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31.
Fisher MJ Backer RT Husain S Hsiung HM Mullaney JT O'Brian TP Ornstein PL Rothhaar RR Zgombick JM Briner K 《Bioorganic & medicinal chemistry letters》2005,15(20):4459-4462
Substitution of the aryl sulfonamide moiety contained in MC4 agonist 1 with bicyclic heterocycles and aminotetralines produced compounds with MC4 activity. The heterocycles represent alternative privileged structures to that contained in 1. Compounds in which the polar group of the privileged structure was displayed in an endocyclic fashion were not as active as the parent agonist 1, while those with an exocyclic polar group afforded activity competitive with 1. 相似文献
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There are accurate but inconclusive data on the association between single nucleotide polymorphisms (SNPs) of interleukin (IL)-28B and sustained virological response (SVR) in chronic hepatitis C (CHC). This meta-analysis aimed to derive a more precise estimation of the effects of IL-28B SNPs locus (rs12979860 and rs8099917) on SVR in naïve CHC patients receiving pegylated interferon alpha (PEG-IFN-α) plus ribavirin. Literature search was conducted up to June, 2011, in PubMed, EMBASE and Cochrane Database of Systematic Reviews. A total of 36 studies involving 10912 cases with CHC receiving PEG-IFN-α plus ribavirin met the inclusion criteria. Analyses were stratified either by ethnicity or genotype of hepatitis C virus. In genotype 1/4 patients, rs12979860 CC was associated with high SVR in CHC patients (Caucasian: odds ratio (OR), 4.567; 95% confidence interval (CI), 3.826–5.452; Asian: OR, 4.033; 95%CI, 3.050–5.333; African American: OR, 4.297; 95%CI, 2.168–8.515; Hispanics: OR, 4.350; 95%CI, 2.817–6.717) but had no effect in genotype 2/3. In Caucasian (genotype 1/4: OR, 2.542; 95%CI, 2.108–3.065; genotype 2/3: OR, 1.363; 95%CI, 1.020–1.820) and Asian (genotype 1/4: OR, 5.214; 95%CI, 3.694–7.360; genotype 2/3: OR, 1.785; 95%CI, 1.095–2.910), rs8099917 TT was associated with high SVR in both genotype 1/4 and 2/3. Meta-regression showed that in Caucasians with CHC genotype 1/4, gender male might contribute to the effect of rs12979860 on SVR but advanced fibrosis might weaken this effect. Furthermore, in Asians with CHC genotype 1/4, high baseline viral load and advanced fibrosis might also undermine the effect of rs8099917 on SVR. This meta-analysis suggested that IL-28B rs12979860 CC and rs8099917 TT were associated with high SVR rate in CHC genotype 1/4. In CHC genotype 2/3, rs8099917 TT carriers also had higher SVR. 相似文献
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Effects of second-codon mutations on expression of the insulin-like growth factor-II-encoding gene in Escherichia coli 总被引:1,自引:0,他引:1
Expression plasmids encoding random sequence mutant proteins of insulin-like growth factor II (IGFII) were constructed by cassette mutagenesis, to improve the efficiency of IGFII synthesis in Escherichia coli. A pool of oligodeoxyribonucleotide linkers containing random trinucleotide sequences were used to introduce second-codon substitutions into the gene encoding Met-Xaa-Trp-IGFII in expression vectors. E. coli RV308 cells transformed with these vectors synthesized IGFII at levels varying from 0-22% of total cell protein. This variable synthesis is a function of the random second-codon sequence and its corresponding amino acid, Xaa. Our data showed that mRNA stability, protein stability and translational efficiency all contributed to variable expression levels of Met-Xaa-Trp-IGFII in E. coli. Furthermore, an efficiently synthesized IGFII mutant protein, Met-His-Trp-IGFII, was converted to natural sequence IGFII by a simple oxidative cleavage reaction. 相似文献
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通过采样调查法和烘干称重法,对分布在青藏高原东缘不同海拔高度的禾叶风毛菊的繁殖分配的特征进行研究。结果表明:(1)随着海拔的升高,禾叶风毛菊的个体大小、营养器官生物量、繁殖器官生物量、个体管状小花数目、雄蕊质量均与海拔呈负相关关系(P<0.01);繁殖分配、管状小花生物量、雌蕊质量均与海拔呈正相关关系(P<0.01);(2)繁殖分配是依赖个体大小的,个体越大,繁殖分配越小(P<0.01);(3)禾叶风毛菊个体管状小花的数目及重量(P<0.05)、雌雄蕊重量(P<0.05)之间存在权衡关系。由此推论:(1)海拔作为外界因子对禾叶风毛菊花期各生物量及繁殖分配有显著的影响,但海拔并不是影响禾叶风毛菊繁殖分配唯一生态因子,植株个体大小也与其繁殖分配策略密切相关;(2)禾叶风毛菊的垂直分布的特征很有可能就是海拔通过影响植株个体大小变化来完成的。 相似文献
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