Distinct pathogenic sequela in rhesus macaques infected with CCR5 or CXCR4 utilizing SHIVs

Infection of macaques with chimeric simian-human immunodeficiency virus (SHIV) provides an excellent in vivo model for examining the influence of envelope on HIV-1 pathogenesis. Infection with a pathogenic CCR5 (R5)-specific enveloped virus, SHIVSF162P, was compared with infection with the CXCR4 (X4)-specific SHIVSF33A.2. Despite comparable levels of viral replication, animals infected with the R5 and X4 SHIV had distinct pathogenic outcomes. SHIVSF162P caused a dramatic loss of CD4+ intestinal T cells followed by a gradual depletion in peripheral CD4+ T cells, whereas infection with SHIVSF33A.2 caused a profound loss in peripheral T cells that was not paralleled in the intestine. These results suggest a critical role of co-receptor utilization in viral pathogenesis and provide a reliable in vivo model for preclinical examination of HIV-1 vaccines and therapeutic agents in the context of the HIV-1 envelope protein.     

Structure of a peptide inhibitor bound to the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase

The structure of a 20-amino acid peptide inhibitor bound to the catalytic subunit of cyclic AMP-dependent protein kinase, and its interactions with the enzyme, are described. The x-ray crystal structure of the complex is the basis of the analysis. The peptide inhibitor, derived from a naturally occurring heat-stable protein kinase inhibitor, contains an amphipathic helix that is followed by a turn and an extended conformation. The extended region occupies the cleft between the two lobes of the enzyme and contains a five-residue consensus recognition sequence common to all substrates and peptide inhibitors of the catalytic subunit. The helical portion of the peptide binds to a hydrophobic groove and conveys high affinity binding. Loops from both domains converge at the active site and contribute to a network of conserved residues at the sites of magnesium adenosine triphosphate binding and catalysis. Amino acids associated with peptide recognition, nonconserved, extend over a large surface area.     

Vasoactive intestinal peptide alters membrane potential and cyclic nucleotide levels in retinal horizontal cells

Vasoactive intestinal peptide stimulated the synthesis of adenosine 3',5'-monophosphate in fractions of isolated carp horizontal cells. When applied extracellularly to isolated and cultured horizontal cells, the peptide also induced a slow depolarization (30 to 40 millivolts) accompanied by a decrease in membrane resistance. However, analogs of adenosine 3',5'-monophosphate applied extracellularly or intracellularly, and forscolin applied extracellularly, had no effect on the membrane potential of cultured horizontal cells, indicating that the induced depolarization was not related to the accumulation of adenosine 3',5'-monophosphate in these cells.     

Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4

The CCR5 co-receptor binds to the HIV-1 gp120 envelope glycoprotein and facilitates HIV-1 entry into cells. Its N terminus is tyrosine-sulfated, as are many antibodies that react with the co-receptor binding site on gp120. We applied nuclear magnetic resonance and crystallographic techniques to analyze the structure of the CCR5 N terminus and that of the tyrosine-sulfated antibody 412d in complex with gp120 and CD4. The conformations of tyrosine-sulfated regions of CCR5 (alpha-helix) and 412d (extended loop) are surprisingly different. Nonetheless, a critical sulfotyrosine on CCR5 and on 412d induces similar structural rearrangements in gp120. These results now provide a framework for understanding HIV-1 interactions with the CCR5 N terminus during viral entry and define a conserved site on gp120, whose recognition of sulfotyrosine engenders posttranslational mimicry by the immune system.     

胃黏膜CXCR4在大鼠实验性胃溃疡愈合过程中的表达及意义

目的：探讨大鼠实验性胃溃疡自愈期间溃疡局部 CXC趋化因子受体4[Chemokine （C-X-C motif） receptor 4,CXCR4]蛋白和mRNA的表达及其在胃溃疡愈合中的意义。方法以免疫组织化学染色和 RT-PCR技术分别检测溃疡组（40只）和正常组（8只）大鼠胃溃疡局部及其周围组织CXCR4蛋白表达和 mRNA的转录情况。结果 CXCR4免疫阳性物质主要位于壁细胞胞质和溃疡底部的炎细胞。溃疡愈合4～23 d,溃疡局部和溃疡周围组织CXCR4蛋白高表达,10 d平均吸光度值最大（P＜0.01）。溃疡组 CXCR4/β-actin吸光度比值在溃疡4～23 d均高于正常组,6 d最高（P＜0.01）。结论大鼠胃溃疡自愈期间溃疡局部和周围组织CXCR4高表达,可能通过不同途径促进周围细胞增殖分化参与溃疡愈合过程。     

联合检测类风湿因子、抗角蛋白抗体及抗环瓜氨酸多肽抗体对类风湿性关节炎的诊断价值

目的探讨类风湿因子（RF）、抗角蛋白抗体（AKA）及抗环瓜氨酸多肽（CCP）抗体联合检测对类风湿性关节炎（RA）的临床诊断价值。方法对83例RA和106例非RA患者用速率散射比浊法检测RF,间接免疫荧光染色法检测AKA,酶联免疫吸附法检测抗CCP抗体,并对3种指标检测进行比较分析。结果3种抗体单独检测对RA诊断的敏感性、特异性分别是：RF为71．1％、74．5％,AKA为49．4％、95．3％,抗CCP抗体为65．1％、94．3％;不同方式联合检测对RA诊断的敏感性、特异性分别是RF＋AKA为34．9％、97．2％,RF＋抗CCP抗体为45．8％、98．1％,RF＋AKA＋抗CCP抗体为28．9％、100％;RF在AKA、抗CCP抗体分别阴性的RA患者中检出率分别为28．6％和34．5％;AKA和抗CCP抗体在RF阴性的RA患者中分别有45．8％和62．5％的阳性率。结论单独检测RF对RA诊断的敏感性最高,特异性最高的是AKA,抗CCP抗体有较高的的敏感性及特异性,3种指标各有优点,可互为补充,联合检测RF、AKA及抗CCP抗体可提高对RA诊断的特异性,有助于早期RA的诊断。     

Synthetic CD4 peptide derivatives that inhibit HIV infection and cytopathicity

Synthetic peptide segments of the CD4 molecule were tested for their ability to inhibit infection of CD4+ cells by the human immunodeficiency virus (HIV) and to inhibit HIV-induced cell fusion. A peptide mixture composed of CD4(76-94), and synthesis side products, blocked HIV-induced cell fusion at a nominal concentration of 125 micromolar. Upon high-performance liquid chromatography, the antisyncytial activity of the peptide mixture was found not in the fraction containing the peptide CD4(76-94) itself, but in a side fraction containing derivatized peptide products generated in the automated synthesis. Derivatized deletion and substitution peptides in the region CD4(76-94) were used to demonstrate sequence specificity, a requirement for benzyl derivatization, and a core seven-residue fragment required for antisyncytial activity. A partially purified S-benzyl-CD4(83-94) peptide mixture inhibited HIV-induced cell fusion at a nominal concentration of less than or equal to 32 micromolar. Derivatized CD4 peptides blocked cell fusion induced by several HIV isolates and by the simian immunodeficiency virus, SIV, and blocked infection in vitro by four HIV-1 isolates with widely variant envelope gene sequences. Purified CD4(83-94) dibenzylated at cysteine 86 and glutamate 87 possessed antisyncytial activity at 125 micromolar. Derivatization may specifically alter the conformation of CD4 holoreceptor peptide fragments, increasing their antiviral efficacy.     

猪骨形态发生蛋白4成熟肽cDNA的克隆及序列分析

克隆猪骨形态发生蛋白4(BMP-4)成熟肽基因。通过提取猪肾的总RNA,通过RT-PCR技术扩增出目的基因,并将其回收后与pMD18-T载体连接,转化大肠杆菌TOP10感受态细胞,进行阳性克隆的筛选与鉴定。琼脂糖凝胶电泳检测RT-PCR产物,显示结果与预期片段大小一致,质粒PCR检测、酶切鉴定证实重组克隆中插入了PCR产物,测序结果揭示BMP-4成熟肽cDNA长为351bp,编码116个氨基酸。序列对比表明,猪与人、小鼠、牛、绵羊BMP-4成熟肽cDNA序列的同源性分别为94.87%、90.60%、94.87%、94.59%,而相应的氨基酸同源性分别为99.12%,99.12%,100%、100%。首次成功地克隆了猪BMP-4成熟肽编码基因,对于进一步研究猪BMP-4全基因结构、功能及其与繁殖性能的关系有重要的意义。     

缺陷和变周期结构光子晶体特性研究

构建了介质柱间距变化的变周期结构以及介质柱半径线缺陷两种二维光子晶体模型,并将时域有限差分法用于其能带特性研究。数值计算结果表明,在二维正方格光子晶体结构的基础上,一定范围内逐渐增加圆介质柱之间的距离,光子晶体的禁带宽度会增大,同时禁带的中心频率偏向低频方向,而采用相邻列介质柱半径交替变化的缺陷结构,也将使光子晶体的禁带发生相应的变化。     

缺陷和变周期结构光子晶体特性研究

构建了介质柱间距变化的变周期结构以及介质柱半径线缺陷两种二维光子晶体模型,并将时域有限差分法用于其能带特性研究。数值计算结果表明,在二维正方格光子晶体结构的基础上,一定范围内逐渐增加圆介质柱之间的距离,光子晶体的禁带宽度会增大,同时禁带的中心频率偏向低频方向,而采用相邻列介质柱半径交替变化的缺陷结构,也将使光子晶体的禁带发生相应的变化。     

Crystal structures of an antibody to a peptide and its complex with peptide antigen at 2.8 A

The three-dimensional structures of an antibody to a peptide and its complex with the peptide antigen have been determined at 2.8 A resolution. The antigen is a synthetic 19-amino acid peptide homolog of the C helix of myohemerythrin (Mhr). The unliganded Fab' crystals are orthorhombic with two molecules per asymmetric unit, whereas the complex crystals are hexagonal with one molecule per asymmetric unit. The Fab' and the Fab'-peptide complex structures have been solved independently by molecular replacement methods and have crystallographic R factors of 0.197 and 0.215, respectively, with no water molecules included. The amino-terminal portion of the peptide sequence (NH2-Glu-Val-Val-Pro-His-Lys-Lys) is clearly interpretable in the electron density map of the Fab'-peptide complex and adopts a well-defined type II beta-turn in the concave antigen binding pocket. This same peptide amino acid sequence in native Mhr is alpha-helical. The peptide conformation when bound to the Fab' is inconsistent with binding of the Fab' to native Mhr, and suggests that binding of the Fab' to conformationally altered forms of the native Mhr or to apo-Mhr. Immunological mapping previously identified this sequence as the peptide epitope, and its fine specificity correlates well with the structural analysis. The binding pocket includes a large percentage of hydrophobic residues. The buried surfaces of the peptide and the antibody are complementary in shape and cover 460 A2 and 540 A2, respectively. These two structures now enable a comparison of a specific monoclonal Fab' both in its free and antigen complexed state. While no major changes in the antibody were observed when peptide was bound, there were some small but significant side chain and main chain rearrangements.     

中国荷斯坦牛CXCR1基因遗传多态性与体细胞评分的关联分析

【目的】研究中国荷斯坦奶牛CXCR1基因的多态性及其与体细胞评分(Somaticcellscore,SCS)的关系,寻找与中国荷斯坦牛SCS相关的分子遗传标记,加快抗病育种进程。【方法】采用PCR-SSCP技术对来自30个公牛家系的610头中国荷斯坦牛CXCR1基因进行多态性检测,利用最小二乘均数法对CRCR1基因的多态位点与SCS进行相关分析,利用PHASE软件对4个多态位点进行单倍型分析。【结果】检测到4个SNPs,在5侧翼区发现了3个SNPs(-1830(A/G)、-1768(T/A)、-344(T/C)),在编码区783(C/A)位点为新发现的SNP。-1830(A/G)位点AA基因型个体SCS极显著低于AG基因型个体(P0.01),-1768(T/A)位点TT基因型个体SCS极显著低于TA基因型个体(P0.01),-344(T/C)位点TT基因型个体SCS极显著低于TC、CC个体(P0.01)。783(C/A)位点基因型个体的SCS差异不显著。单倍型Haplo2(ATTA)纯合基因型的SCS极显著低于Haplo1(ATCA)、Haplo3(GACA)和Haplo4(GATA)单倍型纯合基因型(P0.01)。【结论】-1830(A/G)位点AA基因型、-1768(T/A)位点TT基因型和-344(T/C)位点TT基因型以及单倍型Haplo2(ATTA)纯合体对中国荷斯坦牛的SCS具有较大的遗传效应,可作为分子标记应用于奶牛乳房炎抗性的筛选。     

新疆短命植物东方旱麦草和独行菜C4相关结构的初步研究

短命植物的快速生长及高光效特性使它们能在早春萌发后较短时间内完成生活史并获得大量种子.为探讨高光效产生的内在原因,研究利用树脂半超薄与超薄切片技术对东方旱麦草和独行菜叶片显微及超微结构进行观察,并对维管束相关参数进行了统计分析,结果显示:(1)东方旱麦草显微结构具有类"花环"结构,维管束密度介于C3、C4对照之间,鞘细胞中的叶绿体多数离心分布且数量接近C4植物;超微结构显示其鞘细胞叶绿体的基粒与片层结构与叶肉细胞不同,但又与C4植物存在一定差异.(2)独行菜维管束有类"花环"结构,维管束密度大于C3对照并存在极显著差异,鞘细胞中叶绿体多数离心分布;超微结构显示叶绿体基粒与片层没有叶肉细胞发达.以上研究结果初步说明东方旱麦草和独行菜的解剖结构特点均介于C3、C4植物之间而接近C4植物.     

A cyclic model of the universe

We propose a cosmological model in which the universe undergoes an endless sequence of cosmic epochs that begin with a "bang" and end in a "crunch." Temperature and density at the transition remain finite. Instead of having an inflationary epoch, each cycle includes a period of slow accelerated expansion (as recently observed) followed by contraction that produces the homogeneity, flatness, and energy needed to begin the next cycle.     

晴阴天对不同结构日光温室温度的影响

[目的]研究不同天气条件下不同结构类型日光温室的温度变化规律。[方法]建立2个不同结构的日光温室,在典型的阴晴天观测并记录室外天气情况和室内温度变化。[结果]晴天时,1号温室比2号温室升降温快,17:00后1号温室a点温度比2号温室低;2号温室的升温时间更长;11:00～17:00,1号温室c点温度比2号温室低,其他时间2个温室温度较接近;11:00～16:00,1号温室d点升温较快,其最高温度比2号温室高3.0℃。阴天时,整天内2个温室的温度均呈波动下降趋势;23:00,1号温室a、b点的温度分别降至10.5和7.8℃,2号温室的分别降至8.2和10.5℃;1号温室c点温度一直比2号温室低;1号温室d点温度变化较为平缓。[结论]2号温室的保温效果较好,温度变化较平缓,应作为山东省的重点推广温室类型。     

国内外输油泵的结构特点和维护要点

在对中比转数梯森泵、宾汉姆泵、国产输油泵的结构特点及运行维护分析以比的基础好各种输油泵的外形构造、叶轮、口环、涡室、机械密封室，轴承及轴在润滑系统等主要部件。从泵的特性参数来看，其综合技术指标都比较先进，特别是梯森泵和宾汉姆泵，目前在国内外工输管道中起到了艇，进口泵构合理，性能优良、运行效率高、维修方便、但存在着人格昂贵、购入手续繁琐等问题。     

A small-molecule modulator of poly-alpha 2,8-sialic acid expression on cultured neurons and tumor cells

Poly-alpha2,8-sialic acid (PSA) has been implicated in numerous normal and pathological processes, including development, neuronal plasticity, and tumor metastasis. We report that cell surface PSA expression can be reversibly inhibited by a small molecule, N-butanoylmannosamine (ManBut). Inhibition occurs through a metabolic mechanism in which ManBut is converted to unnatural sialic acid derivatives that effectively act as chain terminators during cellular PSA biosynthesis. N-Propanoylmannosamine (ManProp), which differs from ManBut by a single methylene group, did not inhibit PSA biosynthesis. Modulation of PSA expression by chemical means has a role complementary to genetic and biochemical approaches in the study of complex PSA-mediated events.     

非线性耦合分数阶系统的异结构同步

针对异结构的分数阶混沌系统同步问题,提出了非线性耦合分数阶异结构混沌系统的同步方法,即在α＋β-1=0条件下,利用非线性耦合实现两个异结构分数阶混沌系统同步,并通过数值仿真证明了其有效性.仿真实验显示,随着耦合系数的变化,系统呈现多样性,分数阶混沌系统出现不同混沌状态,而分数阶超混沌系统不仅会出现超混沌状态,还会出现发散的现象.     

高矿质元素糙米品种筛选与亚显微结构研究

[目的]从20种糙米中以蛋白质和矿质元素（Ca、Fe、Se）为主要指标对糙米的营养价值进行初步筛选,并观察筛选品种的形态结构,为功能稻米的选育提供依据。[方法]凯氏定氮法测定蛋白质含量,原子吸收光谱和原子荧光光谱法比较矿质元素含量差异,SPSS软件分析相关性,扫描电子显微镜观察筛选品种的形态。[结果]筛选出高Fe、高蛋白糙米ZT11（Fe 17.29 μg/g,蛋白质9.80%）和高Ca、高Se糙米小品比71（Ca65.50 μg/g,Se 0.050 μg/g）。蛋白质含量与Fe含量在0.01水平有显著正相关性。糙米横断面有一定的差异,蛋白质含量一定程度上影响糙米品种米糠层的分布情况。[结论]筛选的富Fe、Ca、Se糙米具有广阔的市场前景、保健效果和附加价值。