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91.
Xiaobo Wan Yue Ma Christopher L. McClendon Lily Jun-shen Huang Niu Huang 《PLoS computational biology》2013,9(4)
The Janus Kinase 2 (JAK2) plays essential roles in transmitting signals from multiple cytokine receptors, and constitutive activation of JAK2 results in hematopoietic disorders and oncogenesis. JAK2 kinase activity is negatively regulated by its pseudokinase domain (JH2), where the gain-of-function mutation V617F that causes myeloproliferative neoplasms resides. In the absence of a crystal structure of full-length JAK2, how JH2 inhibits the kinase domain (JH1), and how V617F hyperactivates JAK2 remain elusive. We modeled the JAK2 JH1–JH2 complex structure using a novel informatics-guided protein-protein docking strategy. A detailed JAK2 JH2-mediated auto-inhibition mechanism is proposed, where JH2 traps the activation loop of JH1 in an inactive conformation and blocks the movement of kinase αC helix through critical hydrophobic contacts and extensive electrostatic interactions. These stabilizing interactions are less favorable in JAK2-V617F. Notably, several predicted binding interfacial residues in JH2 were confirmed to hyperactivate JAK2 kinase activity in site-directed mutagenesis and BaF3/EpoR cell transformation studies. Although there may exist other JH2-mediated mechanisms to control JH1, our JH1–JH2 structural model represents a verifiable working hypothesis for further experimental studies to elucidate the role of JH2 in regulating JAK2 in both normal and pathological settings. 相似文献
92.
93.
Background
Contradictory results have been reported regarding the association between leptin level and breast cancer. Therefore, a meta-analysis was performed to investigate this issue.Methods
Published literature from PubMed and the Chinese National Knowledge Infrastructure (CNKI) Database was retrieved. This study was performed based on different cases and control groups. The combined effect () with 95% confidence interval (CI) was calculated using fixed-effects or random-effects model analysis.Results
Overall, the mean serum leptin level of case groups was significantly higher than that of control groups. A) For 9 studies comparing breast cancer cases and healthy controls the combined effect was 0.58 with 95% CI (0.48, 0.68). B) For 4 studies comparing premenopausal breast cancer cases and healthy controls the was 0.32 (0.12, 0.52). C) For 5 studies comparing postmenopausal cases and healthy controls the was 0.65 (0.46, 0.84). D) For 4 studies comparing breast cancer cases and breast benign controls the was 0.38 (0.17, 0.59). E) For 2 studies comparing premenopausal breast cancer cases and breast benign controls the was 0.33 (-0.25, 0.91). F) For 6 studies comparing postmenopausal breast cancer cases and breast benign controls the was 0.39 (0.19, 0.60). G) For 4 studies comparing lymph node metastasis positive cases and negative controls the was 0.72 (0.45, 1.00). H) For 3 studies comparing breast benign cases and healthy controls the was 0.71 (0.41, 1.01).Conclusion
This meta-analysis suggests that leptin level plays a role in breast cancer and has potential for development as a diagnostic tool. 相似文献94.
Stomatal movement plays a key role in plant development and response to drought and salt stress by regulating gas exchange and water loss. A number of genes have been demonstrated to be involved in the regulation of this process. Using inverse genetics approach, we characterized the function of a rice (Oryza sativa L.) vacuolar H+-ATPase subunit A (OsVHA-A) gene in stomatal conductance regulation and physiological response to salt and osmotic stress. OsVHA-A was constitutively expressed in different rice tissues, and the fusion protein of GFP-OsVHA-A was exclusively targeted to tonoplast when transiently expressed in the onion epidermal cells. Heterologous expression of OsVHA-A was able to rescue the yeast mutant vma1Δ (lacking subunit A activity) phenotype, suggesting that it partially restores the activity of V-ATPase. Meanwhile, RNAi-directed knockdown of OsVHA-A led to a reduction of vacuolar H+-ATPase activity and an enhancement of plasma membrane H+-ATPase activity, thereby increasing the concentrations of extracellular H+ and intracellular K+ and Na+ under stress conditions. Knockdown of OsVHA-A also resulted in the upregulation of PAM3 (plasma membrane H+-ATPase 3) and downregulation of CAM1 (calmodulin 1), CAM3 (calmodulin 3) and YDA1 (YODA, a MAPKK gene). Altered level of the ion concentration and the gene expression by knockdown of OsVHA-A probably resulted in expanded aperture of stomatal pores and increased stomatal density. In addition, OsVHA-A RNAi plants displayed significant growth inhibition under salt and osmotic stress conditions. Taken together, our results suggest that OsVHA-A takes part in regulating stomatal density and opening via interfering with pH value and ionic equilibrium in guard cells and thereby affects the growth of rice plants. 相似文献
95.
Due to its accuracy, sensitivity and high throughput, real time quantitative PCR (RT-qPCR) has been widely used in analysing gene expression. The quality of data from such analyses is affected by the quality of reference genes used. Expression stabilities for nine candidate reference genes widely used in soybean were evaluated under different stresses in this study. Our results showed that EF1A and ACT11 were the best under salinity stress, TUB4, TUA5 and EF1A were the best under drought stress, ACT11 and UKN2 were the best under dark treatment, and EF1B and UKN2 were the best under virus infection. EF1B and UKN2 were the top two genes which can be reliably used in all of the stress conditions assessed. 相似文献
96.
Jiqiang Zhang Ziru Niu Tianhua Li Yanqiang Wu Rui Xi Yuhua Li Guanghua Li Jialin Hou 《Phyton》2020,89(1):147-166
Considering the current low level of mechanization for domestic green
onion planting and the high labor intensity of artificial planting, a 2ZYX-2 green
onion ditching and transplanting machine, which can complete ditching, ridging,
transplanting, repression, soil covering and other operations, is designed in this
study. The Central Composite test design method was carried out with the speed
of the transplanting machine, the depth of the opener and the horizontal position
of the opener as the experimental factors and with the qualification ratio of
perpendicularity, the variation coefficient of the plant spacing and the
qualification ratio of the planting depth as the test index. Through the analysis of
the model interaction and response surface, the change laws that the influence
the machine’s forward speed, the depth of the opener and the horizontal position
of the opener were studied. The regression model was optimized by
Design-Expert 8.0.6 software, and the accuracy of the predicted results was
verified by experiments. The optimal working parameters showed that the
forward speed of the machine was 0.06 m/s, the depth of the opener was 102 mm,
and the horizontal position of the opener was 29 mm. Under conditions of
optimal working parameters, the qualification rate of the verticality was 86.83%,
the coefficient of variation for the plant spacing was 2.77, and the pass rate of
planting depth was 88.26%. The research related to the thesis can provide a
reference for the mechanized planting of green onion, which is of great
significance to the cost-effectiveness of the green onion industry. 相似文献
97.
Zhang Lin Tao Ye Zhao Suya Yin Xiaoyan Chen Junmei Wang Miao Cai Yingfan Niu Qiuhong 《Plant and Soil》2020,454(1-2):395-409
Plant and Soil - [Aims] To reveal the molecular mechanism of endophytic bacteria in Verticillium wilt-resistant cottons and deeply understand the interaction between soil and plants. [Methods]... 相似文献
98.
99.
Zhongyu Liu Mengyu Xie Zhiqiang Yao Yulong Niu Youquan Bu Chunfang Gao 《Molecular neurobiology》2013,47(1):325-336
Glioma is one of the most common tumors of the central nervous system, and one of its main types is astrocytoma. Microarray technology has been widely used to explore the molecular mechanism of cancer. It is universally accepted that meta-analysis considerably improves the statistical robustness of results, particularly in clinical research. To obtain the maximum reliability, we used three different meta-analyses to integrate the four microarray datasets, GSE16011, GSE4290, GSE2223, and GSE19728 (local), and defined the common differentially expressed genes (DEGs) in astrocytomas compared with normal brain tissue. Four DEGs, PCNA, CDC2, CDK2 and CCNB2, which are components of the cell cycle pathway, were chosen for Real-Time Polymerase Chain Reaction (RT-PCR) and immunohistochemistry validation. PCNA is similar to the P53 gene and has been widely implicated in various cancers including gliomas. Therefore, the expression status of PCNA in our study was considered as a reference to test our whole experimental scheme, and the results indicate that our methodology is valid. Although a few studies have reported the overexpression of the CDC2, CDK2 and CCNB2 genes in glioma cell lines, we are the first to identify the statuses of these genes in human astrocytoma tissues at the mRNA and protein levels. The results of the gene validations strongly suggested that the genes play an important role in astrocytomas and could potentially be valuable in the diagnosis and treatment of astrocytoma. 相似文献
100.