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101.
Molecular dynamics simulation of the ice nucleation and growth process leading to water freezing 总被引:4,自引:0,他引:4
Upon cooling, water freezes to ice. This familiar phase transition occurs widely in nature, yet unlike the freezing of simple liquids, it has never been successfully simulated on a computer. The difficulty lies with the fact that hydrogen bonding between individual water molecules yields a disordered three-dimensional hydrogen-bond network whose rugged and complex global potential energy surface permits a large number of possible network configurations. As a result, it is very challenging to reproduce the freezing of 'real' water into a solid with a unique crystalline structure. For systems with a limited number of possible disordered hydrogen-bond network structures, such as confined water, it is relatively easy to locate a pathway from a liquid state to a crystalline structure. For pure and spatially unconfined water, however, molecular dynamics simulations of freezing are severely hampered by the large number of possible network configurations that exist. Here we present a molecular dynamics trajectory that captures the molecular processes involved in the freezing of pure water. We find that ice nucleation occurs once a sufficient number of relatively long-lived hydrogen bonds develop spontaneously at the same location to form a fairly compact initial nucleus. The initial nucleus then slowly changes shape and size until it reaches a stage that allows rapid expansion, resulting in crystallization of the entire system. 相似文献
102.
Post-translational disruption of dystroglycan-ligand interactions in congenital muscular dystrophies 总被引:24,自引:0,他引:24
Michele DE Barresi R Kanagawa M Saito F Cohn RD Satz JS Dollar J Nishino I Kelley RI Somer H Straub V Mathews KD Moore SA Campbell KP 《Nature》2002,418(6896):417-422
Muscle eye brain disease (MEB) and Fukuyama congenital muscular dystrophy (FCMD) are congenital muscular dystrophies with associated, similar brain malformations. The FCMD gene, fukutin, shares some homology with fringe-like glycosyltransferases, and the MEB gene, POMGnT1, seems to be a new glycosyltransferase. Here we show, in both MEB and FCMD patients, that alpha-dystroglycan is expressed at the muscle membrane, but similar hypoglycosylation in the diseases directly abolishes binding activity of dystroglycan for the ligands laminin, neurexin and agrin. We show that this post-translational biochemical and functional disruption of alpha-dystroglycan is recapitulated in the muscle and central nervous system of mutant myodystrophy (myd) mice. We demonstrate that myd mice have abnormal neuronal migration in cerebral cortex, cerebellum and hippocampus, and show disruption of the basal lamina. In addition, myd mice reveal that dystroglycan targets proteins to functional sites in brain through its interactions with extracellular matrix proteins. These results suggest that at least three distinct mammalian genes function within a convergent post-translational processing pathway during the biosynthesis of dystroglycan, and that abnormal dystroglycan-ligand interactions underlie the pathogenic mechanism of muscular dystrophy with brain abnormalities. 相似文献
103.
Deletion of brain dystroglycan recapitulates aspects of congenital muscular dystrophy 总被引:20,自引:0,他引:20
Moore SA Saito F Chen J Michele DE Henry MD Messing A Cohn RD Ross-Barta SE Westra S Williamson RA Hoshi T Campbell KP 《Nature》2002,418(6896):422-425
Fukuyama congenital muscular dystrophy (FCMD), muscle-eye-brain disease (MEB), and Walker-Warburg syndrome are congenital muscular dystrophies (CMDs) with associated developmental brain defects. Mutations reported in genes of FCMD and MEB patients suggest that the genes may be involved in protein glycosylation. Dystroglycan is a highly glycosylated component of the muscle dystrophin-glycoprotein complex that is also expressed in brain, where its function is unknown. Here we show that brain-selective deletion of dystroglycan in mice is sufficient to cause CMD-like brain malformations, including disarray of cerebral cortical layering, fusion of cerebral hemispheres and cerebellar folia, and aberrant migration of granule cells. Dystroglycan-null brain loses its high-affinity binding to the extracellular matrix protein laminin, and shows discontinuities in the pial surface basal lamina (glia limitans) that probably underlie the neuronal migration errors. Furthermore, mutant mice have severely blunted hippocampal long-term potentiation with electrophysiologic characterization indicating that dystroglycan might have a postsynaptic role in learning and memory. Our data strongly support the hypothesis that defects in dystroglycan are central to the pathogenesis of structural and functional brain abnormalities seen in CMD. 相似文献
104.
Watanabe H Nakashima K Saito H Slaytor M 《Cellular and molecular life sciences : CMLS》2002,59(11):1983-1992
An endo-β-1,4-glucanase (EG) was purified from the hindgut of an Australian mound-building termite, Coptotermes lacteus. The hindgut extract had a peak separate from those for extracts obtained from the salivary glands and the midgut based on
sephacryl S-200 gel chromatography, and also demonstrated an origin different from the endogenous EGs of the termite itself.
The recovery was further purified by SDS-PAGE, and its N-terminal amino acid sequence analyzed. This showed high homology
to EGs from glycoside hydrolase family (GHF) 7. PCR-based cloning methods were applied to the hindgut contents of C. lacteus and individual protozoan symbionts from C. formosanus. cDNAs encoding putative EGs homologous to GHF7 members were then identified. The functionality of one of the putative proteins
was confirmed by its expression in Escherichia coli.
Received 18 September 2002; accepted 20 September 2002
RID="*"
ID="*"Corresponding author. 相似文献
105.
Limited diversity of the rearranged T-cell gamma gene 总被引:1,自引:0,他引:1
106.
107.
R. Ishitani A. Miyakawa R. Saito T. Iwamoto 《Cellular and molecular life sciences : CMLS》1977,33(7):932-933
Summary The myelin fraction of rat brain stem was treated with butanol-water mixtures, and the extracted proteolipids were separated by Sephadex LH20 column chromatography. 2 peaks of proteolipids eluted in chloroform-methanol 4/1 showed the binding capacity for C14·5-HT. This finding suggests the necessity of the more careful investigations for the probability of proteolipids as receptor proteins in the central nervous system. 相似文献
108.
J. S. Kim M. Hirano H. Uchimura M. Saito T. Nakahara M. Itoh 《Cellular and molecular life sciences : CMLS》1979,35(3):302-303
Summary Following thyroidectomy, monoamine oxidase (MAO) activities toward tyramine decreased significantly by 20% in the nucleus periventricularis and the nucleus arcuatus among the 3 hypothalamic nuclei of the rat, while MAO activity toward serotonin decreased significantly by 10% only in the nucleus periventricularis. It is suggested that thyroidectomy induced selective changes on the multiple forms of MAO in the discrete circumventricular nuclei. 相似文献
109.
Summary Same circadian difference in the specific activities of sucrase and maltase was observed in the purified brush border fraction as in the crude homogenate of the mucosa of rat small intestine, suggesting that the disaccharidase rhythm is not due to the mitosis rhythm of epithelial cells. 相似文献