Specificity and mechanism of the histone methyltransferase Pr-Set7

Methylation of lysine residues of histones is an important epigenetic mark that correlates with functionally distinct regions of chromatin. We present here the crystal structure of a ternary complex of the enzyme Pr-Set7 (also known as Set8) that methylates Lys 20 of histone H4 (H4-K20). We show that the enzyme is exclusively a mono-methylase and is therefore responsible for a signaling role quite distinct from that established by other enzymes that target this histone residue. We provide evidence from NMR for the C-flanking domains of SET proteins becoming ordered upon addition of AdoMet cofactor and develop a model for the catalytic cycle of these enzymes. The crystal structure reveals the basis of the specificity of the enzyme for H4-K20 because a histidine residue within the substrate, close to the target lysine, is required for completion of the active site. We also show how a highly variable component of the SET domain is responsible for many of the enzymes' interactions with its target histone peptide and probably also how this part of the structure ensures that Pr-Set7 is nucleosome specific.     

正常成年人与急性脑血管病患者红细胞膜钠钾ATP酶的研究

本文采用钠钾ＡＴＰ酶活力试剂盒，用化学比色法分别测定正常成人各年龄组（青、中、老年组）及急性脑血管病患者红细胞膜钠钾ＡＴＰ酶活力。结果表明成人中、老年组该酶活力明显低于青年组（Ｐ＜０．０１），中、老年组之间无显著差异（Ｐ＞０．０５）。急性脑血管病患者该酶活力明显低于正常成人中老年组（Ｐ＜０．０５），脑出血和脑血栓组之间无显著差异（Ｐ＞０．０５）。认为红细胞膜钠钾ＡＴＰ酶活力可作为观察人体衰老及急性脑血管病诊断参考指标。本文还对其变化机制进行了探讨。     

镉致肾小管细胞内Na~＋－K~＋－ATP酶与钙稳态的变化

通过观察肾小管上皮细胞内Ｎａ＋－Ｋ＋－ＡＴＰ酶活性、胞浆游离钙离子浓度及超微结构的变化，系统研究了重金属镉致肾小管细胞损伤的发病机理。结果表明，镉染毒后，肾小管上皮细胞内Ｎａ＋－Ｋ＋－ＡＴＰ酶活性明显受抑，抑制率为８２．４％，胞浆游离钙离子浓度较对照组明显增加（Ｐ＜０．０１），且伴有一系列超微结构损害。提示，镉致肾损伤时肾小管上皮细胞内Ｎａ＋－Ｋ＋－ＡＴＰ酶活性受抑与胞浆游离钙离子浓度增加有明显的相关关系，胞内钙稳态失衡可能是镉致肾小管损伤的重要因素之一。     

钠钾泵对内皮细胞释放舒张因子的作用

采用瀑布生物测定技术研究钠钾泵对内皮细胞释放的舒张因子（ＥＤＲＦ）的作用。结果表明，利用钠钾泵阻断剂哇巴因（Ｏｕａｂａｉｎ）选择性处理供体动脉的内皮细胞可以增强基础ＥＤＲＦ的释放，但不影响乙酰胆碱（Ａｃｈ）刺激的ＥＤＲＦ的释放。阻断前列腺素合成和β受体对哇巴因的这一作用不产生影响，结果提示：基础ＥＤＲＦ和Ａｃｈ刺激的ＥＤＲＦ其化学性质或作用机制有所不同。哇巴因的作用可能与其增加内皮细胞内钙浓度有关     

Inhibitory effects of chemically-different ‘loop’ diuretics on chloride transport across the bullfrog cornea

Frog (Rana catesbeiam) corneas were mounted in an Ussing chamber, modified to facilitate dissection and to avoid edge damage to the epithelial tissue during mounting and measurements. When bathed in Conway solution of pH 7.4 the corneas displayed highly stable electrical properties, with a transepithelial potential difference (PD) of 16.6 ± 1.0 mV and a short-circuit current (SCC) of 10.3 ± 0.8 μA cm^-2. The DC resistance was 2.0 ± 0.15 k. cm² (mean ± SE, n= 45). An increase in the intracellular cyclic AMP level induced by prostaglandin E₂ and by 3-isobutyl-i-methylxanthine (IBMX) resulted in an increase in SCC. Ortho-vanadate, an inhibitor of Na⁺-K⁺-ATPase, reduced SCC. The acidic loop diuretics furosemide, bumetanide and the le vorotatory form of indacrinone (MK-196) reduced SCC byaboutso%at concentrations of 500,100 and 46 μM, respectively. The (–)form of MK-196 was four times more active than the (+)form. Dimethylation of the SO₂NH₂ group reduced the activity of bumetanide. The basic diuretics muzolimine (Bay G 2821) and MK-447, were found, similarly, to reduce SCC by about 50% at concentrations of 500 μM. In view of their ‘high ceiling’ type of saluretic effects in whole animals, these basic agents should therefore be classified as ‘loop’ diuretics. The effects of these structurally highly different ‘loop’ diuretics are similar in epithelia which secrete (cornea) and in those which absorb (the renal thick ascending limb of Henle's loop; TALH) chloride ions. This could indicate that they interact with the same ‘diuretic receptor’ and have a common mode of action in both types of epithelia. Moreover, their effects on chloride transport parallel their saluretic effects. Amphibian cornea should therefore be a convenient model tissue for studies of the modes of action and the structure-activity relationships of loop diuretics.     

大学英语教学应注重素质教育

全国大学英语四、六级统考极大地促进了大学英语教学,同时也带来了一些令人担忧的问题：应试教育盛行;只重短期效果;考什么就教什么;忽略学生的个体差异;学生的考试成绩与语言应用能力不成正比等。大学英语教育必走素质教育之路,这样才能为学生打下扎实的基础,其语言应用能力才能得到真正的锻炼和提高。     

中医翻译的学术和科普双层次及其人才培养

中医翻译的学术和科普双层次及其人才培养安徽中医学院神经病学研究所（合肥２３００３１）王晓平安徽医科大学外语室任斌现今至少有两种观点：一种强调中医翻译的高层次，采用拉丁、希腊语词根及前后辍，一种注重中医通俗性与形象化，用平常语言。笔者认为要建立两套中医...     

黄芩甙对大鼠心肌缺血再灌注所致脂质过氧化损伤的保护作用

目的：研究黄芩甙（baicalin,Bai)对大鼠心肌缺血再灌注所致脂质过氧化损伤的保护作用。方法：采用结扎在体大鼠冠状动脉左前降支造成心肌缺血30min,随后恢复血流行再灌注120min,复制心肌缺血再灌注损伤模型。结果：Bai能不同程度地降低缺血再灌注所引起心肌组织脂质过氧化物丙二醛（MDA）含量升高,提高超氧化物歧化酶（SOD）活性,保护Na^ -K^ -ATP酶活力,降低血清肌酸激酶（CK）和乳酸脱氢酶（LDH）水平。结论：Bai可通过保护脑组织抗氧化酶的活性,抑制脂质过氧化反应,减轻自由基对心肌组织的损害,对缺血再灌注心肌产生保护作用。     

大豆异黄酮对大鼠脑缺血再灌后ATP酶及bcl-2和bax的影响

目的:观察大豆异黄酮对大鼠脑缺血再灌后ATP酶及bcl-2和bax的影响,探讨其神经保护作用的机制。方法:30只雄性SD大鼠,随机分成对照组、缺血再灌组和大豆异黄酮预处理组。采用三血管阻断法建立大鼠全脑缺血再灌注损伤模型,缺血1 h后再灌1 h。观察各组大鼠脑组织病理学改变,Na+-K+-ATP酶和Ca2+-Mg2+-ATP酶活性改变及bcl-2和bax表达的变化。结果:大豆异黄酮预处理组脑组织损伤较缺血再灌组明显减轻,ATP酶活性升高,并且可以促进bcl-2和抑制bax的表达(P0.05～P0.01)。结论:大豆异黄酮预处理能减轻大鼠脑缺血再灌损伤与提高Na+-K+-ATP酶和Ca2+-Mg2+-ATP酶活性及促进bcl-2和抑制bax的表达有关。     

玻璃体积血对兔视网膜影响的实验研究

目的　观察玻璃体积血时不同阶段丙二醛 (MDA)含量的变化及Na K ATP酶活性的变化 ,探讨玻璃体积血对视网膜的影响及机制。方法　新西兰大耳白兔 4 0只 ,右眼玻璃体内注入 0 2ml自体血作为实验组 ,左眼玻璃体内注入 0 2ml生理盐水作为对照组 ,分别于第 3、 7、 14、 2 1、 2 8天随机处死 8只 ,分离视网膜 ,制成 10 %组织匀浆检测MDA变化及Na K ATP酶活性的变化。结果　第 3、 7天 ,MDA的含量实验组与对照组相比差异无显著性意义(P >0 0 5 ) ,第 14、 2 1、 2 8天实验组较对照组升高 ,差异有显著性意义 (P <0 0 5 )。Na K ATP酶活性在第 3、 7天两组与对照组比较无显著差异意义 (P >0 0 5 ) ,第 14、 2 1、 2 8天 ,实验组Na K ATP酶活性较对照组下降 ,差异有显著性意义 (P <0 0 5 )。结论　玻璃体积血可引起视网膜脂质过氧化损害 ,损害Na K ATP酶活性。