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131.
Subnuclear Trafficking of Glucocorticoid Receptors In Vitro: Chromatin Recycling and Nuclear Export 总被引:1,自引:1,他引:0
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We have used digitonin-permeabilized cells to examine in vitro nuclear export of glucocorticoid receptors (GRs). In situ biochemical extractions in this system revealed a distinct subnuclear compartment, which collects GRs that have been released from chromatin and serves as a nuclear export staging area. Unliganded nuclear GRs within this compartment are not restricted in their subnuclear trafficking as they have the capacity to recycle to chromatin upon rebinding hormone. Thus, GRs that release from chromatin do not require transit through the cytoplasm to regain functionality. In addition, chromatin-released receptors export from nuclei of permeabilized cells in an ATP- and cytosol-independent process that is stimulated by sodium molybdate, other group VI-A transition metal oxyanions, and some tyrosine phosphatase inhibitors. The stimulation of in vitro nuclear export by these compounds is not unique to GR, but is restricted to other proteins such as the 70- and 90-kD heat shock proteins, hsp70 and hsp90, respectively, and heterogeneous nuclear RNP (hnRNP) A1. Under analogous conditions, the 56-kD heat shock protein, hsp56, and hnRNP C do not export from nuclei of permeabilized cells. If tyrosine kinase inhibitors genistein and tyrphostin AG126 are included to prevent increased tyrosine phosphorylation, in vitro nuclear export of GR is inhibited. Thus, our results are consistent with the involvement of a phosphotyrosine system in the general regulation of nuclear protein export, even for proteins such as GR and hnRNP A1 that use distinct nuclear export pathways. 相似文献
132.
Possible role of macrophage-derived soluble mediators in the pathogenesis of encephalomyocarditis virus-induced diabetes in mice. 总被引:4,自引:1,他引:3
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K Hirasawa H S Jun K Maeda Y Kawaguchi S Itagaki T Mikami H S Baek K Doi J W Yoon 《Journal of virology》1997,71(5):4024-4031
Pancreatic islets from DBA/2 mice infected with the D variant of encephalomyocarditis (EMC-D) virus revealed lymphocytic infiltration with moderate to severe destruction of pancreatic beta cells. Our previous studies showed that the major population of infiltrating cells at the early stages of infection is macrophages. The inactivation of macrophages prior to viral infection resulted in the prevention of diabetes, whereas activation of macrophages prior to viral infection resulted in the enhancement of beta-cell destruction. This investigation was initiated to determine whether macrophage-produced soluble mediators play a role in the destruction of pancreatic beta cells in mice infected with a low dose of EMC-D virus. When we examined the expression of the soluble mediators interleukin-1 beta (IL-1beta), tumor necrosis factor alpha (TNF-alpha), and inducible nitric oxide synthase (iNOS) in the pancreatic islets, we found that these mediators were clearly expressed at an early stage of insulitis and that this expression was evident until the development of diabetes. We confirmed the expression of these mediators by in situ hybridization with digoxigenin-labelled RNA probes or immunohistochemistry in the pancreatic islets. Mice treated with antibody against IL-1beta or TNF-alpha or with the iNOS inhibitor aminoguanidine exhibited a significant decrease in the incidence of diabetes. Mice treated with a combination of anti-IL-1beta antibody, anti-TNF-alpha antibody, and aminoguanidine exhibited a greater decrease in the incidence of disease than did mice treated with one of the antibodies or aminoguanidine. On the basis of these observations, we conclude that macrophage-produced soluble mediators play an important role in the destruction of pancreatic beta cells, resulting in the development of diabetes in mice infected with a low dose of EMC-D virus. 相似文献
133.
134.
心肺压力感受器持续卸荷对前臂血流、血管阻力及心率变异性谱的影响 总被引:1,自引:0,他引:1
低压值下体负压(LBNP)可仅使心肺压力感受器卸荷。采用-2kPaLBNP实验结果表明:LBNP既不引起动脉血压变化,也不引起心率改变,但却引起基础胸阻抗(Z。)从对照的21.8±0.4升高到22.5±0.5Ω(P<0.01),前臂血管阻力(FVR)从12.3±0.9升高到19.9±1.4U(P<0.01),前臂血流(FBF)从对照时7.1±0.5降低到4.3±0.3ml·min ̄(-1)·100ml ̄(-1),心率变异性谱(HRV)未发生任何变化,即心肺压力感受器卸荷时心脏自主神经活动水平与均衡性不受影响。由于FVR和FBF的变化可间接反映外周血管交感传出活动水平,上述实验结果提示,心肺压力感受器对外周血管及心脏自主神经活动的调节可能存在机能分化现象。 相似文献
135.
Y Kobayashi T Ogihara Y Yamamura F Watanabe T Kiguchi I Ninomiya Y Kumahara 《Endocrinologia japonica》1984,31(1):49-53
Recent reports on the isolation and identification of 19-nor-deoxycorticosterone from the urine of rats with adrenal regeneration hypertension give rise to the possibility of a role of this steroid in the pathogenesis of low renin essential hypertension. The present study was undertaken to investigate the presence of 19-nor-deoxycorticosterone in normal rat serum both by a sensitive enzyme immunoassay and by gas chromatography-mass spectrometry (GC/MS). 19-Nor-deoxycorticosterone in rat serum was separated from other steroids prior to enzyme immunoassay by using high performance liquid chromatography (HPLC). The average concentration of 19-nor-deoxycorticosterone in normal rat serum was 137 +/- 62 ng/dl (mean +/- SD, n = 32). Pooled normal rat serum (50 ml) was purified by HPLC and the purified sample was acetylated with acetic anhydride for GC/MS measurement. The retention time and m/z ions (358, 285, and 257) on the resulting mass fragmentogram coincided in position with those of authentic 21-acetoxy-19-nor-deoxycorticosterone and acetylated normal rat serum extract. The combined characteristics of HPLC elution, antigen-antibody reaction, GC retention and selected ion responses provided strongly evidence supporting the presence of 19-nor-deoxycorticosterone in normal rat serum. 相似文献
136.
为植物界最大的类群—被子植物建立一个能真正反映植物的进化历史和系统发育(phylogeny)的分类系统一直是许多植物系统学家和进化学家所向往的。到目前为止,已经提出的被子植物分类系统至少有二十多个。问题在于这样的分类系统能否说已符合于系统发育的要求?要回答这个问题,首先必须弄清系统发育的真正含义是什么。 相似文献
137.
The ionic requirement for generating action potentials in ventral longitudinal muscle fibers dissected from beetle larvae was examined by conventional electrophysiological techniques. Muscle fibers that generated only graded responses in physiological saline were able to generate an all-or-none action potential when the potassium permeability of the membrane was inhibited by tetraethylammonium+ added to the saline. The peak of the action potential thus elicited was intimately related to the external Ca++ concentration. The action potential was blocked by Co++ which is known as a competitive inhibitor of Ca-spikes. Neither tetrodotoxin (3 μM) nor a Na-free condition effectively blocked the generation of the action potential. Mg++ induced a shift in the peak of the action potential; this was, however, due to the stabilizing action of Mg++ but not due to the penetration of Mg++ through the muscle membrane. No action potential was elicited in the muscle fiber when immersed in a Ca-free, EGTA saline even when a high concentration of either Mg++, Na+, or tetraethylammonium+ was present. The action potential of the larval muscle fiber was thus concluded to be a Ca-spike, through the channel of which Na+ or Mg++ did not penetrate. 相似文献
138.
MIXED MODEL APPROACHES FOR ESTIMATING GENETIC VARIANCES AND COVARIANCES 总被引:62,自引:4,他引:58
The limitations of methods for analysis of variance(ANOVA)in estimating genetic variances are discussed. Among the three methods(maximum likelihood ML, restricted maximum likelihood REML, and minimum norm quadratic unbiased estimation MINQUE)for mixed linear models, MINQUE method is presented with formulae for estimating variance components and covariances components and for predicting genetic effects. Several genetic models, which cannot be appropriately analyzed by ANOVA methods, are introduced in forms of mixed linear models. Genetic models with independent random effects can be analyzed by MINQUE(1)method whieh is a MINQUE method with all prior values setting 1. MINQUE(1)method can give unbiased estimation for variance components and covariance components, and linear unbiased prediction (LUP) for genetic effects. There are more complicate genetic models for plant seeds which involve correlated random effects. MINQUE(0/1)method, which is a MINQUE method with all prior covariances setting 0 and all prior variances setting 1, is suitable for estimating variance and covariance components in these models. Mixed model approaches have advantage over ANOVA methods for the capacity of analyzing unbalanced data and complicated models. Some problems about estimation and hypothesis test by MINQUE method are discussed. 相似文献
139.
140.
Molecular Analysis of the Hot Spot Region Related to Length Mutations in Wheat Chloroplast Dnas. I. Nucleotide Divergence of Genes and Intergenic Spacer Regions Located in the Hot Spot Region 总被引:4,自引:0,他引:4
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The nucleotide divergence of chloroplast DNAs around the hot spot region related to length mutation in Triticum (wheat) and Aegilops was analyzed. DNA sequences (ca. 4.5 kbp) of three chloroplast genome types of wheat complex were compared with one another and with the corresponding region of other grasses. The sequences region contained rbcL and psaI, two open reading frames, and a pseudogene, rpl23' (pseudogene for ribosomal protein L23) disrupted by AT-rich intergic spacer regions. The evolution of these genes in the closely related wheat complex is characterized by nonbiased nucleotide substitutions in terms of being synonymous/nonsynonymous, having A-T pressure transitions over transversions, and frequent changes at the third codon position, in contrast with the gene evolution among more distant plant groups where biased nucleotide substitutions have frequently occurred. The sequences of these genes had diverged almost in proportion to taxonomic distance. The sequence of the pseudogene rpl23' changed approximately two times faster than that of the coding region. Sequence comparison between the pseudogene and its protein-coding counterpart revealed different degrees of nucleotide homology in wheat, rice and maize, suggesting that the transposition timing of the pseudogene differed and/or that different rates of gene conversion operated on the pseudogene in the cpDNA of the three plant groups in Gramineae. The intergenic spacer regions diverged approximately ten times faster than the genes. The divergence of wheat from barley, and that from rice are estimated based on the nucleotide similarity to be 1.5, 10 and 40 million years, respectively. 相似文献