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991.
Mitochondria contain a complex machinery for the import of nuclear-encoded proteins. Receptor proteins exposed on the outer membrane surface are required for the specific binding of precursor proteins to mitochondria, either by binding of cytosolic signal recognition factors or by direct recognition of the precursor polypeptides. Subsequently, the precursors are inserted into the outer membrane at the general insertion site GIP (general insertion protein). Here we report the analysis of receptors and GIP by crosslinking of translocation intermediates and by coimmunoprecipitation. Surface-accumulated precursors were crosslinked to the receptors MOM19 and MOM72, suggesting a direct interaction of preproteins with surface receptors. We identified three novel mitochondrial outer membrane proteins, MOM7, MOM8, and MOM30 that, together with the previously identified MOM38, seem to form the GIP site and are present in the mitochondrial receptor complex. 相似文献
992.
Close linkage of glucokinase locus on chromosome 7p to early-onset non-insulin-dependent diabetes mellitus. 总被引:22,自引:0,他引:22
P Froguel M Vaxillaire F Sun G Velho H Zouali M O Butel S Lesage N Vionnet K Clément F Fougerousse 《Nature》1992,356(6365):162-164
Non-insulin-dependent diabetes mellitus (NIDDM) is a major health problem, affecting 5% of the world population. Genetic factors are important in NIDDM, but the mechanisms leading to glucose intolerance are unknown. Genetic linkage has been investigated in multigeneration families to localize, and ultimately identify, the gene(s) predisposing to NIDDM. Here we report linkage between the glucokinase locus on chromosome 7p and diabetes in 16 French families with maturity-onset diabetes of the young, a form of NIDDM characterized by monogenic autosomal dominant transmission and early age of onset. Statistical evidence of genetic heterogeneity was significant, with an estimated 45-95% of the 16 families showing linkage to glucokinase. Because glucokinase is a key enzyme of blood glucose homeostasis, these results are evidence that a gene involved in glucose metabolism could be implicated in the pathogenesis of NIDDM. 相似文献
993.
Novel major archaebacterial group from marine plankton. 总被引:77,自引:0,他引:77
Marine bacteria often dominate the plankton biomass and are responsible for much of the cycling of organic matter, but bacterial diversity is poorly understood because conventional identification methods (requiring culturing) miss about 99% of the organisms. Recent advances permit characterization of microbial communities by analysis of 16S ribosomal RNA gene sequences directly from biomass without the need to culture the organisms; such studies from surface ocean samples have found only eubacteria, not archaebacteria (or Archaea), which are profoundly different. Here we report 16S rRNA sequences obtained from Pacific Ocean bacterioplankton samples collected from depths of 100 m and 500 m. Among these we found sequences only distantly related to those of any organisms previously characterized by 16S rRNA sequences, with similarities to the nearest such relatives (extreme thermophiles) approximately the same as those between animals and plants. We suggest that these sequences are from a previously undescribed archaebacterial group that may have diverged from the ancestors of characterized organisms very early in evolution. 相似文献
994.
A human recombinant haemoglobin designed for use as a blood substitute. 总被引:19,自引:0,他引:19
D Looker D Abbott-Brown P Cozart S Durfee S Hoffman A J Mathews J Miller-Roehrich S Shoemaker S Trimble G Fermi 《Nature》1992,356(6366):258-260
The need to develop a blood substitute is now urgent because of the increasing concern over blood-transmitted viral and bacterial pathogens. Cell-free haemoglobin solutions and human haemoglobin synthesized in Escherichia coli and Saccharomyces cerevisiae have been investigated as potential oxygen-carrying substitutes for red blood cells. But these haemoglobins cannot be used as a blood substitute because (1) the oxygen affinity in the absence of 2,3-bisphosphoglycerate is too high to allow unloading of enough oxygen in the tissues, and (2) they dissociate into alpha beta dimers that are cleared rapidly by renal filtration, which can result in long-term kidney damage. We have produced a human haemoglobin using an expression vector containing one gene encoding a mutant beta-globin with decreased oxygen affinity and one duplicated, tandemly fused alpha-globin gene. Fusion of the two alpha-globin subunits increases the half-life of this haemoglobin molecule in vivo by preventing its dissociation into alpha beta dimers and therefore also eliminates renal toxicity. 相似文献
995.
Normal dystrophin transcripts detected in Duchenne muscular dystrophy patients after myoblast transplantation. 总被引:26,自引:0,他引:26
E Gussoni G K Pavlath A M Lanctot K R Sharma R G Miller L Steinman H M Blau 《Nature》1992,356(6368):435-438
996.
D J Roberts A G Craig A R Berendt R Pinches G Nash K Marsh C I Newbold 《Nature》1992,357(6380):689-692
Adhesion of parasitized erythrocytes to post-capillary venular endothelium or uninfected red cells is strongly implicated in the pathogenesis of severe Plasmodium falciparum malaria. Neoantigens at the infected red-cell surface adhere to a variety of host receptors, demonstrate serological diversity in field isolates and may also be a target of the host-protective immune response. Here we use sequential cloning of P. falciparum by micromanipulation to investigate the ability of a parasite to switch antigenic and cytoadherence phenotypes. Our data show that antigens at the parasitized cell surface undergo clonal variation in vitro in the absence of immune pressure at the rate of 2% per generation with concomitant modulations of the adhesive phenotype. A clone has the potential to switch at high frequency to a variety of antigenic and adhesive phenotypes, including a new type of cytoadherence behaviour, 'auto-agglutination' of infected erythrocytes. This rapid appearance of antigenic and functional heterogeneity has important implications for pathogenesis and acquired immunity. 相似文献
997.
Superantigen implicated in dependence of HIV-1 replication in T cells on TCR V beta expression. 总被引:3,自引:0,他引:3
In the pathogenesis of AIDS it is not yet understood whether the small fraction of CD4+ T cells (approximately 1%) infected with the human immunodeficiency virus (HIV) are randomly targeted or not. Here we present evidence that human CD4 T-cell lines expressing selected T-cell antigen receptor V beta gene products can all be infected in vitro with HIV-1, but give markedly different titres of HIV-1 virion production. For example, V beta 12 T-cell lines from several unrelated donors reproducibly yielded up to 100-fold more gag gene product (p24gag antigen) than V beta 6.7a lines. This is consistent with a superantigen effect, because the V beta selectivity was observed with several divergent HIV-1 isolates, was dependent on antigen-presenting cells and on major histocompatibility complex (MHC) class II but was not MHC class II-restricted. The in vivo significance of these findings is supported by the preferential stimulation of V beta 12+ T cells by freshly obtained irradiated antigen-presenting cells from some HIV-1-seropositive but not HIV-1-negative donors. Moreover, cells from patients positive for viral antigen (gp120) were enriched in the V beta 12 subpopulation. V beta 12+ T cells were not deleted in AIDS patients, however, raising the possibility that a variety of mechanisms contribute to T-cell depletion. Our results indicate that a superantigen targets a subpopulation of CD4+ cells for viral replication. 相似文献
998.
S-phase feedback control in budding yeast independent of tyrosine phosphorylation of p34cdc28. 总被引:1,自引:0,他引:1
In somatic cells, entry into mitosis depends on the completion of DNA synthesis. This dependency is established by S-phase feedback controls that arrest cell division when damaged or unreplicated DNA is present. In the fission yeast Schizosaccharomyces pombe, mutations that interfere with the phosphorylation of tyrosine 15 (Y15) of p34cdc2, the protein kinase subunit of maturation promoting factor, accelerate the entry into mitosis and abolish the ability of unreplicated DNA to arrest cells in G2. Because the tyrosine phosphorylation of p34cdc2 is conserved in S. pombe, Xenopus, chicken and human cells, the regulation of p34cdc2-Y15 phosphorylation could be a universal mechanism mediating the S-phase feedback control and regulating the initiation of mitosis. We have investigated these phenomena in the budding yeast Saccharomyces cerevisiae. We report here that the CDC28 gene product (the S. cerevisiae homologue of cdc2) is phosphorylated on the equivalent tyrosine (Y19) during S phase but that mutations that prevent tyrosine phosphorylation do not lead to premature mitosis and do not abolish feedback controls. We have therefore demonstrated a mechanism that does not involve tyrosine phosphorylation of p34 by which cells arrest their division in response to the presence of unreplicated or damaged DNA. We speculate that this mechanism may not involve the inactivation of p34 catalytic activity. 相似文献
999.
本文的实验结果表明,具有开放型本征构型的La_2O_3对甲烷氧化偶联反应有相当好的活性和选择性,在750℃、原料气空速6.O×10~4ml.g~(-1).h~(-1),CH_4:O_2:N_2=3.7:l.0:9.0(V/V)的反应条件下,氧接近全部转化,甲烷转化率达25.4%,C_2烃选择性为43.6%,添加碱土金属(Ca、Sr、Ba)氧化物或碳酸盐能显著地改善催化剂的性能,在上述反应条件下,60mol%Ba-La_2O_3催化剂的C_2烃选择性达到58%。 相似文献
1000.
Treatment with the co-transport inhibitor, furosemide decreased36Cl– flux across perfused Malpighian tubules ofLocusta. However, exclusion of36Cl– from the bathing medium had not effect on22Na+ flux whereas substitution of bathing medium Na+ by K+ increased36Cl– flux. Diuretic extract of corpora cardiaca increased22Na+ (by 106%) and36Cl– (by 335%) fluxes differentially. 相似文献