RNA干扰在疾病治疗上的应用

RNA干扰(RNA interference,RNAi)是一种双链RNA分子在mRNA水平上引发的特异性基因沉默现象。RNAi在基因治疗方面表现出了光明的前景,已成功地应用于多种疾病的临床治疗。本文主要介绍了RNAi在疾病治疗上的应用及研究进展。     

组蛋白去乙酰化酶6与阿尔兹海默病

组蛋白去乙酰化酶6(histone deacetylase 6,HDAC6)在细胞中参与了许多蛋白质的修饰过程,最新证据显示其在阿尔茨海默病(Alzheimer’s disease,AD)发展过程中起了越来越重要的作用,HDAC6不仅可与tau蛋白相互作用并影响其磷酸化过程,而且同时也受到GSK-3β的调控。本文主要介绍了HDAC6在阿尔兹海默病中的作用机制,同时介绍下HDAC6抑制剂对AD的治疗作用。     

镉胁迫对拟南芥的毒害作用及自噬现象的观测

镉离子(Cd2+)具有强植物毒性,可抑制植物生长,甚至导致植物死亡。为了研究重金属镉对拟南芥的毒害作用,采用叶绿素荧光技术、流式细胞技术、激光共聚焦技术及半定量RT-PCR技术,检测光合参数的变化、活性氧(reactive oxygen species,ROS)的累积、自噬的发生,以及病原相关蛋白(pathogenesis-related protein,PR)基因表达的变化。实验结果显示,随着50μmol/L CdCl2处理时间的延长,ROS和Cd2+在细胞中大量积累。而在镉胁迫的初期,会观察到自噬的发生及PR基因表达的变化。说明植物受到外界Cd2+作用的初期,会通过自噬及增强PR基因表达来抵抗外界胁迫。但随着处理时间的延长,植物细胞内累积了大量的ROS和Cd2+,当植物不足以通过自噬途径抵抗胁迫时,就会导致生长受阻,最终对光合系统造成损伤。     

PP-1催化亚基（PP-1c）在成体小白鼠不同组织器官中的分化表达与定位

为了确定蛋白磷酸酶-1(protein phosphatase-1)的催化亚基(PP 1c)在小白鼠不同器官组织(肌肉、卵巢、肾、胃、 脾、大脑、心、肝、肺及乳腺)中的表达模式,运用RT-PCR、Western 印迹及荧光免疫组织化学技术等实验手段进行了检测 和分析.结果表明,在mRNA水平, PP-1c在大脑中表达最高,卵巢及肺中表达次之,在肌肉、肾、心、肝中表达较低,在胃 和乳腺中表达最低;在蛋白质水平,肝中表达最高,肾、大脑、肺和乳腺中表达较高,而肌肉、卵巢、心和脾中表达相对较 低,胃中表达最低.免疫荧光组织化学实验结果显示,PP 1c的表达也具有明显的组织特异性和细胞特异性.这些结果为进一 步探讨PP 1在哺乳动物不同组织器官中的功能提供了重要的实验依据.     

胡瓜钝绥螨对日光大棚茄子上烟粉虱的控制作用

为了评价胡瓜钝绥螨在我国日光大棚中对茄子上烟粉虱虱的控制作用。笔者研究了在24～34℃下胡瓜钝绥螨以烟粉为猎物时的发育历期,并在我国山东省寿光市的蔬菜基地上开展了利用胡瓜钝绥螨控制日光大棚茄子上烟粉虱的研究与应用。结果表明:胡瓜钝绥螨能够取食烟粉虱的卵、成虫、若虫及伪蛹;利用胡瓜钝绥螨能有效地控制烟粉虱成虫、卵、若虫种群数量的增长。根据胡瓜钝绥螨和烟粉虱的生物学特性,结合大棚茄子栽培过程中的环境条件,笔者提出了在日光大棚中应用胡瓜钝绥螨控制茄子上烟粉虱的策略:(1)在茄子的整个生长季节(250d)中需释放胡瓜钝绥螨4～6次,苗期每次每株释放5～10头,结果期每次每株释放20～40头;(2)释放胡瓜钝绥螨的生防区比常规化防区减少农药使用18次;(3)安装防虫网、适时释放胡瓜钝绥螨是生防成功之关键,生防区配合使用黄板效果更好。     

Bacterial Phosphoproteomic Analysis Reveals the Correlation Between Protein Phosphorylation and Bacterial Pathogenicity

Increasing evidence shows that protein phosphorylation on serine, threonine and tyrosine residues is a major regulatory post-translational modification in the bacteria. This review focuses on the implications of bacterial phosphoproteome in bacterial pathogenicity and highlights recent development of methods in phosphoproteomics and the connectivity of the phosphorylation networks. Recent technical developments in the high accuracy mass spectrometry have dramatically transformed proteomics and made it possible the characterization of a few exhaus- tive site-specific bacterial phosphoproteomes. The high abundance of tyrosine phosphorylations in a few bacterial phosphoproteomes suggests their roles in the pathogenicity, especially in the case of pathogen-host interactions; the high abundance of multi-phosphorylation sites in bacterial phosphoprotein is a compensation of the relatively small phosphorylation size and an indicator of the delicate regulation of protein functions.     

Adverse events of interferon beta-1a: a prospective multi-centre international ICH-GCP-based CRO-supported external validation study in daily practice

Background

Due to methodological shortcomings the available post-registration data on the adverse events (AEs) occurring in interferon beta-1a (INFb-1a)-treated patients fail to adequately validate phase III data and only partially inform on safety in daily practice. We assessed AEs in relapsing remitting multiple sclerosis (RRMS) patients treated with intramuscular (IM) INFb-1a in daily practice using data quality assurance measures similar to those in phase III trials.

Methods

A prospective, International Conference on Harmonization (ICH) - Good Clinical Practice (GCP)-based, clinical research organization (CRO)-supported study in 36 practices in the Netherlands, Belgium, the United Kingdom and Luxembourg. During 24 months after start of IM INFb-1a treatment 275 RRMS patients were assessed for AEs'' severity (mild, moderate, severe) and relationship to treatment (not, unlikely, likely, definite). Data were compared with those reported in the pivotal phase III trial.

Findings

75.3% of the patients experienced one or more AEs that were likely or definitely related to INFb-1a. Of all AEs 40.5% were likely or definitely treatment-related; 68.5% of these were mild, and 3% severe. 6.6% of the patients discontinued treatment because of an AE. Compared to the pivotal phase III trial, we found statistically significantly lower incidences for most of the common AEs: headache, muscle ache, fatigue, fever, chills, nausea. One patient died following two cerebral vascular events in study month 22, both AEs were assessed as not related to INFb-1a.

Conclusion

Three out of four RRMS patients treated with IM INFb-1a in daily practice experience treatment-related AEs, most of these being mild. Our data externally validate the favorable phase III safety profile of IM INFb-1a and suggest that the real-life incidence of treatment-related AEs is less than reported in the pivotal phase III trial. Larger studies are needed to detect rare, potentially hazardous AEs of IM INFb-1a.     

光系统II核心复合物的稳态荧光光谱(英文)

在 83K 和 160K 两个温度下,通过激发波长对荧光发射谱的影响研究了光系统II中核心复合物的荧光光谱特性。用不同波长的光激发,核心复合物的发射谱的最大发射峰值不变,用 480、489、495 和 507nm 的光分别激发核心复合物,其光谱最大峰值处的荧光强度随不同激发波长下β-胡萝卜素分子的吸收强度的增大而降低,在长波长区域光谱的变化依赖于首先被激发的色素分子。所以,激发波长的不同影响着核心复合物中能量传递的途径。通过高斯解析,分析出核心复合物中至少存在有 7组叶绿素a组分,它们是Chla660,Chla670,Chla680,Chla682,Chla684,Chla687和Chla690。     

4-氨基吡啶敏感钾通道对神经自发放电节律转迁历程的调节作用

为进一步研究损伤神经放电节律的分岔转迁规律,以实验性神经起步点模型为研究对象,在联合改变胞外的钙离子和钾离子浓度的条件下,记录神经单纤维的放电节律转迁方式。选取4-氨基吡啶(4-aminopyridine,4-AP)作为条件参数,Ca2+浓度作为分岔参数,观察了实验性神经起步点自发放电节律的分岔规律。28例实验结果中,有21例神经对本文所取的条件参数变化不敏感,7例实验性神经起步点的自发放电节律会在不同的条件参数下出现不同类型的分岔序列结构。在不同的4-AP浓度下,随着Ca2+浓度的降低,同一实验性神经起步点会表现出不同的放电节律模式的分岔序列,不同实验性神经起步点,双参数分岔序列是不同的。以上结果说明,不同参数配置下的神经放电节律的变化规律是不同的,而且分岔序列结构是认识放电节律转迁规律的基础。     

马铃薯（Solanum tuberosum L.）茎尖的超低温保存及其遗传变异的初步观察

研究马铃薯茎尖超低温保存技术的结果表明,4℃低温下锻炼6d,在添加二甲基亚砜（DMSO）和乙酰胺的培养基中预培养5d,60％PVS2于室温下装载30min,0℃下PVS2脱水40min时,茎尖成活率最高（71．6％）,再生植株生长分化正常。进一步对再生植株进行AFLP分析,6对引物组合共扩增出385条带,超低温保存前后的材料之间未见到明显差的异带,但用MSAP技术分析超低温保存前后植株甲基化的结果显示：超低温保存后的材料均有不同程度的甲基化。在扩增的624条带中,处理与否之间完全一致的带型为584条;有变化的带型为40条,处理2（茎尖经过完整的超低温保存过程,区别于处理1,增加了冷冻、解冻和洗涤后恢复培养）有13个位点的甲基化增加,21个位点去甲基化。