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171.
172.
组织学与胚胎学是重要的医学基础课,属于形态学科。目前,组织学与胚胎学实验教学多采用数码互动实验教学,切片观察为主要手段,而切片观察主要是观察组织的平面结构,欠缺立体结构的观察。模型实验教学是以组织学与胚胎学的形态为中心组织学生制作立体模型,启发学生思维,充分发挥想象力,培养学生的动手能力和实践能力。 相似文献
173.
Quan Luo Chunqiu Zhang Lu Miao Dongmei Zhang Yushi Bai Chunxi Hou Junqiu Liu Fei Yan Ying Mu Guimin Luo 《Amino acids》2013,44(3):1009-1019
By combining computational design and site-directed mutagenesis, we have engineered a new catalytic ability into the antibody scFv2F3 by installing a catalytic triad (Trp29–Sec52–Gln72). The resulting abzyme, Se-scFv2F3, exhibits a high glutathione peroxidase (GPx) activity, approaching the native enzyme activity. Activity assays and a systematic computational study were performed to investigate the effect of successive replacement of residues at positions 29, 52, and 72. The results revealed that an active site Ser52/Sec substitution is critical for the GPx activity of Se-scFv2F3. In addition, Phe29/Trp–Val72/Gln mutations enhance the reaction rate via functional cooperation with Sec52. Molecular dynamics simulations showed that the designed catalytic triad is very stable and the conformational flexibility caused by Tyr101 occurs mainly in the loop of complementarity determining region 3. The docking studies illustrated the importance of this loop that favors the conformational shift of Tyr54, Asn55, and Gly56 to stabilize substrate binding. Molecular dynamics free energy and molecular mechanics-Poisson Boltzmann surface area calculations estimated the pK a shifts of the catalytic residue and the binding free energies of docked complexes, suggesting that dipole–dipole interactions among Trp29–Sec52–Gln72 lead to the change of free energy that promotes the residual catalytic activity and the substrate-binding capacity. The calculated results agree well with the experimental data, which should help to clarify why Se-scFv2F3 exhibits high catalytic efficiency. 相似文献
174.
目的 探讨微生态学的逻辑起点及其有关问题.方法 理论研究.结果 提出了微生态体的概念,探讨了微生态体作为微生态学的逻辑起点的问题.基于微生态体概念,对微生态学的概念、研究对象、研究目的等有关问题进行了探讨.结论 阐释了微生态学的逻辑起点是微生态体的学术观点,为微生态学理论体系的发展提供逻辑基础. 相似文献
175.
176.
Jiannong Li Keiryn Bennett Alexey Stukalov Bin Fang Guolin Zhang Takeshi Yoshida Isamu Okamoto Jae‐Young Kim Lanxi Song Yun Bai Xiaoning Qian Bhupendra Rawal Michael Schell Florian Grebien Georg Winter Uwe Rix Steven Eschrich Jacques Colinge John Koomen Giulio Superti‐Furga Eric B Haura 《Molecular systems biology》2013,9(1)
We hypothesized that elucidating the interactome of epidermal growth factor receptor (EGFR) forms that are mutated in lung cancer, via global analysis of protein–protein interactions, phosphorylation, and systematically perturbing the ensuing network nodes, should offer a new, more systems‐level perspective of the molecular etiology. Here, we describe an EGFR interactome of 263 proteins and offer a 14‐protein core network critical to the viability of multiple EGFR‐mutated lung cancer cells. Cells with acquired resistance to EGFR tyrosine kinase inhibitors (TKIs) had differential dependence of the core network proteins based on the underlying molecular mechanisms of resistance. Of the 14 proteins, 9 are shown to be specifically associated with survival of EGFR‐mutated lung cancer cell lines. This included EGFR, GRB2, MK12, SHC1, ARAF, CD11B, ARHG5, GLU2B, and CD11A. With the use of a drug network associated with the core network proteins, we identified two compounds, midostaurin and lestaurtinib, that could overcome drug resistance through direct EGFR inhibition when combined with erlotinib. Our results, enabled by interactome mapping, suggest new targets and combination therapies that could circumvent EGFR TKI resistance. 相似文献
177.
Wei Chen Wen Shu Min Wang Yongchun Hou Yinyin Xia Weiguo Xu Liqiong Bai Shaofa Nie Shiming Cheng Yihua Xu 《PloS one》2013,8(3)
The incidence of tuberculosis (TB) and its risk factors in China remains unclear. This study examined TB incidence and relative risk factors in rural areas of China. Participants (n = 177,529) were recruited in Xiangtan County (in the central area of China) and in Danyang County (in the eastern area of China) in 2009 and a followed-up study was conducted for one year. The incidence density of pulmonary TB and smear-positive TB were 91.6 (95% CI: 78.7, 106.0) per 100,000 person-year and 36.7 (95% CI: 33.1, 52.4) per 100,000 person-year respectively in Xiangtan, and 47.3 (95% CI: 38.2, 57.5) per 100,000 person-year and 22.7 (95% CI: 16.5, 30.8) per 100,000 person-year in Danyang. The medical history of TB was associated with TB, with the relative risk (RR) of 7.00 (95% CI: 2.76, 17.18) in Xiangtan and that of 31.08 (95% CI: 13.22, 73.10) in Danyang. The association between TB and per capita living space over median was found in Xiangtan, with the RR of 1.86 (95% CI: 1.15, 3.01). No association was found between TB and the insurance status, the contact history with TB, the history of diabetes, smoking, or per capita annual income. The host genetic susceptibility, and social factors such as education and income could be considered in future studies. 相似文献
178.
Shu Bian Xiaofeng Sun Aiping Bai Chunqing Zhang Linglin Li Keiichi Enjyoji Wolfgang G. Junger Simon C. Robson Yan Wu 《PloS one》2013,8(4)
Background
Extracellular adenosine triphosphate (ATP) functions as a novel danger signal that boosts antitumor immunity and can also directly kill tumor cells. We have previously reported that chronic exposure of tumor cells to ATP provokes P2X7-mediated tumor cell death, by as yet incompletely defined molecular mechanisms.Methodology/Principal Findings
Here, we show that acute exposure of tumor cells to ATP results in rapid cytotoxic effects impacting several aspects of cell growth/survival, leading to inhibition of tumor growth in vitro and in vivo. Using agonist and antagonist studies together with generation of P2X7 deficient tumor cell lines by lentiviral shRNA delivery system, we confirm P2X7 to be the central control node transmitting extracellular ATP signals. We identify that downstream intracellular signaling regulatory networks implicate two signaling pathways: the known P2X7-PI3K/AKT axis and remarkably a novel P2X7-AMPK-PRAS40-mTOR axis. When exposed to high levels of extracellular ATP, these two signaling axes perturb the balance between growth and autophagy, thereby promoting tumor cell death.Conclusions
Our study defines novel molecular mechanisms underpinning the antitumor actions of P2X7 and provides a further rationale for purine-based drugs in targeted cancer therapy. 相似文献179.
Jushan Liu Yuguang Bai Eric G. Lamb Dale Simpson Guofang Liu Yongsheng Wei Deli Wang Daniel W. McKenney Pia Papadopol 《PloS one》2013,8(4)
Seed mass is an adaptive trait affecting species distribution, population dynamics and community structure. In widely distributed species, variation in seed mass may reflect both genetic adaptation to local environments and adaptive phenotypic plasticity. Acknowledging the difficulty in separating these two aspects, we examined the causal relationships determining seed mass variation to better understand adaptability and/or plasticity of selected tree species to spatial/climatic variation. A total of 504, 481 and 454 seed collections of black spruce (Picea mariana (Mill.) B.S.P.), white spruce (Picea glauca (Moench) Voss) and jack pine (Pinus banksiana Lamb) across the Canadian Boreal Forest, respectively, were selected. Correlation analyses were used to determine how seed mass vary with latitude, longitude, and altitude. Structural Equation Modeling was used to examine how geographic and climatic variables influence seed mass. Climatic factors explained a large portion of the variation in seed mass (34, 14 and 29%, for black spruce, white spruce and jack pine, respectively), indicating species-specific adaptation to long term climate conditions. Higher annual mean temperature and winter precipitation caused greater seed mass in black spruce, but annual precipitation was the controlling factor for white spruce. The combination of factors such as growing season temperature and evapotranspiration, temperature seasonality and annual precipitation together determined seed mass of jack pine. Overall, sites with higher winter temperatures were correlated with larger seeds. Thus, long-term climatic conditions, at least in part, determined spatial variation in seed mass. Black spruce and Jack pine, species with relatively more specific habitat requirements and less plasticity, had more variation in seed mass explained by climate than did the more plastic species white spruce. As traits such as seed mass are related to seedling growth and survival, they potentially influence forest species composition in a changing climate and should be included in future modeling of vegetation shifts. 相似文献
180.