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361.
A Schneider P Montague I Griffiths M Fanarraga P Kennedy P Brophy K A Nave 《Nature》1992,358(6389):758-761
Proteolipid protein (PLP; M(r) 30,000) is a highly conserved major polytopic membrane protein in myelin but its cellular function remains obscure. Neurological mutant mice can often provide model systems for human genetic disorders. Mutations of the X-chromosome-linked PLP gene are lethal, identified first in the jimpy mouse and subsequently in patients with Pelizaeus-Merzbacher disease. The unexplained phenotype of these mutations includes degeneration and premature cell death of oligodendrocytes with associated hypomyelination. Here we show that a new mouse mutant rumpshaker is defined by the amino-acid substitution Ile-to-Thr at residue 186 in a membrane-embedded domain of PLP. Surprisingly, rumpshaker mice, although myelin-deficient, have normal longevity and a full complement of morphologically normal oligodendrocytes. Hypomyelination can thus be genetically separated from the PLP-dependent oligodendrocyte degeneration. We suggest that PLP has a vital function in glial cell development, distinct from its later role in myelin assembly, and that this dichotomy of action may explain the clinical spectrum of Pelizaeus-Merzbacher disease. 相似文献
362.
363.
364.
In polarized neurons, axons and dendrites perform different functions, which are reflected in their different molecular organization. Studies on the sorting of viral and endogenous glycoproteins in epithelial cells and hippocampal neurons suggest that there may be similarities in the mechanism of sorting in these two cell types. The mechanisms that maintain the distinct composition of the two plasma membrane domains in these two cell types must, however, be different. We have proposed the existence of a functional barrier at the axonal hillock/initial segment which prevents the intermixing of membrane constituents. Here we test this hypothesis by fusing liposomes containing fluorescent phospholipids into the plasma membrane of polarized hippocampal cells in culture. Fusion was induced by lowering the pH and mediated by influenza virus haemagglutinin expressed on the axonal surface of neurons infected with fowl plague virus. Labelling was found exclusively on axons after fusion. Although the fused lipids were mobile on the axonal membrane, no labelling was detected on the cell body and dendritic surfaces. These results suggest that there is a diffusion barrier at the axonal hillock/initial segment which maintains the compositional differences between the axonal and somatodendritic domains. 相似文献
365.
House mice (Mus musculus domesticus) form communal nests and appear to nurse each other's pups indiscriminately. Communal nesting probably functions to reduce infanticide, but it also makes females vulnerable to exploitation if nursing partners fail to provide their fair share of care. Kinship theory predicts that females will preferentially form communal nests with relatives to minimize exploitation and further increase inclusive fitness. Here we provide evidence from seminatural populations that females prefer communal nesting partners that share allelic forms of major histocompatibility complex genes. Such behaviour would lead to the selection of close relatives as communal nesting partners. Although criteria for the demonstration of kin recognition are currently embroiled in controversy, this is the first vertebrate study to meet Grafen's restrictive requirements: discrimination is based on genetic similarity at highly polymorphic loci, incidental correlations due to relatedness are experimentally controlled, and strong reasons exist for expecting the assayed behaviour to be kin-selected. 相似文献
366.
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
367.
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
368.
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
369.
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
370.
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