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Activating point mutations in the common ?gb?s[beta]-subunit of the human GM-CSF, IL-3 and IL-5 receptors : implications for receptor function and role in disease / by Brendan John Jenkins.Jenkins, Brendan John January 1998 (has links)
Includes bibliographical references (17 leaves) / vii, 113, [89] leaves, [32] leaves of plates : ill. (some col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Generates and exploits activating point mutations in the common ?gb?s subunit (h?gb?sc) of the human GM-CSF, IL-3 and IL-5 receptors. Elucidates the mechanisms by which the isolated mutations confer constitutive activity on h?gb?sc. Identifies the putative all-specific signalling molecules and provides a map of the locations of activating point mutations in h?gb?sc, / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 1998
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Proteomic Investigation of the HIV Receptors CD4 and DC-Sign/CD209Bernhard, Oliver Karl January 2004 (has links)
HIV infection and disease is a multistage process that involves a variety of cell types as the virus spreads through the body. Initially, dendritic cells (DCs) present at the mucosal site of infection bind and internalise HIV for degradation and presentation to T cells. As the DCs migrate to lymph nodes and mature, part of the internalised virions remains infective inside endosomal compartments. During formation of the immunological synapse between CD4 T cells and DCs, infective virions from dendritic cells are transferred to CD4 T cells leading to a strong infection of those cells allowing rapid virus dissemination throughout the body and establishment of the typical HIV infection. Various membrane receptors are involved in this process. Initial HIV binding to DCs is mediated by C-type lectin receptors such as the mannose receptor or DC-SIGN (DC specific intracellular adhesion molecule 3 grabbing non integrin) which is followed by virus internalisation and lysis albeit virus induced changes in endocytic routing prevents a proportion from degradation. Productive infection of DCs has also been observed allowing trans infection of CD4 T cells through a different mechanism. HIV infection of CD4 T cells, DCs and other cells is a multistep process initiated by binding of HIV envelope gp120 to the CD4 receptor, a 55 kDa transmembrane glycoprotein. Subsequent conformational changes in gp120 allow binding to a chemokine receptor, either CCR5 or CXCR4, followed by membrane fusion and infection. The aim of this thesis was to investigate protein associations with the HIV receptors DC-SIGN and CD4 in order to elucidate the mechanism of complex formation, virus entry and/or defining target sites for antiretroviral drugs. This thesis used a proteomic approach for studying the receptors with mass spectrometry-based protein identification as its core technology. A range of different approaches were developed and compared for identification of protein interactions and characterisation of the identified protein associations. An affinity purification of the CD4 receptor complex from lymphoid cells was used as the basis for detecting novel CD4-binding proteins. For this approach a strategy based on mass spectrometry identification of CD4 associating proteins using affinity chromatography and affinity-tag mediated purification of tryptic peptides was developed. This method proved successful for the identification of CD4 interacting proteins such as the strongly associated kinase p56lck, however a limited number of non-specifically bound proteins were also identified along the receptor complex. Using one-dimensional SDS-polyacrylamide gel electrophoresis followed by in-gel digests and mass spectrometry analysis, a large number of non-specifically binding proteins were identified along the CD4/lck complex. Evaluation of different lysis buffers in several independent experiments demonstrated that there was a large and inconsistent array of proteins that were obviously non-specifically bound to the receptor. No further specific binding partners were detected. These data suggested that protein interactions of CD4 on this cell type are of weak and/or transient nature. It also demonstrated a need for careful interpretation of proteomic data in the light of the propensity of non-specific binding under these conditions. To overcome dissociation of weak protein interactions, a method was developed using chemical cross-linking to preserve weak protein interactions on lymphoid cells. Affinity purification was used to purify CD4 along with cross-linked associated proteins and mass spectrometry analysis identified an interaction with the transferrin receptor CD71 and the tyrosine phosphatase CD45. The CD45-CD4 interaction is well known. The CD4-CD71 interaction was demonstrated to be a result from colocalization of the two molecules during formation of endocytic vesicles. Flow cytometry-based fluorescence resonance energy transfer (FRET) measurements were applied to confirm colocalization. A similar interaction was suspected for CD4 and DC-SIGN on the plasma membrane of DCs as cis infection of DCs has been demonstrated i.e. initial binding to DC-SIGN then to CD4/CCR5 on the same cell. Therefore, protein associations of DC-SIGN were investigated using the developed techniques. Using cross-linking, DC-SIGN was shown to assemble in large complexes on the surface of immature monocyte-derived DCs. Mass spectrometry analysis of the purified complexes identified them as homo-oligomers of DC-SIGN. The absence of CD4 suggested that the fraction interacting with CD4 at any one time must be small. The complexes of DC-SIGN were further characterised to be tetramers and successfully co-immunoprecipitated with HIV gp120 and mannan. DC-SIGN monomers were not evident demonstrating that the assembly of DC-SIGN into tetramers is required for high affinity binding of its natural and viral ligands. Thus potential antiviral agents aimed at blocking the early stage of HIV binding to DCs must simulate tetramers in order to neutralise the virus efficiently. Overall the thesis provides new information on protein interactions of CD4 and DC-SIGN, a careful investigation of "proteomics" techniques for identifying the proteins in affinity-purified samples and demonstrates the need for multifaceted analytical approaches to probe complex cellular systems.
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Design and synthesis of artificial receptors for selective and differential sensingZhang, Tianzhi, January 1900 (has links)
Thesis (Ph. D.)--University of Texas at Austin, 2007. / Vita. Includes bibliographical references.
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Ligands for the sigma receptor and the mu-opioid receptorLu, Yu, January 2007 (has links)
Thesis (M.S.)--University of Missouri-Columbia, 2007. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on January 4, 2008) Includes bibliographical references.
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CD23's role as a negative regulator of allergic disease : in vivo effects of murine CD23 destabilization and allelic mutations /Ford, Jill Wallace, January 2007 (has links)
Thesis (Ph. D.)--Virginia Commonwealth University, 2007. / Prepared for: Dept. of Microbiology and Immunology. Bibliography: leaves 233-255. Also available online via the Internet.
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Studies on the atypical orphan receptor SHP /Johansson, Lotta, January 2001 (has links)
Diss. (sammanfattning) Stockholm : Karolinska institutet, 2001. / Härtill 5 uppsatser.
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Signal transduction via estrogen receptors (ERs) and estrogen receptor-related receptors (ERRs) /Pettersson, Katarina, January 1900 (has links)
Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 4 uppsatser.
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The role of cholinergic neurotransmission in the functioning of the SCN /Ferguson, Sally Anne. January 1998 (has links) (PDF)
Thesis (Ph.D.)--University of Adelaide, Dept. of Obstetrics and Gynaecology, 1999. / Errata is tipped in between leaf 9 & 10. Bibliography: leaves 209-235.
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Molecular mechanisms by which salvinorin A binds to and activates the k-opioid receptorYan, Feng. January 2008 (has links)
Thesis (Ph. D.)--Case Western Reserve University, 2008. / [School of Medicine] Department of Biochemistry. Includes bibliographical references.
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G protein-coupled receptors; discovery of new human members and analyses of the entire repertoires in human, mouse and rat /Gloriam, David E., January 2006 (has links)
Diss. (sammanfattning) Uppsala : Uppsala universitet, 2006. / Härtill 6 uppsatser. Med sammanfattning på svenska.
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