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101.
The spindle checkpoint is a cell cycle surveillance system that ensures the fidelity of chromosome segregation. In mitosis, it elicits the “wait anaphase” signal to inhibit the anaphase-promoting complex or cyclosome until all chromosomes achieve bipolar microtubule attachment and align at the metaphase plate. Because a single kinetochore unattached to microtubules activates the checkpoint, the wait anaphase signal is thought to be generated by this kinetochore and is then amplified and distributed throughout the cell to inhibit the anaphase-promoting complex/cyclosome. Several spindle checkpoint kinases participate in the generation and amplification of this signal. Recent studies have begun to reveal the activation mechanisms of these checkpoint kinases. Increasing evidence also indicates that the checkpoint kinases not only help to generate the wait anaphase signal but also actively correct kinetochore-microtubule attachment defects. 相似文献
102.
103.
大豆下胚轴可溶性蛋白中钙激活的蛋白激酶 总被引:6,自引:0,他引:6
大豆(Glycine m ax L.) 下胚轴可溶性蛋白提取液进行自磷酸化,以SDS-PAGE电泳分析其标记产物时发现,当有较高浓度的Ca2+ 存在于反应液中时,有一条18 kD蛋白带被高强度标记,同时也可观察到另一条标记强度不高的67 kD蛋白带. 当反应时间延长到15 或30m in 时,它们的标记强度都逐渐减弱,最终从放射自显影底片上消失;在反应液中加入钙螯合剂EGTA 时,则只有67 kD 被高强度标记;在磷酸化反应过程中加入非标记ATP,蛋白中的32P逐渐被非标记磷取代,表明反应体系处于磷酸化-脱磷酸化的平衡过程中,并有结果显示这一过程是钙依赖性的. 组蛋白H1 可以使反应进程加快,表明提取液中的蛋白激酶可以利用它作为底物. 综合结果表明,18 kD和67 kD蛋白可能是具有自磷酸化能力且对Ca2+ 敏感的蛋白激酶,它们对Ca2+ 的不同反应,使得钙信号的传递更具可控性 相似文献
104.
105.
The stress-activated protein kinase Gcn2 regulates protein synthesis by phosphorylation of translation initiation factor eIF2α. Gcn2 is activated in amino acid-deprived cells by binding of uncharged tRNA to the regulatory domain related to histidyl-tRNA synthetase, but the molecular mechanism of activation is unclear. We used a genetic approach to identify a key regulatory surface in Gcn2 that is proximal to the predicted active site of the HisRS domain and likely remodeled by tRNA binding. Mutations leading to amino acid substitutions on this surface were identified that activate Gcn2 at low levels of tRNA binding (Gcd- phenotype), while other substitutions block kinase activation (Gcn- phenotype), in some cases without altering tRNA binding by Gcn2 in vitro. Remarkably, the Gcn- substitutions increase affinity of the HisRS domain for the C-terminal domain (CTD), previously implicated as a kinase autoinhibitory segment, in a manner dampened by HisRS domain Gcd- substitutions and by amino acid starvation in vivo. Moreover, tRNA specifically antagonizes HisRS/CTD association in vitro. These findings support a model wherein HisRS-CTD interaction facilitates the autoinhibitory function of the CTD in nonstarvation conditions, with tRNA binding eliciting kinase activation by weakening HisRS-CTD association with attendant disruption of the autoinhibitory KD-CTD interaction. 相似文献
106.
Zhaohua Zhang LiLi Ge Shanshan Zhang Jue Wang Wen Jiang Qian Xin Yun Luan 《Journal of cellular and molecular medicine》2020,24(23):13938
The aim of the study was to explore the mechanism of mesenchymal stem cell‐derived exosomes (MSC‐EXO) to protect against experimentally induced pulmonary hypertension (PH). Monocrotaline (MCT)‐induced rat model of PH was successfully established by a single intraperitoneal injection of 50 mg/kg MCT, 3 weeks later the animals were treated with MSC‐EXO via tail vein injection. Post‐operation, our results showed that MSC‐EXO could significantly reduce right ventricular systolic pressure (RVSP) and the right ventricular hypertrophy index, attenuate pulmonary vascular remodelling and lung fibrosis in vivo. In vitro experiment, the hypoxia models of pulmonary artery endothelial cell (PAEC) and pulmonary vascular smooth muscle cell (PASMC) were used. We found that the expression levels of Wnt5a, Wnt11, BMPR2, BMP4 and BMP9 were increased, but β‐catenin, cyclin D1 and TGF‐β1 were decreased in MSC‐EXO group as compared with MCT or hypoxia group in vivo or vitro. However, these increased could be blocked when cells were transfected with Wnt5a siRNA in vitro. Taken together, these results suggested that the mechanism of MSC‐EXO to prevent PH vascular remodelling may be via regulation of Wnt5a/BMP signalling pathway. 相似文献
107.
Ying Jin Dan Long Juan Li Ruichao Yu Yueming Song Jie Fang Xi Yang Shu Zhou Shishu Huang Zhihe Zhao 《Journal of cellular physiology》2019,234(9):14838-14851
Bone and tooth, fundamental parts of the craniofacial skeleton, are anatomically and developmentally interconnected structures. Notably, pathological processes in these tissues underwent together and progressed in multilevels. Extracellular vesicles (EVs) are cell-released small organelles and transfer proteins and genetic information into cells and tissues. Although EVs have been identified in bone and tooth, particularly EVs have been identified in the bone formation and resorption, the concrete roles of EVs in bone and tooth development and diseases remain elusive. As such, we review the recent progress of EVs in bone and tooth to highlight the novel findings of EVs in cellular communication, tissue homeostasis, and interventions. This will enhance our comprehension on the skeletal biology and shed new light on the modulation of skeletal disorders and the potential of genetic treatment. 相似文献
108.
V. G. Grigoryan A. R. Aghababyan A. N. Arakelyan A. Yu. Stepanyan 《Human physiology》2006,32(4):489-491
A comparative analysis of the time and amplitude characteristics of the negative N200 and positive P300 components of visual evoked potentials recorded at symmetric points of the frontal, parietal, temporal, and occipital areas of the right and left hemispheres of the cerebral cortex has been performed in subjects with or without the skill of operating a computer. Subjects inexperienced in an operator’s work exhibited an interhemispheric difference in the time and amplitude characteristics of the studied components. In subjects that had the skill of operating a computer, the interhemispheric difference was little, which suggests that the cortex plays only a small role in the cerebral control of this activity. 相似文献
109.
Cory Bystrom Shijun Sheng Ke Zhang Michael Caulfield Nigel J. Clarke Richard Reitz 《PloS one》2012,7(9)
Measurement of insulin-like growth factor-1 (IGF-I) has utility for the diagnosis and management of growth disorders, but inter-assay comparison of results has been complicated by a multitude of reference standards, antibodies, detection methods, and pre-analytical preparation strategies. We developed a quantitative LC-MS method for intact IGF-I, which has advantages in throughput and complexity when compared to mass spectrometric approaches that rely on stable isotope dilution analysis of tryptic peptides. Since the method makes use of full-scan data, the assay was easily extended to provide quantitative measurement of IGF-II using the same assay protocol. The validated LC-MS assay for IGF-I and IGF-II provides accurate results across the pediatric and adult reference range and is suitable for clinical use. 相似文献
110.
Sam Mavandadi Steve Feng Frank Yu Stoyan Dimitrov Karin Nielsen-Saines William R. Prescott Aydogan Ozcan 《PloS one》2012,7(10)
We propose a methodology for digitally fusing diagnostic decisions made by multiple medical experts in order to improve accuracy of diagnosis. Toward this goal, we report an experimental study involving nine experts, where each one was given more than 8,000 digital microscopic images of individual human red blood cells and asked to identify malaria infected cells. The results of this experiment reveal that even highly trained medical experts are not always self-consistent in their diagnostic decisions and that there exists a fair level of disagreement among experts, even for binary decisions (i.e., infected vs. uninfected). To tackle this general medical diagnosis problem, we propose a probabilistic algorithm to fuse the decisions made by trained medical experts to robustly achieve higher levels of accuracy when compared to individual experts making such decisions. By modelling the decisions of experts as a three component mixture model and solving for the underlying parameters using the Expectation Maximisation algorithm, we demonstrate the efficacy of our approach which significantly improves the overall diagnostic accuracy of malaria infected cells. Additionally, we present a mathematical framework for performing ‘slide-level’ diagnosis by using individual ‘cell-level’ diagnosis data, shedding more light on the statistical rules that should govern the routine practice in examination of e.g., thin blood smear samples. This framework could be generalized for various other tele-pathology needs, and can be used by trained experts within an efficient tele-medicine platform. 相似文献