Structural characteristics and biological functions of the HIV-1 gp120 V3 region

Recent studies demonstrate that the V3 loop of HIV-1 gp120 plays an important role in the attachment of HIV-1 to the target cells. Several amino acids in this domain are involved in the interaction of gp120 with the co-receptors. The V3 loop elicits one of the earliest antiviral antibody responses in HIV-1 infection and has been identified as the principal neutralizing determinant (PND). A subset of antibodies to V3 loop show a broad range of neutralizing activity. Unfortunately, this loop undergoes broad mutation and is one of the hypervariable regions. Mutations of some amino acids in this PND could affect syncytium formation, virus infectivity and neutralization. Knowing the structural characteristics and biological functions of the V3 region could help us to understand mechanism of HIV infection and to develop new strategy against HIV-1. In this review, the structural characteristics, variation and biological functions of the V3 loop as well as immunological responses to the V3 loop are discussed.     

展示白色念珠菌热休克蛋白表位的杂合噬菌体诱导小鼠产生的体液免疫应答反应研究

白色念珠菌HSP90 LKVIRK是一段保守的B细胞线性表位.利用展示有LKVIRK表位的杂合噬菌体作为抗原,免疫C57BL/6J小鼠,然后在小鼠的系统性念珠菌感染模型中评价其免疫保护作用.结果证明该杂合噬菌体能够诱导C57BL/6J小鼠产生高滴度的抗HSP90抗体,而且对系统性念珠菌感染的小鼠具有免疫保护作用.说明展示有白色念珠菌LKVIRK表位的杂合噬菌体有可能成为一种候选的真菌疫苗.     

Three Candidate Epitope—Vaccines in Combination Inducing High Levels of Multiantibodies Against HIV—1

HIV-1 mutation results in immune evasion, which presents a serious challenge for conventional strategies for developing effective vaccines. So far, much experimental evidence indicates that HIV-1 particles in the blood of patients can be cleaned principally by neutralizing antibodies. Based on these facts, we prepared triple combination of epitope-vaccines with the objective of inducing antibodies with predefined multi-epitope-specificity against HW-1. According to the sequences of three neutralizing epitopes (RILAVERYLKD, ELDKWA and GPGRAFY, designated El, E2, and E3, respectively) on HIV-1 envelope proteins, three epitope-peptides ((E1)2: C-(RILAVERYLKDG)2; (E2)4: C-(ELDKWAG)4; and (E3)2:C-(GPGRAFY)2) were synthesized and then conjugated with carrier protein keyhole limpet hemocyanin (KLH) or bovine serum albumin (BSA), and used for immunizing rabbits. After the vaccine course, the triple combination of epitope-vaccines induced high levels of predefined multi-epitope-specific antibodies. An immunoblotting-analysis demonstrated that the antibodies could recognize the native epitopes on both gp41 protein and V3 loop peptide. Furthermore, we compared the immune responses of three doses of epitope-peptides in the candidate epitope-vaccine. Strong antibody responses to three epitopes were observed in a dose dependent manner, with increasing dose raising the immune response. This result indicated that immunotolerance did not occur using an epitope vaccine dose of 80 ~tg. Thus, our results demonstrate that epitope-vaccines in combination can synchronously induce high levels of antibodies with predefined multi-epitope-specificity against HIV-1, and may be used to develop effective vaccines against HIV as a new strategy.     

Prediction of a common neutralizing epitope of H5N1 avian influenza virus by in silico molecular docking

The H5N1 avian influenza virus (AIV) has widely spread in Asia, Europe and Africa, making a large amount of economic loss. Recently, our research group has screened a common neutralizing mono- clonal antibody named 8H5, which can neutralize almost all H5 subtype AIV ever isolated so far. Obvi- ously, this monoclonal antibody would benefit for research and development of the universal AIV vac- cine and design of the drug against H5N1 AIV in high mutation rate. In this study, the homology mod- eling was applied to generate the 3D structure of 8H5 Fab fragment, and "canonical structure" method was used to define the specified loop conformation of CDR regions. The model was subjected to en- ergy minimization in cvff force field with Discovery module in Insight II program. The resulting model has correct stereochemistry as gauged from the Ramachandran plot calculation and good 3D-structure compatibility as assessed by interaction energy analysis, solvent accessible surface (SAS) analysis, and Profiles-3D approach. Furthermore, the 8H5 Fab model was subjected to docking with three H5 subtype hemagglutinin (HA) structures deposited in PDB (ID No: 1jsm, 2ibx and 2fk0) respectively. The result indicates that the three docked complexes share a common binding interface, but differ in bind- ing angle related with HA structure similarity between viral subtypes. In the light of the three HA inter- faces with structural homology analysis, the common neutralizing epitope on HA recognized by 8H5 consists of 9 incontinuous amino acid residues: Asp68, Asn72, Glu112, Lys113, Ile114, Pro118, Ser120, Tyr137, Tyr252 (numbered as for 1jsm sequence). The primary purpose of the present work is to provide some insight into structure and binding details of a common neutralizing epitope of H5N1 AIV, thereby aiding in the structure-based design of universal AIV vaccines and anti-virus therapeutic drugs.     

Prediction of a common neutralizing epitope of H5N1 avian influenza virus by in silico molecular docking

The H5N1 avian influenza virus （AIV） has widely spread in Asia, Europe and Africa, making a large amount of economic loss. Recently, our research group has screened a common neutralizing mono-clonal antibody named 8H5, which can neutralize almost all H5 subtype AIV ever isolated so far. Obviously, this monoclonal antibody would benefit for research and development of the universal AIV vac-cine and design of the drug against H5N1 AIV in high mutation rate. In this study, the homology modeling was applied to generate the 3D structure of 8H5 Fab fragment, and ＂canonical structure＂ method was used to define the specified loop conformation of CDR regions. The model was subjected to energy minimization in cvff force field with Discovery module in Insight II program. The resulting model has correct stereochemistry as gauged from the Ramachandran plot calculation and good 3D-structure compatibility as assessed by interaction energy analysis, solvent accessible surface （SAS） analysis, and Profiles-3D approach. Furthermore, the 8H5 Fab model was subjected to docking with three H5 subtype hemagglutinin （HA） structures deposited in PDB （ID No： ljsm, 2ibx and 2fk0） respectively. The result indicates that the three docked complexes share a common binding interface, but differ in binding angle related with HA structure similarity between viral subtypes. In the light of the three HA inter-faces with structural homology analysis, the common neutralizing epitope on HA recognized by 8H5 consists of 9 incontinuous amino acid residues： Asp^58, Asn^72, Glu^112, Lys^113, lie^114, Pro^118, Ser^120, Tyr^137, Tyr^252 （numbered as for ljsm sequence）. The primary purpose of the present work is to provide some insight into structure and binding details of a common neutralizing epitope of H5N1 AIV, thereby aiding in the structure-based design of universal AIV vaccines and anti-virus therapeutic drugs.     

干扰素中和抗体与乙肝病毒DNA含量的关系

目的：了解干扰素中和抗体对干扰素疗效的影响。方法：用中和生物法检测64例慢性乙型肝炎（CHB）患者干扰素治疗前后血清的干扰素中和抗体（NA）,同时用荧光定量PCR技术检测干扰素治疗前后血清HBV DNA的含量,结果：64例接受干扰素治疗的CHB患者中21例患者治疗后检出NA（32．81％）,治疗前后的血清HBV DNA含量在NA阳性组无显著性差异（P＞0．05）,在NA阴性组有显著性差异＊（P＜0．05）,21例NA阳性者在治疗结束时1例（4．76％）,患者血清中,HBVDNA被清除,43例NA阴性者在治疗结束时16例（37．21％）患者血清中HBV DNA被清除,二者比较P＜0．01,结论：NA能影响干扰素的疗效,并可作为预测干扰素疗效的指标。     

Structure modeling and spatial epitope analysis for HA protein of the novel H1N1 influenza virus

In recent months, a novel influenza virus H1N1 broke out around the world. With bioinformatics technology, the 3D structure of HA protein was obtained, and the epitope residues were predicted with the method developed in our group for this novel flu virus. 58 amino acids were identified as potential epitope residues, the majority of which clustered at the surface of the globular head of HA protein. Although it is located at the similar position, the epitope of HA protein for the novel H1N1 flu virus has obvious differences in the electrostatic potential compared to that of HA proteins from previous flu viruses.     

湘江流域汉语方言中的重复体及其演变

湘江流域汉语方言中存在宽泛的重复体。重复体的用法正在弱化,在一些方言中演变为补偿体,一些方言中已经消失。     

论杜拉斯创作中的重复叙述

杜拉斯在作品的人物、背景、情感之中常常杂糅了对现实生活的回忆,在她不同作品中可以发现她流露着相同的情感基调,体现在故事的叙述上就是一再出现重复的情节和人物。这种创作的重复性源于杜拉斯独特的生活体验和创作心理,也使小说的内涵更富弹性张力。     

人乳头瘤病毒16L1抗血清的制备和鉴定

人乳头瘤病毒16型是导致宫颈癌发生的主要因素,其晚期蛋白L1在体内或体外可自组装形成VLP颗粒.作者构建了DNA疫苗载体pDRVI1.0-16L1,大提质粒后免疫BalB/C小鼠制备抗体,并对抗体进行了特异性鉴定,为HPV16L1预防性疫苗的进一步研究和应用奠定了基础.     

未来的丙型肝炎疫苗

丙型肝炎病毒（hepatitis C virus,HCV）是丙型肝炎的病原体,是导致输血后肝炎和非甲非乙型肝炎的主要致病因子。HCV感染常导致慢性肝炎、肝硬化和肝细胞癌。HCV在细胞内和动物体内复制能力很差,没有理想的细胞模型和动物模型。丙型肝炎目前尚无疫苗,还有很多病人在等待治疗。研制预防性和治疗性疫苗,以控制HCV感染有着重要意义。经过几代科技工作者的努力和奉献,丙型肝炎疫苗研究取得了重大进展。用核酸疫苗作首次免疫,用多肽疫苗或树突状细胞疫苗作加强免疫,不但有预防作用,而且有治疗效果。核酸疫苗将为改善人类和动物健康作出巨大贡献。     

Immune response in cattle inoculated with the recombinant complete polyprotein of foot-and-mouth disease virus from Bombyx mori larvae

The intact open reading frame (ORF) of foot-and-mouth disease virus (FMDV) Asia I/XJ strain was am- plified by RT-PCR and inserted into the transfer vector pVL1393 to generate plasmid pVL-ORF. Bm-N cells were transfected with pVL-ORF and linearized Bm-BacPAK6 DNA, and the recombinant silkworm baculovirus Bm-ORF containing the full ORF of FMDV was obtained. The results of indirect im- munofluorescence assay (IFA) showed that Bm-ORF could be expressed efficiently in Bm-N cell. After inoculating the early 5th instar larvae of silkworm, the polyprotein of FMDV could be detected by sandwich ELISA and empty capsid-like particles could be observed under the electron microscope. Expression products from silkworm were used as the antigen to immunize the cattle. The specific an- tibody was induced in all vaccinated animals. The immunized cattle were challenged with the virulent FMDV Asia I/XJ strain, two of the four cattle were completely protected and clinical symptoms were alleviated and delayed in the others. The results suggest that this strategy might be used to develop the new subunit FMDV vaccine.     

等级反应模型的Gibbs抽样方法

探讨了MCMC算法在多级评分项目反应模型参数估计中的实现及其估计精度.针对等级反应模型,基于数据扩充技术,提出了一种高效灵活的Gibbs抽样方法,得到了各个参数的Markov链.随着潜在变量的引入,每个参数的满条件分布为相应参数的先验分布的截断分布.这种抽样方法适用于任何类型的先验分布,不受先验分布形式的约束.对应每个...     

控制系统闭环响应函数的快速辨识

按照控制系统的传统模型,可以建立近似的闭环传递函数．但其阶跃响应中超调量的偏差将明显地与系统的纯滞后时间相关．对于较复杂的对象,若用数值求解法求取整个闭环响应曲线,将很费时．鉴于一般工业控制系统的闭环响应都包含振荡过程．通过理论分析和论证,并利用阶跃响应的前３个幅值,提出了一组能快速辨识闭环响应函数的公式和综合模型,经对３种典型的仿真实例的验证,结果是准确的．此法也适用于发散振荡的情况．     

CD8<Superscript>+</Superscript> T cell response mediates the therapeutic effects of oncolytic adenovirus in an immunocompetent mouse model

The role of anti-tumor immune responses in oncolytic adenoviral therapy has not been well studied due to lack of efficacious tu- mor model in immunocompetent mice.Here,we evaluated the contributions of immune components to the therapeutic effects of oncolytic adenoviruse in an immunocompetent murine tumor model permissive for infection and replication of adenovirus.We found that CD8+T cells were critical mediator for antitumor efficacy by oncolytic adenovirus.Intratumoral viral therapy induced intensive infiltration of CD8+T cells in tumor,increased tumor-specific IFN-?(interferon-?)production and CTL(cytotoxic T lymphocyte)activity of lymphocytes,and generated a long-term tumor-specific immune memory.Boosting CD8+T cell responses by agonistic anti-4-1BB(cluster differentiation 137,CD137)antibody showed synergistic anticancer effects with oncolytic viro- therapy.Our results provide insight into antitumor mechanisms of oncolytic adenovirus in addition to their direct oncolytic effect.     

具有功能性反应且捕食者有病的生态-流行病模型

建立并研究了一个捕食者具有传染病的生态-流行病(SI)模型,考虑了捕食者具有HollingⅡ功能性反应及食饵具有Logistic增长,且染病的捕食者会因病死亡,以及只有健康的捕食者才具有捕食能力,但这种疾病一旦染上就不再康复.应用特征方程的方法以及构造Liapunov函数的知识,得到了平衡点局部渐近稳定的充分条件,进一步分析了平衡点的全局稳定性,得到了边界平衡点全局稳定的充分条件.     

确定光电探测器线性响应系数的一种新方法

在激光粒度分析仪中,光电探测器各环对光强的线性响应能力常具有一定分散性,通过数学方法环的响应能力,使其具有一同一性的对提高仪器的测量精度有着十分重要的意义,本文提出了一种确定光电探测器各环动态响应校正系数的新方法。     

Topography of acoustic response characteristics in the auditory cortex of the Kunming mouse

Topography of acoustic response characteristics in the auditory cortex (AC) of the Kunming (KM) mouse has been examined by using microelectrode recording techniques. Based on best-frequency (BF) maps, both the primary auditory field (AI) and the anterior auditory field (AAF) are tonotopically organized with a counter running frequency gradient. Within an isofrequency stripe, the width of the frequency-threshold curves of single neurons increases, and minimum threshold (MT) decreases towards more ventral locations. BFs in AI and AAF range from 4 to 38 kHz. Auditory neurons with BFs above 40 kHz are located at the rostrodorsal part of the AC. The findings suggest that the KM mouse is a good model suitable for auditory research.