叶绿体硫氧还蛋白调控谷氨酸-1-半醛氨基转移酶氧化还原状态的研究

5-氨基乙酰丙酸(5-aminolevulinic acid,ALA)是四吡咯化合物合成的前体分子,它以谷氨酰-tRNA为底物经过一个两步反应形成,分别由谷氨酰-tRNA还原酶(glutamyl-tRNA reductase,GLTR)与谷氨酸-1-半醛氨基转移酶(Glutamate-1-semialdehyde aminotransferase,GSAAT)催化。GSAAT作为调控ALA合成的酶之一,对四吡咯化合物的合成起着至关重要的作用。硫氧还蛋白是一类小分子量的氧化还原蛋白(大约12kD)。它们介导其靶蛋白中半胱氨酸的二硫键与巯基之间的转变从而调控其靶蛋白的功能和稳定性。酵母双杂交试验结果显示,GSAAT与叶绿体硫氧还蛋白F(Thioredoxin-F)发生相互作用。利用VIGS技术沉默豌豆叶片中的叶绿体硫氧还蛋白基因,借助Western Blotting分析体内GSAAT的氧化还原状态,发现叶绿体硫氧还蛋白基因的沉默影响了GSAAT的氧化还原状态。     

牛羊朊蛋白基因（PRNP）多态性与抗病性的研究进展

 朊蛋白（PRNP）是近年来造成人和部分哺乳动物传染性海绵状脑病(TSE)的主要根源,该基因的多态性显著影响了人和动物对TSE的易感性或抗病性。本文分析了朊蛋白基因及其编码蛋白的结构与功能;简要介绍了绵羊基因编码区突变与致病性的关系;系统分析了牛科动物启动子区域内23bp的插入/缺失、第一内含子区域内12bp的插入/缺失及其与疯牛病（BSE）抗病性的作用机制;全面总结了全球已经报道的牛科动物12和23bp插入/缺失的等位基因与单倍体频率,评价了其发病的可能性。该研究将为牛的分子育种提供指导。     

Genetic mapping of quantitative trait loci for the stigma exsertion rate in rice(Oryza sativa L.)

The efficiency of hybrid rice seed production can be improved by increasing the percentage of exserted stigmas. To identify quantitative trait loci(QTLs) for this trait, we conducted QTL mapping using 75 chromosome segment substitution lines(CSSLs) developed from a cross between the donor parent, Xieqingzao B(XQZB), a maintainer line which has high stigma exsertion and the recurrent parent, Zhonghui 9308(ZH9308), a restorer line which has low stigma exsertion. A total of nine QTLs(qSSE5, qSSE10, qSSE11, qDSE10, qDSE11, qTSE5, qTSE6, qTSE10, and qTSE11) for single stigma exsertion(SSE), dual stigma exsertion(DSE) and total stigma exsertion(TSE) were assessed in two environments(Hainan and Zhejiang). Six of these QTLs(qSSE10, qSSE11, qDSE10, qDSE11, qTSE10, and qTSE11) were found in both environments, while one QTL(qTSE6) was found in only Hainan, and two QTLs(qSSE5 and qTSE5) were found in only Zhejiang. The qSSE10, qSSE11, qDSE10, qDSE11, qTSE6, qTSE10, and qTSE11 alleles, which are derived from the parent XQZB, exhibited a positive additive effect. In contrast, the qSSE5 and qTSE5 alleles, which are derived from the parent ZH9308, exhibited a negative additive effect. The SSE, DSE and TSE traits were significantly correlated with each other in an environmentally dependent manner. These results indicated that the lines showing higher values for SSE were more likely to exhibit increased values for DSE, which would ultimately increase TSE. To evaluate the advantage of exserted stigmas for cross-pollination, single, dual and total stigma exsertion should be considered separately in future attempts at genetic improvement to achieve increased production of rice hybrid seeds. This study also provides information for fine mapping, gene cloning and particularly marker-assisted selection(MAS), on the latter and with an emphasis the phenotypic effects and implications of the QTLs for practical use in hybrid rice breeding.     

Bacteriophytochromes: phytochrome-like photoreceptors from nonphotosynthetic eubacteria

Phytochromes are a family of photoreceptors used by green plants to entrain their development to the light environment. The distribution of these chromoproteins has been expanded beyond photoautotrophs with the discovery of phytochrome-like proteins in the nonphotosynthetic eubacteria Deinococcus radiodurans and Pseudomonas aeruginosa. Like plant phytochromes, the D. radiodurans receptor covalently binds linear tetrapyrroles autocatalytically to generate a photochromic holoprotein. However, the attachment site is distinct, using a histidine to potentially form a Schiff base linkage. Sequence homology and mutational analysis suggest that D. radiodurans bacteriophytochrome functions as a light-regulated histidine kinase, which helps protect the bacterium from visible light.     

鱼饲料中植物原料抗营养因子的研究

综述了植物原料抗营养因子的种类、化学性质、对鱼的影响和消除方法。鱼饲料中常用的植物原料含有影响蛋白质、矿物质、维生素、能量和其它物质利用的五大类抗营养因子。蛋白酶抑制因子、植酸、凝集素、致甲状腺肿物(goitrogens)和抗维生素因子等为热敏抗营养物;皂苷、非淀粉多糖、抗原性蛋白和某些酚化物为热稳性抗营养物。它们能抑制酶的活性,产生毒素,结合有益物质,影响鱼类的代谢。概述了消除植物原料中抗营养因子的物理(热、压、光等)、化学(药物)和生物(发酵、育种等)方法及合理用量。     

4,4'-二硝基-2,2'-联咪唑及其铜配合物的合成·表征及与DNA相互作用研究

[目的]研究4-硝基咪唑衍生物及其配合物与DNA的相互作用,为药物的定向合成提供理论基础。[方法]合成4,4'-二硝基-2,2'-联咪唑及其铜配合物,对其性质进行表征,并以紫外光谱、荧光光谱及黏度法初步研究配体及其配合物与小牛胸腺DNA之间的相互作用。[结果]元素分析、IR、UV及摩尔电导率等数据表明4,4'-二硝基-2,2'-联咪唑与铜发生了配位;配体及配合物与DNA作用后其紫外光谱和荧光光谱都发生了一定变化,两者对DNA黏度也有不同的影响。[结论]配合物的可能组成为Cu[(NO2)2biim]2SO4.2H2O,配体及其配合物与小牛胸腺DNA之间的相互作用方式分别为非经典插入式和部分插入式。     

微生物生物转化甾体化合物生产雄烯二酮研究进展

雄烯二酮(AD)和雄二烯二酮(ADD)是甾体激素类药物重要的中间体,目前以微生物植物甾醇生物转化生产AD(D)是研究的热点,综述了微生物生物转化植物甾醇生产雄烯二酮的研究进展.     

Mass spectrometry sampling under ambient conditions with desorption electrospray ionization

A new method of desorption ionization is described and applied to the ionization of various compounds, including peptides and proteins present on metal, polymer, and mineral surfaces. Desorption electrospray ionization (DESI) is carried out by directing electrosprayed charged droplets and ions of solvent onto the surface to be analyzed. The impact of the charged particles on the surface produces gaseous ions of material originally present on the surface. The resulting mass spectra are similar to normal ESI mass spectra in that they show mainly singly or multiply charged molecular ions of the analytes. The DESI phenomenon was observed both in the case of conductive and insulator surfaces and for compounds ranging from nonpolar small molecules such as lycopene, the alkaloid coniceine, and small drugs, through polar compounds such as peptides and proteins. Changes in the solution that is sprayed can be used to selectively ionize particular compounds, including those in biological matrices. In vivo analysis is demonstrated.     

含硒化合物联合医用长春新碱应用对艾氏腹水癌的抑制机制

为寻找医治艾氏腹水癌的新型制剂,并评价药效,对小鼠腹腔注射肿瘤细胞,建立荷艾氏腹水癌细胞(EAC)的小鼠模型;并于接种后第7天开始用抗癌药,观察荷瘤小鼠(接种EAC后产生血性腹水的小鼠)的生存周期,通过对动物体内抗氧化水平指标(SOD、GSH、MDA)的检测,判定硒化合物的保护作用;用流式细胞术及对细胞进行DNA梯检测,评估药物对肿瘤细胞调亡的影响。结果表明含硒化合物,尤其是有机硒化合物,甲基硒代半胱氨酸(SeMC)与抗癌药长春新碱联合应用可使荷瘤小鼠的生存期延长、机体的抗氧化水平升高及肿瘤细胞凋亡率增多,较对照组有显著差异(P<0.01)。研究认为,含硒化合物与医用长春新碱联用对荷瘤小鼠的保护性,主要是出于硒的抗氧化能力,以及使长春新碱促进肿瘤细胞的凋亡来实现的。     

澳大利亚厚皮海绵化学成分分离鉴定及其抗肿瘤活性研究

为进一步探求澳大利亚厚皮海绵Craniella australiensis在海洋药物研制中的作用,采用硅胶柱层析及Sephadex LH-20凝胶过滤层析等技术,从澳大利亚厚皮海绵乙酸乙酯层浸膏中分离纯化出两种化合物,并通过波谱数据与文献对照的方法对化合物进行了结构鉴定,采用CCK-8法对2个化合物进行体外抗肿瘤细胞活性试验。结果表明:从澳大利亚厚皮海绵分离得到的2个化合物分别为Aldisin和2-Bromoaldisin;体外抗肿瘤细胞活性试验显示,化合物Aldisin和2-Bromoaldisin对人克隆结肠腺癌细胞(Caco-2)、人结肠癌细胞(HCT116)、人肝癌细胞(7721)、人胶质瘤细胞(U251)和人肾癌细胞(A498)均具有抑制活性的作用,其中化合物Aldisin处理7721细胞的IC50为(67.56±3.06)μg/m L,抑制作用显著。研究表明,两种化合物属于天然产物,可作为潜在的抗肿瘤药物进行进一步研究。     

Anticonvulsant medications extend worm life-span

Genetic studies have elucidated mechanisms that regulate aging, but there has been little progress in identifying drugs that delay aging. Here, we report that ethosuximide, trimethadione, and 3,3-diethyl-2-pyrrolidinone increase mean and maximum life-span of Caenorhabditis elegans and delay age-related declines of physiological processes, indicating that these compounds retard the aging process. These compounds, two of which are approved for human use, are anticonvulsants that modulate neural activity. These compounds also regulated neuromuscular activity in nematodes. These findings suggest that the life-span-extending activity of these compounds is related to the anticonvulsant activity and implicate neural activity in the regulation of aging.     

Ascorbate-nitrite reaction: possible means of blocking the formation of carcinogenic N-nitroso compounds

The formation of carcinogenic N-nitroso compounds by the chemical reaction between nitrous acid and oxytetracycline, morpholine, piperazine, N-methylaniline, methylurea, and (in some experiments) dimethylamine was blocked by ascorbic acid. The extent of blocking depended on the compound nitrosated and on the experimental conditions. Urea and ammonium sulfamate were less effective as blocking agents. The possibility of in vivo formation of carcinogenic N-nitroso compounds from drugs could be lessened by the combination of such drugs with the ascorbic acid.     

盾叶薯蓣提取物对鱼类指环虫的杀灭效果

以寄生在金鱼Carassius auratus鳃部的中型指环虫Dactylogyrus intermedius为指示寄生虫,采用活体感染、活体杀虫的方法,研究了用不同溶剂（石油醚（沸程60-90℃）、氯仿、乙酸乙酯、乙醇和水）分别对盾叶薯蓣Dioscorea zingiberensis进行提取,其5种提取物的杀虫活性。结果表明,盾叶薯蓣的杀虫活性部位是乙醇提取物。将乙醇提取物与甲苯咪唑、伊维菌素、阿维菌素和吡喹酮4种原料药的杀虫效果进行比较,结果表明：盾叶薯蓣乙醇提取物的最高杀虫浓度为17.0 mg/L,平均最高杀虫率为99.37%;其次是甲苯咪唑和吡喹酮,最高杀虫浓度分别为3.4、6.2 mg/L时,平均最高杀虫率分别为99.01%和95.39%;而伊维菌素、阿维菌素对中型指环虫无明显的杀灭作用。盾叶薯蓣乙醇提取物对斑马鱼Brachydanio rerio的24、48、96 h的半致死浓度（LC50）分别为53.47、34.05、19.34 mg/L。     

抗肿瘤药用植物及其内生菌活性代谢产物的研究

综述近年来药用植物及其内生菌抗肿瘤活性代谢产物的研究成果。药用植物内生菌的次生代谢产物中,具有抗肿瘤作用的成分主要包含萜类化合物、生物碱类化合物、苯丙素类化合物、黄酮类化合物等多种活性物质,该研究结果为利用药用植物内生菌开发抗癌药物提供一条新的途径。     

Imaging of Plasmodium liver stages to drive next-generation antimalarial drug discovery

Most malaria drug development focuses on parasite stages detected in red blood cells, even though, to achieve eradication, next-generation drugs active against both erythrocytic and exo-erythrocytic forms would be preferable. We applied a multifactorial approach to a set of >4000 commercially available compounds with previously demonstrated blood-stage activity (median inhibitory concentration < 1 micromolar) and identified chemical scaffolds with potent activity against both forms. From this screen, we identified an imidazolopiperazine scaffold series that was highly enriched among compounds active against Plasmodium liver stages. The orally bioavailable lead imidazolopiperazine confers complete causal prophylactic protection (15 milligrams/kilogram) in rodent models of malaria and shows potent in vivo blood-stage therapeutic activity. The open-source chemical tools resulting from our effort provide starting points for future drug discovery programs, as well as opportunities for researchers to investigate the biology of exo-erythrocytic forms.     

Targeting tyrosine kinases in cancer: the second wave

One of the most exciting developments in cancer research in recent years has been the clinical validation of molecularly targeted drugs that inhibit the action of pathogenic tyrosine kinases. Treatment of appropriately selected patients with these drugs can alter the natural history of their disease and improve survival. The clinical validation of these "first-generation" tyrosine kinase inhibitors has been the prelude to a second wave of advances in molecular targeting that is expected to further change the way we classify and treat cancer. Efforts are now being directed at identifying the tumor subtypes and patients who will benefit the most from these drugs. In addition, new compounds that circumvent acquired resistance to the first-generation tyrosine kinase inhibitors are being tested in patients with refractory disease. Agents directed against new molecular targets are also being explored.     

Crystal structures of human cytochrome P450 3A4 bound to metyrapone and progesterone

Cytochromes P450 (P450s) metabolize a wide range of endogenous compounds and xenobiotics, such as pollutants, environmental compounds, and drug molecules. The microsomal, membrane-associated, P450 isoforms CYP3A4, CYP2D6, CYP2C9, CYP2C19, CYP2E1, and CYP1A2 are responsible for the oxidative metabolism of more than 90% of marketed drugs. Cytochrome P450 3A4 (CYP3A4) metabolizes more drug molecules than all other isoforms combined. Here we report three crystal structures of CYP3A4: unliganded, bound to the inhibitor metyrapone, and bound to the substrate progesterone. The structures revealed a surprisingly small active site, with little conformational change associated with the binding of either compound. An unexpected peripheral binding site is identified, located above a phenylalanine cluster, which may be involved in the initial recognition of substrates or allosteric effectors.     

食品动物组织中兽药结合残留的毒性

动物性食品中兽药残留对人类健康的影响日益被人们所重视。动物用药后,其体内可能存在两类残留:第一类是以游离或结合形式存在的原药及其主要代谢物;除高亲脂性化合物外,因代谢和排泄迅速,这些代谢物出现得早,且不在动物体内蓄积。但这些物质具有毒性,且在人体内可生成高度活化的中间产物（亲电子基团、自由基等）,导致核酸、蛋白质烷基化、膜脂质过氧化等,从而对消费者具有潜在的危害性;第二类包括出现较晚的共价结合代谢物（结合残留）,其排出相对较慢。它们的存在对于靶动物预示着潜在的毒性作用,而对于消费者,由于结合残留在人体内不可能再活化,以及其生物利用度和含量均低,因而可能只显示很低的毒性。     

三萜与苦木味素类天然产物抗马铃薯Y病毒的活性研究

采用适时荧光定量聚合酶链式反应技术,以培育2个月的普通烟草为材料,对从药用植物苦楝中分离得到的8种三萜类成分与从臭椿中分离得到的7种苦木味素类成分进行抗马铃薯Y病毒的活性研究,结果表明：（1）3个三萜类成分(methylkulonate, dubionel B, isotoosendanin)与3个苦木味素萜类成分(ailanthone, chaparrinone, shinjudilactone)显示出比较强的抗病毒活性;（2）三萜类成分结构中C-20位的羧基与C-16位的羟基为活性基团;（3）苦木味素萜类成分结构中A环的α,β-不饱和酮为活性必需基团,此外C-15位酯基侧链的引入可增强活性。该研究对这15种天然产物来说为首次进行抗马铃薯Y病毒的报道,其构效关系的研究可为新型抗植物病毒药物的设计提供信息。     

Methylene-C14-dioxyphenyl compounds: metabolism in relation to their synergistic action

The methylene-C(14) group is hydroxylated yielding formate-C(14) in the microsome-reduced nicotinamide-adenine dinucleotide phosphate system in vitro and yielding expired C(14)O(2), in living mice and houseflies. Methylenedioxyphenyl compounds apparently serve as alternate substrates for this enzymatic hydroxylation system of microsomes, and thus reduce the rate of metabolism and prolong the action of certain drugs and insecticide chemicals.