Discovery of an irreversible HCV NS5B polymerase inhibitor

The discovery of lead compound 2e was described. Its covalent binding to HCV NS5B polymerase enzyme was investigated by X-ray analysis. The results of distribution, metabolism and pharmacokinetics were reported. Compound 2e was demonstrated to be potent (replicon GT-1b EC₅₀ = 0.003 μM), highly selective, and safe in in vitro and in vivo assays.     

SPARC regulates collagen interaction with cardiac fibroblast cell surfaces

Cardiac tissue from mice that do not express secreted protein acidic and rich in cysteine (SPARC) have reduced amounts of insoluble collagen content at baseline and in response to pressure overload hypertrophy compared with wild-type (WT) mice. However, the cellular mechanism by which SPARC affects myocardial collagen is not clearly defined. Although expression of SPARC by cardiac myocytes has been detected in vitro, immunohistochemistry of hearts demonstrated SPARC staining primarily associated with interstitial fibroblastic cells. Primary cardiac fibroblasts isolated from SPARC-null and WT mice were assayed for collagen I synthesis by [(3)H]proline incorporation into procollagen and by immunoblot analysis of procollagen processing. Bacterial collagenase was used to discern intracellular from extracellular forms of collagen I. Increased amounts of collagen I were found associated with SPARC-null versus WT cells, and the proportion of total collagen I detected on SPARC-null fibroblasts without propeptides [collagen-α(1)(I)] was higher than in WT cells. In addition, the amount of total collagen sensitive to collagenase digestion (extracellular) was greater in SPARC-null cells than in WT cells, indicating an increase in cell surface-associated collagen in the absence of SPARC. Furthermore, higher levels of collagen type V, a fibrillar collagen implicated in collagen fibril initiation, were found in SPARC-null fibroblasts. The absence of SPARC did not result in significant differences in proliferation or in decreased production of procollagen I by cardiac fibroblasts. We conclude that SPARC regulates collagen in the heart by modulating procollagen processing and interactions with fibroblast cell surfaces. These results are consistent with decreased levels of interstitial collagen in the hearts of SPARC-null mice being due primarily to inefficient collagen deposition into the extracellular matrix rather than to differences in collagen production.     

Genetic structure in fragmented populations of Hippophae rhamnoides ssp. sinensis in China investigated by ISSR and cpSSR markers

Hippophae rhamnoides ssp. sinensis is an ecologically and economically important species that has been widely used as a pioneer plant in China. In this study, we employed both nuclear ISSR and maternal cpSSR markers to survey the genetic diversity and structure of populations of ssp. sinensis representing three different landscapes, the northwestern desert and grassland region, the alpine vegetation region of the Qinghai-Tibetan Plateau, and the northeastern humid forest region. In all, 12 natural populations with a scattered distribution in the area were studied. The genetic diversities of populations were found to be uneven, and the total genetic diversity was low on the basis of both types of marker. Mantel tests based on both individual Euclidean distance matrices and population genetic distance (measured by ??pt) matrices showed that the two marker systems detected similar trends with respect to genetic distances between populations. The analysis of molecular variance (AMOVA) revealed significant differentiation among populations and among regions for both types of marker. Although the detected pattern of isolation-by-distance among all sampled populations confirmed the earlier colonization pathway, the low level of gene flow and the lack of isolation by distance within each region suggested the presence of an additional dispersal barrier. UPGMA dendrograms and PCA plots also revealed clear clustering and significant regional differentiation. Our results indicate that the genetic structure of ssp. sinensis has been affected by habitat fragmentation and restricted population sizes. We propose that the biology of reproduction and ecology have played determinant roles in the development of the regional structure of populations. The genetic information obtained will help to establish conservation strategies and programs for sustainable management of H. rhamnoides ssp. sinensis.     

不同水稻土甲烷氧化菌和产甲烷菌数量与甲烷排放量之间相关性的研究

对不施用任何肥料的浙江黄松土（发育于河流沉积物母质的水稻田土）、老黄筋泥田土（发育于第四纪红壤母质的水稻田土）、青紫泥田土（发育于滨海盐土母质的象山青紫泥水稻土）中甲烷氧化菌、产甲烷菌种群数量及甲烷排放量之间关系作了研究。结果表明,甲烷氧化菌种群数量范围在10^6-10^8cfu/g干土之间,其变化在2个数量级范围内,产甲烷细菌种群数量变化较大,其范围在10^3-10^7cfu/g干土之间,水稻田土壤的甲烷排放量受到甲烷氧化菌、产甲烷菌种群数量及其活性及土壤理化性状的影响,提出了当水稻田土壤的甲烷氧化菌种群数量在10^cfu/g干土、产甲烷菌种群数量在10^5cfu/g干土时,水稻田土壤几乎没有多余的CH4气体排放这一甲烷形成与甲烷氧化两类群微生物之间的数量关系。甲烷排量也与土壤砂粒（＜0．02mm的砂数）含量呈正相关性,土壤砂粒含量越高,其甲烷排放量亦高。     

开放式空气CO2增高对水稻物质生产与分配的影响

在大田栽培条件下,研究开放式空气CO2增加(FACE)200μmol·mol^-1的处理对水稻物质生产与分配的影响．结果表明,FACE处理使移栽至抽穗后20d的干物质积累量显著增加,使抽穗后20d至成熟期的干物质生产量显著减少,生物产量显著提高．移栽至抽穗期的干物质积累量增加是由于叶面积系数和净同化率共同提高所致;抽穗期至抽穗后20d的干物质积累量增加主要是由于叶面积系数的增加所致;抽穗后20d至成熟期的干物质生产量减少主要是由于净同化率的下降所造成．提高茎鞘占全株干物重的比例,降低叶片占全株干物重的比例,对穗占全株干物重的比例无显著影响,能显著提高水稻抽穗期茎鞘中可溶性糖、淀粉的含有率和含量,提高FACE处理的生物产量能极显著提高水稻产量(r＝0．7825)．     

阴山荠属和泡果荠属的数量分类研究

阴山荠属和泡果荠属隶于十字花科,两属有一些共同特征,也有一系列性状差异,数量分类结果支持两属处理为各自独立的属。本文同时对属下类群和一些种间关系进行了讨论。     

细菌视紫红质膜质子(电荷)转移过程中的瞬态吸收研究

用自行设计的“连续泵浦－探测光＋脉冲泵浦光”的实验系统,研究细菌视紫红质（ＢＲ）的光循环过程;着重以Ｈｅ－Ｎｅ激光（６３２．８ｎｍ）为连续泵浦－探测光,研究在脉冲光共同作用下ＢＲ各能态的光吸收的动力学过程,及该吸收特性与两束光强度的关系     

Vesicular stomatitis virus-based therapeutic vaccination targeted to the E1, E2, E6, and E7 proteins of cottontail rabbit papillomavirus

Persistent human papillomavirus (HPV)-associated benign and malignant lesions are a major cause of morbidity and mortality worldwide. Vaccination against HPV early proteins could provide an effective means of treating individuals with established infections. Recombinant vesicular stomatitis virus (VSV) vectors have been used previously to elicit strong humoral and cellular immune responses and develop prophylactic vaccines. We have shown that VSV vectors also can be used to elicit therapeutic immunity in the cottontail rabbit papillomavirus (CRPV)-rabbit model of high-risk HPV infection. In the present study, three new VSV vectors expressing the CRPV E1, E2, or E7 protein were produced and compared to the previously generated VSV-E6 vector for therapeutic efficacy. To determine whether vaccine efficacy could be augmented by simultaneous vaccination against two CRPV proteins, the four vaccines were delivered individually and in all possible pairings to rabbits 1 week after CRPV infection. Control rabbits received the recombinant wild-type VSV vector or medium only. Cumulative papilloma volumes were computed for analysis of the data. The analyses showed that VSV-based vaccination against the E1, E2, E6, or E7 protein significantly reduced papilloma volumes relative to those of the controls. Furthermore, VSV-based CRPV vaccination cured all of the papillomas in 5 of 30 rabbits. Of the individual vaccines, VSV-E7 was the most effective. The VSV-E7 vaccine alone was the most effective, as it reduced cumulative papilloma volumes by 96.9% overall, relative to those of the controls, and ultimately eliminated all of the disease in all of the vaccinees. Vaccine pairing was not, however, found to be beneficial, suggesting antigenic competition between the coexpressed CRPV proteins. These preclinical results, obtained in a physiologically relevant animal model of HPV infection, demonstrate that VSV vectors deserve serious consideration for further development as therapeutic antitumor vaccines.