.
The spittlebug, Aphrophora canadensis Walley (Homoptera: Cercopidae), was discovered at Moscow, Idaho, in 1979 infesting Pinus mugo Turra, an exotic ornamental pine. Masses of spittle, densely populated with nymphs, have continued to be abundant since then. The nymphs congregated and fed mainly on cones and did not cause visible reddening of foliage that is typical of other pine-infesting spittlebugs. Immature stages and behavior are described for the first time and are compared to other nearctic pine-infesting species. Beginning in mid-August, eggs were laid under fascicle sheaths at the bases of needles, where they overwintered. Nymphs appeared in late April and began transforming to adults in mid-July. Mating occurred from early August to late September. Adults lingered in diminishing numbers until mid-October. 相似文献
27.
Summary Evidence from light and electron microscopic studies indicates that differentiation of myocardial cells in moth embryos begins at 6 days post-oviposition and is completed on eclosion. Fibrillogenesis, and development of cytoplasmic organelles and membranes are described. The heart is fully differentiated and functional at eclosion.Acknowledgments. This work was supported by the New Hampshire Heart Association and the National Science Foundation. 相似文献
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Structure of the inositol 1,4,5-trisphosphate receptor binding core in complex with its ligand 总被引:8,自引:0,他引:8
Bosanac I Alattia JR Mal TK Chan J Talarico S Tong FK Tong KI Yoshikawa F Furuichi T Iwai M Michikawa T Mikoshiba K Ikura M 《Nature》2002,420(6916):696-700
In a variety of cells, the Ca2+ signalling process is mediated by the endoplasmic-reticulum-membrane-associated Ca2+ release channel, inositol 1,4,5-trisphosphate (InsP3) receptor (InsP3R). Being ubiquitous and present in organisms ranging from humans to Caenorhabditis elegans, InsP3R has a vital role in the control of cellular and physiological processes as diverse as cell division, cell proliferation, apoptosis, fertilization, development, behaviour, memory and learning. Mouse type I InsP3R (InsP3R1), found in high abundance in cerebellar Purkinje cells, is a polypeptide with three major functionally distinct regions: the amino-terminal InsP3-binding region, the central modulatory region and the carboxy-terminal channel region. Here we present a 2.2-A crystal structure of the InsP3-binding core of mouse InsP3R1 in complex with InsP3. The asymmetric, boomerang-like structure consists of an N-terminal beta-trefoil domain and a C-terminal alpha-helical domain containing an 'armadillo repeat'-like fold. The cleft formed by the two domains exposes a cluster of arginine and lysine residues that coordinate the three phosphoryl groups of InsP3. Putative Ca2+-binding sites are identified in two separate locations within the InsP3-binding core. 相似文献
30.
Frances E. Arrighi Priscilla P. Saunders Grady F. Saunders T. C. Hsu 《Cellular and molecular life sciences : CMLS》1971,27(8):964-966
Zusammenfassung Studien von in situ DNS/RNS-Hybriden (oder Mischflüssigkeiten) zwischen RNS und verschiedenen Fraktionen von DNS und Metaphase-Chromosomen des Menschen ergaben, dass hauptsächlich die wiederholt vorkommende DNS-Fraktion C
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t = 0 0.005 sich in der centromeren und telomeren Region befindet.
Supported in part by grants No. G-267 and No. G-373 from the Robert A. Welch Foundation, and grants No. DRG-269 and No. 1061 from the Damon Runyon Memorial Fund for Cancer Research 相似文献
Supported in part by grants No. G-267 and No. G-373 from the Robert A. Welch Foundation, and grants No. DRG-269 and No. 1061 from the Damon Runyon Memorial Fund for Cancer Research 相似文献