Sequence of simian immunodeficiency virus from macaque and its relationship to other human and simian retroviruses

Because of the growing incidence of AIDS (acquired immune deficiency syndrome), the need for studies on animal models is urgent. Infection of chimpanzees with the retroviral agent of human AIDS, the human immunodeficiency virus (HIV), will have only limited usefulness because chimpanzees are in short supply and do not develop the disease. Among non-human primates, both type D retroviruses and lentiviruses can be responsible for immune deficiencies. The D-type retroviruses, although important pathogens in macaque monkey colonies, are not satisfactory as a model because they differ in genetic structure and pathophysiological properties from the human AIDS viruses. The simian lentivirus, previously referred to as simian T-cell lymphotropic virus type III (STLV-III), now termed simian immunodeficiency virus (SIV) is related to HIV by the antigenicity of its proteins and in its main biological properties, such as cytopathic effect and tropism for CD4-bearing cells. Most importantly, SIV induces a disease with remarkable similarity to human AIDS in the common rhesus macaques, which therefore constitute the best animal model currently available. Natural or experimental infection of other monkeys such as African green monkeys or sooty mangabeys has not yet been associated with disease. Molecular approaches of the SIV system will be needed for biological studies and development of vaccines that could be tested in animals. We have cloned and sequenced the complete genome of SIV isolated from a naturally infected macaque that died of AIDS. This SIVMAC appears genetically close to the agent of AIDS in West Africa, HIV-2, but the divergence of the sequences of SIV and HIV-2 is greater than that previously observed between HIV-1 isolates.     

Structure of the Ebola virus glycoprotein bound to an antibody from a human survivor

Ebola virus (EBOV) entry requires the surface glycoprotein (GP) to initiate attachment and fusion of viral and host membranes. Here we report the crystal structure of EBOV GP in its trimeric, pre-fusion conformation (GP1+GP2) bound to a neutralizing antibody, KZ52, derived from a human survivor of the 1995 Kikwit outbreak. Three GP1 viral attachment subunits assemble to form a chalice, cradled by the GP2 fusion subunits, while a novel glycan cap and projected mucin-like domain restrict access to the conserved receptor-binding site sequestered in the chalice bowl. The glycocalyx surrounding GP is likely central to immune evasion and may explain why survivors have insignificant neutralizing antibody titres. KZ52 recognizes a protein epitope at the chalice base where it clamps several regions of the pre-fusion GP2 to the amino terminus of GP1. This structure provides a template for unravelling the mechanism of EBOV GP-mediated fusion and for future immunotherapeutic development.     

Sequence of simian immunodeficiency virus and its relationship to the human immunodeficiency viruses

The characterization of HIV-1 (HTLV-III/LAV), the human retrovirus associated with AIDS (acquired immune deficiency syndrome) has led to the identification of a group of related human and simian retroviruses which also infect CD4-bearing T lymphocytes. Simian T-lymphotropic virus type III (simian immodeficiency virus) from macaques (STLV-IIIMAC) induces symptoms similar to those of AIDS in infected macaques, but isolates from African green monkeys (STLV-IIIAGM) and mangabeys (STLV-IIMM) appear to be non-pathogenic in these animals. A human virus immunologically related to STLV-IIIAGM (HTLV-IV), reported to have been isolated from healthy humans, has been shown to be almost identical to STLV-IIIAGM, which has called into question the independent origin of these viruses. Here we report the complete DNA sequence of STLV-IIIAGM and analyse its relationship with the genomes of the HTLV-IIIB strain of HIV-1, HIV-2ROD (previously called LAV-2) and several ungulate lentiretroviruses. STLV-IIIAGM and HIV-2 are closely related, and more distantly related to HIV-1.     

Pc 1 Duarte, a common polymorphism of a human brain protein, and its relationship to depressive disease and multiple sclerosis

Pc 1 Duarte, a common variant of a human brain-specific protein, is present in one-third of the control population and has a gene frequency of 0.17. There was a significantly increased frequency of mutant heterozygotes and homozygotes among individuals with depressive disease. This is consistent with a model in which Pc 1 Duarte is the major gene in depressive disease, acting in conjunction with an environmental threshold effect.     

面向功能分区的大型商场建筑冷负荷预测方法

针对大型商场面向建筑整体冷负荷预测不能为商场各区域按需供冷提供合理控制策略的问题,通过研究商场不同区域冷负荷特点,采用灰色关联度分析法筛选影响商场不同区域冷负荷的关键影响因素,针对实际情况中各输入特征对冷负荷影响程度的不稳定性,提出了基于双重注意力机制和LSTM的短期分区冷负荷预测模型。LSTM网络充分考虑空调冷负荷与相关特征变量之间的非线性关系,特征注意力自主分析历史信息和输入变量之间的关系,提取重要特征,时序注意力选取LSTM网络关键时刻的历史信息,提升较长时间段预测效果的稳定性。以西安某大型商场建筑的冷负荷数据集为实验数据,实验结果表明所提模型相比于LSTM模型、CNN-LSTM模型和Attention-LSTM模型,误差指标MAPE和RMSE均有显著降低,R2明显增加且稳定0.99以上,具有较好的泛化能力和较强的稳定性。     

谈推拿在治疗风寒型普通感冒中的临床体会

笔者在推拿治疗风寒型普通感冒中，以中医基本理论为指导，根据经络学说和藏象学说的理论，明确治疗原则是发汗解表，基本治法是汗法，操作部位的选择，则以头背部，膀胱经两侧线为主，并且从中医和现代医学的角度，论证了推拿治疗风寒型普通感冒中的方法。     

Structure and collaboration relationship analysis in a scientific collaboration network

We construct a weighted network of scientific collaboration in computational geometry and study the statistical properties of the network. In addition, we introduce a parameter called the collaboration relationship parameter to measure the collaboration between scientists. The collaboration relationship parameter of two scientists depends not only on the connection weights between the nodes, but also on the network’s structure. The stability of the network’s structure in terms of different edge removal strategies is also studied. According to the parameter, we find that a community structure exists in this type of network.     

Transfer of a functional human immune system to mice with severe combined immunodeficiency

The pressing need for a better experimental system for AIDS research has brought into sharp focus the shortcomings of available animal models and the practical and ethical limitations of studies of immune responses and viral pathogenesis in humans. Current studies of the human immune responses are limited to relatively restrictive in vivo experiments and several in vitro systems that, although useful, allow only short-term studies and support responses to a few antigens. Neither model is particularly amenable to studies of the pathogenesis of diseases of the immune system. We report here that injection of human peripheral blood leukocytes (PBL) can result in the stable long-term reconstitution of a functional human immune system in mice with severe combined immunodeficiency (SCID). Human PBL transplanted to SCID mice increase in number and survive for at least six months; reconstituted mice show spontaneous secretion of human immunoglobulin and a specific human antibody response is induced following immunization with tetanus toxoid. All of the major cell populations present in PBL are found in the lymphoid tissue and blood of SCID recipients, although the relative proportions of B cells, T-cell subsets and monocytes/macrophages in long-term recipients differ from those found in normal PBL and, in mice transplanted with 50 x 10(6) or more PBL from Epstein-Barr virus (EBV)-seropositive donors, EBV-positive B-cell lymphomas often develop. Our results suggest that xenogeneic transplantation of human lymphoid cells into SCID mice may provide a useful model for the study of normal human immune function, the response of the immune system to pathogenic agents and early events in lymphomagensis.     

Structure of a cannabinoid receptor and functional expression of the cloned cDNA

Marijuana and many of its constituent cannabinoids influence the central nervous system (CNS) in a complex and dose-dependent manner. Although CNS depression and analgesia are well documented effects of the cannabinoids, the mechanisms responsible for these and other cannabinoid-induced effects are not so far known. The hydrophobic nature of these substances has suggested that cannabinoids resemble anaesthetic agents in their action, that is, they nonspecifically disrupt cellular membranes. Recent evidence, however, has supported a mechanism involving a G protein-coupled receptor found in brain and neural cell lines, and which inhibits adenylate cyclase activity in a dose-dependent, stereoselective and pertussis toxin-sensitive manner. Also, the receptor is more responsive to psychoactive cannabinoids than to non-psychoactive cannabinoids. Here we report the cloning and expression of a complementary DNA that encodes a G protein-coupled receptor with all of these properties. Its messenger RNA is found in cell lines and regions of the brain that have cannabinoid receptors. These findings suggest that this protein is involved in cannabinoid-induced CNS effects (including alterations in mood and cognition) experienced by users of marijuana.     

Structure and expression of a human oxytocin receptor.

Just before the onset of labour, uterine myometrium becomes extremely sensitive to oxytocin, for which it is a primary target tissue, because of a dramatic increase in the number of oxytocin receptors. We report here the structure and expression of the human oxytocin receptor complementary DNA isolated by expression cloning. The encoded receptor is a 388-amino-acid polypeptide with 7 transmembrane domains typical of G protein-coupled receptors. The oxytocin receptor, expressed in Xenopus oocytes, specifically responds to oxytocin and induces an inward membrane current. Messenger RNAs for the receptor are of two sizes, 3.6 kilobases in breast, and 4.4 kilobases in ovary, uterine endometrium and myometrium. The mRNA level in the myometrium is very high at term. We conclude that the increase in receptor number in the myometrium at labour is, at least in part, due to the increase in mRNA.