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111.
McGregor L Makela V Darling SM Vrontou S Chalepakis G Roberts C Smart N Rutland P Prescott N Hopkins J Bentley E Shaw A Roberts E Mueller R Jadeja S Philip N Nelson J Francannet C Perez-Aytes A Megarbane A Kerr B Wainwright B Woolf AS Winter RM Scambler PJ 《Nature genetics》2003,34(2):203-208
Fraser syndrome (OMIM 219000) is a multisystem malformation usually comprising cryptophthalmos, syndactyly and renal defects. Here we report autozygosity mapping and show that the locus FS1 at chromosome 4q21 is associated with Fraser syndrome, although the condition is genetically heterogeneous. Mutation analysis identified five frameshift mutations in FRAS1, which encodes one member of a family of novel proteins related to an extracellular matrix (ECM) blastocoelar protein found in sea urchin. The FRAS1 protein contains a series of N-terminal cysteine-rich repeat motifs previously implicated in BMP metabolism, suggesting that it has a role in both structure and signal propagation in the ECM. It has been speculated that Fraser syndrome is a human equivalent of the blebbed phenotype in the mouse, which has been associated with mutations in at least five loci including bl. As mapping data were consistent with homology of FRAS1 and bl, we screened DNA from bl/bl mice and identified a premature termination of mouse Fras1. Thus, the bl mouse is a model for Fraser syndrome in humans, a disorder caused by disrupted epithelial integrity in utero. 相似文献
112.
Résumé Des souris ont été immunisées avec l'albumine du sérum humain dans l'adjuvant complet de Freund. Un jour après une injection de rappel de l'antigène la taille des mitoses, parmi les macrophages du foie dépasse celle des mitoses des souris témoins.
This work was supported by grants from the National Health and Medical Research Council of Australia and from the Postgraduate Medical Foundation of the University of Sydney. We thank MissMaria van Deventer for skilled assistance. 相似文献
This work was supported by grants from the National Health and Medical Research Council of Australia and from the Postgraduate Medical Foundation of the University of Sydney. We thank MissMaria van Deventer for skilled assistance. 相似文献
113.
Genome sequence of Silicibacter pomeroyi reveals adaptations to the marine environment 总被引:2,自引:0,他引:2
Moran MA Buchan A González JM Heidelberg JF Whitman WB Kiene RP Henriksen JR King GM Belas R Fuqua C Brinkac L Lewis M Johri S Weaver B Pai G Eisen JA Rahe E Sheldon WM Ye W Miller TR Carlton J Rasko DA Paulsen IT Ren Q Daugherty SC Deboy RT Dodson RJ Durkin AS Madupu R Nelson WC Sullivan SA Rosovitz MJ Haft DH Selengut J Ward N 《Nature》2004,432(7019):910-913
Since the recognition of prokaryotes as essential components of the oceanic food web, bacterioplankton have been acknowledged as catalysts of most major biogeochemical processes in the sea. Studying heterotrophic bacterioplankton has been challenging, however, as most major clades have never been cultured or have only been grown to low densities in sea water. Here we describe the genome sequence of Silicibacter pomeroyi, a member of the marine Roseobacter clade (Fig. 1), the relatives of which comprise approximately 10-20% of coastal and oceanic mixed-layer bacterioplankton. This first genome sequence from any major heterotrophic clade consists of a chromosome (4,109,442 base pairs) and megaplasmid (491,611 base pairs). Genome analysis indicates that this organism relies upon a lithoheterotrophic strategy that uses inorganic compounds (carbon monoxide and sulphide) to supplement heterotrophy. Silicibacter pomeroyi also has genes advantageous for associations with plankton and suspended particles, including genes for uptake of algal-derived compounds, use of metabolites from reducing microzones, rapid growth and cell-density-dependent regulation. This bacterium has a physiology distinct from that of marine oligotrophs, adding a new strategy to the recognized repertoire for coping with a nutrient-poor ocean. 相似文献
114.
115.
Organic FAQs 总被引:1,自引:0,他引:1
116.
Brenner R Peréz GJ Bonev AD Eckman DM Kosek JC Wiler SW Patterson AJ Nelson MT Aldrich RW 《Nature》2000,407(6806):870-876
Small arteries exhibit tone, a partially contracted state that is an important determinant of blood pressure. In arterial smooth muscle cells, intracellular calcium paradoxically controls both contraction and relaxation. The mechanisms by which calcium can differentially regulate diverse physiological responses within a single cell remain unresolved. Calcium-dependent relaxation is mediated by local calcium release from the sarcoplasmic reticulum. These 'calcium sparks' activate calcium-dependent potassium (BK) channels comprised of alpha and beta1 subunits. Here we show that targeted deletion of the gene for the beta1 subunit leads to a decrease in the calcium sensitivity of BK channels, a reduction in functional coupling of calcium sparks to BK channel activation, and increases in arterial tone and blood pressure. The beta1 subunit of the BK channel, by tuning the channel's calcium sensitivity, is a key molecular component in translating calcium signals to the central physiological function of vasoregulation. 相似文献
117.
Sawaya MR Sambashivan S Nelson R Ivanova MI Sievers SA Apostol MI Thompson MJ Balbirnie M Wiltzius JJ McFarlane HT Madsen AØ Riekel C Eisenberg D 《Nature》2007,447(7143):453-457
Amyloid fibrils formed from different proteins, each associated with a particular disease, contain a common cross-beta spine. The atomic architecture of a spine, from the fibril-forming segment GNNQQNY of the yeast prion protein Sup35, was recently revealed by X-ray microcrystallography. It is a pair of beta-sheets, with the facing side chains of the two sheets interdigitated in a dry 'steric zipper'. Here we report some 30 other segments from fibril-forming proteins that form amyloid-like fibrils, microcrystals, or usually both. These include segments from the Alzheimer's amyloid-beta and tau proteins, the PrP prion protein, insulin, islet amyloid polypeptide (IAPP), lysozyme, myoglobin, alpha-synuclein and beta(2)-microglobulin, suggesting that common structural features are shared by amyloid diseases at the molecular level. Structures of 13 of these microcrystals all reveal steric zippers, but with variations that expand the range of atomic architectures for amyloid-like fibrils and offer an atomic-level hypothesis for the basis of prion strains. 相似文献
118.
All higher organisms on Earth receive energy directly or indirectly from oxygenic photosynthesis performed by plants, green algae and cyanobacteria. Photosystem I (PSI) is a supercomplex of a reaction centre and light-harvesting complexes. It generates the most negative redox potential in nature, and thus largely determines the global amount of enthalpy in living systems. We report the structure of plant PSI at 3.4 A resolution, revealing 17 protein subunits. PsaN was identified in the luminal side of the supercomplex, and most of the amino acids in the reaction centre were traced. The crystal structure of PSI provides a picture at near atomic detail of 11 out of 12 protein subunits of the reaction centre. At this level, 168 chlorophylls (65 assigned with orientations for Q(x) and Q(y) transition dipole moments), 2 phylloquinones, 3 Fe(4)S(4) clusters and 5 carotenoids are described. This structural information extends the understanding of the most efficient nano-photochemical machine in nature. 相似文献
119.
Nelson Ferretti Patricio Cavallo Juan C. Chaparro Duniesky Ríos-Tamayo Tracie A. Seimon Rick West 《Journal of Natural History》2018,52(29-30):1927-1984
120.
Willer T Lee H Lommel M Yoshida-Moriguchi T de Bernabe DB Venzke D Cirak S Schachter H Vajsar J Voit T Muntoni F Loder AS Dobyns WB Winder TL Strahl S Mathews KD Nelson SF Moore SA Campbell KP 《Nature genetics》2012,44(5):575-580
Walker-Warburg syndrome (WWS) is clinically defined as congenital muscular dystrophy that is accompanied by a variety of brain and eye malformations. It represents the most severe clinical phenotype in a spectrum of diseases associated with abnormal post-translational processing of a-dystroglycan that share a defect in laminin-binding glycan synthesis1. Although mutations in six genes have been identified as causes of WWS, only half of all individuals with the disease can currently be diagnosed on this basis2. A cell fusion complementation assay in fibroblasts from undiagnosed individuals with WWS was used to identify five new complementation groups. Further evaluation of one group by linkage analysis and targeted sequencing identified recessive mutations in the ISPD gene (encoding isoprenoid synthase domain containing). The pathogenicity of the identified ISPD mutations was shown by complementation of fibroblasts with wild-type ISPD. Finally, we show that recessive mutations in ISPD abolish the initial step in laminin-binding glycan synthesis by disrupting dystroglycan O-mannosylation. This establishes a new mechanism for WWS pathophysiology. 相似文献