排序方式: 共有26条查询结果,搜索用时 15 毫秒
1.
Roscioli T Kamsteeg EJ Buysse K Maystadt I van Reeuwijk J van den Elzen C van Beusekom E Riemersma M Pfundt R Vissers LE Schraders M Altunoglu U Buckley MF Brunner HG Grisart B Zhou H Veltman JA Gilissen C Mancini GM Delrée P Willemsen MA Ramadža DP Chitayat D Bennett C Sheridan E Peeters EA Tan-Sindhunata GM de Die-Smulders CE Devriendt K Kayserili H El-Hashash OA Stemple DL Lefeber DJ Lin YY van Bokhoven H 《Nature genetics》2012,44(5):581-585
Walker-Warburg syndrome (WWS) is an autosomal recessive multisystem disorder characterized by complex eye and brain abnormalities with congenital muscular dystrophy (CMD) and aberrant a-dystroglycan glycosylation. Here we report mutations in the ISPD gene (encoding isoprenoid synthase domain containing) as the second most common cause of WWS. Bacterial IspD is a nucleotidyl transferase belonging to a large glycosyltransferase family, but the role of the orthologous protein in chordates is obscure to date, as this phylum does not have the corresponding non-mevalonate isoprenoid biosynthesis pathway. Knockdown of ispd in zebrafish recapitulates the human WWS phenotype with hydrocephalus, reduced eye size, muscle degeneration and hypoglycosylated a-dystroglycan. These results implicate ISPD in a-dystroglycan glycosylation in maintaining sarcolemma integrity in vertebrates. 相似文献
2.
3.
Although the image of crocodyliforms as 'unchanged living fossils' is naive, several morphological features of the group are thought to have varied only within narrow limits during the course of evolution. These include an elongate snout with an array of conical teeth, a dorsoventrally flattened skull and a posteriorly positioned jaw articulation, which provides a powerful bite force. Here we report an exquisitely preserved specimen of a new taxon from the Late Cretaceous of Madagascar that deviates profoundly from this Bauplan, possessing an extremely blunt snout, a tall, rounded skull, an anteriorly shifted jaw joint and clove-shaped, multicusped teeth reminiscent of those of some ornithischian dinosaurs. This last feature implies that the diet of the new taxon may have been predominantly if not exclusively herbivorous. A close relationship with notosuchid crocodyliforms, particularly Uruguaysuchus (Late Cretaceous, Uruguay) is suggested by several shared derived features; this supports a biogeographical hypothesis that Madagascar and South America were linked during the Late Cretaceous. 相似文献
4.
5.
J T Buckley 《Experientia》1991,47(5):418-419
Aeromonas hydrophila exports aerolysin as a protoxin which is activated by proteolysis after release. Aerolysin binds to the eucaryotic cell receptor glycophorin and oligomerizes, forming holes in the membrane. Important regions of the molecule have been identified by site-directed mutagenesis, and channel formation has been studied in planar lipid bilayers. 相似文献
6.
Chemical treatments were an essential element of ancient Egyptian mummification. Although the inorganic salt natron is recognized as having a central role as a desiccant, without the application of organic preservatives the bodies would have decomposed in the humid environment of the tombs. The nature of the organic treatments remains obscure, because the ancient Egyptians left no written record of the process. Secondary textual evidence for mummification is provided by Herodotus, Diodorus Siculus, Strabo and Pliny. The most important account is that of Herodotus (about 450 yr bc), although archaeological evidence shows that by this time the process had declined significantly and the best results had been achieved centuries before. His account mentions myrrh, cassia, palm wine, 'cedar oil' (still widely disputed) and 'gum'; however, it is vague with respect to the specific natural products used. Here we report the results of chemical investigations of a substantial collection of samples of tissues, wrappings and 'resinous/bituminous' materials from provenanced and dated Egyptian mummies. We focused on examples of the 'classic' mummy-making culture of the Pharaonic or dynastic period, from which we can begin to track the development of mummification chronologically. 相似文献
7.
RGD peptides induce apoptosis by direct caspase-3 activation 总被引:36,自引:0,他引:36
Buckley CD Pilling D Henriquez NV Parsonage G Threlfall K Scheel-Toellner D Simmons DL Akbar AN Lord JM Salmon M 《Nature》1999,397(6719):534-539
Synthetic peptides containing the arginine-glycine-aspartate (RGD) motif have been used extensively as inhibitors of integrin-ligand interactions in studies of cell adhesion, migration, growth and differentiation, because the RGD motif is an integrin-recognition motif found in many ligands. Here we report that RGD-containing peptides are able to directly induce apoptosis without any requirement for integrin-mediated cell clustering or signals. We show that RGD-containing peptides enter cells and directly induce autoprocessing and enzymatic activity of procaspase-3, a pro-apoptotic protein. Using the breast carcinoma cell line MCF-7, which has a functional deletion of the caspase-3 gene, we confirm that caspase-3 is required for RGD-mediated cell death. In addition to an RGD motif, pro-caspase-3 also contains a potential RGD-binding motif, aspartate-aspartate-methionine (DDM), near the site of processing to produce the p12 and p17 subunits. On the basis of the ability of RGD-DDX interactions to trigger integrin activation, we suggest that RGD peptides induce apoptosis by triggering conformational changes that promote pro-caspase-3 autoprocessing and activation. These findings provide an alternative molecular explanation for the potent proapoptotic properties of RGD peptides in models of angiogenesis, inflammation and cancer metastasis. 相似文献
8.
Bovee D Zhou Y Haugen E Wu Z Hayden HS Gillett W Tuzun E Cooper GM Sampas N Phelps K Levy R Morrison VA Sprague J Jewett D Buckley D Subramaniam S Chang J Smith DR Olson MV Eichler EE Kaul R 《Nature genetics》2008,40(1):96-101
The human genome sequence has been finished to very high standards; however, more than 340 gaps remained when the finished genome was published by the International Human Genome Sequencing Consortium in 2004. Using fosmid resources generated from multiple individuals, we targeted gaps in the euchromatic part of the human genome. Here we report 2,488,842 bp of previously unknown euchromatic sequence, 363,114 bp of which close 26 of 250 euchromatic gaps, or 10%, including two remaining euchromatic gaps on chromosome 19. Eight (30.7%) of the closed gaps were found to be polymorphic. These sequences allow complete annotation of several human genes as well as the assignment of mRNAs. The gap sequences are 2.3-fold enriched in segmentally duplicated sequences compared to the whole genome. Our analysis confirms that not all gaps within 'finished' genomes are recalcitrant to subcloning and suggests that the paired-end-sequenced fosmid libraries could prove to be a rich resource for completion of the human euchromatic genome. 相似文献
9.
R. Dixon S. East M. Buckley A. Darragh 《Cellular and molecular life sciences : CMLS》1973,29(4):483-484
Zusammenfassung Nach i. v. Verabreichung von Thyrotrophin-releasing Hormonen an Versuchspersonen ergibt sich eine biphasische Kurve für den Abfall der Tritiumaktivität im Plasma mit einer Exkretions-Halbwertszeit von 3 h.
Acknowledgements. The authors wish to express their gratitude to Hoffmann-La Roche and Co. AG, Basel for the research funds which supported this work. We are indebted to Dr.C. Metzler, Upjohn Co., Kalamazoo for a gift of the NON-LIN computer programme. 相似文献
Acknowledgements. The authors wish to express their gratitude to Hoffmann-La Roche and Co. AG, Basel for the research funds which supported this work. We are indebted to Dr.C. Metzler, Upjohn Co., Kalamazoo for a gift of the NON-LIN computer programme. 相似文献
10.
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