目的:对ATP6V1H内含子区域的4个目标SNPs(rs2376011,rs4738884,rs10435587,rs41321146)等位基因进行深度分析,并探讨这些SNPs的生物学意义。方法:运用3DSNP数据库、LncSNP 2.0数据库、LNCipedia version 5.2、NCBI网站信息及RPIseq数据...目的:对ATP6V1H内含子区域的4个目标SNPs(rs2376011,rs4738884,rs10435587,rs41321146)等位基因进行深度分析,并探讨这些SNPs的生物学意义。方法:运用3DSNP数据库、LncSNP 2.0数据库、LNCipedia version 5.2、NCBI网站信息及RPIseq数据库等多种信息分析方法对4个SNPs的生物学信息及相关lncRNA的功能进行预测。结果:该4个SNPs位于8号染色体,其等位基因频率在亚洲人群约0.35,高于国际平均水平(约0.18)。染色质状态预测发现其中3个SNPs在不同组织或细胞的ATP6V1H中定位于增强子区域,可通过形成约800 kb的染色质环与NPBWR1进行三维交互作用。采用LncSNP2.0预测分析发现,rs4738884和rs10435587位于lncRNA编码基因NONHSAG050234和lnc-TCEA1-3之上,而lnc-TCEA1-3与ATP6V1H存在较强的相互作用,与自闭症和冠状动脉疾病的发生发展相关。结论:4个内含子区域SNPs通过增强子效应与lncRNA影响基因表达及相关功能。展开更多
The immune efficiency of a recombinant adenovirus type 5 with type 35 fiber containing HIV-1 gag gene (rAd5/F35-mod.gag) was investigated in BALB/c mice, in which the rAd5/F35-mod.gag was firstly identified with PCR, ...The immune efficiency of a recombinant adenovirus type 5 with type 35 fiber containing HIV-1 gag gene (rAd5/F35-mod.gag) was investigated in BALB/c mice, in which the rAd5/F35-mod.gag was firstly identified with PCR, then transfected to 293 cells and the in vitro expression level of Gag protein was determined by Western blotting and indirect immuno-fluorescent assay. Mice were immunized with intramuscular injections of rAd5/F35-mod.gag, rAd5-mod.gag or DNA and were boosted after 3 weeks. To test the effect of pre-existing anti-viral immunity on immunization, mice were also injected with Ad5-GFP vector and then immunized 4 and 7 weeks later with Ad5/F35-mod. gag vector. The P24-specific IgG antibody in sera of immunized mice was determined by ELISA and the specific cytotoxic T lymphocyte (CTL) response was assayed by intracellular cytokine staining. It was demonstrated that the rAd5/F35-mod. gag vector could express efficiently the HIV Gag protein in 293 cells in vitro and induce strong HIV-specific immune responses in vivo. The strongest CTL and serum IgG response occurred when mice were immunized twice with injection of rAd5/F35 alone, but the anti-Ad5 antibody after primary infection with adenovirus could inhibit the specific immune responses induced by rAd5/F35 vector. It is concluded that single immunization with recombinant adenovirus rAd5/F35-mod. gag can induce specific CTL and serum IgG antibody responses in mice, but the immunogenicity of rAd5/F35 is comparably weaker than that of rAd5.展开更多
采用分子表面随机采样分析对26个香豆素类衍生物抗艾滋病药物进行定量构效关系研究。运用多元线性回归(multiple linear regression,MLR)建模,同时采用内部及外部双重验证的办法对所得模型稳定性能进行深入分析和检验。MLR建模的复相关...采用分子表面随机采样分析对26个香豆素类衍生物抗艾滋病药物进行定量构效关系研究。运用多元线性回归(multiple linear regression,MLR)建模,同时采用内部及外部双重验证的办法对所得模型稳定性能进行深入分析和检验。MLR建模的复相关系数(_(cum)~2)、留一法(1eave-one-out,LOO)交互校验(cross-validation,CV)复相关系数(Q_(CV)~2)和外部样本校验复相关系数r^2(test)分别为0.936、0.894、0.772。结果表明,RASMS能较好表征香豆素类衍生物抗艾滋病药物分子的结构信息,且所建模型具有良好稳定性和预测能力,可用于研发新型HIV整合酶抑制剂。展开更多
文摘目的:对ATP6V1H内含子区域的4个目标SNPs(rs2376011,rs4738884,rs10435587,rs41321146)等位基因进行深度分析,并探讨这些SNPs的生物学意义。方法:运用3DSNP数据库、LncSNP 2.0数据库、LNCipedia version 5.2、NCBI网站信息及RPIseq数据库等多种信息分析方法对4个SNPs的生物学信息及相关lncRNA的功能进行预测。结果:该4个SNPs位于8号染色体,其等位基因频率在亚洲人群约0.35,高于国际平均水平(约0.18)。染色质状态预测发现其中3个SNPs在不同组织或细胞的ATP6V1H中定位于增强子区域,可通过形成约800 kb的染色质环与NPBWR1进行三维交互作用。采用LncSNP2.0预测分析发现,rs4738884和rs10435587位于lncRNA编码基因NONHSAG050234和lnc-TCEA1-3之上,而lnc-TCEA1-3与ATP6V1H存在较强的相互作用,与自闭症和冠状动脉疾病的发生发展相关。结论:4个内含子区域SNPs通过增强子效应与lncRNA影响基因表达及相关功能。
文摘The immune efficiency of a recombinant adenovirus type 5 with type 35 fiber containing HIV-1 gag gene (rAd5/F35-mod.gag) was investigated in BALB/c mice, in which the rAd5/F35-mod.gag was firstly identified with PCR, then transfected to 293 cells and the in vitro expression level of Gag protein was determined by Western blotting and indirect immuno-fluorescent assay. Mice were immunized with intramuscular injections of rAd5/F35-mod.gag, rAd5-mod.gag or DNA and were boosted after 3 weeks. To test the effect of pre-existing anti-viral immunity on immunization, mice were also injected with Ad5-GFP vector and then immunized 4 and 7 weeks later with Ad5/F35-mod. gag vector. The P24-specific IgG antibody in sera of immunized mice was determined by ELISA and the specific cytotoxic T lymphocyte (CTL) response was assayed by intracellular cytokine staining. It was demonstrated that the rAd5/F35-mod. gag vector could express efficiently the HIV Gag protein in 293 cells in vitro and induce strong HIV-specific immune responses in vivo. The strongest CTL and serum IgG response occurred when mice were immunized twice with injection of rAd5/F35 alone, but the anti-Ad5 antibody after primary infection with adenovirus could inhibit the specific immune responses induced by rAd5/F35 vector. It is concluded that single immunization with recombinant adenovirus rAd5/F35-mod. gag can induce specific CTL and serum IgG antibody responses in mice, but the immunogenicity of rAd5/F35 is comparably weaker than that of rAd5.
文摘采用分子表面随机采样分析对26个香豆素类衍生物抗艾滋病药物进行定量构效关系研究。运用多元线性回归(multiple linear regression,MLR)建模,同时采用内部及外部双重验证的办法对所得模型稳定性能进行深入分析和检验。MLR建模的复相关系数(_(cum)~2)、留一法(1eave-one-out,LOO)交互校验(cross-validation,CV)复相关系数(Q_(CV)~2)和外部样本校验复相关系数r^2(test)分别为0.936、0.894、0.772。结果表明,RASMS能较好表征香豆素类衍生物抗艾滋病药物分子的结构信息,且所建模型具有良好稳定性和预测能力,可用于研发新型HIV整合酶抑制剂。
