Potential of community-wide chemotherapy or immunotherapy to control the spread of HIV-1

Whether zidovudine (3'-azido-3'-deoxythymidine, AZT) should be offered to symptomless individuals infected with human immunodeficiency virus type-1 (HIV-1), in the hope of delaying or even preventing progression to AIDS, has been much debated. The discussion has focused on the efficacy of the drug in delaying progression to disease, the severity of its side-effects, and the likelihood of its prolonged and widespread use resulting in zidovudine-resistant strains of the virus. Little attention has been given to the degree to which treatment reduces the infectiousness of symptomless patients, and to the concomitant implications for the overall transmission rate of HIV-1 in the community. Here we use simple mathematical models to show that community treatment with antiviral drugs or immunotherapies that lengthen the incubation period of AIDS without significantly reducing the infectiousness of treated individuals, can increase the rate at which HIV-1 infection spreads (which is fairly obvious) and can even, under certain circumstances, increase the AIDS-related death rate in the community (which is less obvious).     

High levels of unintegrated HIV-1 DNA in brain tissue of AIDS dementia patients

In the host cell, retroviral DNAs exist in three main forms: unintegrated linear, unintegrated circular, and integrated (the provirus). High levels of unintegrated forms of retroviral DNA often correlate with superinfection and accompanying cytopathic effects, as, for example, in the case of feline acquired immunodeficiency. In culture, HIV-1 infection also results in high levels of unintegrated viral DNA although direct correlations with cytopathicity have not been made. The low frequency of HIV-1-infected cells in patients has made it difficult to determine the structure of the viral DNA in fresh tissue samples from AIDS patients by standard methods such as Southern hybridization. The PCR technique however, which allows the detection of viral DNA at levels far below that possible by other hybridization methods is, in its conventional form, of limited use for quantitative analysis. To study the amount and form of HIV-1 DNA in primary tissue of AIDS patients we have therefore modified the PCR method. Our results indicate that each of the three species of viral DNA are detectable in blood and brain of AIDS patients, and that in autopsy samples from patients with HIV encephalitis there is a considerably higher proportion of unintegrated viral DNA.     

HIV in Africa (Communication arising): chemokine-receptor genes and AIDS risk

Schliekelman et al. have provided a model to quantify the speed at which HIV-resistance haplotypes can become enriched in a susceptible population through a delay in the onset of AIDS, permitting greater lifetime reproduction and the selection of AIDS-delaying haplotypes. But we question their conclusion that there could be a rapid evolution of resistance to AIDS onset in some African populations if the current HIV epidemic persists, as this depends on an untested assumption: that variant forms of the chemokine-receptor-5 (CCR5) gene impart selective advantages or disadvantages in Africa that are comparable to those reported for African Americans. Here we test this premise in a large Ugandan population, and find that CCR5 variants are not associated with HIV/AIDS disease risk in Africa--the origin and centre of the current AIDS pandemic. This gene may therefore not be subject to rapid evolutionary change as a result of the HIV epidemic in Africa.     

The interaction between the membrane-proximal external region and the N-trimer region of HIV-1 gp41: Involvement in viral fusion

The membrane proximal external region (MPER) of gp41 is extremely conserved among diverse HIV-1 variants, implying its important role in viral infection. Interestingly, two of the most broadly neutralizing antibodies, 2F5 and 4E10, specifically recognize this region. Our previous study demonstrated that the antigenicity and immunogenicity of 4E10 epitope are affected by remodeling gp41 fusion core, suggesting that the MPER may be associated with gp41 core and involved in gp41-mediated membrane fusion. Here we measured the binding activity of 4E10 epitope peptide (D4E10P) with various gp41 core-derived peptides and found that the N-trimer region in a construct designated N-trimer-6HB interacted significantly with D4E10P. Using N-trimer-6HB to screen a phage library, we identified a motif (WF) located in 4E10 epitope that may play a certain role in the interaction of gp41 MPER with the N-trimer in gp41 fusion core and, we thus speculated upon the potential involvement of MPER in the fusion process between viral envelope and target cell membrane. Supported by National Key Basic Research and Development Program of China (Grant No. 2007CB914402)     

HIV-1相关蛋白与细胞自噬在HIV相关神经认知障碍中的研究进展

细胞自噬作为真核细胞的一种自我保护机制,能降解细胞内的大分子蛋白质和病原微生物以及一些受损或老化的细胞器,使细胞维持平衡状态,在预防神经退行性疾病及免疫系统疾病等过程中有重要作用.研究发现,HIV-1(Human immunodeficiency virus type-1)能通过各种机制改变细胞自噬的正常功能,以利于自身的复制、感染等,本文就HIV-1的相关蛋白与细胞自噬的相互作用,及其在HIV相关神经认知障碍(HIV-1 associated neurocognitive disorder,HAND)的发生和发展中的重要作用进行综述.     

Challenges in the development of an HIV-1 vaccine

The development of a safe and effective human immunodeficiency virus (HIV)-1 vaccine is a critically important global health priority. Despite recent advances in our understanding of HIV-1 pathogenesis and immunology, however, major scientific obstacles remain. Prototype HIV-1 vaccine candidates aimed at eliciting humoral and cellular immune responses have so far failed to protect against HIV-1 infection or to reduce viral loads after infection in clinical efficacy studies. A renewed and coordinated commitment to basic discovery research, preclinical studies and clinical trials will therefore be required to overcome the hurdles currently facing the field. Here I review key challenges and future prospects in the quest to develop a prophylactic HIV-1 vaccine.     

榆科地区沙一段储层特征及对产能的影响

为研究榆科地区沙一段储层特征、储层与产能关系以及储层特征对产能的影响,运用薄片、电镜等分析化验资料,在确定榆科地区发育曲流河三角洲相和湖泊相的前提下,从岩石学特征、物性、储集空间及孔隙结构、成岩作用四方面着手进行分析,发现储层岩性以长石岩屑质石英砂岩和长石砂岩为主,成分成熟度偏低,结构成熟度中等,整体属于中-低孔、中-低渗储层,粒间溶孔为主要孔隙类型,喉道类型以微喉道和片状喉道为主;成岩作用类型中以压实、胶结作用使砂岩储集体孔隙大大降低;溶蚀、溶解作用使孔隙喉道增加,储层渗透性变好。优选孔隙度、渗透率、泥质含量、沉积相和砂岩厚度5个特征参数,将榆科地区沙一段储层分为Ⅰ、Ⅱ、Ⅲ、Ⅳ类,结合试油资料进行分析,发现不同类型的储层其油层发育及产能具有较大的差异,且控制作用明显,表现为Ⅱ类储层单位产能达到1.40 t/m,日产量达到96.19 t/d,为最具潜力储层;Ⅲ类储层单位产能为0.96t/m的情况下,日产仍能达到80.23 t/d,为主要产油储层类型之一。     

Imaging the biogenesis of individual HIV-1 virions in live cells

Observations of individual virions in live cells have led to the characterization of their attachment, entry and intracellular transport. However, the assembly of individual virions has never been observed in real time. Insights into this process have come primarily from biochemical analyses of populations of virions or from microscopic studies of fixed infected cells. Thus, some assembly properties, such as kinetics and location, are either unknown or controversial. Here we describe quantitatively the genesis of individual virions in real time, from initiation of assembly to budding and release. We studied fluorescently tagged derivatives of Gag, the major structural component of HIV-1-which is sufficient to drive the assembly of virus-like particles-with the use of fluorescence resonance energy transfer, fluorescence recovery after photobleaching and total-internal-reflection fluorescent microscopy in living cells. Virions appeared individually at the plasma membrane, their assembly rate accelerated as Gag protein accumulated in cells, and typically 5-6 min was required to complete the assembly of a single virion. These approaches allow a previously unobserved view of the genesis of individual virions and the determination of parameters of viral assembly that are inaccessible with conventional techniques.     

艾滋病疗法的评价及疗效的预测

艾滋病迄今为止没有根治的疗法,依据美国艾滋病医疗试验机构ACTG公布的2组临床数据,建立了艾滋病疗法的评价及疗效的预测模型。模型基于CD4浓度的讨论,建立了CD4浓度与时刻之间的预测函数,能够预测继续治疗的效果,为进一步诊治提供相关依据。模型通过分析各年龄段病人分布的稠密程度,比较了临床主要采取的4种疗法的优劣,同时还基于医疗成本的考虑,探讨了采取诊疗实施方案的合理政策。该模型提供的方法扩展性好,可以适用其他疾病诊疗方案的评价。     

广西三城市HIV-1型流行毒株gag基因亚型分析

为了解广西近年确诊的HIV-1感染者流行病学及HIV-1亚型分布情况,分别在桂林、来宾、钦州采取样本100例、102例和103例,收集流行病学资料、采集抗凝全血、提取病毒RNA、用RT-PCR进行gag基因扩增并对产物进行测序和序列分析。结果显示:在305例样本中,男女性别比1.99∶1;青壮年年龄组患者占56.72%,50岁年龄组患者构成比例为44.62%;职业为农民的患者比例为50.82%;初中及以下文化水平患者占76.39%;经异性性接触途径传播构成比为95.74%。最终成功扩增得到155份样本的gag基因序列,共发现4种亚型:CRF01-AE亚型124例、CRF07-BC亚型12例、CRF08-BC亚型14例、B亚型5例。     

Discovery of a 25-cm asteroid clast in the giant Morokweng impact crater, South Africa

Meteorites provide a sample of Solar System bodies and so constrain the types of objects that have collided with Earth over time. Meteorites analysed to date, however, are unlikely to be representative of the entire population and it is also possible that changes in their nature have occurred with time. Large objects are widely believed to be completely melted or vaporized during high-angle impact with the Earth. Consequently, identification of large impactors relies on indirect chemical tracers, notably the platinum-group elements. Here we report the discovery of a large (25-cm), unaltered, fossil meteorite, and several smaller fragments within the impact melt of the giant (> 70 km diameter), 145-Myr-old Morokweng crater, South Africa. The large fragment (clast) resembles an LL6 chondrite breccia, but contains anomalously iron-rich silicates, Fe-Ni sulphides, and no troilite or metal. It has chondritic chromium isotope ratios and identical platinum-group element ratios to the bulk impact melt. These features allow the unambiguous characterization of an impactor at a large crater. Furthermore, the unusual composition of the meteorite suggests that the Morokweng asteroid incorporated part of the LL chondrite parent body not represented by objects at present reaching the Earth.     

模因论下网络语言的表现形式及作用

自模因以及模因论出现以来,国内外语言学家和从事语言工作的人将这一理论引入到语言学的研究中来。从语言学的角度来看,模因论可以用来解释多种语言现象。以国内外模因学的研究成果为依据,应用话语分析的研究方法,来探讨和分析模因论在网络语言中的作用和影响。     

战时西安广播电台的创建与科技传播

通过文献调研和实地踏勘,对创建于1935年的西安广播电台及其自制天线、地线、发射传播装备技术和科学广播节目作了考察。认为该台的创建标志着中国西北地区无线电广播事业的开端,并认为张学良在其开播典礼上的讲话是为中国政要关于无线电广播科技知识的最早一篇广播稿范本,而且作了很贴切的口语化处理,以苏俄建设伯力无线电台中心网为例,强调无线电在启迪民智、传达消息、统制舆论方面的重要功能,从而丰富了早期科技广播稿体裁的内涵与外延。     

Exploiting the defensive sugars of HIV-1 for drug and vaccine design

The sustained effort towards developing an antibody vaccine against HIV/AIDS has provided much of our understanding of viral immunology. It is generally accepted that one of the main barriers to antibody neutralization of HIV is the array of protective structural carbohydrates that covers the antigens on the virus's surface. Intriguingly, however, recent findings suggest that these carbohydrates, which have evolved to protect HIV and promote its transmission, are also attractive therapeutic targets.