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31.
Platelet activation--a role for a 40K anti-phospholipase A2 protein indistinguishable from lipocortin 总被引:7,自引:0,他引:7
Stimulus-response (S-R) coupling in platelets requires an intermediary other than an elevation in cytosolic free calcium ([Ca2+]i). While an increase in [Ca2+]i is essential in S-R coupling, effecting phosphorylation of myosin of relative molecular mass (Mr) 20,000 (20 K), platelet activation is also associated with phosphorylation of a 40K protein, which can occur in the absence of changes in [Ca2+]i. The 40K protein is the substrate for protein kinase C (PKC). Mounting evidence suggests that activation of PKC by diacylglycerol is the other signal involved in S-R coupling. Although phosphorylation of the 40K protein is associated with certain platelet functional responses, no precise role has been accredited to it. Recently, we and others have described several proteins (collectively known as lipocortin) which inhibit phospholipase A2 (PLA2). One of the most conspicuous proteins of this group is a 40K peptide whose inhibitory activity can be suppressed by prior phosphorylation. We hypothesized that the 40K protein described in platelets may possess anti-PLA2 activity and that phosphorylation by PKC, suppressing its inhibitory activity, may represent the mechanism underlying mobilization of arachidonic acid, the precursor of prostaglandins. The results of the present study strongly support this hypothesis. 相似文献
32.
ICAM-1 a ligand for LFA-1-dependent adhesion of B, T and myeloid cells 总被引:60,自引:0,他引:60
M W Makgoba M E Sanders G E Ginther Luce M L Dustin T A Springer E A Clark P Mannoni S Shaw 《Nature》1988,331(6151):86-88
Cell-cell adhesion is essential for many immunological functions. The LFA-1 molecule, a member of a superfamily of adhesion molecules, participates in adhesion which is critical to the function of each of the three major subsets of leukocytes: lymphocytes, monocytes and granulocytes. Putative LFA-1 ligands have been identified functionally in different laboratories using three different monoclonal antibodies that inhibit LFA-1-mediated leukocyte adhesion in particular model systems; however, there may be more than one LFA-1 ligand. We have directly compared the three relevant monoclonal antibodies, and show that each binds to the same molecule, intercellular-adhesion molecule-1 (ICAM-1). Most important, B, T and myeloid cells adhere specifically to purified ICAM-1-coated surfaces; such adhesion has distinctive requirements for Mg2+ and Ca2+. This constitutes biochemical evidence that ICAM-1 functions as a ligand for LFA-1-dependent adhesion by a variety of leukocytes. 相似文献
33.
34.
The envelope glycoprotein of human immunodeficiency virus (HIV) initiates infection by mediating fusion of the viral envelope with the cell membrane. Fusion activity requires proteolytic cleavage of the gp160 protein into gp120 and gp41 at a site containing several arginine and lysine residues. Activation at basic cleavage sites is observed with many membrane proteins of cellular and viral origin. We have recently found that the enzyme activating the haemagglutinin of fowl plague virus (FPV), an avian influenza virus, is furin. Furin, a subtilisin-like eukaryotic endoprotease, has a substrate specificity for the consensus amino-acid sequence Arg-X-Lys/Arg-Arg at the cleavage site. We show here that the glycoprotein of HIV-1, which has the same protease recognition motif as the FPV haemagglutinin, is also activated by furin. 相似文献
35.
Van Heuverswyn F Li Y Neel C Bailes E Keele BF Liu W Loul S Butel C Liegeois F Bienvenue Y Ngolle EM Sharp PM Shaw GM Delaporte E Hahn BH Peeters M 《Nature》2006,444(7116):164
Chimpanzees (Pan troglodytes troglodytes) from west central Africa are recognized as the reservoir of simian immunodeficiency viruses (SIVcpzPtt) that have crossed at least twice to humans: this resulted in the AIDS pandemic (from human immunodeficiency virus HIV-1 group M) in one instance and infection of just a few individuals in Cameroon (by HIV-1 group N) in another. A third HIV-1 lineage (group O) from west central Africa also falls within the SIVcpzPtt radiation, but the primate reservoir of this virus has not been identified. Here we report the discovery of HIV-1 group O-like viruses in wild gorillas. 相似文献
36.
Patrick J. Shaw Bin Qu Markus Hoth Stefan Feske 《Cellular and molecular life sciences : CMLS》2013,70(15):2637-2656
Calcium (Ca2+) influx is required for the activation and function of all cells in the immune system. It is mediated mainly by store-operated Ca2+ entry (SOCE) through Ca2+ release-activated Ca2+ (CRAC) channels located in the plasma membrane. CRAC channels are composed of ORAI proteins that form the channel pore and are activated by stromal interaction molecules (STIM) 1 and 2. Located in the membrane of the endoplasmic reticulum, STIM1 and STIM2 have the dual function of sensing the intraluminal Ca2+ concentration in the ER and to activate CRAC channels. A decrease in the ER’s Ca2+ concentration induces STIM multimerization and translocation into puncta close to the plasma membrane where they bind to and activate ORAI channels. Since the identification of ORAI and STIM genes as the principal mediators of CRAC channel function, substantial advances have been achieved in understanding the molecular regulation and physiological role of CRAC channels in cells of the immune system and other organs. In this review, we discuss the mechanisms that regulate CRAC channel function and SOCE, the role of recently identified proteins and mechanisms that modulate the activation of ORAI/STIM proteins and the consequences of CRAC channel dysregulation for lymphocyte function and immunity. 相似文献
37.
Griffin Douglas Shaw Patricia Stacey Ralph 《Systemic Practice and Action Research》1999,12(3):295-309
As practitioners working with groups and organizations, we have reflected together on what we think is happening when we find ourselves acting into situations in which the intention motivating the action as its goal is itself emerging in the very action. Along with others, we have been excited by the ideas of self-organization in the natural sciences and also theories of practice, for example, tacit and explicit knowledge, in the social sciences. Together, these promise fresh insights into the potential of organizations. However, we find ourselves diverging significantly from writers who at first sight seem to be using similar ideas, but they do so with an exclusive focus on strategic choice and intention. To illustrate what we mean, we explore the work of Nonaka and Takeuchi and how they use Polanyi's idea of the participant observer. We do this to identify contradictions we see in their approach. We also discuss the implications of an alternative understanding of participation and what this indicates about what can and cannot be managed in the creation of new knowledge. 相似文献
38.
Systematic generation of high-resolution deletion coverage of the Drosophila melanogaster genome 总被引:1,自引:0,他引:1
Parks AL Cook KR Belvin M Dompe NA Fawcett R Huppert K Tan LR Winter CG Bogart KP Deal JE Deal-Herr ME Grant D Marcinko M Miyazaki WY Robertson S Shaw KJ Tabios M Vysotskaia V Zhao L Andrade RS Edgar KA Howie E Killpack K Milash B Norton A Thao D Whittaker K Winner MA Friedman L Margolis J Singer MA Kopczynski C Curtis D Kaufman TC Plowman GD Duyk G Francis-Lang HL 《Nature genetics》2004,36(3):288-292
In fruit fly research, chromosomal deletions are indispensable tools for mapping mutations, characterizing alleles and identifying interacting loci. Most widely used deletions were generated by irradiation or chemical mutagenesis. These methods are labor-intensive, generate random breakpoints and result in unwanted secondary mutations that can confound phenotypic analyses. Most of the existing deletions are large, have molecularly undefined endpoints and are maintained in genetically complex stocks. Furthermore, the existence of haplolethal or haplosterile loci makes the recovery of deletions of certain regions exceedingly difficult by traditional methods, resulting in gaps in coverage. Here we describe two methods that address these problems by providing for the systematic isolation of targeted deletions in the D. melanogaster genome. The first strategy used a P element-based technique to generate deletions that closely flank haploinsufficient genes and minimize undeleted regions. This deletion set has increased overall genomic coverage by 5-7%. The second strategy used FLP recombinase and the large array of FRT-bearing insertions described in the accompanying paper to generate 519 isogenic deletions with molecularly defined endpoints. This second deletion collection provides 56% genome coverage so far. The latter methodology enables the generation of small custom deletions with predictable endpoints throughout the genome and should make their isolation a simple and routine task. 相似文献
39.
Polarized light responses from crab retinula cells 总被引:4,自引:0,他引:4
40.
Well-known epistemologies of science have implications for how best to understand knowledge transfer (KT). Yet, to date, no serious attempt has been made to explicate these particular implications. This paper infers views about KT from two popular epistemologies; what we characterize as incommensurabilitist views (after Devitt, 2001; Bird, 2002, 2008; Sankey and Hoyningen-Huene 2013) and voluntarist views (after Van Fraassen, 1984; Dupré, 2001; Chakravartty, 2015). We argue views of the former sort define the methodological, ontological, and social conditions under which research operates within ‘different worlds’ (to use Kuhn's expression), and entail that genuine KTs under those conditions should be difficult or even impossible. By contrast, more liberal voluntarist views recognize epistemological processes that allow for transfers across different sciences even under such conditions. After outlining these antithetical positions, we identify two kinds of KTs present in well-known episodes in the history of ecology—specifically, successful model transfers from chemical kinetics and thermodynamics into areas of ecological research—which reveal significant limitations of incommensurabilitist views. We conclude by discussing how the selected examples support a pluralistic voluntarism regarding KT. 相似文献