CD69 acts downstream of interferon-alpha/beta to inhibit S1P1 and lymphocyte egress from lymphoid organs

Naive lymphocytes continually enter and exit lymphoid organs in a recirculation process that is essential for immune surveillance. During immune responses, the egress process can be shut down transiently. When this occurs locally it increases lymphocyte numbers in the responding lymphoid organ; when it occurs systemically it can lead to immunosuppression as a result of the depletion of recirculating lymphocytes. Several mediators of the innate immune system are known to cause shutdown, including interferon alpha/beta (IFN-alpha/beta) and tumour necrosis factor, but the mechanism has been unclear. Here we show that treatment with the IFN-alpha/beta inducer polyinosine polycytidylic acid (hereafter 'poly(I:C)') inhibited egress by a mechanism that was partly lymphocyte-intrinsic. The transmembrane C-type lectin CD69 was rapidly induced and CD69-/- cells were poorly retained in lymphoid tissues after treatment with poly(I:C) or infection with lymphocytic choriomeningitis virus. Lymphocyte egress requires sphingosine 1-phosphate receptor-1 (S1P1), and IFN-alpha/beta was found to inhibit lymphocyte responsiveness to S1P. By contrast, CD69-/- cells retained S1P1 function after exposure to IFN-alpha/beta. In coexpression experiments, CD69 inhibited S1P1 chemotactic function and led to downmodulation of S1P1. In a reporter assay, S1P1 crosslinking led to co-crosslinking and activation of a CD69-CD3zeta chimaera. CD69 co-immunoprecipitated with S1P1 but not the related receptor, S1P3. These observations indicate that CD69 forms a complex with and negatively regulates S1P1 and that it functions downstream of IFN-alpha/beta, and possibly other activating stimuli, to promote lymphocyte retention in lymphoid organs.     

T-cell receptor triggering is critically dependent on the dimensions of its peptide-MHC ligand

The binding of a T-cell antigen receptor (TCR) to peptide antigen presented by major histocompatibility antigens (pMHC) on antigen-presenting cells (APCs) is a central event in adaptive immune responses. The mechanism by which TCR-pMHC ligation initiates signalling, a process termed TCR triggering, remains controversial. It has been proposed that TCR triggering is promoted by segregation at the T cell-APC interface of cell-surface molecules with small ectodomains (such as TCR-pMHC and accessory receptors) from molecules with large ectodomains (such as the receptor protein tyrosine phosphatases CD45 and CD148). Here we show that increasing the dimensions of the TCR-pMHC interaction by elongating the pMHC ectodomain greatly reduces TCR triggering without affecting TCR-pMHC ligation. A similar dependence on receptor-ligand complex dimensions was observed with artificial TCR-ligand systems that span the same dimensions as the TCR-pMHC complex. Interfaces between T cells and APCs expressing elongated pMHC showed an increased intermembrane separation distance and less depletion of CD45. These results show the importance of the small size of the TCR-pMHC complex and support a role for size-based segregation of cell-surface molecules in TCR triggering.     

Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor

Pituitary adenylate cyclase-activating polypeptide (PACAP) is known to broadly regulate the cellular stress response. In contrast, it is unclear if the PACAP-PAC1 receptor pathway has a role in human psychological stress responses, such as post-traumatic stress disorder (PTSD). Here we find, in heavily traumatized subjects, a sex-specific association of PACAP blood levels with fear physiology, PTSD diagnosis and symptoms in females. We examined 44 single nucleotide polymorphisms (SNPs) spanning the PACAP (encoded by ADCYAP1) and PAC1 (encoded by ADCYAP1R1) genes, demonstrating a sex-specific association with PTSD. A single SNP in a putative oestrogen response element within ADCYAP1R1, rs2267735, predicts PTSD diagnosis and symptoms in females only. This SNP also associates with fear discrimination and with ADCYAP1R1 messenger RNA expression in human brain. Methylation of ADCYAP1R1 in peripheral blood is also associated with PTSD. Complementing these human data, ADCYAP1R1 mRNA is induced with fear conditioning or oestrogen replacement in rodent models. These data suggest that perturbations in the PACAP-PAC1 pathway are involved in abnormal stress responses underlying PTSD. These sex-specific effects may occur via oestrogen regulation of ADCYAP1R1. PACAP levels and ADCYAP1R1 SNPs may serve as useful biomarkers to further our mechanistic understanding of PTSD.     

阵列声波测井中反射纵波和横波信号提取方法

将双树复小波(DT-CWT)和慢度时间相关法(STC)相结合,同时利用尺度-时间域及阵列慢度信息,提出一种提取反射波信号的多尺度相关分析方法。应用倾角叠加来进一步压制直达模式波和噪声以增强反射信号,同时可以对P-P反射和S-S反射进行分离。通过有限差分模拟的数据和声反射成像测井仪器对某油田测得的实际数据进行处理。结果表明,所提出的反射信号处理方能更有效地去除各种噪声,更精确地分离反射波小信号。     

Type 1 diabetes in mice is linked to the interleukin-1 receptor and Lsh/Ity/Bcg genes on chromosome 1.

Human type 1 (insulin-dependent) diabetes is a common auto-immune disease of the insulin-producing beta cells of the pancreas which is caused by both genetic and environmental factors. Several features of the genetics and immunopathology of diabetes in nonobese diabetic (NOD) mice are shared with the human disease. Of the three diabetes-susceptibility genes, Idd-1 -3 and -4 that have been mapped in mice to date, only in the case of Idd-1 is there any evidence for the identity of the gene product: allelic variation within the murine immune response I-A beta gene and its human homologue HLA-DQB1 correlates with susceptibility, implying that I-A beta is a component of Idd-1. We report here the mapping of Idd-5 to the proximal region of mouse chromosome 1. This region contains at least two candidate susceptibility genes, the interleukin-1 receptor gene and Lsh/Ity/Bcg, which encodes resistance to bacterial and parasitic infections and affects the function of macrophages.     

基于P2P及B/S搭建教育云平台与流量管理分析

云计算、教育云的快速发展为打造开放式的教育平台,实现教育资源的共享与管理奠定了坚实的基础.而中国目前的教育云建设基本采用集中式管理,随着时间的推移,教学资源的大量积累,云计算中心将变得不堪重负,管理效率下降,甚至导致系统崩溃.该文以搭建区域性教育云平台为研究对象,提出了综合型P2P流量检测计算模型,为集成集中式和分布式云平台的建设和管理做了一些有益的探索.     

The adult T-cell receptor delta-chain is diverse and distinct from that of fetal thymocytes

T lymphocytes recognize foreign molecules using the T-cell receptor (TCR), a disulphide-linked heterodimer closely associated with the CD3 polypeptide complex on the cell surface. The TCR alpha beta heterodimers seem largely responsible for the recognition properties of both helper (TH) and cytotoxic (TC) T cells. Recently, a second CD3-associated T-cell receptor heterodimer, gamma delta, has been described. Cells bearing the gamma delta receptor appear before those bearing alpha beta during thymic ontogeny and persist as a minor component (1-10%) of mature peripheral T cells. Their function is unknown. As there are a limited number of functional TCR V gamma gene segments, the size and potential diversity of the V delta repertoire is important for the number of different antigens that may be recognized by gamma delta heterodimers. The delta-chain locus is located 75 kilobases (kb) 5' to the TCR C alpha coding region, raising the possibility that the alpha and delta V-region repertoires may overlap. Also, analysis of rearrangements at the delta-chain locus in developing thymocytes shows distinct fetal and adult patterns indicating that there may be differences between the fetal and adult V delta repertoires. To address these questions, we have characterized a large number of delta-containing complementary DNA clones from adult double-negative thymocytes (CD4-8-), an immature population that is enriched for gamma delta-bearing cells. We find that a limited number of V delta sequences are used, showing little overlap with known adult V alpha s and differing significantly from fetal V delta s. But as two D elements may participate simultaneously in V delta gene assembly, and random nucleotides may be added at any one of three junctional points, the potential number of different delta chains that can be made in the adult thymus is very large (approximately 10(13)).     

鄂尔多斯盆地西南部山1、盒8段孔隙特征及物性研究

近年来,鄂尔多斯盆地西南部逐渐成为致密气勘探开发的重点区块。然而,对该地区主力产气层山1段和盒8段的储集空间以及物性特征的研究还十分不足。利用偏光显微镜、扫描电镜观察,结合压汞实验数据,对研究区山1、盒8段砂岩的孔隙微观特征及类型、孔隙结构及物性关系进行了详细的分析。结果表明:研究区主要发育的孔隙类型为残余粒间孔、岩屑溶孔、杂基溶孔和晶间孔;孔喉大小、分选性以及连通性的分析显示,盒8上亚段的孔隙结构最好,其次为盒8下亚段,山1段的孔隙结构相对较差;山1段和盒8段均为低渗透储层,孔隙度与渗透率呈指数相关,其中盒8上亚段的孔渗高于下亚段,盒8段的孔渗性明显优于山1段。综合来看,储层物性以盒8上亚段最好,其次为盒8下亚段,山1段的物性最差。     

(1R,3S)-樟脑酸制备(1S,3R)-樟脑酸酐过程中构型翻转的研究

(1S,3R)-樟脑酸酐由(1R,3S)-樟脑酸制得并经过元素分析、红外光谱、比旋光度和X-射线单晶衍射表征.通过晶体结构和量子化学计算的结果对该化合物中两个手性碳原子同时发生构型翻转进行了讨论.(1S,3R)-樟脑酸酐的晶体学数据正交晶系,空间群为P2(1)2(1)2(1),a=0.648 72(15)nm,b=1.119 0(3)nm,c=1.301 0(3)nm,V=0.944 4(4)nm3,Z=4,Dc=1.282 Mg·m-3,Rint=0.055 5,S=1.001,I＞2σ(I)dataR1=0.045 4,wR2=0.092 7,all dataR1=0.058 8,wR2=0.095 9.     

胸腺素α1对鸡生长性能及免疫器官发育的影响

通过对照试验在4日龄和7日龄时,低剂量组、中剂量组和高剂量组每只鸡分别肌注0.015 mg*kg-1,0.03 mg*kg-1和0.06 mg*kg-1体重剂量的胸腺素α1(Tα1),对照组注射等量的生理盐水.试验期为56 d,观察Tα1对鸡体重、饲料转化率、法氏囊指数、胸腺指数、和脾脏指数的影响.结果表明在35,42和56日龄时,低剂量组鸡的体重显著高于其他各组(P<0.05),而在14和21日龄时各组平均体重差异不显著(P>0.05).在整个试验期间,低剂量组的饲料报酬均高于其他三组;低剂量组的法氏囊指数均高于其他三组,并在14日龄时与对照组和中剂量组差异显著(P<0.05),而在35日龄与对照组和高剂量组差异显著(P<0.05);低剂量组的胸腺指数也高于其他三组,14日龄时与对照组差异显著(P<0.05),而与中剂量组和高剂量组差异不显著(P>0.05),但在35和56日龄时差异显著(P<0.05);低剂量组的脾脏指数高于其他三组,且在35和56日龄差异显著(P<0.05).     

拟阵S(M_1,M_2)与P(M_1,M_2)的基及其应用

对拟阵S(M1,M2)与P(M1,M2)的基及其应用进行了研究.用CS的定义证明了B∈B(S(M1,M2))的充分必要条件.用基的相互关系证明了r(S(M1,M2))和r(P(M1,M2))的计算公式,并由此推出:(1)P(M1,M2)=S(M1,M2);(2)若M/p=M1⊕M2,则M=P(M-E(M1),M-E(M2)).     

龙葵多糖对荷瘤小鼠脾指数和胸腺指数的影响

研究龙葵多糖对荷瘤小鼠脾指数和胸腺指数的影响,从免疫学角度初步探讨龙葵多糖的抗肿瘤药效学作用.实验采用MTT法观察龙葵多糖对Hep G-2和SGC-7901两种人肿瘤细胞的生长抑制作用.测定S180小鼠瘤重,H22荷瘤小鼠生存时间以及胸腺指数、脾指数等.实验结果表明龙葵多糖对Hep G-2细胞和SGC-7901细胞的IC50分别为189.60μg/m L和186.56μg/m L.龙葵多糖能够显著降低S180荷瘤小鼠平均瘤重,与阴性对照组比较具有显著性差异(P0.01),龙葵多糖能明显延长H22荷瘤小鼠的生存时间(P0.05或P0.01),显著提高荷瘤小鼠的胸腺指数和脾指数(P0.05或P0.01).表明龙葵多糖的肿瘤作用是通过改善机体免疫力实现的,而不是通过细胞毒作用发挥的.     

溴氰菊酯降解菌Pseudomonas sp.P1-1-B3产酶条件的优化

农药降解酶对去除农药残留污染具有良好的应用前景.从海洋沉积物中筛选到一株高产溴氰菊酯降解酶的菌株Pseudomonas sp.P1-1-B3,研究了碳源、氮源、pH值、培养温度、培养时间、接种量及溴氰菊酯对菌株产酶的影响.结果表明,降解菌产酶的最适条件为:以可溶性淀粉作为碳源,m(蛋白胨):m(酵母浸膏)=2:1为氮源,pH 7.5,温度30℃,培养时间2 d,接种量3%,溴氰菊酯含量15μmol/L.在此条件下,菌株产酶的比活力最大为113.3 U/mg.该降解酶对溴氰菊酯的降解,在12 h内降解率达54.6%.     

莲子对黄曲霉毒素（B_1）诱发的人体淋巴细胞姐妹染色单体互换和细胞周期状态的影响

莲子对黄曲霉毒素（Ｂ_１）诱发的人体淋巴细胞姐妹染色单体互换和细胞周期状态的影响干侣仙，廖绵初，黄少珍（厦门大学抗癌研究中心，广西壮族自治区肿瘤研究所）肿瘤细胞遗传学和肿瘤形成过程的研究已表明［１］在细胞恶性转化和肿瘤形成的多阶段过程中，存在着突变，...     

The conserved protein DCN-1/Dcn1p is required for cullin neddylation in C. elegans and S. cerevisiae

SCF-type E3 ubiquitin ligases are multi-protein complexes required for polyubiquitination and subsequent degradation of target proteins by the 26S proteasome. Cullins, together with the RING-finger protein Rbx1, form the catalytic core of the ligase, and recruit the substrate-recognition module. Cycles of covalent modification of cullins by the ubiquitin-like molecule Nedd8 (neddylation) and removal of Nedd8 by the COP9 signalosome (deneddylation) positively regulate E3 ligase activity. Here we report the identification and analysis of a widely conserved protein that is required for cullin neddylation in the nematode Caenorhabditis elegans and the yeast Saccharomyces cerevisiae. C. elegans DCN-1 and S. cerevisiae Dcn1p (defective in cullin neddylation) are characterized by a novel UBA-like ubiquitin-binding domain and a DUF298 domain of unknown function. Consistent with their requirements for neddylation, DCN-1 and Dcn1p directly bind Nedd8 and physically associate with cullins in both species. Moreover, overexpression of Dcn1p in yeast results in the accumulation of Nedd8-modified cullin Cdc53p. Both in vivo and in vitro experiments indicate that Dcn1p does not inhibit deneddylation of Cdc53p by the COP9 signalosome, but greatly increases the kinetics of the neddylation reaction.     

Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition.

Tissue injury generates endogenous factors that heighten our sense of pain by increasing the response of sensory nerve endings to noxious stimuli. Bradykinin and nerve growth factor (NGF) are two such pro-algesic agents that activate G-protein-coupled (BK2) and tyrosine kinase (TrkA) receptors, respectively, to stimulate phospholipase C (PLC) signalling pathways in primary afferent neurons. How these actions produce sensitization to physical or chemical stimuli has not been elucidated at the molecular level. Here, we show that bradykinin- or NGF-mediated potentiation of thermal sensitivity in vivo requires expression of VR1, a heat-activated ion channel on sensory neurons. Diminution of plasma membrane phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) levels through antibody sequestration or PLC-mediated hydrolysis mimics the potentiating effects of bradykinin or NGF at the cellular level. Moreover, recruitment of PLC-gamma to TrkA is essential for NGF-mediated potentiation of channel activity, and biochemical studies suggest that VR1 associates with this complex. These studies delineate a biochemical mechanism through which bradykinin and NGF produce hypersensitivity and might explain how the activation of PLC signalling systems regulates other members of the TRP channel family.     

水稻体细胞无性系及其杂种F1粒形的遗传变异

比较了水稻体细胞无性系与供体亲本、体细胞无性系杂种F1与供体亲本杂种F1在8个谷粒性状上的差异,结果表明:体细胞无性系除千粒重及谷粒厚2性状显著小于亲本外,其余性状与亲本差异不显著;体细胞无性系杂种F1的长厚比显著大于亲本杂种F1,而谷粒厚则相反.聚类分析将53个体细胞无性系及53个相应的杂种F1分别聚为4类 ,R3及R1F2各类别间8个谷粒性状均存在极显著差异.R3与R1F2谷粒性状间的相关性表现也存在一定的差异.     

基于改进P-S模型工程抢修抢建风险预警方法

为适应风险预警“风险可能性低、安全满意度高”的心理特征与期望,提出了一种基于改进可能满意度的震后工程抢修抢建风险预警方法。在介绍可能满意度方法原理基础上,建立了震后工程抢修抢建风险预警模式,划分预警等级,确定多层次风险预警等级的可能度、满意度函数,分析风险可能度与满意度的互逆变化特征,确定风险预警可能满意度的并合形式化表达,运用数据包络分析方法改进风险预警的可能满意度模型,确定震后工程抢修抢建风险预警的相对可能满意度模型。模型应用于边坡工程抢修作业进程中整体安全风险预警案例,结果表明方法合理、可行,具有较好的预警能力。