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Impaired SERCA2a phosphorylation causes diabetic cardiomyopathy through impinging on cardiac contractility and precursor protein processing

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Life Metabolism 2022年第1期1卷 54-66页

作者： Chao Quan Sangsang Zhu Ruizhen Wang Jiamou Chen Qiaoli Chen Min Li Shu Su Qian Du minjun Liu Hong-Yu Wang Shuai Chen MOE Key Laboratory of Model Animal for Disease Study Department of CardiologyNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolModel Animal Research CenterSchool of MedicineNanjing UniversityNanjingJiangsu 210061China State Key Laboratory of Pharmaceutical Biotechnology Department of EndocrinologyNanjing Drum Tower HospitalModel Animal Research CenterSchool of MedicineNanjing UniversityNanjingJiangsu 210061China Jiangsu Key Laboratory of Molecular Medicine Model Animal Research CenterSchool of MedicineNanjing UniversityNanjing 210061China

Diabetic cardiomyopathy(DCM)is currently a progressive and nonstoppable complication in type 2 diabetic *** insults and insulin resistance are involved in its pathogenesis;however,the underlying mechanisms are still not clearly *** we show that calcium dysregulation can be both a cause and a consequence of cardiac insulin resistance that leads to DCM.A western diet induces the development of DCM through at least three phases in mice,among which an early phase depends on impaired Thr^(484)-phosphorylation of sarcoplasmic/endoplasmic reticulum calcium ATPase 2a(SERCA2a)elicited by insulin *** of SERCA2a-Thr^(484) to a nonphosphorylatable alanine delays calcium re-uptake into the sarcoplasmic reticulum in the cardiomyocytes and decreases cardiac function at the ***,this mutation blunts the early phase of DCM,but has no effect on disease progression in the following ***,impairment of sarcoplasmic reticulum calcium re-uptake caused by the SERCA2a-Thr^(484) mutation inhibited processing of insulin receptor precursor through FURIN convertase,resulting in cardiac insulin ***,these data reveal a bidirectional relationship between insulin resistance and impairment of calcium homeostasis,which may underlie the early pathogenesis of *** findings have therapeutic implications for early intervention of DCM.

关键词： SERCA SPEG phosphorylation calcium insulin diabetic cardiomyopathy

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中国生态脆弱带人地关系行为机制模型及应用

地理学报 2005年第1期60卷 165-174页

作者：石敏俊王涛筑波大学生命环境科学研究生院日本筑波中国科学院研究生院北京100049 中国科学院寒区旱区环境与工程研究所兰州730000

以农牧交错带为研究对象,通过建立人地关系行为机制模型,探讨外部社会经济因素影响土地退化的机制,并重点就当前正在实施的退耕还林还草政策所带来的生态经济效果进行分析。模型拟合结果显示,利用玉米及农作物秸秆作为饲料,扩大舍饲动... 详细信息

以农牧交错带为研究对象,通过建立人地关系行为机制模型,探讨外部社会经济因素影响土地退化的机制,并重点就当前正在实施的退耕还林还草政策所带来的生态经济效果进行分析。模型拟合结果显示,利用玉米及农作物秸秆作为饲料,扩大舍饲动物饲养,或者扩大种植葵花或油料作物等商品作物以替代自给性作物糜子,将可以在不加剧水土流失的前提下增加农户收入。模型结果还显示,非农就业机会增加时,农户会减少坡地垦殖。这表明推进农村工业化和城镇化发展,增加农民非农就业机会,鼓励农民进城的政策对于黄土高原的水土保持也是有促进作用的。

关键词：中国生态脆弱带人地关系行为机制模型土地退化农村环境问题

Ultraviolet-attenuated cercariae ofSchistosoma japonicum fail to effectively induce a Th1 response in spite of up-regulating expression of cytotoxicity-related genes in C57BL/6 mice

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The Journal of Biomedical Research 2010年第4期24卷 277-284页

作者： Meijuan Zhang Fang Tian Yanan Gao minjun Ji Guanling Wu Department of Pathogen Biology and Immunology Nanjing Medical University Nanjing 210029 Jiangsu Province China Department of Clinical Laboratory the first Affiated Hospital of Nanjing Medical University Nanjing 210029 Jiangsu Province China Jiangsu Province Key Laboratory of Modern Pathogen Biology Nanjing 210029 Jiangsu Province China

Objective： To better understand the reason that Schistosoma japonicurn （S. japonicum） ultraviolet （UV）- radiated cercariae could not induce high level of protection in C57BL/6 mice. Methods： Microarray technology was performed to investigate the gene transcription profile in skin draining lymph nodes （sdLNs） at 1 w after exposure to attenuated cercariae （AC） or normal cercariae （NC） of S. japonicum in C57BL/6 mice. The expressions of some representative genes were further confirmed by real-time PCR. Subsequently, the expressions of Th1/Th2 cytokine genes, cytotoxicity-related genes, as well as co-stimulator genes in spleens from AC-vaccinated and NC- infected mice were analyzed by real-time PCR at w 3 and 6 post-exposure. Results： The gene expressions of Th1 cytokines, including interferon-y （IFN-γ）, interleukin （IL）-12 and tumor necrosis factor-α （TNF-α） in the sdLNs were significantly lower in AC-vaccinated mice than in NC-infected mice. Furthermore, the gene expressions of Th1- and Th2- cytokines, including IFN-γ, IL-12, TNF-α, IL-4 and IL-10, in the spleens from AC-vaccinated mice showed little changes at w 3 and 6 post-vaccination. In addition, cytotoxicity-related molecules including granzyme A, granzyme B, granzyme K, perforin 1 and Fas L were up-regulated from the early stage of vaccination, and peaked at the 3rd w after vaccination with UV-AC. Conclusion： UV-AC of S. japonicum could not ef- fectively induce a Thl response in C57BL/6 mice, which may be an explanation for the low protection against parasite challenge, and the role played by up-regulated expression of cytotoxicity-related genes in mice needs to be further investigated.

关键词： Schistosoma japonicum ultraviolet-attenuated cercariae Thl response cytotoxicity-related genes,C57BL/6 mice

Construction and Expression of Serratia Marcescens ECU1010 Lipase （lipA） in Pichia Pastoris

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Journal of Life Sciences 2010年第3期4卷 9-16页

作者： Faxiang Ye Liqiang Fan Jianhe Xu Jian Zhao Wanhong He minjun Ni State Key Laboratory of Bioreactor Engineering East China University of Science and Technology Shanghai 200237 China

Serratia marcescens ECUI010, as an extracellular lipase and a significant catalyst, which had been widely employed to catalyze various chemical reactions such as non-specific, stereo-specific hydrolysis and esterification for industrial biocatalytic applications, was previously mostly expressed intracellularly as inclusion bodies in Escherichia coli. Denaturation and renaturation of inclusion bodies had a significant influence on the lipase activity. Thereupon, our present work described the secretion expression of gene encoding of this lipase in Pichia pastoris GS 115 and characterization of the recombinant enzyme. Firstly, the obtained lipA gene fragment was introduced into P. pastoris expression vector pPIC9K, the lipA gene without its signal sequence were cloned downstream to the alpha-mating factor signal and expressed in P. pastoris GS115 under the control of AOXI promoter, and the recombinant plasmid pPIC9K-lipA was transformed into P. pastoris strain GS115 by electroporation, and this recombinant P. pastoris were identified by PCR. Then lipase activity was detected on BMMY-tributyrin and olive oil agar plates containing Rhodamine B. Transformants with lipase activity by screening were induced 6 days by methanol, one band of 77 kDa protein could be observed by 10% SDS-PAGE. p-nitrophenyl esters of fatty acids were used as the substrates in an automated activity assay of liquid culture media. The pH and temperature optimum of lipase were pH 8.5 and 40℃ respectively. The stability and effects of metal ions and other reagents were also determined. However, the recombinant fusion intended for secretion was efficiently secreted in a percentage of close to 90% and remained stable even in rich medium at high cell density cultures, yielding values of over 4 U of lipase activity per milliliter of culture media supernatant.

关键词： Serratia marcescens ECUI010 lipase secretion expression P. pastoris GS115.

潞安矿区高河井田煤层气地面抽采有利区段评价

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煤田地质与勘探 2012年第3期40卷 36-39页

作者：冀敏俊山西高河能源有限公司山西长治047100

煤层气地面抽采技术是解决高瓦斯矿井安全生产的重要手段之一,正逐渐被煤炭企业所重视和采用。以潞安矿区高河井田为例,在缺乏煤层气勘探资料的情况下,运用现代煤层气地质理论,重新解读煤田地质勘探成果,挖潜出有利区段评价的关键性地... 详细信息

煤层气地面抽采技术是解决高瓦斯矿井安全生产的重要手段之一,正逐渐被煤炭企业所重视和采用。以潞安矿区高河井田为例,在缺乏煤层气勘探资料的情况下,运用现代煤层气地质理论,重新解读煤田地质勘探成果,挖潜出有利区段评价的关键性地质资料——煤体结构;并结合煤炭开采规划,对其井田构造、煤体结构、含气量、煤层埋深和厚度等地质条件进行了单项评价和区段综合评价。结果显示,高河井田西北区段为煤层气地面抽采的有利区段,建议作为煤炭规划区的首期煤层气地面抽采区。

关键词：煤层气地面抽采有利区段高河井田

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盲目反卷积算法在高超流场星图复原中的应用

红外与激光工程 2013年第8期42卷 2231-2237页

作者：杨博刘文东李旻珺北京航空航天大学宇航学院北京100191

近年来高超声速飞行器的研究受到世界各国的重视,具有重大的军事意义,其中导航、制导和控制是高超声速研究的关键技术。鉴于星光导航有着抗干扰能力强、导航精度高、自助式导航等特点,文中主要研究了高超声速飞行器使用星光导航方法的... 详细信息

近年来高超声速飞行器的研究受到世界各国的重视,具有重大的军事意义,其中导航、制导和控制是高超声速研究的关键技术。鉴于星光导航有着抗干扰能力强、导航精度高、自助式导航等特点,文中主要研究了高超声速飞行器使用星光导航方法的星图复原算法。考虑到高超带来的气动光学效应,在分析高速层流以及湍流流场的基础上,应用增量Wiener滤波器和有限支持域上的盲解卷积复原算法进行退化星图的复原。针对高速飞行器星光导航对复原星图的要求,仿真分析了复原星图的质心偏差及识别特征量变化。仿真结果显示,有限支持域上的盲解卷积复原算法精度较高,且经复原后的星图,能快速被高速飞行器星光导航系统正确识别。

关键词：高超声速飞行器星光导航湍流退化复原盲解卷积

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计及电动汽车入网的电价联动模型

电力自动化设备 2014年第11期34卷 34-40页

作者：施泉生平宗飞陈敏骏上海电力学院经济与管理学院上海200090

电动汽车不同的充放电控制与利用策略对电网负荷曲线产生不同的影响,从而影响到峰谷分时电价政策的制定与实施。提出计及电动汽车入网的电价联动模型。首先,应用蒙特卡洛模拟法模拟一定数量电动汽车充放电功率曲线;然后,供电侧基于用户... 详细信息

电动汽车不同的充放电控制与利用策略对电网负荷曲线产生不同的影响,从而影响到峰谷分时电价政策的制定与实施。提出计及电动汽车入网的电价联动模型。首先,应用蒙特卡洛模拟法模拟一定数量电动汽车充放电功率曲线;然后,供电侧基于用户需求响应调整销售侧峰谷分时电价,以优化用户负荷曲线;最后,将用户响应后的用户负荷曲线与电动汽车充放电功率曲线叠加得到新的电网负荷曲线,在此基础上,调整发电侧峰谷上网电价,以平衡用户侧削峰填谷及电动汽车入网给发、供电侧带来的效益。结合实际数据,设置3种电动汽车入网方式和2种充放电电价模式对模型进行仿真,结果验证了模型的有效性。

关键词：峰谷分时电价电价联动电动汽车充放电功率需求模型

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学生工作与大学生主体性成长浅议

现代大学教育 2005年第2期21卷 95-99页

作者：方明军湖南师范大学

中国大学生为什么少有个性?是什么在防碍大学生的主体性成长?这其中高校的学生工作系统应该承担怎样的责任?本文分析学生工作系统防碍大学生主体性成长的主要表征在于管理者的专制、管理主义的泛滥以及关怀的肤浅,认为造成这种状况的主... 详细信息

中国大学生为什么少有个性?是什么在防碍大学生的主体性成长?这其中高校的学生工作系统应该承担怎样的责任?本文分析学生工作系统防碍大学生主体性成长的主要表征在于管理者的专制、管理主义的泛滥以及关怀的肤浅,认为造成这种状况的主要原因是行政权力的泛化和社会本位思想的渗透,由此笔者提出以建立指导型学生工作方式为核心的改进对策。

关键词：学生主体性学生工作学生的主体性工作系统中国大学生管理主义本位思想行政权力改进对策工作方式管理者指导型个性高校

从学习性评价的视角反观MOOC之理念与设计

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中国电化教育 2016年第9期 66-73页

作者：蔡旻君马光仲陈萍西北师范大学教育技术学院甘肃兰州730070

MOOC的学习特点和当前欧美评价领域所兴起的学习性评价理念有着千丝万缕的联系。学习性评价和MOOC除了共同关心学习者的评价任务设计之外,它们之间还存在共同的价值基础:即倡导终身学习的理念、推动教师的角色地位发生转变、提升教师的... 详细信息

MOOC的学习特点和当前欧美评价领域所兴起的学习性评价理念有着千丝万缕的联系。学习性评价和MOOC除了共同关心学习者的评价任务设计之外,它们之间还存在共同的价值基础:即倡导终身学习的理念、推动教师的角色地位发生转变、提升教师的职业素养和以促进学生的学习为目的。从学习性评价实践的视角审视MOOC,其设计应用既有很大的优势,也存在明显的不足。为了更好地发挥其学习的优势,MOOC资源应从以下几方面优化设计:分享学习成功标准、加强学生评价的引导、让反馈更加有效、积极倡导建构的学习观和坚持以评促学的原则。

关键词：学习性评价自主 MOOC 互动反馈