Blocking of HIV-1 infectivity by a soluble, secreted form of the CD4 antigen

The initial event in the infection of human T lymphocytes, macrophages, and other cells by human immunodeficiency virus (HIV-1) is the attachment of the HIV-1 envelope glycoprotein gp120 to its cellular receptor, CD4. As a step toward designing antagonists of this binding event, soluble, secreted forms of CD4 were produced by transfection of mammalian cells with vectors encoding versions of CD4 lacking its transmembrane and cytoplasmic domains. The soluble CD4 so produced binds gp120 with an affinity and specificity comparable to intact CD4 and is capable of neutralizing the infectivity of HIV-1. These studies reveal that the high-affinity CD4-gp120 interaction does not require other cell or viral components and may establish a novel basis for therapeutic intervention in the acquired immune deficiency syndrome (AIDS).     

Recognition of histone H3 lysine-4 methylation by the double tudor domain of JMJD2A

Biological responses to histone methylation critically depend on the faithful readout and transduction of the methyl-lysine signal by "effector" proteins, yet our understanding of methyl-lysine recognition has so far been limited to the study of histone binding by chromodomain and WD40-repeat proteins. The double tudor domain of JMJD2A, a Jmjc domain-containing histone demethylase, binds methylated histone H3-K4 and H4-K20. We found that the double tudor domain has an interdigitated structure, and the unusual fold is required for its ability to bind methylated histone tails. The cocrystal structure of the JMJD2A double tudor domain with a trimethylated H3-K4 peptide reveals that the trimethyl-K4 is bound in a cage of three aromatic residues, two of which are from the tudor-2 motif, whereas the binding specificity is determined by side-chain interactions involving amino acids from the tudor-1 motif. Our study provides mechanistic insights into recognition of methylated histone tails by tudor domains and reveals the structural intricacy of methyl-lysine recognition by two closely spaced effector domains.     

Inhibition of T cell receptor expression and function in immature CD4+CD8+ cells by CD4

Most immature CD4+CD8+ thymocytes express only a small number of T cell receptor (TCR) molecules on their surface, and the TCR molecules they do express are only marginally capable of transducing intracellular signals. TCR expression and function was not intrinsically low in immature CD4+CD8+ thymocytes, but was found to be actively inhibited by CD4-mediated signals. Indeed, release of CD4+CD8+ thymocytes from CD4-mediated signals resulted in significant increases in both TCR expression and signaling function. These results suggest that, in CD4+CD8+ cells developing in the thymus, increased TCR expression and function requires release from CD4-mediated inhibition.     

Metabolic regulation of brain Abeta by neprilysin

Amyloid beta peptide (Abeta), the pathogenic agent of Alzheimer's disease (AD), is a physiological metabolite in the brain. We examined the role of neprilysin, a candidate Abeta-degrading peptidase, in the metabolism using neprilysin gene-disrupted mice. Neprilysin deficiency resulted in defects both in the degradation of exogenously administered Abeta and in the metabolic suppression of the endogenous Abeta levels in a gene dose-dependent manner. The regional levels of Abeta in the neprilysin-deficient mouse brain were in the distinct order of hippocampus, cortex, thalamus/striatum, and cerebellum, where hippocampus has the highest level and cerebellum the lowest, correlating with the vulnerability to Abeta deposition in brains of humans with AD. Our observations suggest that even partial down-regulation of neprilysin activity, which could be caused by aging, can contribute to AD development by promoting Abeta accumulation.     

Induction by soluble factors of organized axial structures in chick epiblasts

Inductive action of soluble factors was tested on isolated chick epiblasts. An assay was developed wherein conditioned medium derived from the Xenopus XTC cell line induced the formation of a full-length notochord and rows of bilaterally symmetric somites. Basic fibroblast growth factor, epidermal growth factor, retinoic acid, and transforming growth factor type B1 and B2 were not capable of inducing axial structures. Thus, soluble factors can elicit the development of polarity stored in the epiblast and behave as true morphogens since they can induce the formation of the organized complex structures that constitute the embryonic axis.     

Generation of calcium oscillations in fibroblasts by positive feedback between calcium and IP3

A wide variety of nonexcitable cells generate repetitive transient increases in cytosolic calcium ion concentration ([Ca2+]i) when stimulated with agonists that engage the phosphoinositide signalling pathway. Current theories regarding the mechanisms of oscillation disagree on whether Ca2+ inhibits or stimulates its own release from internal stores and whether inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DG) also undergo oscillations linked to the Ca2+ spikes. In this study, Ca2+ was found to stimulate its own release in REF52 fibroblasts primed by mitogens plus depolarization. However, unlike Ca2+ release in muscle and nerve cells, this amplification was insensitive to caffeine or ryanodine and required hormone receptor occupancy and functional IP3 receptors. Oscillations in [Ca2+]i were accompanied by oscillations in IP3 concentration but did not require functional protein kinase C. Therefore, the dominant feedback mechanism in this cell type appears to be Ca2+ stimulation of phospholipase C once this enzyme has been activated by hormone receptors.     

多肽提取物对鸡生长性能和抗球虫感染及调节免疫功能的影响

[目的]为寻找在缓解家禽疾病中能够替代抗生素的中药提取物.[方法]取健康1日龄仔鸡随机分阴性对照组、阳性对照组、盐霉素组、地鳖肽组、蛴螬肽组、联合肽组,除阴性对照组外,所有14 d肉仔鸡攻毒柔嫩艾美耳球虫卵囊5×103/只,测定21 d仔鸡生长性能、脏器指数、免疫功能及抗球虫效果.[结果]各组间21d仔鸡日增重、采食量、料重比无显著差异;鸡感染球虫第7天联合肽组仔鸡肠道损伤和鸡排出卵囊数比阳性对照组显著降低;阳性对照组和联合肽组鸡抗球虫指数(ACI)分别为126.44和159.79;地鳖肽、蛴螬肽和联合肽组21d仔鸡肝脏、脾脏、胸腺和法氏囊器官指数均极显著升高;联合肽组21d仔鸡肠道绒毛长度显著加长、隐窝深度明显变浅,绒毛高度与隐窝深度比值极显著提高;联合肽组仔鸡血液T和B淋巴细胞转化明显高于阳性对照组.[结论]结果表明,多肽提取物可显著降低卵囊排出呈现一定抗球虫效果,且能够提高受到柔嫩艾美耳球虫感染后仔鸡的调节免疫功能.     

miR-125a对人脑微血管内皮细胞功能的调节作用

目的 探讨miR-125a对人脑微血管内皮细胞(HBMECs)功能的影响.方法 体外培养HBMECs,慢病毒感染法沉默HBMEC中miR-125a,qRT-PCR检测HBMECs中miR-125a表达.在正常条件及低密度脂蛋白(ox-LDL)刺激条件下,采用MTT法检测HBMEC细胞增殖能力,血管形成检测试剂盒检测细胞血管形成,分别采用衰老试剂盒和流式细胞仪检测细胞的衰老及凋亡.结果 在正常及ox-LDL处理条件下,miR-125a敲除均能抑制HBMEC细胞增殖及血管形成能力,促进细胞衰老及凋亡.结论 miR-125a调控生理及病理条件下HBMECs多种功能.     

Prevention of HIV-1 infection and preservation of CD4 function by the binding of CPFs to gp120

Infection by human immunodeficiency virus type-1 (HIV-1) is initiated when its envelope protein, gp120, binds to its receptor, the cell surface glycoprotein CD4. Small molecules, termed N-carbomethoxycarbonyl-prolyl-phenylalanyl benzyl esters (CPFs), blocked this binding. CPFs interacted with gp120 and did not interfere with the binding of CD4 to class II major histocompatibility complex molecules. One CPF isomer, CPF(DD), preserved CD4-dependent T cell function while inhibiting HIV-1 infection of H9 tumor cells and human T cells. Although the production of viral proteins in infected T cells is unaltered by CPF(DD), this compound prevents the spread of infection in an in vitro model system.     

The endocrine regulation of aging by insulin-like signals

Reduced signaling of insulin-like peptides increases the life-span of nematodes, flies, and rodents. In the nematode and the fly, secondary hormones downstream of insulin-like signaling appear to regulate aging. In mammals, the order in which the hormones act is unresolved because insulin, insulin-like growth factor-1, growth hormone, and thyroid hormones are interdependent. In all species examined to date, endocrine manipulations can slow aging without concurrent costs in reproduction, but with inevitable increases in stress resistance. Despite the similarities among mammals and invertebrates in insulin-like peptides and their signal cascade, more research is needed to determine whether these signals control aging in the same way in all the species by the same mechanism.     

Positive supercoiling of mitotic DNA drives decatenation by topoisomerase II in eukaryotes

DNA topoisomerase II completely removes DNA intertwining, or catenation, between sister chromatids before they are segregated during cell division. How this occurs throughout the genome is poorly understood. We demonstrate that in yeast, centromeric plasmids undergo a dramatic change in their topology as the cells pass through mitosis. This change is characterized by positive supercoiling of the DNA and requires mitotic spindles and the condensin factor Smc2. When mitotic positive supercoiling occurs on decatenated DNA, it is rapidly relaxed by topoisomerase II. However, when positive supercoiling takes place in catenated plasmid, topoisomerase II activity is directed toward decatenation of the molecules before relaxation. Thus, a topological change on DNA drives topoisomerase II to decatenate molecules during mitosis, potentially driving the full decatenation of the genome.     

不同提取方法下茶园土壤可溶性有机氮含量差异

以相似地形条件、相同成土母质和土壤类型的两个品种(黄旦和福云6号)茶园生态系统为研究对象,采用H2O(室温)、H2O(70℃)和KCl(2 mol.L-1)3种提取方法研究两个品种茶园土壤可溶性有机氮(SON)含量差异.结果表明,茶园不同土层3种提取方法的土壤SON含量间呈显著或极显著差异,SON含量大小均表现为:KCl(2 mol.L-1)>H2O(70℃)>H2O(室温);H2O(室温)、H2O(70℃)、KCl(2 mol.L-1)提取测定的黄旦和福云6号茶园上层(0-15 cm)土壤SON含量分别比下层(15-30 cm)高9.62%、17.93%、11.64%和36.57%、46.23%、25.54%,垂直差异达显著或极显著水平;H2O(70℃)和KCl(2 mol.L-1)提取测定的黄旦茶园上层土壤SON含量分别比福云6号上层高17.44%和7.88%,差异达显著水平.可见,茶园土壤SON含量因提取剂及茶树品种的不同而差异明显.     

Control of calcium carbonate nucleation and crystal growth by soluble matrx of oyster shell

A calcium-binding soluble protein extracted from oyster shell suppresses calcium carbonate nucleation and decreases the rate of crystal growth in vitro. These findings suggest that soluble matrix may regulate shell growth.     

Regulation of alloreactivity in vivo by a soluble form of the interleukin-1 receptor

In vitro studies have shown that cytokines are involved in the regulation of the immune response, but their role in vivo is less well defined. Specific cytokine antagonists enable the identification of particular cytokines involved in the response and offer a means for modifying it. Systemic administration of a soluble, extracellular portion of the receptor for interleukin-1 (sIL-1R) had profound inhibitory effects on the development of in vivo alloreactivity. Survival of heterotopic heart allografts was prolonged from 12 days in controls to 17 days in mice treated with sIL-1R. Lymph node hyperplasia in response to a localized injection of allogeneic cells was completely blocked by sIL-1R treatment. The inhibition was overcome by simultaneous administration of interleukin-1 (IL-1); thus, sIL-1R acts by neutralizing IL-1. These results implicate IL-1 as a regulator of allograft rejection and demonstrate the in vivo biological efficacy of a soluble cytokine receptor.