R-loop的调控及其生理功能

R环（R-loop）是一种DNA∶RNA杂合链（DNA∶RNA hybrids）,由一条RNA单链侵入双链DNA,与其中一条DNA模板链结合,从而释放出一条DNA单链而产生。R-loop在细胞生命活动中扮演着重要角色,与基因组稳定性、转录调控,以及表观修饰等重要生物学过程有着密不可分的关系。很多因素参与对R-loop的调控,例如RNA转录和加工、染色体的修饰、DNA损伤反应等;同时,许多酶蛋白,如核糖核酸酶、解旋酶和拓扑异构酶等也参与调节细胞内的R-loop水平。了解R-loop的调控机制及其生物学功能有助于更好地理解基因组稳定性的维持机制,为治疗骨髓增生异常综合征、白血病、乳腺癌、前列腺癌等疾病开拓新思路。     

新型表达载体 pEC34 试用于人 γ 干扰素基因的高表达

构建了一个新的双顺反子表达载体ｐＥＣ３４,它的第一个顺反子是已高表达的ｅｒａ基因的部分序列,并带有原核翻译增强子。当检测ｐＥＣ３４的可用性时,获得了人γ－干扰素的极高表达。目的蛋白占菌体总蛋白的８５．５％,诱导后经ＳＤＳ－ＰＡＧＥ分析,出现分子量为１５．５ｋＤａ左右的蛋白表达带。Ｗｅｓｔｅｒｎ ｂｌｏｔ结果证实为人γ－干扰素。无压力传代３０次表达质粒仍然稳定,表明ｐＥＣ３４可能用作真核蛋白质高表达     

Macrophage migration inhibitory factor in the regulation of myoblast proliferation and differentiation

Obesity is documented to be a state of chronic mild inflammation associated with increased macrophage infiltration into adipose tissue and liver and skeletal muscle. As a pleiotropic inflammatory mediator, macrophage migration inhibitory factor (MIF) is associated with metabolic disease, so MIF may signal molecular links between adipocytes and myocytes. MIF expression was modified during myoblast differentiation, but the role of MIF during this process is unclear. C2C12 cells were transfected with MIF to investigate their role during differentiation. MIF expression attenuated C2C12 differentiation. It did not change proliferation, but downregulated cyclin D1 and CDK4, causing cell accumulation in the G1 phase. p21 protein was increased significantly and MyoD, MyoG, and p21 mRNA also increased significantly in the C2C12 cells treated with ISO-1, suggesting that inhibition of MIF promotes differentiation. MIF inhibits the myoblast differentiation by affecting the cell cycle progression, but does not affect proliferation.     

QRAR models for cardiovascular system drugs using biopartitioning micellar chromatography

The capability of biopartitioning micellar chromatography (BMC) to describe and estimate pharmacological parameters of cardiovascular system drugs has been studied. The retention of cardiovascular system drugs was studied using different pH of Brij-35 as micellar mobile phase in modified C(18) stationary phase. Quantitative retention-activity relationships (QRAR) in BMC were investigated for these compounds. An adequate correlation between the retention factors (log k) and the toxicity (LD(50)) of cardiovascular system drugs was obtained.     

The blood system and the organism adaptation to extreme factor

The formation of blood system adoptive reaction in many cases is defined by the type of action and the condition of hemopoietic inductive microenvironment: hemodynamics of hemopoietic tissue, functional conditions of bone marrow macrophages, mast cells and glycosaminoglycans content. The shift in hemodlobin fraction occurs in extreme conditions requiring an increased gas transport by the blood. In case of tissue lesion, lymphocytes stimulate their regeneration. Morphogenetic function of lymphoid cells may be alerted by immunomodulators. Blood cells participate in angiogenesis, and this property may be used for vessel grafts production.     

L-精氨酸和/或维生素E对高脂膳家兔脂质过氧化损伤的保护作用

目的：通过脂质过氧化物（LPO）、谷胱甘肽过氧化物酶（GSH－PX）、超氧化物歧化酶（SOD）以及一氧化氮合酶（NOS）M定探讨L－精氨酸（L－Arg）（35kg／kg）和／或维生素E（74mg／kg）对高脂膳诱发的新西兰纯种白兔实验性动脉粥样硬化形成的多脏器各生化指标（包括LPO、GSH－PX、SOD及NOS活性）的影响。方法：成年新西兰家兔随机分为正常对照组：（基础饲料加普通饮水）高脂对照组：（高脂饲料加普通饮水）L－Ars组：（高脂饲料加含有L－Ars35kg／kg饮水）L－Arg＋VE组（高脂饲料加含有L－Arg35kg／kg再加VE74mg／kg饮水）VE组（高脂饲料加含有VE74mg／kg饮水）观察12周。结果：L－精氨酸和／或维生素E能有效地抑制脂质过氧化损伤增强SOD、NOS和GSH－PX活性,提高机体抗氧化能力及减轻动脉粥样硬化形成的作用。结论：这些变化可能在动脉粥样硬化的发生发展中起重要作用。     

Evaluation of biogenic and anthropogenic inputs of aliphatic hydrocarbons to Lake Taihu sediments using biomarkers

Surficial sediments from 13 sites throughout Lake Taihu, one of the largest urbanized freshwater lake systems in China, were analyzed for biomarkers (e.g., n-alkanes and hopanes) to track the origin of organic inputs (biogenic or anthropogenic), and, thus, to identify any ‘hot spots’ of hydrocarbon contamination. A distinct spatial distribution of aliphatic hydrocarbons in sediments was observed in Lake Taihu. At the northern tip of the lake (i.e., Meiliang and Wuli Bays), the highest mean aliphatic hydrocarbon concentration, with a significant contribution of an unresolved complex mixture (UCM), was found, indicating possible anthropogenic petroleum contamination (mainly from untreated and partially treated industrial and domestic sewage from Wuxi, Changzhou and other cities). This was supported by the n-alkane indices (e.g., small Carbon Preference Index and odd-to-even values) and a high degree of maturity of the hopane biomarkers. However, hydrocarbons from East Taihu were mainly biogenic, with the lowest mean concentrations, negligible or no contribution of UCM, abundance of vascular plant C₂₃–C₃₃ n-alkanes with a high odd-to-even predominance, and the presence of biogenic hopanes (e.g., 17β(H), 21β(H)-hopanes and hopenes). In the other areas of the lake, however, the predominance of biogenic in combination with petrogenic hydrocarbons was indicated by the biomarkers.     

The antiviral drug ribavirin is a selective inhibitor of S-adenosyl-L-homocysteine hydrolase from Trypanosoma cruzi

Ribavirin (1,2,4-triazole-3-carboxamide riboside) is a well-known antiviral drug. Ribavirin has also been reported to inhibit human S-adenosyl-L-homocysteine hydrolase (Hs-SAHH), which catalyzes the conversion of S-adenosyl-L-homocysteine to adenosine and homocysteine. We now report that ribavirin, which is structurally similar to adenosine, produces time-dependent inactivation of Hs-SAHH and Trypanosoma cruzi SAHH (Tc-SAHH). Ribavirin binds to the adenosine-binding site of the two SAHHs and reduces the NAD(+) cofactor to NADH. The reversible binding step of ribavirin to Hs-SAHH and Tc-SAHH has similar K(I) values (266 and 194 microM), but the slow inactivation step is 5-fold faster with Tc-SAHH. Ribavirin may provide a structural lead for design of more selective inhibitors of Tc-SAHH as potential anti-parasitic drugs.