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Receptor Specificity (receptor + specificity)
Selected AbstractsDendritic cell activation by danger and antigen-specific T-cell signallingEXPERIMENTAL DERMATOLOGY, Issue 5 2000A. D. McLellan Abstract: Recent transplantation, animal and in vitro studies suggest a dependence of some immune reactions on tissue damage. Although many factors involved in enhancing immune responses through tissue damage have yet to be identified, recent data suggests that one of the targets of these cellular stress factors is the bone marrow derived dendritic cell ( DC). DC are potent initiators of primary immune responses and hold the key to immune reactions through their ability to sense changes in their local environment and respond appropriately to induce T-cell immunity, or possibly tolerance. In the lymph node, DC are also influenced by antigen-specific signalling from T cells, which may extend and amplify DC antigen presenting capabilities, especially for the stimulation of cytotoxic responses. It now appears that both tissue damage and antigen-specific T-cell derived signals act together on the DC to promote the appropriate immune reaction to antigen. Thus DC antigen presenting behaviour is not only dependent on the context of antigen encounter in the periphery, but also on the availability of antigen-specific T cells and their T-cell receptor specificities. [source] The plasticity of immunoglobulin gene systems in evolutionIMMUNOLOGICAL REVIEWS, Issue 1 2006Ellen Hsu Summary:, The mechanism of recombination-activating gene (RAG)-mediated rearrangement exists in all jawed vertebrates, but the organization and structure of immunoglobulin (Ig) genes, as they differ in fish and among fish species, reveal their capability for rapid evolution. In systems where there can exist 100 Ig loci, exon restructuring and sequence changes of the constant regions led to divergence of effector functions. Recombination among these loci created hybrid genes, the strangest of which encode variable (V) regions that function as part of secreted molecules and, as the result of an ancient translocation, are also grafted onto the T-cell receptor. Genomic changes in V-gene structure, created by RAG recombinase acting on germline recombination signal sequences, led variously to the generation of fixed receptor specificities, pseudogene templates for gene conversion, and ultimately to Ig sequences that evolved away from Ig function. The presence of so many Ig loci in fishes raises interesting questions not only as to how their regulation is achieved but also how successive whole-locus duplications are accommodated by a system whose function in other vertebrates is based on clonal antigen receptor expression. [source] REVIEW: The phosphate regulating hormone fibroblast growth factor-23ACTA PHYSIOLOGICA, Issue 2 2010R. Marsell Abstract Over the last decade, the regulation of phosphate (Pi) homeostasis has been under intense investigation. By utilizing modern biochemical and genetic tools, the pathophysiological mechanisms behind several known hereditary and acquired hypo- and hyperphosphatemic diseases have been clarified. The results of these efforts have opened new insights into the causes of Pi dysregulation and hereby also the physiological mechanisms determining Pi homeostasis. Although several potential Pi-regulating proteins have been discovered and investigated, current data strongly argues for fibroblast growth factor-23 (FGF23), a hormonal factor produced in bone, as a particularly important regulator of Pi homeostasis. In this article, we review the discovery of the FGF23 protein, as well as its biochemistry, localization of production, receptor specificity and mechanisms of action. [source] An expression system for the functional analysis of pheromone genes in the tetrapolar basidiomycete Schizophyllum communeJOURNAL OF BASIC MICROBIOLOGY, Issue 2 2003Susanne Gola The investigation of putative pheromone genes of basidiomycetes has been difficult since the small open reading frames are essentially annotated on the basis of a C-terminal farnesylation signal. In order to identify the functional reading frame, expression of small DNA fragments in the fungus is necessary. The expression system developed in the presented paper allows fusion to the promoter of the tef1 gene encoding the constitutively and highly expressed translation elongation factor EF1,. This system has been shown to be functional using an easily selectable gene, ura1. The application to identification of functional pheromone genes has been shown with the newly detected bap2(4) gene. The Bap2(4) pheromone is the first B, pheromone gene activating only a single receptor specificity. [source] Opioids in the Hypothalamic Paraventricular Nucleus Stimulate Ethanol IntakeALCOHOLISM, Issue 2 2010Jessica R. Barson Background:, Specialized hypothalamic systems that increase food intake might also increase ethanol intake. To test this possibility, morphine and receptor-specific opioid agonists were microinjected in the paraventricular nucleus (PVN) of rats that had learned to drink ethanol. To cross-validate the results, naloxone methiodide (m-naloxone), an opioid antagonist, was microinjected with the expectation that it would have the opposite effect of morphine and the specific opioid agonists. Methods:, Sprague,Dawley rats were trained, without sugar, to drink 4 or 7% ethanol and were then implanted with chronic brain cannulas aimed at the PVN. After recovery, those drinking 7% ethanol, with food and water available, were injected with 2 doses each of morphine or m-naloxone. To test for receptor specificity, 2 doses each of the ,-receptor agonist [d -Ala2,N -Me-Phe4,Gly5 -ol]-Enkephalin (DAMGO), ,-receptor agonist d -Ala-Gly-Phe-Met-NH2 (DALA), or ,-receptor agonist U-50,488H were injected. DAMGO was also tested in rats drinking 4% ethanol without food or water available. As an anatomical control for drug reflux, injections were made 2 mm dorsal to the PVN. Results:, A main result was a significant increase in ethanol intake induced by PVN injection of morphine. The opposite effect was produced by m-naloxone. The effects of morphine and m-naloxone were exclusively on intake of ethanol, even though food and water were freely available. In the analysis with specific receptor agonists, PVN injection of the ,-agonist DALA significantly increased 7% ethanol intake without affecting food or water intake. This is in contrast to the ,-agonist U-50,488H, which decreased ethanol intake, and the ,-agonist DAMGO, which had no effect on ethanol intake in the presence or absence of food and water. In the anatomical control location 2 mm dorsal to the PVN, no drug caused any significant changes in ethanol, food, or water intake, providing evidence that the active site was close to the cannula tip. Conclusions:, The ,-opioid receptor agonist in the PVN increased ethanol intake in strong preference over food and water, while the ,-opioid agonist suppressed ethanol intake. Prior studies show that learning to drink ethanol stimulates PVN expression and production of the peptides enkephalin and dynorphin, which are endogenous agonists for the ,- and ,-receptors, respectively. These results suggest that enkephalin via the ,-opioid system can function locally within a positive feedback circuit to cause ethanol intake to escalate and ultimately contribute to the abuse of ethanol. This is in contrast to dynorphin via the ,-opioid system, which may act to counter this escalation. Naltrexone therapy for alcoholism may act, in part, by blocking the enkephalin-triggered positive feedback cycle. [source] A 76-residue polypeptide of colicin E9 confers receptor specificity and inhibits the growth of vitamin B12 -dependent Escherichia coli 113/3 cellsMOLECULAR MICROBIOLOGY, Issue 3 2000Christopher N. Penfold The mechanism by which E colicins recognize and then bind to BtuB receptors in the outer membrane of Escherichia coli cells is a poorly understood first step in the process that results in cell killing. Using N- and C-terminal deletions of the N-terminal 448 residues of colicin E9, we demonstrated that the smallest polypeptide encoded by one of these constructs that retained receptor-binding activity consisted of residues 343,418. The results of the in vivo receptor-binding assay were supported by an alternative competition assay that we developed using a fusion protein consisting of residues 1,497 of colicin E9 fused to the green fluorescent protein as a fluorescent probe of binding to BtuB in E. coli cells. Using this improved assay, we demonstrated competitive inhibition of the binding of the fluorescent fusion protein by the minimal receptor-binding domain of colicin E9 and by vitamin B12. Mutations located in the minimum R domain that abolished or reduced the biological activity of colicin E9 similarly affected the competitive binding of the mutant colicin protein to BtuB. The sequence of the 76-residue R domain in colicin E9 is identical to that found in colicin E3, an RNase type E colicin. Comparative sequence analysis of colicin E3 and cloacin DF13, which is also an RNase-type colicin but uses the IutA receptor to bind to E. coli cells, revealed significant sequence homology throughout the two proteins, with the exception of a region of 92 residues that included the minimum R domain. We constructed two chimeras between cloacin DF13 and colicin E9 in which (i) the DNase domain of colicin E9 was fused onto the T+R domains of cloacin DF13; and (ii) the R domain and DNase domain of colicin E9 were fused onto the T domain of cloacin DF13. The killing activities of these two chimeric colicins against indicator strains expressing BtuB or IutA receptors support the conclusion that the 76 residues of colicin E9 confer receptor specificity. The minimum receptor-binding domain polypeptide inhibited the growth of the vitamin B12 -dependent E. coli 113/3 mutant cells, demonstrating that vitamin B12 and colicin E9 binding is mutually exclusive. [source] | |||||||||||||