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991.
992.
993.
Membrane depolarization causes many kinds of ion channels to open, a process termed activation. For both Na+ channels and Ca2+ channels, kinetic analysis of current has suggested that during activation the channel undergoes several conformational changes before reaching the open state. Structurally, these channels share a common motif: the central element is a large polypeptide with four repeating units of homology (repeats I-IV), each containing a voltage-sensing region, the S4 segment. This suggests that the distinct conformational transitions inferred from kinetic analysis may be equated with conformational changes of the individual structural repeats. To investigate the molecular basis of channel activation, we constructed complementary DNAs encoding chimaeric Ca2+ channels in which one or more of the four repeats of the skeletal muscle dihydropyridine receptor are replaced by the corresponding repeats derived from the cardiac dihydropyridine receptor. We report here that repeat I determines whether the chimaeric Ca2+ channel shows slow (skeletal muscle-like) or rapid (cardiac-like) activation. 相似文献
994.
Human immunodeficiency virus genetic variation that can escape cytotoxic T cell recognition. 总被引:87,自引:0,他引:87
R E Phillips S Rowland-Jones D F Nixon F M Gotch J P Edwards A O Ogunlesi J G Elvin J A Rothbard C R Bangham C R Rizza 《Nature》1991,354(6353):453-459
In a longitudinal study of HIV seropositive patients, there were fluctuations in the specificity of cytotoxic T cells for the virus. This was matched by variability in proviral gag DNA epitope sequences in the lymphocytes of these patients. Some of these viral variants are not recognized by autologous T cells. Accumulation of such mutations in T-cell antigenic targets would provide a mechanism for immune escape. 相似文献
995.
CD4+ and CD8+ T cells acquire specific lymphokine secretion potentials during thymic maturation. 总被引:10,自引:0,他引:10
Peripheral CD4+ and CD8+ T lymphocytes carry out different functions during immune reactions, partly as a result of the distinct patterns of lymphokines that they secrete upon stimulation. Using thymic cells from adult and newborn mice as well as from fetal organ cultures, we show here that this functional differentiation occurs inside the thymus and is completed during the single positive stage by the time the T-cell receptor becomes fully coupled to the intracellular activation pathways leading to lymphokine secretion. Surprisingly, CD4+8- thymocytes differ from their immediate progeny, naive peripheral CD4+ cells, in that they secrete a broader range of lymphokines, including interleukins 4, 5 and 10 and gamma-interferon, and more closely resemble immunologically experienced (activated or memory) CD4+ lymphocytes. 相似文献
996.
997.
Sensitivity of human foetal intestine to interferon 总被引:1,自引:0,他引:1
998.
Novel human serum protein from fibroblast plasma membrane 总被引:25,自引:0,他引:25
999.
The quantal hypothesis proposes that chemical synaptic transmission involves the probabilistic release of multimolecular packets of transmitter. Analysis of the resulting trial-to-trial fluctuations in postsynaptic response can provide estimates both of the number of quanta released and of the size of their postsynaptic effect. This in turn permits the quantification of the relative contributions of pre- and postsynaptic factors to the strength of a given synapse. Quantal analysis of excitatory synapses in the hippocampus has proved difficult and has led to contradictory conclusions when applied to long-term potentiation. Here we report the use of a combination of quantal analysis procedures to provide evidence that both pre- and postsynaptic changes can contribute substantially to the maintenance of long-term potentiation in the CA1 region of the hippocampus. The initial setting of the presynaptic release mechanism seems to determine their relative importance. 相似文献
1000.
Studies of intracellular traffic in yeast and mammalian systems have implicated members of the Rab family of small GTP-binding proteins as regulators of membrane fusion. We have used the patch clamp technique to measure exocytotic fusion events directly and investigate the role of GTP-binding proteins in regulating exocytosis in mast cells. Intracellular perfusion of mast cells with GTP-gamma S is sufficient to trigger complete exocytotic degranulation in the absence of other intracellular messengers. Here we show that GTP is a potent inhibitor of GTP-gamma S-induced degranulation, indicating that sustained activation of a GTP-binding protein is sufficient for membrane fusion. We have found that synthetic oligopeptides, corresponding to part of the effector domain of Rab3a, stimulate complete exocytotic degranulation, similar to that induced by GTP-gamma S. The response is selective for Rab3a sequence and is strictly dependent on Mg2+ and ATP. This suggests that sustained activation of a Rab3 protein causes exocytotic fusion. The peptide response can be accelerated by GDP-beta S, suggesting that Rab3a peptides compete with endogenous Rab3 proteins for a binding site on a target effector protein, which causes fusion on activation. 相似文献