77 research outputs found

    An Investigation of the Professional Development of Primary and Secondary School P. E. Backbone Teachers in Fujian Province

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    采用文献法、调查法、统计法、逻辑法等研究方法,以参加2013—2015年福建省基础教育万名骨干教师培训中的190名中小学体育骨干教师为调查对象,对教师基本情况和教师专业发展的认识、态度、知识、能力、继续教育等现状进行调查,在此基础上对教师专业发展现状进行分析,总结出我省中小学体育骨干教师专业发展的特点及存在的问题,并提出相应的建议,给我省中小学体育教师培训机构的改革提供依据,同时为我省中小学体育教师专业发展提供参考与借鉴,为进一步深化我省中小学体育教育改革提供人才保障.结果表明:1)目前,福建省中小学体育骨干教师以年富力强者居多,年龄、职称结构较合理;教师专业发展意识强,学历层次由大专逐步向本科、硕士过度,但硕士比例小;2)教师专业发展态度端正,职业的稳定性和责任感强烈,但部分年轻教师缺乏专业发展的自主性;3)教师对专业知识的掌握比较扎实,主要通过互联网、图书资料、专家报告或讲座等方法来获取专业知识;4)专业能力水平方面,教师在体育教学、课外指导、体育保健、现代教育技术运用等方面能力比较强,而创新教育和科研两方面能力相对比较薄弱;5)当下,我省中小学体育骨干教师最需要强化的培训是课题申报技能、论文写作能力、专题讲座能力、教育科研方法、提高学历层次、教学设计能力,其中提高科研能力和水平是教师们最迫切的愿望.2014年福建省中青年教师教育科研项目(社科A类)(JAS14023

    低温胁迫对长苞铁杉幼苗的生理影响

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    经模拟低温(-12、-8、-4、0、4℃)胁迫处理后,长苞铁杉幼苗叶片和根系相关生理指标均发生明显变化.随着温度降低,叶片光合色素含量增加,但反映光合活性强弱的Chla/Chlb降低;叶片中渗透调节物质脯氨酸和可溶性糖含量增加,呈极显著正相关(r=0.804,p<0.01),根系中可溶性糖含量的减少说明根对低温胁迫的渗透调节更依赖于脯氨酸的累积.幼苗在-4℃及更低温度胁迫下受到严重的冻害使SOD活性持续下降,叶片中POD活性与SOD活性变化呈极显著负相关(r=-0.908,p<0.01),但根系中POD活性与SOD活性没有相关性,说明长苞铁杉幼苗对抗外界胁迫机理的复杂性.叶片MDA含量比根系低可能与叶片中Car能缓解1O2对细胞的伤害有关

    戊型病毒性肝炎研究进展

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    戊型病毒性肝炎是全球最主要的病毒性肝炎之一,近半个世纪多次发生大规模暴发,孕妇感染戊型肝炎后病死率高达20%.近年随着基于构象型表位多肽E2的戊型肝炎诊断试剂的出现,戊型肝炎的病原学诊断及流行病学调查均获得了较大的发展,越来越引起人们的重视.由我国自主创新研制的重组戊型肝炎疫苗现已在中国完成世界上首个Ⅲ期临床试验,其预防戊型肝炎的保护率达到100%(95%CI,72.1%~100.0%)

    Critical tidal level for Kandelia candel forestation in strong tidal range area

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    以国内最大潮差值的乐清湾西门岛海域为研究地点,选定黄零为1.96、1.66、1.35和1.03M4个高程断面,对各高程上1年生和3年生秋茄(kAndElIA CAndEl)幼苗的成活率、生长指标以及污损生物(藤壶)等因子进行了统计分析.结果表明:不同高程内,1年生和3年生秋茄幼苗的生长存在显著性差异;秋茄幼林植株上附生有白脊藤壶(bAlAnuS AlbICOSTATuS)和纹藤壶(bAlAnuS AMPHITrITE AMPHITrITE)2种藤壶,其中优势种白脊藤壶在黄零1.35M的高程对秋茄的污损最为严重.西门岛秋茄的宜林线为黄零1.66M,即不低于当地平均海平面以上1.29M、每个潮水周期平均淹水时间小于3.65H的潮滩.藤壶、强潮和极端天气是该地区秋茄宜林线明显高于当地平均海平面的主要原因.Taking Ximen island of Yueqing bay,the biggest tidal range area among the coasts of China,as study site,an investigation was made on the survival rate,growth characteristics,and attached barnacles of 1-and 3-year old Kandelia candel seedlings at the elevations 1.96,1.66,1.35,and 1.03 m above the zero tidal level of Yellow Sea.Significant differences were observed in the survival rate and growth situation of the seedlings among the elevations.There were two barnacle species,Balanus albicostatus and Balanus amphitrite amphitrite,and B.albicostatus was the major species which attached K.candel most seriously at elevation 1.35 m.The critical tidal level for K.candel in the site was 1.66 m above the zero tidal level,i.e.,at least 1.29 m higher than the local mean sea level,and the flooding time per tide cycle being less than 3.65 h.Barnacle,strong tide,and extreme weather event were the main reasons for the higher critical tidal level.海洋公益性行业科研专项(200805072);浙江省科技计划项目(2008F1009);温州市科技计划项目(S20060037);浙江省科技厅创新团队建设与人才培养项目(2009F20009)资

    人乳头瘤病毒16型假病毒中和实验的建立和初步应用

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    探讨了应用多质粒磷酸钙共转染方法在293FT细胞中生产HPV16(human papillomavirus type 16)假病毒。蛋白印迹检测显示在转染后细胞的裂解上清中具有很好的L1蛋白活性,通过透射电镜可观察到形态与天然病毒粒子相似的假病毒颗粒。对293FT细胞的感染实验显示,该假病毒可有效将EGFP报告质粒导入靶细胞中进行表达,经测定其滴度约为2×107TU/mL。通过与4株HPV16对照单抗的中和实验证明该假病毒可有效应用于中和实验。应用该方法从18株抗HPV16L1的单克隆抗体中鉴定获得了2株中和单抗3D10、PD1。所建立的HPV16假病毒生产和中和实验方法具有快速高效、低成本和易于检测的优点,适于进行较大规模应用,为快速准确鉴定HPV16中和单抗和候选疫苗的免疫保护效果提供了有效手段

    戊型肝炎诊断中血清学及核酸检测意义的研究

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    目的 利用恒河猴感染模型评估血清学检测和核酸检测在戊型肝炎诊断中的临床意义。 方法对86只戊型肝炎病毒(HEV)实验感染猴的系列血清和粪便标本,用反转录聚合酶链反应方法进行病毒学检测,用4种酶联免疫吸附抗体检测试剂(E2-IgM,E2-IgG,GL-IgG和YES-IgG)进行血清学检测。 结果 感染猴均产生E2-IgG抗体,除1只感染猴未检出粪便排毒和E2—IgM外,其余感染猴均出现粪便排毒和E2-IgM阳转。GL-IgG和YES-IgG的阳转率较低,而且与感染剂量相关。急性肝炎主要开始于感染后3~7周内。病毒学指标在潜伏早期即已出现,较疾病的发生约早2周,并在急性期迅速下降。E2-IgM在发病时已有约2/3阳转,并在发病后10周内完全转阴。E2—IgG几乎与E2—IgM同时阳转,在所有感染猴中持续存在,直至86周后仍无阴转。GL-IgG和YES-IgG抗体较E2抗体晚约1周,在感染后20周内已有过半数转阴。结论 E2-IgM是一个良好的戊型肝炎急性感染诊断指标,E2-IgG是一个良好的戊型肝炎既往感染诊断指标,GL-IgG和YES-IgG抗体的阳转或双份血清滴度升高可以作为辅助诊断指标,病毒核酸检测仅在发病的极早期具有诊断价值

    Viral neutralization by antibody-imposed physical disruption

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    中和抗体是机体抵御病毒入侵的一类免疫球蛋白,也是疫苗发挥作用的主要效应分子。目前已知的中和抗体作用机制,主要包括阻断病毒-细胞相互作用和介导免疫调理作用。最近我校夏宁邵教授团队研究结果揭示了一种由抗体诱导病毒原位崩解的中和新机制。该研究首次揭示了抗体的直接物理碰撞中和机制,并提出诱导这类中和抗体的方法,有助于病毒保护性抗体和疫苗设计,适用于多种病原体,而不仅限于戊型肝炎病毒。分子疫苗学和分子诊断学国家重点实验室夏宁邵教授、李少伟教授和顾颖副教授为该论文的共同通讯作者,郑清炳博士、硕士生蒋婕、博士生何茂洲和郑子峥副教授为共同第一作者。In adaptive immunity, organisms produce neutralizing antibodies (nAbs) to eliminate invading pathogens. Here, we explored whether viral neutralization could be attained through the physical disruption of a virus upon nAb binding. We report the neutralization mechanism of a potent nAb 8C11 against the hepatitis E virus (HEV), a nonenveloped positive-sense single-stranded RNA virus associated with abundant acute hepatitis. The 8C11 binding flanks the protrusion spike of the HEV viruslike particles (VLPs) and leads to tremendous physical collision between the antibody and the capsid, dissociating the VLPs into homodimer species within 2 h. Cryo-electron microscopy reconstruction of the dissociation intermediates at an earlier (15-min) stage revealed smeared protrusion spikes and a loss of icosahedral symmetry with the capsid core remaining unchanged. This structural disruption leads to the presence of only a few native HEV virions in the ultracentrifugation pellet and exposes the viral genome. Conceptually, we propose a strategy to raise collision-inducing nAbs against single spike moieties that feature in the context of the entire pathogen at positions where the neighboring space cannot afford to accommodate an antibody. This rationale may facilitate unique vaccine development and antimicrobial antibody design.This research was supported by grants from the Natural Science Foundation of Fujian Province (Grant 2017J07005), the National Science and Technology Major Project of Infectious Diseases (Grant 2018ZX10101001-002), and the National Natural Science Foundation of China (Grants 81871247, 81991490, and 81571996).国家自然科学基金重大项目、海峡联合项目和面上项目、福建省自然科学杰出青年基金、国家传染病科技重大专项等资助了该项研究

    Atomic structures of enterovirus D68 in complex with two monoclonal antibodies define distinct mechanisms of viral neutralization

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    11月5日,《自然》子刊《自然•微生物学》(Nature Microbiology)在线刊出了我校夏宁邵教授团队发表的题为“Atomic Structures of Enterovirus D68 in Complex with Two Monoclonal Antibodies Define Distinct Mechanisms of Viral Neutralization”的研究论文。这是夏宁邵教授团队在《自然•通讯》(Nature Communications,2017)、《科学•进展》(Science Advances,2018)上发表手足口病重要病原体CVA6、CVA10研究论文之后的又一项关于肠道病毒的重要研究成果。该研究通过解析肠道病毒D组68型(EV-D68)不同类型病毒颗粒及其免疫复合物的高分辨率结构,系统阐明了EV-D68病毒的生活周期及各时期的病毒中和机制,进一步完善了小RNA病毒的吸附入胞及感染机制理论,为EV-D68新型疫苗、抗病毒治疗药物的研发提供重要的理论指导。该研究依托电镜技术平台,解析了EV-D68病毒生活周期中的三种代表性颗粒成熟颗粒、脱衣壳中间态和前体病毒衣壳的近原子分辨率结构,阐明了三种病毒颗粒间的结构差异,以及成熟颗粒转变为脱衣壳中间态的分子机制。夏宁邵教授、李少伟教授、程通副教授和美国国立卫生研究院(NIH)高级研究员Barney Graham博士为该论文的共同通讯作者。郑清炳工程师、博士生朱瑞、博士后徐龙发、博士生何茂洲和美国加州大学圣地亚哥分校颜晓东博士为该论文共同第一作者。【Abstract】Enterovirus D68 (EV-D68) undergoes structural transformation between mature, cell-entry intermediate (A-particle) and empty forms throughout its life cycle. Structural information for the various forms and antibody-bound capsids will facilitate the development of effective vaccines and therapeutics against EV-D68 infection, which causes childhood respiratory and paralytic diseases worldwide. Here, we report the structures of three EV-D68 capsid states representing the virus at major phases. We further describe two original monoclonal antibodies (15C5 and 11G1) with distinct structurally defined mechanisms for virus neutralization. 15C5 and 11G1 engage the capsid loci at icosahedral three-fold and five-fold axes, respectively. To block viral attachment, 15C5 binds three forms of capsids, and triggers mature virions to transform into A-particles, mimicking engagement by the functional receptor ICAM-5, whereas 11G1 exclusively recognizes the A-particle. Our data provide a structural and molecular explanation for the transition of picornavirus capsid conformations and demonstrate distinct mechanisms for antibody-mediated neutralization.This work was supported by a grant from the National Science and Technology Major Projects for Major New Drugs Innovation and Development (no. 2018ZX09711003-005-003), the National Science and Technology Major Project of Infectious Diseases (no. 2017ZX10304402-002-003), the National Natural Science Foundation of China (no. 81401669 and 81801646) and the Natural Science Foundation of Fujian Province (no. 2015J05073). This work was supported in part by funding by the National Institutes of Health (grants R37-GM33050, GM071940, DE025567 and AI094386). We acknowledge the use of instruments at the Electron Imaging Center for Nanomachines supported by UCLA and by instrumentation grants from the NIH (1S10RR23057 and 1U24GM116792) and NSF (DBI-1338135 and DMR-1548924). 该研究获得了国家自然科学基金、新药创制国家科技重大专项、传染病防治国家科技重大专项和美国国立卫生研究院基金的资助

    Discovery and structural characterization of a therapeutic antibody against coxsackievirus A10

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    9月20日,《科学》子刊《科学•进展》(Science Advances)刊出了我校夏宁邵教授团队发表的题为“Discovery and structural characterization of a therapeutic antibody against coxsackievirus A10”的研究论文。该研究首次发现手足口病重要病原体柯萨奇病毒A组10型(CVA10)不同类型病毒颗粒共有的优势中和表位,揭示了病毒颗粒及其与优势中和抗体复合物的精确三维结构,阐明了中和抗体的功能与作用机制,为新型疫苗和治疗药物的研制提供了重要的理论基础。 该研究首次揭示并描绘了CVA10的病毒颗粒及其优势中和表位的精确特征,发现了具有良好应用潜能的治疗性中和抗体,为新型疫苗和特异性治疗药物的研究提供了关键基础。 我校夏宁邵教授、程通副教授和美国加州大学洛杉矶分校纳米系统研究所Z. Hong Zhou(周正洪)教授、美国加州大学圣地亚哥分校颜晓东博士为该论文的共同通讯作者。我校博士生朱瑞、徐龙发博士后、郑清炳工程师、李少伟教授和美国加州大学洛杉矶分校崔彦祥博士后为该论文共同第一作者。【Abstract】Coxsackievirus A10 (CVA10) recently emerged as a major pathogen of hand, foot, and mouth disease and herpangina in children worldwide, and lack of a vaccine or a cure against CVA10 infections has made therapeutic antibody identification a public health priority. By targeting a local isolate, CVA10-FJ-01, we obtained a potent antibody, 2G8, against all three capsid forms of CVA10. We show that 2G8 exhibited both 100% preventive and 100% therapeutic efficacy against CVA10 infection in mice. Comparisons of the near-atomic cryo–electron microscopy structures of the three forms of CVA10 capsid and their complexes with 2G8 Fab reveal that a single Fab binds a border region across the three capsid proteins (VP1 to VP3) and explain 2G8’s remarkable cross-reactivities against all three capsid forms. The atomic structures of this first neutralizing antibody of CVA10 should inform strategies for designing vaccines and therapeutics against CVA10 infections.This work was supported by grants from the National Science and Technology Major Projects for Major New Drugs Innovation and Development (2018ZX09711003-005-003), the National Science and Technology Major Project of Infectious Diseases (2017ZX10304402-002-003), the National Natural Science Foundation of China (31670933 and 81801646), and the National Institutes of Health (R37-GM33050, GM071940, DE025567, and AI094386). We acknowledge the use of instruments at the Electron Imaging Center for Nanomachines supported by the University of California, Los Angeles and by instrumentation grants from NIH (1S10RR23057 and 1U24GM116792) and NSF (DBI-1338135 and DMR-1548924). 该研究获得了国家自然科学基金、新药创制国家科技重大专项、传染病防治国家科技重大专项和美国国立卫生研究院基金的资助

    Near-atomic cryo-electron microscopy structures of varicella-zoster virus capsids

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    VZV是一种广泛存在并且具有高度传染性的人类α-疱疹病毒。初次感染VZV可导致水痘,人群普遍易感(感染率约为61%~100%)。该病毒可在背根神经节潜伏感染,持续终生。夏宁邵教授团队长期开展VZV相关基础与新型疫苗研究,通过系统和精细探索建立了高效的VZV规模化培养和病毒颗粒纯化技术体系,成功获得高质量的VZV颗粒样品。首次揭示了疱疹病毒α家族的水痘-带状疱疹病毒(VZV)不同类型核衣壳的近原子分辨率结构,阐明了VZV核衣壳不同组成蛋白的相互作用网络与衣壳装配机制,可为进一步开展新型载体疫苗设计及抗病毒药物等研究提供重要支持。 我校博士后王玮、高级工程师郑清炳、博士生潘德全和俞海副教授为该论文共同第一作者,我校夏宁邵教授、程通副教授、李少伟教授以及美国罗格斯大学朱桦(Hua Zhu)教授、加利福尼亚大学洛杉矶分校周正洪(Z. Hong Zhou)教授为该论文的共同通讯作者。【Abstract】Varicella-zoster virus (VZV) is a medically important human herpesvirus that causes chickenpox and shingles, but its cell-associated nature has hindered structure studies. Here we report the cryo-electron microscopy structures of purified VZV A-capsid and C-capsid, as well as of the DNA-containing capsid inside the virion. Atomic models derived from these structures show that, despite enclosing a genome that is substantially smaller than those of other human herpesviruses, VZV has a similarly sized capsid, consisting of 955 major capsid protein (MCP), 900 small capsid protein (SCP), 640 triplex dimer (Tri2) and 320 triplex monomer (Tri1) subunits. The VZV capsid has high thermal stability, although with relatively fewer intra- and inter-capsid protein interactions and less stably associated tegument proteins compared with other human herpesviruses. Analysis with antibodies targeting the N and C termini of the VZV SCP indicates that the hexon-capping SCP—the largest among human herpesviruses—uses its N-terminal half to bridge hexon MCP subunits and possesses a C-terminal flexible half emanating from the inner rim of the upper hexon channel into the tegument layer. Correlation of these structural features and functional observations provide insights into VZV assembly and pathogenesis and should help efforts to engineer gene delivery and anticancer vectors based on the currently available VZV vaccine.This research was supported by grants from the National Science and Technology Major Projects for Major New Drugs Innovation and Development (no. 2018ZX09711003-005-003), the National Science and Technology Major Project of Infectious Diseases (no. 2017ZX10304402), the National Natural Science Foundation of China (no. 81871648, 81601762), the Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical Sciences (no. 2019RU022) and the US National Institutes of Health (DE025567/028583). 该研究获得了国家自然科学基金、新药创制国家科技重大专项和传染病防治国家科技重大专项等资助
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