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目的 探讨丹龙醒脑方对脑缺血再灌注模型大鼠海马区Notch信号通路相关蛋白Notch1、Notch2及Hes1表达的影响。方法 将80只雄性SD大鼠随机分为假手术组、模型组、丹龙醒脑方小剂量组（丹小组7.4 g/kg）、大剂量组（丹大组14.8 g/kg）,线栓法建立局灶性脑缺血再灌注大鼠模型,再灌注7 d取缺血侧海马组织。采用免疫组织化学法、免疫印迹法检测大鼠海马区Notch1、Notch2及Hes1蛋白表达。结果 与假手术组比较,各组Notch1、Notch2及Hes1蛋白表达显著升高（P<0.05,P<0.01）;与模型组比较,丹小组、丹大组Notch1、Notch2及Hes1蛋白表达显著升高（P<0.05,P<0.01）。结论 丹龙醒脑方能通过上调海马区Notch1、Notch2及Hes1蛋白表达水平,调节Notch信号转导通路,这可能是其促进脑缺血损伤后神经功能修复的机制之一。 相似文献
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目的 研究Notch1在肝癌组织及细胞中的表达并初步探讨Notch1下调后诱导肝癌细胞调亡的机制。方法 2016年3月至2016年9月于广东医科大学附属医院肝胆外科收集32例肝癌病人样本,利用qRT-PCR方法检测肝癌癌组织及癌旁组织中Notch1基因的表达,免疫组化检测组织中Notch1蛋白表达,siRNA沉默肝癌细胞Notch1表达,流式细胞术检测细胞凋亡情况,Western blot方法检测Notch1、Bcl2和Bax蛋白表达,统计分析Notch1表达水平与肝癌病人临床诊断指标甲胎蛋白（AFP）的相关性。结果 肝癌组织标本中Notch1高表达率为71.9%（23/32）,明显高于癌旁组织的28.1%（9/32）,差异具有显著统计学意义（P<0.01）;Pearson相关性分析显示,Notch1与AFP存在正相关性（R2=0.3376,P=0.0036）;免疫组化验证Notch1蛋白分别在肝癌癌组织样本中高表达和癌旁组织中低表达;siRNA干扰Notch1基因表达后,镜下发现肝癌细胞4401增殖抑制,流式检测示转染组明显凋亡,蛋白免疫印迹显示凋亡相关蛋白Bcl2蛋白下调、Bax表达上调。结论 Notch1与肝癌的发生、发展相关,下调Notch1可诱导肝癌细胞凋亡,同时Notch1还可作为临床治疗肝癌的潜在新靶点。 相似文献
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Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells 总被引：1，自引：0，他引：1
Shen Q Goderie SK Jin L Karanth N Sun Y Abramova N Vincent P Pumiglia K Temple S 《Science (New York, N.Y.)》2004,304(5675):1338-1340
Neural stem cells are reported to lie in a vascular niche, but there is no direct evidence for a functional relationship between the stem cells and blood vessel component cells. We show that endothelial cells but not vascular smooth muscle cells release soluble factors that stimulate the self-renewal of neural stem cells, inhibit their differentiation, and enhance their neuron production. Both embryonic and adult neural stem cells respond, allowing extensive production of both projection neuron and interneuron types in vitro. Endothelial coculture stimulates neuroepithelial cell contact, activating Notch and Hes 1 to promote self-renewal. These findings identify endothelial cells as a critical component of the neural stem cell niche. 相似文献
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Notch proteins are receptors for a conserved signaling pathway that affects numerous cell fate decisions. We found that in Drosophila, Protein O-fucosyltransferase 1 (OFUT1), an enzyme that glycosylates epidermal growth factor-like domains of Notch, also has a distinct Notch chaperone activity. OFUT1 is an endoplasmic reticulum protein, and its localization was essential for function in vivo. OFUT1 could bind to Notch, was required for the trafficking of wild-type Notch out of the endoplasmic reticulum, and could partially rescue defects in secretion and ligand binding associated with Notch point mutations. This ability of OFUT1 to facilitate folding of Notch did not require its fucosyltransferase activity. Thus, a glycosyltransferase can bind its substrate in the endoplasmic reticulum to facilitate normal folding. 相似文献
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A blood cell type termed crystal cell in Drosophila functions in clotting and wound healing and requires Notch for specification and maintenance. We report that crystal cells express elevated levels of Sima protein orthologous to mammalian hypoxia-inducible factor-α (Hif-α) even under conditions of normal oxygen availability. In these platelet-like crystal cells, Sima activates full-length Notch receptor signaling via a noncanonical, ligand-independent mechanism that promotes hemocyte survival during both normal hematopoietic development and hypoxic stress. This interaction initiates in early endosomes, is independent of Hif-β (Τangο in Drosophila), and does not activate hypoxia response targets. Studies in vertebrate myeloid cells have shown a similar up-regulation of Hif-α protein in well-oxygenated environments. This study provides a mechanistic paradigm for Hif-α/Notch interaction that may be conserved in mammals. 相似文献
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Daily 20-hour encephalic photophases (DEPP), transmitted (hours 0 to 20) via chronically implanted light-conducting fibers to selected sites in the basal hypothalamus of male white-crowned sparrows, were superimposed on daily 8-hour (hours 0 to 8) external ambient photophases (DAPP). Initially the birds displayed motor activity only during the 8-hour DAPP. After a delay of at least 2 weeks, some of the birds became intensively active during hours 8 to 20. We postulate that this period of "nocturnal" activity is equivalent to the nocturnal Zugunruhe shown by caged individuals of many nocturnally migratory species subjected to long days; such activity is generally regarded as the expression of migratory behavior. 相似文献
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A hallmark of aging is diminished regenerative potential of tissues, but the mechanism of this decline is unknown. Analysis of injured muscle revealed that, with age, resident precursor cells (satellite cells) had a markedly impaired propensity to proliferate and to produce myoblasts necessary for muscle regeneration. This was due to insufficient up-regulation of the Notch ligand Delta and, thus, diminished activation of Notch in aged, regenerating muscle. Inhibition of Notch impaired regeneration of young muscle, whereas forced activation of Notch restored regenerative potential to old muscle. Thus, Notch signaling is a key determinant of muscle regenerative potential that declines with age. 相似文献
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对果糖—BrO_3~-—H_2SO_4—丙酮体系在Mn~(2+)催化下的振荡反应动力学及其机理,以及各种因素对振荡反应的影响作了实验研究,得到了振荡反应诱导期t_(in)及振荡周期t_p与各反应物浓度间的关系式。 相似文献
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在这篇文章里,我们讨论了二阶非线性微分方程〔(y’~(2n+1)〕′+f(x,y)=0 (1)的振荡性。这篇文章的主要成果是推广了[1]的结果,[1]中研究了方程y'十f(x,y)=0的振荡情况。本文推导出我们关于f(x,y)的假设条件足以使方程(I)振荡. 相似文献
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Brambles OJ Lotko W Zhang B Wiltberger M Lyon J Strangeway RJ 《Science (New York, N.Y.)》2011,332(6034):1183-1186
The sawtooth mode of convection of Earth's magnetosphere is a 2- to 4-hour planetary-scale oscillation powered by the solar wind-magnetosphere-ionosphere (SW-M-I) interaction. Using global simulations of geospace, we have shown that ionospheric O(+) outflows can generate sawtooth oscillations. As the outflowing ions fill the inner magnetosphere, their pressure distends the nightside magnetic field. When the outflow fluence exceeds a threshold, magnetic field tension cannot confine the accumulating fluid; an O(+)-rich plasmoid is ejected, and the field dipolarizes. Below the threshold, the magnetosphere undergoes quasi-steady convection. Repetition and the sawtooth period are controlled by the strength of the SW-M-I interaction, which regulates the outflow fluence. 相似文献
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Increased tolerance of leukemic mice to arabinosyl cytosine with schedule adjusted to circadian system 总被引：1，自引：0，他引：1
E Haus F Halberg J E Pauly S Cardoso J F Kühl R B Sothern R N Shiotsuka D S Hwang 《Science (New York, N.Y.)》1972,177(43):80-82
Mice (BDF(1)) inoculated with L1210 leukemia survive for a statistically significantly longer span when four courses of arabinosyl cytosine are administered at 4-day intervals-not in courses consisting of eight equal doses at 3-hour intervals, but in sinusoidally increasing and decreasing 24-hour courses, the largest amount being given at previously mapped circadian and circannual times of peak host resistance to the drug. This finding relates to the many therapeutic situations involving rhythmic, and thus predictable, cycles in the host's tolerance of undesired effects from the agent used. 相似文献
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Turnover of rat liver tyrosine transaminase: stabilization after inhibition of protein synthesis 总被引：39，自引：0，他引：39
F T Kenney 《Science (New York, N.Y.)》1967,156(774):525-528
Turnover of the rat liver tyrosine transaminase in vivo was measured by a label and chase procedure under conditions where the amount of enzyme undergoes no change. Half-life of the (14)C-labeled enzyme in this basal condition was found to be 1.5 +/- 0.3 hours. Inhibitors of protein synthesis (cycloheximide or puromycin) do not appreciably influence the basal enzyme level over a 5-hour period, although these drugs will block hormonal induction of this enzyme. In pulse-labeling experiments, cycloheximide blocked transaminase synthesis almost completely. The conclusion that enzyme degradation, as well as synthesis, must be blocked when protein synthesis is stopped was confirmed in experiments showing that labeled enzyme is stable in the liver of rats treated with cycloheximide The participation of a continuously synthesized polypeptide in the degradative phase of transaminase turnover is suggested. 相似文献
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To examine the cellular mechanisms responsible for transition from a short-term to a long-term behavioral modification, a rapid training procedure was developed for producing long-term habituation of the defensive withdrawal of gill and siphon in Aplysia. Four ten-trial training sessions, with 1(1/2)-hour intersession intervals, produced habituation that was retained for more than 1 week. This 5-hour procedure could be applied to a test system in the isolated abdominal ganglion where the cellular changes accompanying the acquisition of long-term habituation can be examined. During acquisition, intracellular recordings were obtained from L7, a major gill and siphon motor neuron, and the pattern of stimulation used in the behavioral experiments was applied to an afferent nerve. Acquisition was associated with a progressive decrease in the complex excitatory synaptic potential produced in L7 by afferent nerve stimulation. When retention was tested 24 hours later, the synaptic decrement was still evident. Thus, a behaviorally meaningful stimulus sequence, consisting of only 40 patterned stimuli, leads to changes in synaptic effectiveness lasting one or more days in a neural pathway involved in short-term habituation of this reflex. 相似文献
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电液压脉冲技术在油田集输管网清垢中的应用 总被引：6，自引：0，他引：6
在油田集输管网清垢中，电泳压脉冲技术的应用是以电液压脉冲技术体外冲击波碎石的实践和先进的振荡脉冲射流喷嘴理论为基础，利用电液压脉冲清除管道内表面垢层。为产生电液压效应，需满足４个必要条件；（１）具有辅助间隙；（２）电流以幅值大；（３）电流升高陡度幅度大；（４）尾短。提出了液中放电产生压力波波前压力简化计算公式及电液压脉硒应用方案。 相似文献
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Intracellular signaling networks receive and process information to control cellular machines. The mitogen-activated protein kinase (MAPK) 1,2/protein kinase C (PKC) system is one such network that regulates many cellular machines, including the cell cycle machinery and autocrine/paracrine factor synthesizing machinery. We used a combination of computational analysis and experiments in mouse NIH-3T3 fibroblasts to understand the design principles of this controller network. We find that the growth factor-stimulated signaling network containing MAPK 1, 2/PKC can operate with one (monostable) or two (bistable) stable states. At low concentrations of MAPK phosphatase, the system exhibits bistable behavior, such that brief stimulus results in sustained MAPK activation. The MAPK-induced increase in the amounts of MAPK phosphatase eliminates the prolonged response capability and moves the network to a monostable state, in which it behaves as a proportional response system responding acutely to stimulus. Thus, the MAPK 1, 2/PKC controller network is flexibly designed, and MAPK phosphatase may be critical for this flexible response. 相似文献