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891.
Expression of cystic fibrosis transmembrane conductance regulator corrects defective chloride channel regulation in cystic fibrosis airway epithelial cells. 总被引:53,自引:0,他引:53
D P Rich M P Anderson R J Gregory S H Cheng S Paul D M Jefferson J D McCann K W Klinger A E Smith M J Welsh 《Nature》1990,347(6291):358-363
The cystic fibrosis transmembrane conductance regulator (CFTR) was expressed in cultured cystic fibrosis airway epithelial cells and Cl- channel activation assessed in single cells using a fluorescence microscopic assay and the patch-clamp technique. Expression of CFTR, but not of a mutant form of CFTR (delta F508), corrected the Cl- channel defect. Correction of the phenotypic defect demonstrates a causal relationship between mutations in the CFTR gene and defective Cl- transport which is the hallmark of the disease. 相似文献
892.
Presynaptic enhancement shown by whole-cell recordings of long-term potentiation in hippocampal slices 总被引:28,自引:0,他引:28
Long-term potentiation (LTP) of synaptic transmission in the hippocampus is a widely studied model system for understanding the cellular mechanisms of memory. In region CA1, LTP is triggered postsynaptically by Ca2(+)-dependent activation of protein kinases, but the locus of persistent modification remains controversial. Statistical analysis of synaptic variability has been proposed as a means of settling this debate, although a major obstacle has been the poor signal-to-noise ratio of conventional intracellular recordings. We have applied the whole-cell voltage clamp technique to study synaptic transmission in conventional hippocampal slices (compare refs 28-30). Here we report that robust LTP can be recorded with much improved signal resolution and biochemical access to the postsynaptic cell. Prolonged dialysis of the postsynaptic cell blocks the triggering of LTP, with no effect on expression of LTP. The improved signal resolution unmasks a large trial-to-trial variability, reflecting the probabilistic nature of transmitter release. Changes in the synaptic variability, and a decrease in the proportion of synaptic failures during LTP, suggest that transmitter release is significantly enhanced. 相似文献
893.
An initiation site for meiotic gene conversion in the yeast Saccharomyces cerevisiae 总被引:56,自引:0,他引:56
An initiation site for meiotic gene conversion has been identified in the promoter region of the ARG4 gene of Saccharomyces cerevisiae. The chromosome on which initiation occurs is the recipient of genetic information during gene conversion. 相似文献
894.
Coexistence of A- and B-form DNA in a single crystal lattice 总被引:5,自引:0,他引:5
It is well known that DNA can exist in a variety of conformations which can be interconverted by relatively mild changes in conditions. The in vivo conformation of DNA is usually thought to be the B form, but there is recent evidence that other conformations may be important in DNA-protein recognition. Different fragments of DNA crystallized under virtually identical conditions can form A, B or Z helices. A fragment that adopted an A conformation in a crystal was found in the B conformation in solution, whereas NMR spectroscopy of A-DNA films revealed the presence of a substantial amount of disordered B-DNA. Until now, however, a DNA fragment of a given sequence has not been crystallized in more than one global conformation. We report here an X-ray diffraction study of crystals of the DNA octamer dGGBrUABrUACC. In addition to a 'framework' of A-DNA, which gives discrete X-ray reflections, there are partially disordered B-DNA helices, recognized by their diffuse scattering features. 相似文献
895.
采用雪崩热电子注入技术和高频C-V准静态C-V特性测试,研究了新型快速热氮化的SiOxNy介质膜界面陷阱的特征,侧重于研究界面陷阱的特性与分布。结果表明:这种SiOxNy薄膜禁带中央界面陷阱密度随氮化时间的分布变化呈现”回转效应“,且存在着不同类型、密度悬殊很大的电子陷阱、指出雪崩热电子注入过程中在Si/SiOxNy界面上产生两种性质不同的快界面态陷阱;给出了这两种界面态陷阱密度在禁带中能量的分布 相似文献
896.
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
897.
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
898.
Tyrosine phosphorylation of vav proto-oncogene product containing SH2 domain and transcription factor motifs. 总被引:30,自引:0,他引:30
B Margolis P Hu S Katzav W Li J M Oliver A Ullrich A Weiss J Schlessinger 《Nature》1992,356(6364):71-74
899.
Cell-surface adherence reactions are fundamental to the biology of lymphocytes, monocytes and granulocytes. The lymphocyte function-associated 1 (LFA-1) and macrophage 1 (Mac-1) glycoproteins mediate differing types of adhesion reactions on these cells. LFA-1 participates in T-lymphocyte and natural killer-cell adhesion to target cells, whereas the Mac-1 antigen is identical to the complement receptor type 3, which mediates adhesion of monocytes and granulocytes to C3bi-sensitized particles. Deficiency of these proteins, in a heritable disease, results in multiple adhesion-related leukocyte defects. LFA-1 and Mac-1 resemble one another in overall structure, having alpha-subunits of relative molecular mass (Mr) 180,000 and 170,000, respectively, which are non-covalently associated with beta-subunits of Mr 95,000 in alpha 1 beta 1 complexes. Peptide mapping and immunological cross-reactivity have shown that the beta-subunits are highly related if not identical, but have revealed no similarities between the alpha-subunits. Nonetheless, the shared beta-subunit suggested that LFA-1 and Mac-1 might be members of a protein family containing diversified but evolutionarily related alpha-subunits. Therefore, we examine here the structure of the alpha-subunits by N-terminal amino-acid sequencing. Sequence homology shows that the alpha-subunits are members of a novel leukocyte adhesion protein family, and suggests that their evolution occurred by gene duplication. A search for similarities to previously sequenced proteins reveals a further unexpected homology between LFA-1 and leukocyte (alpha) interferons. 相似文献
900.
DNA sequences of telomeres maintained in yeast 总被引:95,自引:0,他引:95
Telomeres, the ends of eukaryotic chromosomes, have long been recognized as specialized structures. Their stability compared with broken ends of chromosomes suggested that they have properties which protect them from fusion, degradation or recombination. Furthermore, a linear DNA molecule such as that of a eukaryotic chromosome must have a structure at its ends which allows its complete replication, as no known DNA polymerase can initiate synthesis without a primer. At the ends of the relatively short, multi-copy linear DNA molecules found naturally in the nuclei of several lower eukaryotes, there are simple tandemly repeated sequences with, in the cases analysed, a specific array of single-strand breaks, on both DNA strands, in the distal portion of the block of repeats. In general, however, direct analysis of chromosomal termini presents problems because of their very low abundance in nuclei. To circumvent this problem, we have previously cloned a chromosomal telomere of the yeast Saccharomyces cerevisiae on a linear DNA vector molecule. Here we show that yeast chromosomal telomeres terminate in a DNA sequence consisting of tandem irregular repeats of the general form C1-3A. The same repeat units are added to the ends of Tetrahymena telomeres, in an apparently non-template-directed manner, during their replication on linear plasmids in yeast. Such DNA addition may have a fundamental role in telomere replication. 相似文献