Rapid progression to AIDS in HIV+ individuals with a structural variant of the chemokine receptor CX3CR1

Human immunodeficiency virus (HIV) enters cells in vitro via CD4 and a coreceptor. Which of 15 known coreceptors are important in vivo is poorly defined but may be inferred from disease-modifying mutations, as for CCR5. Here two single nucleotide polymorphisms are described in Caucasians in CX3CR1, an HIV coreceptor and leukocyte chemotactic/adhesion receptor for the chemokine fractalkine. HIV-infected patients homozygous for CX3CR1-I249 M280, a variant haplotype affecting two amino acids (isoleucine-249 and methionine-280), progressed to AIDS more rapidly than those with other haplotypes. Functional CX3CR1 analysis showed that fractalkine binding is reduced among patients homozygous for this particular haplotype. Thus, CX3CR1-I249 M280 is a recessive genetic risk factor in HIV/AIDS.     

Recruitment of HIV and its receptors to dendritic cell-T cell junctions

Monocyte-derived dendritic cells (MDDCs) can efficiently bind and transfer HIV infectivity without themselves becoming infected. Using live-cell microscopy, we found that HIV was recruited to sites of cell contact in MDDCs. Analysis of conjugates between MDDCs and T cells revealed that, in the absence of antigen-specific signaling, the HIV receptors CD4, CCR5, and CXCR4 on the T cell were recruited to the interface while the MDDCs concentrated HIV to the same region. We propose that contact between dendritic cells and T cells facilitates transmission of HIV by locally concentrating virus, receptor, and coreceptor during the formation of an infectious synapse.     

Identification of a T3-associated gamma delta T cell receptor on Thy-1+ dendritic epidermal Cell lines

The murine epidermis contains a subpopulation of bone marrow-derived lymphocytes that have a dendritic morphology and that express Thy-1 and T3 cell-surface antigens but not other markers (L3T4 or Lyt-2) characteristic of mature peripheral T lymphocytes. An alternative type of T cell receptor was earlier identified on a subpopulation of murine thymocytes with a similar phenotype (T3+, L3T4-, Lyt-2-), but not on peripheral murine T lymphocytes. Two independently derived Thy-1+, L3T4-, and Lyt-2- dendritic cell lines of epidermal origin that express a T3-associated disulfide-linked heterodimer composed of a 34-kilodalton gamma-chain and 46-kilodalton partner (the delta chain) have now been identified. Analysis of N-linked glycosylation revealed that this receptor is similar to that detected on thymocytes. These results demonstrate that Thy-1+ dendritic epidermal cell lines can express gamma delta T cell receptors in vitro and suggest that Thy-1+ dendritic epidermal cells express such receptors in vivo. The localization of these gamma delta T cell receptor-expressing cells in the epidermis may be of importance for understanding the function of these receptors.     

RacA,a bacterial protein that anchors chromosomes to the cell poles

Eukaryotic chromosomes are anchored to a spindle apparatus during mitosis, but no such structure is known during chromosome segregation in bacteria. When sister chromosomes are segregated during sporulation in Bacillus subtilis, the replication origin regions migrate to opposite poles of the cell. If and how origin regions are fastened at the poles has not been determined. Here we describe a developmental protein, RacA, that acts as a bridge between the origin region and the cell poles. We propose that RacA assembles into an adhesive patch at a centromere-like element near the origin, causing chromosomes to stick at the poles.     

Requirement of Rac1 and Rac2 expression by mature dendritic cells for T cell priming

Upon maturation, dendritic cells (DCs) acquire the unique ability to activate na?ve T cells. We used time-lapse video microscopy and two-photon imaging of intact lymph nodes to show that after establishing initial contact between their dendrites and na?ve T lymphocytes, mature DCs migrate toward the contacted lymphocytes. Subsequently, the DCs tightly entrap the T cells within a complex net of membrane extensions. The Rho family guanosine triphosphatases Rac1 and Rac2 but not Rho itself control the formation of dendrites in mature DCs, their polarized short-range migration toward T cells, and T cell priming.     

Pertussis toxin inhibition of B cell and macrophage responses to bacterial lipopolysaccharide

Lipopolysaccharide, a component of the outer membrane of Gram-negative bacteria, activates B lymphocytes and macrophages. Pertussis toxin, which inactivates several members of the G protein family of signaling components, including Gi and transducin, was found to inhibit the lipopolysaccharide-induced responses of the WEHI-231 B lymphoma cell line and the P388D1 macrophage cell line. These results, combined with the demonstration that lipopolysaccharide inhibits adenylate cyclase activity in P388D1 cells, strongly argues that lipopolysaccharide activation of cells is mediated by a Gi-like receptor-effector coupling protein.     

Chemokine gene silencing in decidual stromal cells limits T cell access to the maternal-fetal interface

The chemokine-mediated recruitment of effector T cells to sites of inflammation is a central feature of the immune response. The extent to which chemokine expression levels are limited by the intrinsic developmental characteristics of a tissue has remained unexplored. We show in mice that effector T cells cannot accumulate within the decidua, the specialized stromal tissue encapsulating the fetus and placenta. Impaired accumulation was in part attributable to the epigenetic silencing of key T cell-attracting inflammatory chemokine genes in decidual stromal cells, as evidenced by promoter accrual of repressive histone marks. These findings give insight into mechanisms of fetomaternal immune tolerance, as well as reveal the epigenetic modification of tissue stromal cells as a modality for limiting effector T cell trafficking.     

A bacterial protein targets the BAHD1 chromatin complex to stimulate type III interferon response

Intracellular pathogens such as Listeria monocytogenes subvert cellular functions through the interaction of bacterial effectors with host components. Here we found that a secreted listerial virulence factor, LntA, could target the chromatin repressor BAHD1 in the host cell nucleus to activate interferon (IFN)-stimulated genes (ISGs). IFN-λ expression was induced in response to infection of epithelial cells with bacteria lacking LntA; however, the BAHD1-chromatin associated complex repressed downstream ISGs. In contrast, in cells infected with lntA-expressing bacteria, LntA prevented BAHD1 recruitment to ISGs and stimulated their expression. Murine listeriosis decreased in BAHD1(+/-) mice or when lntA was constitutively expressed. Thus, the LntA-BAHD1 interplay may modulate IFN-λ-mediated immune response to control bacterial colonization of the host.     

TRB3 links the E3 ubiquitin ligase COP1 to lipid metabolism

During fasting, increased concentrations of circulating catecholamines promote the mobilization of lipid stores from adipose tissue in part by phosphorylating and inactivating acetyl-coenzyme A carboxylase (ACC), the rate-limiting enzyme in fatty acid synthesis. Here, we describe a parallel pathway, in which the pseudokinase Tribbles 3 (TRB3), whose abundance is increased during fasting, stimulates lipolysis by triggering the degradation of ACC in adipose tissue. TRB3 promoted ACC ubiquitination through an association with the E3 ubiquitin ligase constitutive photomorphogenic protein 1 (COP1). Indeed, adipocytes deficient in TRB3 accumulated larger amounts of ACC protein than did wild-type cells. Because transgenic mice expressing TRB3 in adipose tissue are protected from diet-induced obesity due to enhanced fatty acid oxidation, these results demonstrate how phosphorylation and ubiquitination pathways converge on a key regulator of lipid metabolism to maintain energy homeostasis.     

某豆科植物粗提物(JA1)对人肝癌细胞株端粒酶活性的抑制和细胞周期的改变

采用单管法一步完成端粒重复序列扩增法检测人肝癌细胞株,经不同浓度JA1及不同时间的作用前后端粒酶活性的变化,并采用流式细胞仪分析细胞周期的变化。结果显示,JA1可显著抑制人肝癌细胞端粒酶活性,而且这种抑制效果有剂量依赖性和时间依赖性。流式细胞仪分析细胞周期的变化表明,端粒酶活性被抑制后,肝癌细胞被阻滞在G2/M。同时,在检测标本中显示有明显的DNA低含量颗粒(“亚G1期”峰),表明肝癌细胞凋亡的存在。     

Identification of the envelope V3 loop as the primary determinant of cell tropism in HIV-1

Cells of the monocyte-macrophage lineage are targets for human immunodeficiency virus-1 (HIV-1) infection in vivo. However, many laboratory strains of HIV-1 that efficiently infect transformed T cell lines replicate poorly in macrophages. A 20-amino acid sequence from the macrophage-tropic BaL isolate of HIV-1 was sufficient to confer macrophage tropism on HTLV-IIIB, a T cell line--tropic isolate. This small sequence element is in the V3 loop, the envelope domain that is the principal neutralizing determinant of HIV-1. Thus, the V3 loop not only serves as a target of the host immune response but is also pivotal in determining HIV-1 tissue tropism.     

The inhibitory receptor PD-1 regulates IgA selection and bacterial composition in the gut

Immunoglobulin A (IgA) is essential to maintain the symbiotic balance between gut bacterial communities and the host immune system. Here we provide evidence that the inhibitory co-receptor programmed cell death-1 (PD-1) regulates the gut microbiota through appropriate selection of IgA plasma cell repertoires. PD-1 deficiency generates an excess number of T follicular helper (T(FH)) cells with altered phenotypes, which results in dysregulated selection of IgA precursor cells in the germinal center of Peyer's patches. Consequently, the IgAs produced in PD-1-deficient mice have reduced bacteria-binding capacity, which causes alterations of microbial communities in the gut. Thus, PD-1 plays a critical role in regulation of antibody diversification required for the maintenance of intact mucosal barrier.     

保险资金入市的必要性及其风险管理

保险资金入市是提高我国保险投资收益率,完善保险投资结构的内在要求,有利于保险公司扩大资金运作空间,实现保险市场与资本市场的良性互动。但同时,我们也必须看到保险资金入市所面临的一系列风险。本文在分析我国保险资金入市的必要性的基础上,对保险资金入市所面临的风险进行了分析,最后提出了针对性的风险管理对策。     

T cell CD3-zeta eta heterodimer expression and coupling to phosphoinositide hydrolysis

The T cell antigen receptor consists of an antigen-binding heterodimer that is noncovalently associated with at least five CD3 subunits (gamma, delta, epsilon, zeta, and eta). The CD3-zeta chains are either disulfide-linked homodimers (CD3-zeta 2) or disulfide-linked heterodimers with eta (CD3-zeta eta). Variants of a murine antigen-specific T cell hybridoma that express normal amounts of CD3-zeta 2 but decreased amounts of CD3-zeta eta were isolated. When activated, the parental cell line increased both phosphatidylinositol hydrolysis and serine-specific protein kinase activity to a much greater extent than the variants. In contrast, the activation of a tyrosine-specific kinase after stimulation with a cross-linking antibody to CD3 was similar among these cells. There was a positive linear relation between the expression of CD3-zeta eta and phosphoinositide hydrolysis stimulated by the TCR, suggesting a differential coupling of the T cell alpha beta heterodimer to signal transduction mechanisms due to alpha beta association with either CD3-zeta 2 or CD3-zeta eta.     

堆肥臭味物质——粪臭素高效降解菌Rp3的分离和鉴定

为获得粪臭素高效降解菌株,采用摇瓶富集培养和平板划线方法进行降解菌分离,通过感官法和趋化反应初步判定菌株的降解效果,利用高效液相色谱测定菌株对粪臭素的降解率,采用16S rRNA基因序列分析和Biolog鉴定系统对降解菌株进行初步鉴定。结果表明：从羊粪堆肥下土壤分离出的菌株Rp3对粪臭素具有趋化性;菌株Rp3对粪臭素的降解时间随粪臭素浓度的升高而延长。当粪臭素浓度为50 mg·L^-1时,28℃培养24 h,菌株Rp3对粪臭素的降解率达100%;当粪臭素浓度提高到100 mg·L^-1时,培养48 h降解率达到98.4%。菌株Rp3生长适宜pH为7~8;具有较强的耐盐性,在0~10%盐度下,菌株能生长正常。根据其形态特征、16S rRNA基因序列同源性分析和Biolog鉴定系统结果,将该降解菌鉴定为嗜吡啶红球菌Rhodococcus pyridinivorans。上述结果表明：菌株Rp3可以高效降解堆肥臭味物质粪臭素,为堆肥臭味物质的降解提供了新的微生物资源。     

防御酶与植物抗青枯病关系研究进展

青枯病是由青枯劳尔氏菌引起的一种毁灭性土传病害.综述了植物体内抗病相关防御酶(SOD、POD、PPO、PAL)及酶基因在植物抗青枯病方面的研究进展,发现病原物的侵染诱导导致植物体内防御酶活性变化.这些防御酶,或由于维持体内的活性氧代谢平衡,或由于参与酚类物质的氧化,或由于提高了木质素的生物合成而形成物理屏障,从而与植物抗青枯病存在一定的相关性.