CRMPs对神经元突起生长的调控

神经元突起是建立神经网络的物质基础,其生长为生长信号启动胞内信号促使神经元不断极化的过程.作为Rho GTPases的下游信号,CRMPs富集于神经系统,参与神经元的发育过程,可作为不同信号通路的共同受体后分子,通过改变细胞骨架的运动调控突起生长.其不同亚基的功能分化、不同亲和性特点显示其具有突起生长调控的分子开关特征...     

Oligodendrocyte-myelin glycoprotein is a Nogo receptor ligand that inhibits neurite outgrowth

The inhibitory activity associated with myelin is a major obstacle for successful axon regeneration in the adult mammalian central nervous system (CNS). In addition to myelin-associated glycoprotein (MAG) and Nogo-A, available evidence suggests the existence of additional inhibitors in CNS myelin. We show here that a glycosylphosphatidylinositol (GPI)-anchored CNS myelin protein, oligodendrocyte-myelin glycoprotein (OMgp), is a potent inhibitor of neurite outgrowth in cultured neurons. Like Nogo-A, OMgp contributes significantly to the inhibitory activity associated with CNS myelin. To further elucidate the mechanisms that mediate this inhibitory activity of OMgp, we screened an expression library and identified the Nogo receptor (NgR) as a high-affinity OMgp-binding protein. Cleavage of NgR and other GPI-linked proteins from the cell surface renders axons of dorsal root ganglia insensitive to OMgp. Introduction of exogenous NgR confers OMgp responsiveness to otherwise insensitive neurons. Thus, OMgp is an important inhibitor of neurite outgrowth that acts through NgR and its associated receptor complex. Interfering with the OMgp/NgR pathway may allow lesioned axons to regenerate after injury in vivo.     

A threshold effect of the major isoforms of NCAM on neurite outgrowth

Interactions between recognition molecules on the surface of neuronal growth cones and guidance cues present in the local cellular environment are thought to account for the growth of neurites in the highly stereospecific manner that contributes to correct target cell innervation. In vitro assays have been used to identify candidate molecular components of this system, either directly by demonstrating their ability to promote neurite outgrowth, or indirectly by the ability of specific antibodies to inhibit neurite outgrowth. The role of the neural cell adhesion molecule (NCAM) in pathway finding is not fully understood. Some immunological studies support a positive role; others do not, and it has been reported that purified NCAM does not support neurite outgrowth. We have previously shown that an arbitrary biochemical index of neurite outgrowth, the relative level of immunoreactive neurofilament protein, is increased when human and rat dorsal root ganglion neurons are cultured on monolayers of cells expressing transfected human NCAM. But, the complexity of growth precluded a simple morphological analysis and we did not determine the 'dose-response' relationship between NCAM expression and neuronal response. Here, we report on the morphology of rat cerebellar neurons cultured on monolayers of 3T3 cells transfected with complementary DNAs encoding all of the main NCAM isoforms found in cells such as astrocytes, Schwann cells and skeletal muscle. The data indicate that both transmembrane and glycosyl-phosphatidylinositol linked NCAM isoforms are potent substrates for neurite extension. A critical threshold value of NCAM expression is required for increased neurite outgrowth. Above this threshold, small increases in NCAM induce substantial increases in neurite outgrowth.     

Selective inhibition of neurite outgrowth on mature astrocytes by Thy-1 glycoprotein.

THY-1, the smallest member of the immunoglobulin superfamily, is a major cell-surface component expressed by several tissues. The protein, carbohydrate and gene structures of this molecule are known, yet its function is not. It is highly expressed in nervous tissue, where it appears on virtually all neurons after the cessation of axonal growth. Here we show that expression of Thy-1 by a neural cell line inhibits neurite outgrowth on mature astrocytes, but not on other cellular substrata which include Schwann cells and embryonic glia. This inhibition of neurite extension on astrocytes can be reversed by low concentrations (nanomolar) of soluble Thy-1. If a similar interaction between neuronal Thy-1 and astrocytes occurs in vivo, it could stabilize neuronal connections and suppress axonal regrowth after injury in the astrocyte-rich areas of adult central nervous system.     

Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1

The capacity of the adult brain and spinal cord to repair lesions by axonal regeneration or compensatory fibre growth is extremely limited. A monoclonal antibody (IN-1) raised against NI-220/250, a myelin protein that is a potent inhibitor of neurite growth, promoted axonal regeneration and compensatory plasticity following lesions of the central nervous system (CNS) in adult rats. Here we report the cloning of nogo A, the rat complementary DNA encoding NI-220/250. The nogo gene encodes at least three major protein products (Nogo-A, -B and -C). Recombinant Nogo-A is recognized by monoclonal antibody IN-1, and it inhibits neurite outgrowth from dorsal root ganglia and spreading of 3T3 fibroblasts in an IN-1-sensitive manner. Antibodies against Nogo-A stain CNS myelin and oligodendrocytes and allow dorsal root ganglion neurites to grow on CNS myelin and into optic nerve explants. These data show that Nogo-A is a potent inhibitor of neurite growth and an IN-1 antigen produced by oligodendrocytes, and may allow the generation of new reagents to enhance CNS regeneration and plasticity.     

Rho激酶抑制剂诱导PC12和PC12Adh细胞突起生长的差异比较

 PC12细胞是研究神经分化最常用的细胞之一.在rho激酶(ROCK)抑制剂的作用下,PC12细胞能够长出神经样突起.最近,美国菌种保存中心(ATCC)同时提供PC12细胞和PC12 Adh细胞.研究的主要目的是观察ROCK抑制剂诱导这2种细胞长突起是否存在差异.PC12细胞和PC12Adh细胞按照ATCC方法进行培养,用神经生长因子(NGF,1000ng/mL)或ROCK抑制剂(33μmol/L Y27632,33μmol/L法舒地尔)处理细胞1~4d.结果发现NGF能够诱导这2种细胞生长突起,而ROCK抑制剂只诱导PC12Adh细胞长突起,对PC12细胞不明显.因此,ROCK抑制剂诱导这2种细胞突起生长存在明显差异,PC12Adh细胞更适合用于ROCK抑制剂的神经诱导分化实验.     

Parochial altruism in humans

Social norms and the associated altruistic behaviours are decisive for the evolution of human cooperation and the maintenance of social order, and they affect family life, politics and economic interactions. However, as altruistic norm compliance and norm enforcement often emerge in the context of inter-group conflicts, they are likely to be shaped by parochialism--a preference for favouring the members of one's ethnic, racial or language group. We have conducted punishment experiments, which allow 'impartial' observers to punish norm violators, with indigenous groups in Papua New Guinea. Here we show that these experiments confirm the prediction of parochialism. We found that punishers protect ingroup victims--who suffer from a norm violation--much more than they do outgroup victims, regardless of the norm violator's group affiliation. Norm violators also expect that punishers will be lenient if the latter belong to their social group. As a consequence, norm violations occur more often if the punisher and the norm violator belong to the same group. Our results are puzzling for evolutionary multi-level selection theories based on selective group extinction as well as for theories of individual selection; they also indicate the need to explicitly examine the interactions between individuals stemming from different groups in evolutionary models.     

Egalitarian motives in humans

Participants in laboratory games are often willing to alter others' incomes at a cost to themselves, and this behaviour has the effect of promoting cooperation. What motivates this action is unclear: punishment and reward aimed at promoting cooperation cannot be distinguished from attempts to produce equality. To understand costly taking and costly giving, we create an experimental game that isolates egalitarian motives. The results show that subjects reduce and augment others' incomes, at a personal cost, even when there is no cooperative behaviour to be reinforced. Furthermore, the size and frequency of income alterations are strongly influenced by inequality. Emotions towards top earners become increasingly negative as inequality increases, and those who express these emotions spend more to reduce above-average earners' incomes and to increase below-average earners' incomes. The results suggest that egalitarian motives affect income-altering behaviours, and may therefore be an important factor underlying the evolution of strong reciprocity and, hence, cooperation in humans.     

Inhibition of neurite polarity by tau antisense oligonucleotides in primary cerebellar neurons

Neurons in culture can have fundamentally distinct morphologies which permit their cytological identification and the recognition of their neurites as axons or dendrites. Microtubules may have a role in determining morphology by the selective stabilization of spatially distinct microtubule subsets. The plasticity of a neurite correlates inversely with the stability of its component microtubules: microtubules in growth cones are very dynamic, and in initial neurites there is continuous incorporation of labelled subunits, whereas in mature neurites, microtubules are highly stabilized. The binding of microtubule-associated proteins to the microtubules very probably contributes to this stability. Cerebellar neurons in dissociated culture initially extend exploratory neurites and, after a relatively constant interval, become polarized. Polarity becomes evident when a single neurite exceeds the others in length. These stable neurites cease to undergo the retractions and extensions characteristic of initial neurites and assume many features of axons and dendrites. We have now studied the role of the neuronal microtubule-associate protein tau in neurite polarization by selectively inhibiting tau expression by the addition of antisense oligonucleotides to the culture media. Although the extension of initial exploratory neurites occurred normally, neurite asymmetry was inhibited by the failure to elaborate an axon.     

IA-SSS-MA三元共聚物的阻垢性能研究

以衣康酸(IA),苯乙烯磺酸钠(SSS),马来酸酐(MA)为单体,采用水溶液自由基聚合方法合成了IA-SSS-MA共聚物.静态试验条件下分别评价了其对碳酸钙、磷酸钙的阻垢性能和对氧化铁的分散性能,探讨了共聚物投加量、钙离子质量浓度、溶液pH值和溶液温度对共聚物阻垢率的影响,实验结果表明:IA-SSS-MA共聚物具有优良的阻垢分散性能,特别适用于高温、高硬度的循环冷却水.     

GSK3抑制剂的合成

4-甲酰基-2E-丁烯酸乙酯(8)经醛基保护、与2-氨基吡啶反应成环、加压氨化得到(11);5-氟-2-硝基苯甲醛(1)经醛基保护、Bartoli合成法制成吲哚、与乙醇胺反应并氢化、Boc保护、甲磺酰化、碱环合、与草酰氯甲醇钠反应制得(12);(11)与(12)对接、去保护、酰化得到目标化合物3-[9-氟2-(哌啶-1-羰基)-1,2,3,4-四氢-[1,4]-二氮杂卓艹并[6,7,1-hi]吲哚基-7]-4-咪唑并[1,2-a]吡啶基-3-吡咯-2,5-二酮.以化合物(1)为起始原料计算,共10步反应,总收率18%.     

Cyclosporin A promotes spontaneous outgrowth in vitro of Epstein-Barr virus-induced B-cell lines

Cyclosporin A (CSA) is a fungal metabolite which exerts profound effects on the immune system and has potential as a selective immuno-suppressive agent. Clinical trials with human renal allograft recipients have confirmed this potential but there have been disturbing reports of lymphoma in a significant number of patients. Despite extensive animal studies, the specificity of this drug for human lymphocyte subpopulations is largely unknown. We demonstrate here that in vitro CSA has no apparent effect on Epstein-Barr virus (EBV)-induced B-lymphocyte activation, but totally inhibits the T-cell dependent pokeweed mitogen (PWM) B-cell response. In addition, CSA markedly facilitates the outgrowth of B-lymphoblastoid cell lines from both EBV-infected and non-infected lymphocytes of EBV immune donors cultured in vitro. These results indicate that CSA can interfere with the lymphocytes normally responsible for maintaining the life-long carrier state initiated by primary infection with EBV, allowing outgrowth of the persistently infected cells circulating in the peripheral blood.     

油田采油阻垢剂筛选研究

为了筛选出适合某油田使用的阻垢剂,通过分析油田水质及垢样的 XRD,发现垢样成分主要为碳酸钙和硫酸钙. 在测定了 11 种阻垢剂钙容忍度的基础上,采用静态实验法和模拟油田水体法,测定了各种阻垢剂的阻垢率,对比后,筛选出了适合油田水质特点和垢体类型的 POCA 阻垢剂,在 80 ℃油田水质环境下,其添加质量浓度为 20 mg/L 时,阻垢率为 81.27%,钙容忍度高于 20 000.     

缓蚀剂与阻垢剂联合法制HEDP的研究

文中提出了一种新型的制备HEDP的方法,即利用缓蚀剂与阻垢剂联合法制备HEDP.该方法解决了常规方法中存在的污染环境、浪费原料、产品质量较低的问题.实验给出当反应温度为35～40℃,原料配比为1:0.9,保温时间为3 h,保温温度为120℃时,产率较高,为最佳反应条件.     

酸性介质中的钢铁有机缓蚀剂

概述了近几年酸性介质中钢铁有机缓蚀剂各类及研究方法的进展。着重讨论了有机缓蚀剂在酸性介质中的缓蚀作用及缓蚀机理,简述了将最子化学、人工神经网络、激光拉曼光谱等方法用于缓蚀剂研制的成果,对这研究方法进行了评述,对缓蚀剂的发展方向进行了展望。