抗原受体基因重组的表观遗传学调控研究新进展

淋巴细胞是哺乳动物唯一能发生体细胞基因组变化的一类细胞,淋巴细胞在发育过程中通过V(D)J重组获得成熟的特异的抗原受体基因,实现了免疫细胞抗原识别惊人的多样性.关于V(D)J重组的调控机制一直是免疫学研究的重要问题,然而直到将表观遗传学研究引入这一领域,综合遗传学和表观遗传学的研究才真正揭示V(D)J重组精细的调控机制.综述了新近发现的V(D)J重组过程中重要的表观遗传学调控机制,如CpG甲基化,组蛋白修饰,核小体重塑及核拓扑学变化.     

Low concentration of condensed tannins from catechu significantly inhibits fatty acid synthase and growth of MCF-7 cells

Tannins exist widely in plants, but because they precipitate proteins, scientists frequently ignore them in search of bioactive components. Catechu, a traditional astringent, is rich in tannins. In this study, we found that condensed tannins from catechu potently inhibited animal fatty acid synthase (FAS). Among them, trimeric condensed tannin showed the most potent inhibition with IC₅₀ of 0.47 μg/ml and it also exhibited strong time-dependent inhibition. Its inhibitory kinetics and reacting sites on FAS were obviously different from the known inhibitors of FAS. Furthermore, condensed tannins were found to suppress the growth of MCF-7 breast cancer cells, and the effect was related to their activity of FAS inhibition. The inhibition of both FAS activity and MCF-7 growth was exhibited by low concentrations of condensed tannins without FAS being precipitated. These results suggest tannins would be a valuable resource of bioactive substances.     

bHLH转录因子在大脑皮质发育中的作用

在大脑新皮质发育过程中,bHLH转录因子参与了关键事件的调节。Id和Hes家族的bHLH因子对维持大脑皮质多能祖细胞(cortical mutipotent progenitor)处于增殖状态非常重要。前神经bHLH因子(Mash1、Neurogenin1和Neurogenin2)活性增强和Hes、Id因子的活性相应减弱,引起皮质多能祖细胞由增殖状态向神经生成转变。随着发育的皮质祖细胞中前神经bHLH因子的抑制,促使星形胶质细胞的生成。最后,bHEH因子Olig1和Olig2活性的增加和Id活性的减弱启动了少突胶质细胞的形成。     

旱地小麦根际细菌中产生1-氨基环丙烷-1-羧酸(ACC)脱氨酶菌株的分离和鉴定

采用富集定向筛选法,从旱地小麦的根际土壤中分离到2株产生1-氨基环丙烷-1-羧酸(ACC)脱氨酶的菌株AS和CS。经测定菌株AS和CS的ACC脱氨酶的比活力分别为0.018 6 U/mg和0.016 7 U/mg蛋白。根据培养特征观察和生理生化指标测定结果,结合16S rDNA碱基序列测定和系统发育同源性分析,确定菌株AS和菌株CS分别属于霍氏肠杆菌(Enterobacter hormaechei)和变形斑沙雷氏菌(Serratia proteamaculans)。     

糖抗原sTn是Ⅰ型子宫内膜癌的新型标记物

Sialyl-Tn(sTn)是肿瘤相关糖抗原的一种,在多种上皮来源的肿瘤组织中都存在sTn的过表达．但是,关于sTn在子宫内膜癌中的表达情况目前研究得很少,而且仅有的报道也互相矛盾．为了阐明这一问题,我们选取了111例临床样本,其中包括82例子宫内膜癌,16例非典型增生内膜,13例正常内膜,利用免疫组化的方法分析了sTn的表达情况．结果表明,sTn在子宫内膜癌中高表达,但仅限于Ⅰ型子宫内膜癌(80%),而在Ⅱ型子宫内膜癌中表达率仅为45%,二者具有显著性差异(P < 0.05)．这是我们首次报道sTn特异性与Ⅰ型子宫内膜癌相关,有利于解释过去前后不一的矛盾结果．在非典型组织中,sTn的表达率较正常组织高,分别为31%(正常组织)和44%(非典型组织)．这说明sTn参与了子宫内膜癌的发生发展．同时,我们的结果表明,sTn的表达与肿瘤的组织分级具有相关性,其在高、中分化的肿瘤组织中表达率明显高于低分化的肿瘤组织．这预示着sTn可能与子宫内膜癌的良好预后相关．我们的研究为诊断Ⅰ型子宫内膜癌提供了一个新的标记物和诊断试剂,同时提示我们,将来对于子宫内膜癌的研究,有必要对Ⅰ型子宫内膜癌和Ⅱ型子宫内膜癌区别对待．     

促肾上腺皮质激素释放激素及其受体在痛觉调节中作用的研究进展

最近的大量研究表明,促肾上腺皮质激素释放激素(CRF)和CRF类似肽广泛分布于脑、脊髓和内脏器官。CRF和CRF类似肽均可与CRF受体结合。CRF受体(CRFR)可分为CRFR1、CRFR2和CRFR3三种类型。CRFR2又分为A、B、C三个亚型。各种CRF受体激活时,对细胞产生相应的功能调节。CRF参与机体多层次的痛觉调节,CRF、CRF类似肽及与CRF有关的生物活性物质都有可能成为新一代的镇痛药。     

Numerical investigation of the non-Newtonian pulsatile blood flow in a bifurcation model with a non-planar branch

The pulsatile flow of non-Newtonian fluid in a bifurcation model with a non-planar daughter branch is investigated numerically by using the Carreau-Yasuda model to take into account the shear thinning behavior of the analog blood fluid. The objective of this study is to deal with the influence of the non-Newtonian property of fluid and of out-of-plane curvature in the non-planar daughter vessel on wall shear stress (WSS), oscillatory shear index (OSI), and flow phenomena during the pulse cycle. The non-Newtonian property in the daughter vessels induces a flattened axial velocity profile due to its shear thinning behavior. The non-planarity deflects flow from the inner wall of the vessel to the outer wall and changes the distribution of WSS along the vessel, in particular in systole phase. Downstream of the bifurcation, the velocity profiles are shifted toward the flow divider, and low WSS and high shear stress temporal oscillations characterized by OSI occur on the outer wall region of the daughter vessels close to the bifurcation. Secondary motions become stronger with the addition of the out-of-plane curvature induced by the bending of the vessel, and the secondary flow patterns swirl along the non-planar daughter vessel. A significant difference between the non-Newtonian and the Newtonian pulsatile flow is revealed during the pulse cycle; however, reasonable agreement between the non-Newtonian and the rescaled Newtonian flow is found. Calculated results for the pulsatile flow support the view that the non-planarity of blood vessels and the non-Newtonian properties of blood are an important factor in hemodynamics and may play a significant role in vascular biology and pathophysiology.     

一种利用生理指标评价玉米弯孢菌叶斑病抗性的方法

本试验以4种不同抗性的玉米自交系幼苗为材料,比较了新月弯孢菌毒素浓度和处理时间对玉米主要防御酶系苯丙氨酸解氨酶（PAL）、过氧化酶（POD）和超氧化物歧化酶（SOD）比活力的影响。结果表明：在不同毒素浓度和胁迫时间下,PAL、POD和SOD比活力与品种抗病性的相关程度不一致。稀释200倍的毒素溶液处理玉米幼苗12h时,PAL比活力与抗病性呈极显著线性正相关,POD比活力与抗病性呈曲线正相关,SOD比活力与玉米抗病性呈极显著线性负相关。因此,可利用稀释200倍的新月弯孢菌毒素溶液处理12h时测得的玉米幼苗PAL、POD及SOD比活力估算玉米自交系弯孢菌叶斑病的抗性水平。     

Epstein-Barr病毒潜伏蛋白1通过核转录因子κB诱导鼻咽上皮细胞表达端粒酶活性

利用已建立的原代人胚鼻咽上皮细胞和Tet-on-LMP1系统等良好的实验模型,采用荧光酶报道基因分析法和端粒酶TRAP-ELISA技术,分别检测EB病毒潜伏蛋白1(LMP1)诱导的核转录因子κB(NFκB)活性和端粒酶活性,从LMP1介导NFκB信号传导途径角度,探讨LMP1诱导端粒酶表达的分子机制.结果表明,LMP1可诱导鼻咽上皮细胞表达端粒酶活性,将LMP1羧基端胞浆区突变后,可同时下调NFκB活性和端粒酶活性.在Doxycycline诱导LMP1表达状态下,NFκB反式激活活性增强,同时端粒酶活性升高;进一步应用硫代磷酸化修饰的反义NFκB p65寡脱氧核苷酸和IκBα的显性负性突变体分别阻断NFκB活性,可降低由LMP1诱导的端粒酶活性.因此,NFκB作为LMP1信号传导途径上的枢纽,可能介导了LMP1对端粒酶的表达调控.     

抗SARS 人源单链抗体H12的表达及复性

从SARS免疫抗体库获得的一株抗SARS-CoV人源单链抗体H12,亟待鉴定.为了快速制备大量具有生物活性的单链抗体H12,构建了pET28a-H12原核高表达载体,表达量占菌体总蛋白质30%以上.采用稀释复性和分子筛柱复性两种方法对包涵体蛋白进行复性与纯化,结果显示两种方法都能使得单链抗体复性.与稀释复性法相比,柱复性效果更好,其抗原结合活性是稀释复性法的1.51倍.柱复性后的单链抗体亲和力测定的解离常数Kd为73.5nmol/mL.为进一步研究单链抗体H12的功能奠定了基础.