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931.
932.
Elongation factor-1 alpha (EF-1 alpha), an essential component of the eukaryotic translational apparatus, is a GTP-binding protein that catalyses the binding of aminoacyl-transfer RNAs to the ribosome. Expression of the EF-1 alpha gene decreases towards the end of the lifespans of mouse and human fibroblasts, but forced expression of EF-1 alpha prolongs the lifespan of Drosophila melanogaster. Eukaryotic initiation factor-4E, another component of the translational machinery, is mitogenic or oncogenic when constitutively expressed in some mammalian cells. Thus, components of the protein synthesis apparatus seem to be involved in the control of cell proliferation. Using expression cloning, we have isolated a complementary DNA clone from a BALB/c 3T3 mouse fibroblast variant, A31-I-13 (ref. 10), which specifies a factor determining the susceptibility of BALB/c3T3 to chemically and physically induced transformation. Here we report that the factor is EF-1 alpha and that its constitutive expression causes BALB/c 3T3 A31-I-1 (ref. 10), C3H10T1/2 (ref. 11) and Syrian hamster SHOK fibroblasts to become highly susceptible to transformation induced by 3-methylcholanthrene and ultraviolet light. EF-1 alpha messenger RNA is also constitutively expressed in a quiescent culture of the highly susceptible variant A31-I-13. We conclude that the removal of regulation of the expression of these components of the translational machinery may predispose cells to become more susceptible to malignant transformation. 相似文献
933.
Mutation of the beta-amyloid precursor protein in familial Alzheimer's disease increases beta-protein production. 总被引:41,自引:0,他引:41
M Citron T Oltersdorf C Haass L McConlogue A Y Hung P Seubert C Vigo-Pelfrey I Lieberburg D J Selkoe 《Nature》1992,360(6405):672-674
Progressive cerebral deposition of the 39-43-amino-acid amyloid beta-protein (A beta) is an invariant feature of Alzheimer's disease which precedes symptoms of dementia by years or decades. The only specific molecular defects that cause Alzheimer's disease which have been identified so far are missense mutations in the gene encoding the beta-amyloid precursor protein (beta-APP) in certain families with an autosomal dominant form of the disease (familial Alzheimer's disease, or FAD). These mutations are located within or immediately flanking the A beta region of beta-APP, but the mechanism by which they cause the pathological phenotype of early and accelerated A beta deposition is unknown. Here we report that cultured cells which express a beta-APP complementary DNA bearing a double mutation (Lys to Asn at residue 595 plus Met to Leu at position 596) found in a Swedish FAD family produce approximately 6-8-fold more A beta than cells expressing normal beta-APP. The Met 596 to Leu mutation is principally responsible for the increase. These data establish a direct link between a FAD genotype and the clinicopathological phenotype. Further, they confirm the relevance of the continuous A beta production by cultured cells for elucidating the fundamental mechanism of Alzheimer's disease. 相似文献
934.
The thymus positively selects thymocytes that bear T-cell receptors which recognize antigen presented by self major histocompatibility complex (MHC) proteins. Positive selection is usually driven by MHC products on radiation-resistant cortical epithelial cells. It is unknown whether positive selection is mediated by all thymic epithelial cells or by some specialized subsets. Here we introduce an H-2b-expressing thymic epithelial cell line into the thymuses of lethally irradiated H-2k animals reconstituted with H-2b/k F1 BM or fetal liver cells. I-Ab-restricted T cells are found in these animals, demonstrating that selection occurs on the introduced epithelial cells. 相似文献
935.
Optical imaging of animal somatosensory, olfactory and visual cortices has revealed maps of functional activity. In non-human primates, high-resolution maps of the visual cortex have been obtained using only an intrinsic reflection signal. Although the time course of the signal is slower than membrane potential changes, the maximum optical changes correspond to the maximal neuronal activity. The intrinsic optical signal may represent the flow of ionic currents, oxygen delivery, changes in blood volume, potassium accumulation or glial swelling. Here we use similar techniques to obtain maps from human cortex during stimulation-evoked epileptiform afterdischarges and cognitively evoked functional activity. Optical changes increased in magnitude as the intensity and duration of the afterdischarges increased. In areas surrounding the afterdischarge activity, optical changes were in the opposite direction and possibly represent an inhibitory surround. Large optical changes were found in the sensory cortex during tongue movement and in Broca's and Wernicke's language areas during naming exercises. The adaptation of high-resolution optical imaging for use on human cortex provides a new technique for investigation of the organization of the sensory and motor cortices, language, and other cognitive processes. 相似文献
936.
937.
Escherichia coli divides by forming a septum across the middle of the cell. The biochemical mechanism underlying this process is unknown. Genetic evidence suggests that of all the fts (filamentation temperature sensitive) genes involved in E. coli cell division, ftsZ plays a central role at the earliest known step of septation. Here we show that FtsZ protein binds GTP in vitro using unusual sequence elements. In contrast, such binding to the product of the conditional-lethal ftsZ84 allele is impaired. Purified FtsZ displays a Mg(2+)-dependent GTPase activity which is markedly reduced in the FtsZ84 protein. FtsZ copurifies with near stoichiometric amounts of noncovalently-bound GDP, implying the presence of a GTPase cycle in vivo, similar to that known for signal-transducing GTP-binding proteins. We also show that a small fraction of FtsZ exists as a distinct membrane-associated species that binds GTP. The membrane association of FtsZ and the known ability of GTPases to act as molecular switches implicate FtsZ in a GTP-activated signal transduction pathway that may regulate the start of septation in E. coli. 相似文献
938.
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
939.
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
940.
Susceptibility of beta 2-microglobulin-deficient mice to Trypanosoma cruzi infection. 总被引:8,自引:0,他引:8
The beta 2-microglobulin (beta 2m) protein associates with the products of the class I major histocompatibility (MHC) loci; this combination functions in the thymic development of and antigen presentation to CD8+ T cells. Mice in which the beta 2m gene has been disrupted by homologous recombination fail to express class I MHC gene products, and therefore lack CD8+ T cells and measurable cytotoxic T-cell responses. However, beta 2m- mice appear to have normal development of both CD4+ alpha/beta T-cell receptor (TCR+) and gamma/delta TCR+ T cells and are not overtly more susceptible than beta 2m+ mice to potential environmental agents of infection or to experimental viral infection. Here we show that beta 2m- mice suffer high parasitaemias and early death when infected with the obligate cytoplasmic protozoan parasite Trypanosoma cruzi. Despite this increased susceptibility, the beta 2m- mice are more responsive than their beta 2m+ littermates in terms of lymphokine production, making higher levels of both interleukin-2 and interferon-gamma in response to mitogen stimulation. In addition, the beta 2m- mice show essentially no inflammatory response in parasite-infected tissues. These results confirm previous experiments on mice depleted of CD8+ cells using antibody treatment in demonstrating the importance of CD8+ T cells in immune protection in T. cruzi infection. They also implicate CD8+ T cells and/or class I MHC molecules in regulation of lymphokine production and recruitment of inflammatory cells. 相似文献