天蓝淡红链霉菌SIPI 1482及其突变株的研究：I.发酵过程中 …

用光学显微镜和透射电子显微镜，研究天蓝淡红链霉素ＳＩＰＩ １４８２及其突变株ＳＩＰＩ １４８２－ＮＳ－４在发酵过程中细胞形态和超微结构的变化。发现两者最大的不同在于：亲株能合成柔红霉素，产抗期细胞内含物丰富，但脂肪颗粒较少；突变株不能合成柔红霉素，细胞中含有丰富的脂肪颗粒。由于柔红霉素的生物合成与脂肪酸的合成密切相关，提示超微结构中脂肪颗粒的变化可能与柔红霉素的合成有关。     

天蓝淡红链霉菌SIPI 1482及其突变株的研究：Ⅱ.钠离子？…

ＳＩＰＩ １４８２－ＢＳ－４柔红霉素产生菌天蓝淡红链霉菌ＳＩＰＩ １４８２经紫外诱变获得的阻断突变株,没有合成柔红霉素的能力。但在ＧＭ培养其中添加２％ＮａＣｌ后,该突变株的菌体生长量虽有所减少,却能恢复合成柔红霉素２２％～２４％（以亲株为对照）。研究还发现使突变株恢复合成柔红霉素起主要作用的是Ｎａ＾＋,而非离渗透压、Ｃｌ＾－１或整个ＮａＣｌ分子。     

柔红霉素生物合成调节因子的初步研究

本实验研究发现，玉米粉中存在调节柔红霉素产生菌ＳＩＰＩ－１４８２生物合成柔红霉素的因子。这种调节因子的性质可能类似于已经报道的Ｂ因子，它不仅具有恢复突变株产生柔红霉素的能力，且能明显地提高亲株ＳＩＰＩ－１４８２和另一柔红霉素产生菌ＳＩＰＩ－ＰＦ－２５的生产能力。     

质粒PIJ702转化天蓝淡红链霉菌SIPI1482菌种的条件研究

天蓝淡红链霉菌ＳＩＰＩ１４８２是一株蒽环类抗生素柔红霉素的产生菌，在建立该菌种基因工程研究所需的载体宿主系统的研究中，发现从变青链霉菌分离的质粒ＰＩＪ７０２不能直接转化ＳＩＰＩ１４８２菌种，经排除ＳＩＰＩ１４８２菌种自身内含质粒，试验了热休克衰减ＤＮＡ酶活性，不同时间培养的菌丝体制备的原生质体，ＰＥＧ１０００的浓度以及硫链丝菌素选择时间等因素对ＰＩＪ７０２转化ＳＩＰＩ１４８２菌种的影响，证实上述绪     

链霉素抗性筛选法在选育博来霉素A2组分高产菌株中的应用

应用链霉素抗性筛选法提高博来霉素产生菌Streptomycin verticillus SIPI 7011产博来霉素A2组分的产量，将经紫外线诱变处理过的博来霉素产生菌孢子涂布在含有链霉素最小抑制浓度（180μg／ml）的培养基平板上，获得了151株链霉素抗性突变株。其中博来霉素A2产量高于出发菌株的有19株，产量阳性效率达到12．6％，并获得一株产抗生素能力为出发菌株约1．25倍的突变株。     

ARTP诱变结合抗性筛选选育西索米星高产菌株

目的 利用等离子体诱变,结合抗生素抗性筛选,获得西索米星高产菌株。方法 首先通过链霉素抗性筛选,获得一株比出发菌株产抗能力高的S4;随后以S4为出发菌株,经等离子体处理40s,借助巴龙霉素抗性筛选,得到双重抗性菌株。最后对突变株进行再次诱变,并结合高浓度链霉素抗性筛选。结果 获得一株高产突变株M. inyoensis SAAP22,比出发菌株效价提高了38.18%,具有稳定的遗传性能。结论 通过等离子体诱变,结合抗生素抗性筛选,可有效提升伊尼奥小单孢菌的西索米星合成能力,所得高产菌株具有潜在应用价值。     

链霉素抗性突变理性筛选avermectin高产菌株

为提高菌株avermectin的产量，本文以链霉素抗性为选择压力，对除虫链霉菌Streptomyces avermi-tilis进行紫外诱变（253.7nm,30w，照射时间45s)，得到在摇瓶发酵水平比出发菌株产量提高25%以上的4株突变株，其中2株提高水平达30%以上，实验表明了链霉素抗性突变与产抗生素突变之间的密切联系。同时，对其机理和意义作了一些探讨。     

通过获得链霉素抗性基因(str)突变株筛选梅岭霉素高产菌株

本文通过链霉素对梅岭霉素（meilingmycin）产生菌南昌链霉菌NS－41－80菌株孢子致死浓度的测定，采用诱变剂EMS四种不同诱变剂量对菌株的孢子进行诱变处理，诱变处理的孢子涂布在含链霉素致死浓度的高氏平板上，获得了大量的链霉素抗性基因（str）突变株。然后从链霉素抗性基因突变株进一步筛选到梅岭霉素高产菌株80－5．11－221，在摇瓶条件下，只产梅岭霉素不产南昌霉素，梅岭霉素活性效价达1500μg/ml，比出发菌株NS－41－80的摇瓶发酵效价855μg/ml提高了77．9％，该菌株连续传代六代进行摇瓶发酵，其F2代和F3代梅岭霉素发酵效价稳定，F4代至F6代随着传代数增加，其梅岭霉素发酵效价急速下降。通过EMS诱变剂量分别与抗药性突变率和链霉素抗性基因突变株产梅岭霉素产量的产势统计分析表明，菌株抗药性突变与产抗生素突变密切相关，产抗生素突变的EMS诱变剂量高于链霉素抗性基因突变诱变剂量。在0．03mol/L的EMS剂量作用下，菌株致死率为99．43％，而抗药性突变率为0．0440％，建立了梅岭霉素产生菌链霉素抗性基因突变筛选方法，为南昌链霉菌高产菌种选育研究作了有益的尝试，并有助于其它链霉菌属的抗生素产生菌育种研究。     

硝吡咯菌素菌种选育

目的把一种新的方法应用于提高硝吡咯菌素工业生产菌株的生产能力。方法在硝吡咯假单胞菌中引入氨基糖苷类抗生素抗性突变 ,以提高硝吡咯菌素的生产能力。结果从含 3倍和 1 0倍MIC抗生素的GYM筛选平板上挑取抗性突变株 ,挑选出产抗能力提高 5倍以及 1 0倍以上的突变株 ;引入链霉素抗性突变对提高硝砒咯菌素的生产能力的效果最佳 ;Geniticin和庆大霉素的抗性突变对提高抗生素生产能力的效果较差 ;潮霉素抗性突变对提高抗生素生产能力具有一定的效果。结论引入氨基糖苷类抗生素抗性突变 ,可以有效提高硝吡咯菌的生产能力。     

高产纳他霉素的褐黄孢链霉菌选育

目的　以褐黄孢链霉菌 (Streptomyces gilvosporeus) S- 71为出发菌株 ,筛选纳他霉素的高产菌株。方法　紫外线对孢子悬浮液照射 4 0 s后 ,分别用链霉素抗性和琼脂块法进行筛选纳他霉素高产菌株 ,之后对高产菌株进行生产稳定性实验。结果　通过链霉素抗性法筛选获得了约 10 %的正选率突变株 ,其中突变株SG- 5 6摇瓶效价单位为 2 4 10μg/ ml,为出发菌株的 14 6 % ;通过琼脂块筛选法获得了约 1%的正选率突变株 ,其中突变株 SG- 2 0 0 2摇瓶效价单位为 2 6 5 0μg/ ml,为出发菌株的 16 1% ,该菌株无链霉素抗性标记。结论　链霉素抗性筛选和琼脂块筛选均可以获得纳他霉素的高产菌株 ,其中链霉素抗性筛选法效率高 ,琼脂块法筛选全面。     

Trichloroethylene. I. Carcinogenicity of trichloroethylene.

Trichloroethylene (TCE) as an industrial pollutant may damage human health and can be considered as carcinogen. TCE has been detected in the environment and in various human organs, e.g., liver, kidney and brain etc. There are histological alterations such as depletion of glycogen and hydropic degeneration in the liver, however, other signs of TCE effects can be found in various organs as well. TCE and its metabolites, e.g., trichlorethanol, trichloro-acetic acid and epoxides were recently identified as strong mutagens in Ames mutagenicity test inducing frameshift and base-substitution mutations. TCE induced predominantly hepatocellular carcinoma after long term administration in mice. In these animals, kidneys and liver were supposed to be primary target organs with low epoxy-hydrolase activity. A high level of mitotic gene conversion (or gene rearrangement) was indicated by the metabolism of TCE after repeated administration. Purified TCE by was a weak mutagen in the presence of S9 microsomal fraction of rats and as a consequence, the carcinogenic activity was low in the kidney of rats. However, a dose related increase of Leydig cell tumors was found in male rats.     

Trichloroethylene. II. Mechanism of carcinogenicity of trichloroethylene.

The cancer inducing effect of trichloroethylene (TCE) was studied by various methods. DNA complexing activity and apoptosis inhibition were found to be the key elements of the carcinogenicity of TCE and its metabolites. The ability of TCE to interact with DNA was low, but its incorporation into the RNA and DNA of the brain, testis, pancreas, kidney, liver, lung and spleen, cannot be excluded. Exposure to TCE and its metabolites provides a selective growth advantage to spontaneously occurring mutations in some K- and H-ras oncogenes (as non specific results of secondary DNA or RNA damage). The amount of DNA-TCE adducts was higher in mouse hepatocytes than in rat hepatocytes. These differences may explain the species difference in carcinogenicity of TCE, which was dose dependent (due to metabolism) in mice but independent in rats. The blood level kinetics of TCE confirmed the faster metabolic rate in mice, including peroxisome proliferation and induction in hepatocytes. Dichloroacetic- and trichloroacetic acid were found to be hepatic carcinogens in mice, and the specificity depends on peroxisome proliferation induction. Possibly, TCE and related compounds down regulated apoptosis in mouse liver, and the reduced ability to remove initiated cells by apoptosis could be responsible for liver cancer induction by TCE.     

Studies in antifertility agents. 11. Secosteroids. 5. Synthesis of 9,11-secoestradiol.

9,11-Secoestradiol (9) and 11-hydroxy-9,11-secoestradiol (12) have been synthesized starting from 17-acetoxyestradiol 3-methyl ether (1) and found to possess significant antifertility activity in rats. 3-Methoxy-9,11-seco-9-oxo-17beta-acetoxyestra-1,3,5(10)-trien-11-oic acid (2), prepared by CrO3 oxidation of 1, on hydrogenolysis gave methyl 17beta-hydroxy-3-methoxy-9,11-secoestra-1,3,5(10)-triene-11-carboxylate (3). The 17-O-THP derivative of 3 was treated with LiAlH4 to give 17beta-(O-tetrahydropyranyl)-3-methoxy-11-hydroxy-9,11-secoestra-1,3,5(10)-triene (5). The 11-O-mesylate of 5 on LiAlH4 reduction followed by mild acid treatment and demethylation under alkaline conditions gave 9. LiAlH4 reduction of 3 gave 9,11-seco-11-hydroxyestradiol 3-methyl ether (11) which on demethylation gave 9,11-seco-11-hydroxyestradiol (12).     

Metabolism of benzothiazole. I. Identification of ring-cleavage products.

1. The metabolic fate of benzothiazole in guinea pig has been investigated following i.p. administration at a dose of 30 mg/kg. 2. Five ring-cleavage products were identified in urinary extracts by g.l.c.-mass spectra. By reference to authentic compounds the three major metabolites were shown to be 2-methylmercaptoaniline (I), 2-methylsulphinylaniline (II) and 2-methylsulphonylaniline (III). On the basis of the mass spectrometric evidence the remaining two metabolites were postulated to be 2-methylsulphinylphenylhydroxylamine (IV) and 2-methylsulphonylphenylhydroxylamine (V). 3. I, II and III were present in conjugated and unconjugated forms; IV and V were identified only after hydrolysis with sulphatase.     

Discussion of S.G. Donald et al. and R. Davidson

Summary This paper discusses aspects of the papers by S.G. Donald et al. and R. Davidson, which were presented at The Econometrics Journal sponsored special session on the econometrics of inequality measurement, held at the Royal Economics Society Meeting in Surrey in 2010.