Unconventional Sequence Requirement for Viral Late Gene Core Promoters of Murine Gammaherpesvirus 68

Infection with the human gammaherpesviruses, Epstein-Barr virus (EBV) and Kaposi''s sarcoma-associated herpesvirus (KSHV), is associated with several cancers. During lytic replication of herpesviruses, viral genes are expressed in an ordered cascade. However, the mechanism by which late gene expression is regulated has not been well characterized in gammaherpesviruses. In this study, we have investigated the cis element that mediates late gene expression during de novo lytic infection with murine gammaherpesvirus 68 (MHV-68). A reporter system was established and used to assess the activity of viral late gene promoters upon infection with MHV-68. It was found that the viral origin of lytic replication, orilyt, must be on the reporter plasmid to support activation of the late gene promoter. Furthermore, the DNA sequence required for the activation of late gene promoters was mapped to a core element containing a distinct TATT box and its neighboring sequences. The critical nucleotides of the TATT box region were determined by systematic mutagenesis in the reporter system, and the significance of these nucleotides was confirmed in the context of the viral genome. In addition, EBV and KSHV late gene core promoters could be activated by MHV-68 lytic replication, indicating that the mechanisms controlling late gene expression are conserved among gammaherpesviruses. Therefore, our results on MHV-68 establish a solid foundation for mechanistic studies of late gene regulation.     

Nitrosothiol Formation and Protection against Fenton Chemistry by Nitric Oxide-induced Dinitrosyliron Complex Formation from Anoxia-initiated Cellular Chelatable Iron Increase

Dinitrosyliron complexes (DNIC) have been found in a variety of pathological settings associated with ^•NO. However, the iron source of cellular DNIC is unknown. Previous studies on this question using prolonged ^•NO exposure could be misleading due to the movement of intracellular iron among different sources. We here report that brief ^•NO exposure results in only barely detectable DNIC, but levels increase dramatically after 1–2 h of anoxia. This increase is similar quantitatively and temporally with increases in the chelatable iron, and brief ^•NO treatment prevents detection of this anoxia-induced increased chelatable iron by deferoxamine. DNIC formation is so rapid that it is limited by the availability of ^•NO and chelatable iron. We utilize this ability to selectively manipulate cellular chelatable iron levels and provide evidence for two cellular functions of endogenous DNIC formation, protection against anoxia-induced reactive oxygen chemistry from the Fenton reaction and formation by transnitrosation of protein nitrosothiols (RSNO). The levels of RSNO under these high chelatable iron levels are comparable with DNIC levels and suggest that under these conditions, both DNIC and RSNO are the most abundant cellular adducts of ^•NO.     

中药联合微生态制剂防治呼吸、消化系统病毒病

本文阐述了中药防治病毒病的历史及其应用概况,中药联合微生态制剂防治呼吸、消化系统病毒病的理论依据、临床应用和发展前景。     

基于指标自动筛选的新疆开孔河流域生态健康评价

生态健康评价对了解区域生态健康状况和促进区域可持续发展具有重要意义,如何自动筛选出能反映生态系统特性的重要指标,是生态健康定量评估的关键问题。基于压力-状态-响应(PSR,Press-State-Response)框架和生态等级网络框架(EHN,Ecological Hierarchy Network),通过文献调研和因果分析建立要素层与指标层之间的交叉联系,构建了生态健康评价"网状"指标体系;在保证指标体系完备性基础上,通过结合主成分分析和熵权法的候选指标权重的客观计算,基于目标优化理论构建了评价指标的自动筛选模型,并基于中选指标计算了新疆开孔河流域2001—2017年生态健康指数(EHCI,Ecological Health Comprehensive Indexes),分析其空间分异和时间变化特征。结果表明:利用所建立的评价指标自动筛选模型,开孔河流域生态健康评价指标由31个候选指标自动筛选出了17个中选指标,用54.8%的指标表达了85.98%的信息,中选的17个指标在干旱/半干旱区域有关文献中应用较多,使用频次比例都在20%以上,其中归一化植被指数(NDVI,Normalized Difference Vegetation Index)、年降水量和植被覆盖度(FVC,Fractional Vegetation Coverage)3个指标的使用频次百分比均超过了50%,说明指标自动筛选模型的合理性;开孔河流域空间分布差异显著,总体上西北高、东南低,东南部和中部绿洲区外围生态健康状况较差,西北部河谷地带和中部两大绿洲区生态健康状况较好;17年来,流域生态质量整体趋于改善,显著改善区域占10.26%,远高于显著退化的1.61%,显著改善区域以孔雀河绿洲最为明显。开孔河流域生态健康的总体好转趋势说明区域生态综合治理取得一定成效。