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Björnström, Linda. "Molecular mechanisms of alternative estrogen receptor signaling /". Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-509-3/.
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Kovoor, Abraham. "Molecular regulation of opioid receptors /". Thesis, Connect to this title online; UW restricted, 1998. http://hdl.handle.net/1773/6278.
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Meira, Guilherme Louzada Silva. "Analíse da expressão do receptor olfativo M93 em sistemas heterólogos". Universidade de São Paulo, 2004. http://www.teses.usp.br/teses/disponiveis/46/46131/tde-31082016-115408/.
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O sistema olfatório de mamífero pode discriminar milhares de odores presentes no meio ambiente. Aproximadamente 1000 diferentes receptores olfatórios (ORs) são expressos no epitélio olfatório (OE) do nariz, Os ORs detectam os odores e transmitem os sinais resultantes para o bulbo olfatório (OB) no cérebro. Os ORs pertencem a super família dos receptores acoplados a proteína G (GPCR) e apresentam sete domínios transmembrânicos putativos. Por razões desconhecidas, os ORs são retidos no retículo endoplasmático quando expressos em linhagens de células de mamíferos heterólogas. Provavelmente, proteínas acessórias sejam requeridas para o endereçamento dos Ors para a superficie celular. No presente estudo, utilizamos o OR M93 para estudar os mecanismos de expressão de um ORo A dissertação teve como objetivos específicos: (l) construção de um vetor para expressão do OR M93 em fusão com GFP em levedura e análise de sua localização celular; (2) identificar proteínas expressas no epitélio olfatório de camundongo que interajam com os ORs. A análise por microscopia de fluorescência revelou que a expressão do OR M93 fusionado a GFP demonstrou um padrão de fluorescência que sugere a retenção do OR M93 no retículo endoplasmático. Nós utilizamos o sistema de duplo híbrido em levedura para varrer uma biblioteca de cDNA de epitélio olfatório de camundongo com uma isca correspondente à região N-terminal do OR M93. Quatro proteínas candidatas foram identificadas: HLA-B associado ao transcrito 3 (BAT-3/ Scythe), superfamília transmembrana 4 (membro CD82), superfamília transmembrana 4 (membro OAP-I) e sindecan (membro SDC2) (\"GenBank accession numbers\": BC026647, D14883, BC0430n e BC047144). A análise da hibridação in situ destas proteínas, revelou que a proteína OAP-1 é a melhor candidata a interação com OR M93. Dessa maneira, nós indicamos a proteína OAP-1 como possível proteína candidata a auxiliar o OR a ser expresso de maneira funcional em sistemas heterólogos.The mammalian olfactory system can discrim inate thousands of odorants present in the environrnent. Approximately 1000 different olfactory receptors (ORs) are expressed in the olfactory epithelium (OE) of the nose. The ORs detect odorants and transmit the resulting signals to the olfactory bulb (OB) of the brain. ORs belong to the G-protein-coupled receptor (GPCR) super family and have seven putative transmembrane domains. For unknown reasons, the ORs are retained in the endoplasmatic reticulum when expressed in heterologous mammalian cell lines. Probably accessory proteins are required for the sorting of the ORs to the cell surface. In the present work, we used the OR M93 to study the mechanisms of OR expression. Our goals were to (1) construct an expression vector for OR M93 in fusion with GFP in yeast and (2) to identify proteins expressed in the mouse OE that interact with ORs. The analysis by fluorescence microscopy suggested that OR M93 in fusion with GFP was retained in the endoplasmic reticulum (ER) of yeast. We used the yeast two-hybrid system to screen a mouse OE cDNA library with a bait corresponding to the N-terminal region ofthe üR M93. Four potential candidates were identified: HLA-B associated transcript 3 (BAT-3/Scythe), transmembrane 4 superfamily (CD82 member), transmembrane 4 superfamily (TSPN-3 member) and syndecan (SDC2). In situ hybridization analysis suggests that OAP-l protein represents the best candidate for interaction with OR M93. We suggest the OAP-l protein could be an accessory protein required for the sorting of the ORs to the cell surface in heterologous cell lines.
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McGinley, Paula Lynn. "Molecular complementation of mutant hormone receptors". Access to citation, abstract and download form provided by ProQuest Information and Learning Company; downloadable PDF file, 189 p, 2008. http://proquest.umi.com/pqdweb?did=1456289611&sid=5&Fmt=2&clientId=8331&RQT=309&VName=PQD.
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Kuswandi, Susi Iravati. "Molecular genetic analysis of aerobactin receptors". Thesis, University of Leicester, 1996. http://hdl.handle.net/2381/34438.
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Some Enterobacteriaceae produce a low molecular weight compound, aerobactin, with a high affinity for ferric iron. The genes encoding the aerobactin system have been identified in plasmid or chromosomal DNA; they are arranged in an operon consisting of five genes; four genes encode enzymes responsible for the biosynthesis of aerobactin and the fifth encodes an outer membrane receptor protein specific for ferric aerobactin. The aerobactin receptor protein appears to be different in size (molecular weight) in different species. Escherichia coli (ColV-K30) express a 74 kDa protein, while Shigella spp. express a 76 kDa protein. The aerobactin receptor protein also acts as a receptor for the bacteriocin cloacin DF13. Shigella spp. expressing the aerobactin receptor protein were less sensitive to cloacin DF13 than E. coli (ColV-K30). The aerobactin receptor genes of several Shigella spp. isolate have been cloned and the aerobactin receptor gene from Shigella flexneri ser.6 {iutAsh) has been sequenced. The restriction maps of iutAsh and iutA (aerobactin receptor gene from ColV-K30) were similar. The main difference was the existence of a BamHI site in the middle of iutAsh but not in iutA. The predicted protein product of iutAsh consists of 732 amino acid residues, the same as the aerobactin receptor protein from ColV-K30 (iutA), and with 93% similarity. Construction of iutA::iutAsh hybrid genes demonstrated that although verious parts of iutA were able to increase the cloacin sensitivity function of iutAsh, the main function was located in the 3'-terminus of iutA. Constructs with the 3'-terminus of iutA expressed a 74 kDa, while constructs with 3'-terminus of iutAsh expressed a 76 kDa outer membrane protein. The aerobactin uptake of E. coli strains carrying constructs with the 3'-terminus of iutAsh was higher than that of E. coli strains carrying constructs with the 3'-terminus of the iutA. The highest aerobactin uptake was showed by E. coli strain carrying construct 2, which consist of the iutA fragment upstream of the ClaI site and the iutAsh fragment downstream of the ClaI site. Bacteriophage B74K was capable of using the aerobactin receptor protein, but it was also capable of using other outer membrane proteins as receptors, and so could not be used for aerobactin receptor protein identification. In addition, the presence of aerobactin receptor protein increased the sensitivity of E. coli strains to phage BF23.
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Beltrán, Sáez Elisa. "Information transmission through a nonlinear molecular signaling system: ErbB as a case study". Doctoral thesis, Universitat Autònoma de Barcelona, 2019. http://hdl.handle.net/10803/667354.
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La capacitat dels éssers vius d’obtenir i processar informació és clau per adaptar-se i sobreviure en l’ambient que els envolta. Les cèl·lules, des de procariotes unicel·lulars fins a organismes multicel·lulars (eucariotes), capten informació de l’entorn mitjançant diversos mecanismes, entre ells a través de receptors de membrana, que fan de canal per a la informació entre l’exterior i l’interior de la cèl·lula. Per tant, aquestos receptors representen un canal de transmissió d’informació a través del qual la informació ambiental pot afectar el comportament cel·lular per adaptar-se a l’ambient.
En aquesta tesi, hem estudiat la transmissió d’informació a través del sistema de receptors ErbB, una família de receptors involucrats en diferents comportaments cel·lulars, com per exemple la proliferació o la migració. Gràcies a l’estudi de malalties complexes -centrem-nos en el càncer- des d’una perspectiva molecular, s’han pogut identificar els receptors de la família ErbB com a factors que causen l’enfermetat: quan els receptors ErbB es troben sobreexpressats (produïts en excés), les cèl·lules deixen d’interpretar correctament la informació extracel·lular i proliferen descontroladament, formant tumors. Per tant, la desregulació dels receptors ErbB està molt lligada al que podriem anomenar malalties de la informació, és a dir, malalties causades per la pèrdua de la capacitat d’obtenir i interpretar informació extracel·lular.
Per tal de quantificar la informació que es transmet a través del sistema ErbB, hem modelitzat matemàticament la dinàmica dels receptors a la membrana mitjançant sistemes d’equacions diferencials ordinàries. Els nostres models incorporen la dimerització (formació d’un complex de dos receptors) entre receptors de diferents tipus. Aquesta interacció és necessària per a l’activació dels receptors i introdueix una no linialitat al sistema. La dimerització i activació són els primers passos en la transducció d’informació a l’interior cel·lular, i vénen seguits de la interacció de proteïnes intracel·lulars amb els receptors actius, que hem modelitzat mitjançant models estocàstics (processos de Poisson). Gràcies a la modelització d’aquestos dos processos hem pogut obtenir una estimació de l’estat intracel·lular en termes probabilístics que ens permet aplicar eines de teoria de la informació per quantificar la transmissió d’informació entre l’exterior i l’interior cel·lular.
Els nostres resultats mostren una disminució en la informació transmesa a través del receptors ErbB quan la quantitat de receptors a la membrana augmenta. Aquesta pèrdua de informació depén de la dinàmica entre receptors, així com de la interacció d’aquestos amb les proteïnes intracel·lulars. En particular, hem estudiat la interacció dels receptors actius amb diferents proteïnes intracel·lulars i hem observat que la tendència que es dóna en les proteïnes a interaccionar amb diferents llocs d’unió dels receptors amb afinitats similars es tradueix en un augment en la sinèrgia entre les diferents proteïnes en quant a la informació que detecten.
La quantificació i anàlisi d’aquestes interaccions i de la transmissió de informació que en resulta és clau per entendre millor els processos de senyalització cel·lular i serà útil en el diseny d’estratègies per tractar les malaties de la informació.The ability of organisms to extract and store information from their surroundings marked a revolution in the history of life and allowed survival and adaptation to the environment. Cells, from prokaryots to eukaryots, use specific receptors inserted in their membranes to detect extracellular molecules that cannot cross into the cell, where cell decisions are taken. Hence, those membrane receptors represent an information channel through which the environmental information can affect cell behavior and adaptation. In this Thesis, we modeled information transmission through the ErbB system, a family of receptors involved in many different cellular behaviors, such as cell proliferation or migration. Thanks to the study of complex diseases - let us think of cancer – from a molecular perspective, the ErbB receptors have been identified as factors causing the disease: when they are overexpressed (produced in excess), cells cease to interpret correctly extracellular information, which results in uncontrolled cell proliferation forming tumors. Therefore, dysregulation of ErbB receptors is at the core of what can be called information diseases, that is, diseases that arise from the loss of the capacity to obtain and interpret extracellular information. With the aim of quantifying the information transmitted through the ErbB system, we modeled the dynamics of membrane receptors by means of systems of ordinary differential equations. Our models considers the dimerization (formation of pairs of receptors) between receptors of differet types. This interaction is necessary for receptor activation and introduces a nonlinearity in the system. Dimerization and activation are the first steps in the signaling cascade, followed by the interaction of intracellular proteins with the active receptors. We modeled these interactions by means of stochastic models (Poisson processes). Thanks to the modeling of these two processes (receptor dynamics and interactions with the intracellular proteins), we obtained an estimation of the intracellular stat in probabilistic terms which has allowed us to use tools from information theory to quantify information transmission between the exterior and the interior of the cell. Our results show a decrease in the information transmitted through the ErbB channel as the amount of ErbB receptors at the membrane increases. We considered different dynamics of the receptors and showed that the loss of information depends on the dynamics of interaction between the receptors, as well as on their interactions with the intracellular signaling machinery. In particular, we studied the interaction of active receptors with several signaling intracellular proteins and showed that the observed tendency of proteins to bind several binding sites with similar affinities translates into an increased synergy between the signaling proteins. All in all, quantifying and analysing these interactions results in a better understanding of the dynamics and information transmission through ErbB and similar molecular systems and it can be used for the design of therapeutic strategies for information diseases.
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Zhang, Gaiping. "Bovine IgG Fc receptors". Thesis, University of Hertfordshire, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.387187.
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Torvinen, Maria. "Adenosine receptor/dopamine receptor interactions : molecular and biochemical aspects /". Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-298-1/.
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Cordomí, Montoya Arnau. "Molecular dynamics simulations of seven-transmembrane receptors". Doctoral thesis, Universitat Politècnica de Catalunya, 2008. http://hdl.handle.net/10803/6464.
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Seven transmembrane (7-TM) G protein coupled receptors (GPCR) constitute the largest family of integral membrane proteins in eukaryotes with more than 1000 members and encoding more than 2% of the human genome. These proteins play a key role in the transmission and transduction of cellular signals responding to hormones, neurotransmitters, light and other agonists, regulating basic biological processes. Their natural abundance together with their localization in the cell membrane makes them suitable targets for therapeutic intervention. Consequently, GPCR are proteins with enormous pharmacologic interest, representing the targets of about 50% of the currently marketed drugs. The current limitations in the experimental techniques necessary for microscopic studies of the membrane as well as membrane proteins emerged the use of computational methods and specifically molecular dynamics simulations. The lead motif of this thesis is the study of GPCR by means of this technique, with the ultimate goal of developing a methodology that can be generalized to the study of most 7-TM as well as other membrane proteins. Since the bovine rhodopsin was the only protein of the GPCR family with a known threedimensional structure at an atomic level until very recently, most of the effort is centered in the study of this receptor as a model of GPCR.
The scope of this thesis is twofold. On the one hand it addresses the study of the simulation conditions, including the procedure as well as the sampling box to get optimal results, and on the other, the biological implications of the structural and dynamical behavior observed in the simulations. Specifically, regarding the methodological aspects of the work, the bovine rhodopsin has been studied using different treatments of long-range electrostatic interactions and sampling conditions, as well as the effect of sampling the protein embedded in different one-component lipid bilayers. The binding of ions to lipid bilayers in the absence of the protein has also been investigated.
Regarding the biological consequences of the analysis of the MD trajectories, it has been carefully addressed the binding site of retinal and its implications in the process of isomerization after photon uptake, the alteration a group of residues constituting the so-called electrostatic lock between helices TM3 and TM6 in rhodopsin putatively used as common activation mechanism of GPCR, and the structural effects caused by the dimerization based on a recent semi-empirical model. Finally, the specific binding of ions to bacteriorhodopsin has also been studied.
The main conclusion of this thesis is provide support to molecular dynamics as technique capable to provide structural and dynamical informational about membranes and membrane proteins, not currently accessible from experimental methods). Moreover, the use of an explicit lipidic environment is crucial for the study the membrane protein dynamics as well as for the protein-protein and lipidprotein interactions.
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Hodyl, Jozef Andrew Zbigniew, i jozef hodyl@flinders edu au. "Silica Immobilised Metal Ion Activated Molecular Receptors". Flinders University. School of Chemistry, Physics and Earth Sciences, 2008. http://catalogue.flinders.edu.au./local/adt/public/adt-SFU20090301.162335.
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Immobilisation of functional entities, such as, enzymes, onto solid supports, as a means of facilitating their removal from the surrounding environment and subsequent regeneration has been in practice for many decades. This work focuses on the immobilisation and analysis of three-walled (pendant armed), cyclen based receptor complexes immobilised onto a silica surface for the purpose of sequestering aromatic anions from aqueous solution: Si-GPS-[Cd(Trac)](ClO4)2, Si-GPS-[Cd(DiPTrac)](ClO4)2, and Si-GPS-[Cd(TriPTrac)](ClO4)2 were the immobilised receptors used.
Initially, synthesis of a three-walled model receptor, [Cd(TracHP12)](ClO4)2, that is not bound to silica yet mimics the properties of the silica anchored receptor complexes with a hydroxypropyl pendant arm was effected. Aromatic anion binding constant measurements were made on the model receptor using 1H NMR monitored titrations in DMSO-d6 which showed that, in comparison to the first generation four-walled receptors, the removal of one of the pendant arms did not affect the binding capability of the receptor's cavity significantly. It was shown that the binding strength correlated well with the pKa of the particular anion with, for example, p-hydroxybenzoate > m-hydroxybenzoate > o-hydroxybenzoate. The precursor to this receptor was then immobilised onto a silica surface and subjected to metal ion uptake studies to gauge its coordination properties with a number of divalent metal(II) ions: Cd(II), Pb(II), Zn(II), Cu(II) and Ca(II). The three Cd(II) coordinated receptor complexes mentioned above were then subjected to inclusion studies with a number of aromatic anions in aqueous conditions whereupon a reversal of the previously mentioned trend, i.e. o-hydroxybenzoate > m-hydroxybenzoate > p-hydroxybenzoate was observed. This indicated that the presence of water in the system changes the hydrogen bonding mode of the host-guest complexes, and was a major discovery arising from this work.
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Kasorn, Anongnard. "The molecular pharmacology of lysophosphatidic acid receptors". Thesis, University of Nottingham, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.441003.
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Rocheville, Magalie. "Oligomerization of somatostatin receptors". Thesis, McGill University, 2002. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=84425.
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Oligomerization of membrane proteins in response to external stimulation is a common event in cell signalling for generating functional diversity. In the case of the heptahelical receptor (HHR) superfamily, the traditional view has been that these receptors function as monomers, although a number of recent studies have suggested that this class of membrane proteins may exist as dimers or higher order oligomers, and play an important role in signalling. We addressed this question using as a model the somatostatin receptor (SSTR) family, which comprises five molecular subtypes (SSTR1--5). Receptors were expressed at physiological levels in CHO-K1 cells and characterized pharmacologically and physically by photobleaching fluorescence resonance energy transfer (pbFRET) in intact cells. We first demonstrated homo-oligomerization of SSTR5 by functional complementation of two partially active mutant receptors, whose function was rescued by coexpression. pbFRET analysis showed that hSSTR5 exists in the basal state as a monomer and that activation by somatostatin (SST) induces oligomerization in a time-dependent manner. In contrast, expression of SSTR5 at higher levels in CHO-K1 cells revealed the presence of an appreciable level of preformed oligomers, although SST could still induce dose-dependent extra-formation of receptor oligomers. Next, we investigated SSTR heteromerization, and showed that SSTR5 forms heteromers with some (SSTR1,2,3) but not other (SSTR4) subtypes of SSTRs. In particular, the hSSTR1/5 oligomer displayed altered pharmacological properties such as binding affinity and agonist-induced receptor regulation, as compared to individual receptors. Furthermore, heteromerization between unrelated HHRs was examined using SSTR5 and the dopamine receptor (D2R) as models. SSTR5/D2R heteromers were formed following application of either or both agonist molecules, and displayed altered binding and signalling properties compared to the indiv
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Nilsson, Isabelle. "The cholecystokinin receptor family : molecular cloning and pharmacological characterization /". Linköping : Univ, 2003. http://www.bibl.liu.se/liupubl/disp/disp2003/med791s.pdf.
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Josephson, Anna. "Spinal cord injury: mechanical and molecular aspects /". Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-235-3/.
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Slessareva, Janna Eugenievna. "Molecular mechanisms of G protein-receptor coupling". Morgantown, W. Va. : [West Virginia University Libraries], 2003. http://etd.wvu.edu/templates/showETD.cfm?recnum=2907.
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Thesis (Ph. D.)--West Virginia University, 2003.Title from document title page. Document formatted into pages; contains vi, 200 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references.
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Ma, Hongzheng. "Molecular mechanisms of G protein-receptor coupling". Morgantown, W. Va. : [West Virginia University Libraries], 2003. http://etd.wvu.edu/templates/showETD.cfm?recnum=2978.
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Thesis (Ph. D.)--West Virginia University, 2003.Title from document title page. Document formatted into pages; contains viii, 264 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references.
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Nawaz, Zafar. "Molecular Mechanism of Action of Steroid Hormone Receptors". Thesis, University of North Texas, 1992. https://digital.library.unt.edu/ark:/67531/metadc798398/.
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A novel bacterial expression system that is capable of producing high levels of soluble, stable, biologically active human vitamin D3 and estrogen receptors has been developed. The method utilizes ubiquitin fusion technology and a low temperature nalidixic acid induction of the lambda PL promoter. This system can produce large quantities of receptor antigen, but only a small fraction displays wild-type DNA and hormone binding properties. Therefore, the use of this system to overproduce receptors for crystallization studies is not practical. To overcome these problems, a 2 um based ubiquitin fusion system which allows regulated expression of the estrogen receptor in yeast (Saccharomyces cerevisiae) was developed. This system produces the estrogen receptor to a level of 0.2% of the total soluble protein. Moreover, this protein is undegradable, soluble, and biologically active. To test the transcriptional activity of the estrogen receptor produced in yeast, a cis-trans transcription assay was developed. This assay revealed that the transcriptional activity of the human estrogen receptor expressed in yeast was similar to that observed in transfected mammalian cells. This reconstituted estrogen transcription unit in Saccharomyces cerevisiae was utilized to examine the regulation of estrogen receptor functions by antiestrogens, to develop a random and rapid approach for identifying novel estrogen response elements, to characterize estrogen receptor variants cloned from human breast tumors, and to examine the effect of estrogen receptor on the regulation of osteocalcin gene.
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Tremblay, Annie. "Transcriptional regulation by the estrogen-related receptors". Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=86701.
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The Estrogen-Related receptors (ERRα, ERRβ and ERRγ) are ubiquitous, constitutively active, orphan nuclear receptors and little is known concerning post-translational modifications affecting their transcriptional activity. We observed that the conserved phosphorylation-dependent sumoylation motif (PDSM) within the N-terminal domain of the ERRs represses their transcriptional activity on compound promoters via a synergy control mechanism. We also identified protein inhibitor of activated stat y (PIASy), a SUMO E3 ligase, as a new interacting partner of ERRα which promotes the sumoylation of ERRα and represses its transcriptional activity in a PDSM-dependent manner. Furthermore, by showing that an ERRα phosphoS19-specific antibody, but not a polyclonal ERRα antibody with a minimal affinity for phosphorylated S19, allows detection of endogenous sumoylated ERRα in mouse liver extract, we confirmed that the ERRα phospho-sumoyl switch is functional in vivo.ERRα is highly expressed in the kidney, but its role in this organ is unknown. Therefore, we used a combination of physiological studies, gene expression and genome-wide location analysis to explore the role of ERRα in the kidney. A defect in sodium and potassium homeostasis was observed in the ERRα null mice, which correlated with the ERRα renal transcriptional program comprising key sodium and potassium channels. Furthermore, telemetry monitoring revealed that the ERRα null mice display a significantly reduced blood pressure at nighttime and this correlated the renal transcriptional program of ERRα comprising genes involved in blood pressure regulation. In addition, we identified the Renin-Angiotensin pathway genes as direct ERRα target genes in the kidney. These results identify a role for ERRα in renal sodium/potassium handling, intra-renal renin-angiotensin pathway, blood pressure regulation and possibly hypertension.
Les récepteurs reliés aux récepteurs de l'estrogène (ERRs) sont ubiquitaires et constitutivement actifs et le rôle joué par les modifications post-traductionnelles sur leur activité transcriptonnelle est peu connu. Nous avons démontré qu'un motif consensus de sumoylation phospho-dependente (PDSM) situé dans le domaine N-terminal diminue l'activité transcriptionnelle des ERRs sur des promoteurs à élements de réponses multiples grâce à un mécanisme de contrôle de la synergie. Nous avons aussi établi que les ERRs intéragissent avec la E3-SUMO-ligase PIASy et que cette dernière promouvoit la sumoylation du ERRα de manière phospho-dépendante. De plus, en montrant que la forme sumoylée endogène de ERRα dans de l'extrait de foie de souris n'était détectable qu'avec un anticorps spécifique dirigé contre la sérine 19 phoshorylée nous avons confirmé la validité de l'interrelation phosphorylation-sumoylation dans un contexte physiologique in vivo.
Même si le haut niveau d'expression de ERRα dans les reins est reconnu, son rôle dans cet organe est inconnu. Nous avons donc utilisé une approche combinatoire d'analyses physiologiques, d'expression génique et d'identification de sites spécifiques de liaison à l'ADN au niveau génomique afin d'explorer plus avant le rôle physiologique de ERRα dans le rein. Nous avons observé que les souris knock-out pour le gène de ERRα présentent un problème au niveau de l'homéostasie sodique et potassique corrèlant directement avec le programme transcriptionnel rénal qui comprends plusieurs canaux sodiques et potassiques importants. De plus, la mesure des paramètres cardiovasculaires par télémétrie a révélé que les souris knock-out pour le gène du ERRα ont une pression sanguine nocturne plus faible qui corrèle avec le programme transcriptionnel comprenant plusieurs gènes influençant la pression sanguine. Nous avons aussi identifié les promoteurs de certains gènes composant le système rénine-angiotensine comme gènes cibles potentiels de ERRα dans les reins. Nos résultats suggèrent une implication du ERRα dans le contrôle de la pression sanguine basale et possiblement dans l'hypertension.
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Trupp, Miles. "Neurotrophic signalling by GDNF and its receptors /". Stockholm, 1998. http://diss.kib.ki.se/search/diss.se.cfm?19980602trup.
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Futch, Tracy Ann. "Extracellular matrix protein receptors in Drosophila melanogaster". Diss., The University of Arizona, 2004. http://hdl.handle.net/10150/280545.
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The extracellular matrix (ECM) is defined as the many different proteins and secreted substances between cells. The ECM plays a major role in the signaling pathways that stimulate cells to perform many varied functions, ranging from control of gene expression at the cellular level to differentiation and development of tissues, organs, and ultimately the entire organism. A portion of this work describes the identification of the division abnormally delayed gene, which encodes a proteoglycan, that is involved in growth factor reception with important developmental consequences in Drosophila melanogaster. The remainder of this work deals with three Drosophila homologs of vertebrate proteins that may interact with integrins, a family of cell surface receptors for extracellular matrix ligands. The three integrin-interacting proteins are referred to by their vertebrate names, and include CD81, a member of the tetraspanin family, ILK, integrin-linked kinase, and CD98hc, a type II transmembrane glycoprotein which is the heavy chain of a multi-protein complex. In this work, the mutant phenotype of CD98hc is larval lethal and not temperature sensitive. Clonal analyses of CD98hc mutants show no phenotype of mutant clones in the eye. Genetic interactions in adult tissues or interactions affecting larval lethality between CD98hc and Drosophila integrin mutants were not observed, and it remains unclear whether CD98hc physically interacts with Drosophila integrins in tissue culture cells. Since no correlation was seen between the interactions of CD98hc and integrins in vertebrate cells and similar putative interactions in flies, this raises the question as to what role, if any, does CD98hc play as an integrin modulator in this organism.
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Tam, Kal-van, i 譚珈詠. "Molecular evolution of secretin/glucagon receptor superfamily in osteichthyans". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B45693092.
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Talvik, Mirjam. "Clinical molecular imaging of schizophrenia /". Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-587-5/.
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Marcu, Jahan Phillip. "Novel Insights into CB1 Receptor Signaling and the Anabolic Role of Cannabinoid Receptors in Bone". Diss., Temple University Libraries, 2013. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/233543.
Pełny tekst źródłaStreszczenie:
Cell BiologyPh.D.
Activation of the CB1 receptor is modulated by aspartate residue D2.63176 in transmembrane helix (TMH) II. Interestingly, D2.63 does not affect the affinity for ligand binding at the CB1 receptor. Studies in class A GPCRs have suggested an ionic interaction between residues of TMHII and VII. In this report, modeling studies identified residue K373, in the extracellular (EC)-3 loop, in charged interactions with D2.63. We investigated this possibility by performing reciprocal mutations and biochemical studies. D2.63176A, K373A, D2.63176A-K373A, and the reciprocal mutant with the interacting residues juxtaposed, D2.63176K-K373D were characterized using radioligand binding and guanosine 5'-3-O-(thio)triphosphate functional assays. None of the mutations resulted in a significant change in the binding affinity of CP55,940 or SR141716A. Computational results indicate that the D2.63176-K373 ionic interaction strongly influences the conformation(s) of the EC-3 loop, providing a structure-based rationale for the importance of the EC-3 loop to signal transduction in CB1. Specifically, the putative ionic interaction results in the EC-3 loop pulling over the top (extracellular side) of the receptor; this EC-3 loop conformation may serve protective and mechanistic roles. These results suggest that the ionic interaction between D2.63176 and K373 is crucial for CB1 signal transduction. This work may help to aide drug design efforts for the effective treatment of different diseases. The cannabinoid receptors of osteoblasts may represent a target for the treatment of bone disorders such as osteoporosis. Our research demonstrates that cannabinoids can affect important signaling molecules in osteoblasts. In MC3T3-E1 osteoblastic cells, the CB1 antagonist, AM251, has been reported to induce increases in Runx2 mRNA, mineralized bone nodule formation, and activation of signaling molecules such as ERK and AKT (Wu et al., 2011). Studies from our lab characterizing mice in which both CB1 and CB2 receptors were inactivated by homologous recombination have demonstrated increased bone mass coupled with enhanced osteoblast differentiation of bone marrow stromal cells in culture (manuscript in preparation). We explored the effect of antagonizing CB1 and CB2 cannabinoid receptors in osteoblastic cells to gain insights into molecular pathways that may help to explain the effects of the endocannabinoid system (ECS) in bone development. Our data was generated by running time course experiments with MC3T3-E1 cells under the influence of SR141716A, SR144528 or both in combination. The cells were harvested with a lysis buffer at specific time points and analyzed by western blot analysis. Quantification of protein activation was calculated using LiCor imaging equipment and software. Within 15 minutes, treatment with the CB1 receptor antagonist SR141716A resulted in several fold increases in pERK, pSMAD158, and pAKT. SR144528, a CB2 receptor antagonist, caused increases in pERK and pSMAD158, but not pAKT. When both antagonists were applied together, pERK and pSMAD158 levels increased, while pAKT signaling was diminished compared to SR141716A alone. The finding that cannabinoid receptor antagonists alter the activity of the SMAD158 complex is a novel finding, which suggests that cannabinoids can influence bone morphogenic signaling pathways, and therefore play a significant role in osteoblast differentiation and function.
Temple University--Theses
24
Carlsson, Peter. "Nuclear receptors studied by molecular dynamics computer simulations /". Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-823-8.
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Salaneck, Erik. "Molecular Evolution of Neuropeptide Y Receptors in Vertebrates". Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2001. http://publications.uu.se/theses/91-554-4988-3/.
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Kwok, Ho-yan Amy, i 郭可茵. "Molecular cloning and characterization of chicken prostaglandin receptors". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B41508336.
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Kwok, Ho-yan Amy. "Molecular cloning and characterization of chicken prostaglandin receptors". Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B41508336.
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Gupta, Srishti. "Molecular analysis of Bacillus megaterium spore germinant receptors". Thesis, University of Cambridge, 2014. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708193.
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Collins, T. "Molecular pharmacological characterisation of neuronal nicotinic acetylcholine receptors". Thesis, University College London (University of London), 2010. http://discovery.ucl.ac.uk/624494/.
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Neuronal nicotinic acetylcholine receptors (nAChRs) are excitatory ligand‐gated ion channels that perform important roles throughout the nervous systems of both vertebrate and invertebrate organisms. Impairments to human nAChRs and cholinergic transmission are thought to underlie the pathophysiologies of several neurological and psychological diseases including schizophrenia, Alzheimer’s disease, Parkinson’s disease and certain forms of epilepsy. They are also the receptors that mediate the effects of tobacco smoking and contribute to the physiological and psychological changes associated with nicotine addiction. The aim of this thesis is to further our understanding of neuronal nAChRs from a pharmacological and molecular viewpoint. Research described in this thesis focuses on numerous aspects of neuronal nAChRs; allosteric modulators, insect nAChRs and chaperone proteins. Allosteric modulators of nAChRs are ligands that alter the receptor’s responsiveness to agonists via sites that are separate from the agonist‐binding site (the orthosteric site). Positive allosteric modulators (PAMs) increase the receptor's sensitivity to agonist acetylcholine whereas negative allosteric modulators (NAMs) decrease sensitivity. Using molecular and electrophysiological techniques on the α7 nAChR, studies have been conducted with three PAMs (ivermectin, NS‐1738 and PNU‐120596) and one NAM (methanandamide). Chimeric receptor constructs and site‐directed mutagenesis studies, together with ligand docking simulations, have highlighted the importance of the transmembrane region of the α7 nAChR for modulation by these ligands. The second topic covered by this thesis is insect nAChRs and the molecular chaperone RIC‐3 (resistance to cholinesterase inhibitors); a protein that facilitates folding and assembly of nAChRs. In the past, recombinant expression of insect receptors has proved largely unsuccessful and in some (but not all) circumstances co‐expression with RIC‐3 has alleviated the problems. This research is aimed at investigating the influence of alternatively spliced isoforms of Drosophila melanogaster RIC‐3 on the maturation of a variety Drosophila recombinant nAChR subunits. Lastly, ongoing work is also described on the cloning of insect nAChR subunits from pest species Frankliniella occidentalis (western flower thrip), which has developed resistance to the insecticide spinosad.
30
Takase, Masayoshi. "Molecular Recognition Abilities of Ferrocene-Modified Multitopic Receptors". 京都大学 (Kyoto University), 2003. http://hdl.handle.net/2433/149097.
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Barkhem, Tomas. "Molecular mechanisms of estrogen and antiestrogen action /". Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-359-7/.
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馬智謙 i Chi-him Eddie Ma. "Molecular studies of gonadotropin releasing hormone receptors and estrogen receptors in goldfish (Carassius auratus)". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2000. http://hub.hku.hk/bib/B4257531X.
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Ma, Chi-him Eddie. "Molecular studies of gonadotropin releasing hormone receptors and estrogen receptors in goldfish (Carassius auratus)". Click to view the E-thesis via HKUTO, 2000. http://sunzi.lib.hku.hk/hkuto/record/B4257531X.
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Lau, Suk-ling Joanna, i 劉淑玲. "Molecular characterization of the chicken growth hormone receptorgene". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B45015430.
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Nakahara, Thiago Seike 1989. "Caracterização molecular e funcional de receptores da classe OR expressos no órgão vomeronasal de mamíferos". [s.n.], 2014. http://repositorio.unicamp.br/jspui/handle/REPOSIP/316387.
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Orientador: Fabio PapesTexto em português e inglês
Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia
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Resumo: O Sistema Olfativo é um Sistema Sensorial complexo, composto por diversos subsistemas cuja integração no cérebro resulta na interação entre os animais e seus respectivos ambientes de maneira adequada. Essa adequação pode significar respostas comportamentais e fisiológicas distintas para situações diversas a que esses animais tenham sido expostos. Esse Sistema exibe compartimentos especializados na detecção de estímulos de uma mesma natureza e nesse contexto, o Sistema Olfativo Principal é responsável pela detecção de odorantes voláteis em geral e o Sistema Olfativo Acessório é responsável pela detecção de feromônios. Apesar dessa divisão formal, estudos recentes questionam essa divisão e propõem sobreposição entre a função desses subsistemas. Nesse estudo investigamos a expressão de receptores OR sendo expressos no Órgão Vomerosasal em níveis comparáveis aos receptores V2R ("endógenos"). Desses receptores, isolamos o receptor Olfr692 que possui o nível de expressão mais alto entre os OR estudados ou relatados anteriormente na literatura. As células que expressam o receptor Olfr692 foram caracterizadas molecularmente e foram feitos estudos preliminares a fim de investigar a função do receptor Olfr692 frente a possíveis funções biológicas que fossem capazes de explicar a expressão robusta de um receptor de classe OR no Órgão Vomeronasal
Abstract: The Olfactory System is a complex Sensorial System, comprised of some subsystems whose integration in the brain results in the appropriated interaction between animals and their environment, that is, proper behavioral or physiological answers to diverse situations to which these animals are exposed. This System exhibits specialized features for detection of a given kind of stimuli. The Main Olfactory System detects volatile odorants in general while the Accessory Olfactory System detects pheromones. Apart from this formal distinction, recent studies have questioned this division and propose some overlap between them. In the present study, we have investigated the expression of OR receptors in the Vomeronasal Organ whose expression level is compared to V2R Receptors (endogenous). We have isolated from these genes the Olfr692, which has the higher levels among the VNO-OR here studied and those discussed in the literature. These cells have been molecularly characterized and preliminary functional studies were also performed, searching for the possible biological functions of this Receptor, which could explain its expression in the Vomeronasal Organ
Mestrado
Genetica Animal e Evolução
Mestre em Genética e Biologia Molecular
36
Andersson, Monika. "Thyroid hormones and their receptors in transcriptional regulation /". Stockholm, 1997. http://diss.kib.ki.se/1997/91-628-2744-8.
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Ryan, Tomás John. "Functional investigation of NMDA receptor molecular evolution". Thesis, University of Cambridge, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.608544.
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Silveira, Rodrigo Leandro 1986. "Simulações de dinâmica molecular do receptor ativado de proliferadores de peroxissomos isoforma y". [s.n.], 2010. http://repositorio.unicamp.br/jspui/handle/REPOSIP/248857.
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Orientador: Munir Salomão SkafDissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Química
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Resumo: O Receptor Ativado de Proliferadores de Peroxissomos Isoforma g (PPARg ) é uma proteína pertencente à superfamília dos Receptores Nucleares. Através da ligação de pequenas moléculas, o PPARg controla a transcrição de genes ligados à diferenciação de adipócitos e ao metabolismo de glicose e de lipídeos. O PPARg tem uma enorme cavidade de ligação que permite a ligação de várias moléculas estruturalmente distintas que geram respostas fisiológicas também distintas. O PPARg é o receptor de uma classe de drogas antidiabéticas cujo principal representante é a rosiglitazona. Além disso, diversos ligantes naturais ativam o receptor e, recentemente, foi descoberto que ácidos graxos de cadeia média podem se ligar e ativar o PPARg . A estrutura cristalográfica do PPARg na presença de ácido nonanóico mostrou que havia 3 ligantes simultaneamente ligados ao receptor. Neste trabalho, utilizamos simulações de dinâmica molecular para investigar a dinâmica do PPARg ligado à rosiglitazona e aos ácidos nonanóico, cáprico e láurico. Observamos que a rosiglitazona não ocupa todo o sítio de ligação, havendo uma complementaridade entre o ligante e o receptor na base do domínio de ligação. Os ácidos graxos, por outro lado, ocupam quase 100% da cavidade de ligação. Vimos que moléculas de água dentro do sítio são essenciais para a ligação dos ácidos graxos. A capacidade de ativação dos diferentes áacidos graxos foi correlacionada à capacidade dos mesmos manter ligação de hidrogênio com o resíduo Y473, localizado na hélice 12, a qual deve ser estabilizada para ativar o receptor. Além disso, simulações de complexos formados pela ligação simultânea da rosiglitazona e de um ácido nonanóico sugeriram que o receptor pode comportar diferentes ligantes simultaneamente. Por m, utilizamos uma técnica especial de dinâmica molecular para investigar as possíveis rotas de dissociação dos ácidos graxos do receptor. Observamos que existe um caminho preferencial para a dissociação dos ligantes e que as principais flutuações estruturais da proteína envolvidas no processo ocorrem na hélice 3 do PPARg
Abstract: The Peroxisome Proliferator-Activated Receptor Isoform (PPAR ) is a protein belonging to the Nuclear Receptors superfamily. PPAR controls the transcription of genes related to adipocyte di erentiation and lipid and glucose metabolism. PPAR has a large ligand-binding pocket that allows the binding of many molecules with uncorrelated structure that generate distinct physiologic responses. PPAR is the receptor of a class of antidiabetic drugs whose the main representant is rosiglitazone. Moreover, several natural ligands activate the receptor and, recently, it was discovered that medium chain fatty acids can bind and activate PPAR . The crystallographic structure of the complex formed by PPAR and nonanoic acid showed 3 ligands simultaneously binded to the receptor. In this work, we performed molecular dynamics simulations to investigate the dynamics of PPAR in the presence of rosiglitazone and nonanoic, capric and lauric acids. We observed that rosiglitazone does not occupy the whole binding pocket and there is a complementarity between ligand and receptor. The fatty acids, on the other hand, occupy almost 100% of the binding pocket. We saw that some water molecules within the binding pocket are essential to the binding of the fatty acids. The activation capacity of the di erent fatty acids were correlated to the capacity to keep hydrogen bond with the residue Y473 of helix 12, which must be stabilized in order to activate the transcription. Furthermore, some simulations of the complex formed by simultaneus binding of rosiglitazone and nonanoic acid suggested that the receptor can bear di erent ligands simultaneously. Finally, we used a special technique of molecular dynamics to investigate the possible dissociation paths of the nonanoic acids from the receptor. The simulations suggest that there is a preferential path to the dissociation of the ligands and the main structural uctuations involved in the process take place in the helix 3 of the receptor
Mestrado
Físico-Química
Mestre em Química
39
Im, Jin Seon. "Molecular characterization of T cell receptors and non-MHC restricted T cell receptor binding peptides". Diss., The University of Arizona, 1999. http://hdl.handle.net/10150/284969.
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T cells recognize antigenic peptides presented by MHC molecules on antigen presenting cells (APC) through T cell receptors (TCRs). Since TCRs are very similar to antibodies in structure and genetics, TCRs might have the potential to bind free antigens as antibodies do. Here, peptides which bound TCRs irrespective of MHC molecules have been identified by screening "one-bead one-peptide" combinatorial libraries. Peptides: VRENAR, RTGNYV, GKMHFK, KDAVKR and RKPQAI bound recombinant Jurkat single chain T cell receptors (scTcrs). GKMHFK, KDAVKR and RKPQAI were also specific for natural TCRs on the Jurkat cell surface. Molecular modeling implies that Glu96 in the CDR3 loop of TCR alpha chain is a candidate for the peptide interaction site. However, TCR-binding peptides did not induce biological effects on parental Jurkat cells. To extend this study to a biologically relevant system, diabetogenic T cells involved in insulin-dependent diabetes mellitus (IDDM) have been characterized. GAD(524-543) responding T cells showed restricted TCR variable gene usage, which utilized preferentially Vα17 and Vβ12. Three domain single chain T cell receptors (3D scTcr) were constructed as tools to investigate potential therapies for IDDM and to identify peptides which bind to TCR without association of MHC molecules. Functional analysis has demonstrated that GAD(524-543)-specific scTcrs retained the ability to bind GAD(524-543)/IAg7 complex. This work shows that recombinant scTcrs can bind cognate peptide presented by MHC molecules, therefore they can be used as substitutes for natural TCRs in screening "one-bead one-peptide" combinatorial libraries to identify TCR-binding peptide.
40
Chung, Ming-kar Karl, i 鍾銘家. "Molecular characterization of chicken glutamate receptor, metabotropic1 (GRM 1)". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B49617941.
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Glutamate is the most abundant excitatory neurotransmitter in the mammalian nervous system. Ionotropic glutamate receptors used to be the only type of glutamate receptors, bringing about essential functions including synaptic transmissions. Since 1991, eight metabotropic glutamate receptors have been discovered. Belonging to the subfamily C of G protein-coupled receptor (GPCR) superfamily, these receptors have unique structural features. They couple to their own specific G proteins and transduce signals via pathways not recognized in other subfamilies. To date, little information on these receptors have been revealed in mammals, and even less is known about them in non-mammalian species including chicken.
In the present study, various cDNAs of the chicken glutamate receptor, metabotropic 1 (GRM1) as well as its splice variants were cloned from adult brain tissue. At least 11 exons were identified in the chicken (c-) GRM1 gene, in which the alternative usage of exons and splice acceptor sites results in at least three variants, namely cGRM1a, cGRM1b and cGRM1f. The predicted coding regions of cGRM1a, cGRM1b and cGRM1f are 3459 base pairs (bp), 2736 bp and 2697 bp in length, which were deduced to encode receptor peptides of 1152 amino acids (aa), 911 aa and 898 aa, respectively. The predicted cGRM1a peptide shows high amino acid sequence identities (87.5% to 88%) to its counterparts in humans, rats, mice, chimpanzees and cattle. cGRM1b transcript differs from cGRM1a transcript by inclusion of two additional exons (7b and 7c), which contains a premature stop codon and results in its shorter C-terminal tail. cGRM1f is a novel splice variant that lacks exon 7b and is 13 aa shorter than cGRM1b. Reverse transcription-polymerase chain reaction (RT-PCR) assays showed that the transcripts of cGRM1a, cGRM1b and cGRM1f were preferentially expressed in adult chicken brains, in which cGRM1f mRNA was additionally identified in pituitary, lungs and gonads. Functional assay demonstrated that cGRM1a and cGRM1b receptors, expressed in Chinese hamster ovary cells, were induced by glutamate in dose-dependent manners via the Fura-2 dye calcium assays. In addition, dual luciferase reporter assays suggested that cGRM1a and cGRM1b receptors have no significant effects on the activation of cAMP/PKA and MAPK/ERK signaling pathways upon glutamate treatment.
Taken together, the present study has provided the first step in understanding the possible roles of GRM1 in chickens.published_or_final_version
Biological Sciences
Master
Master of Philosophy
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Aust, Jonathan Gavin. "Molecular and physiological investigations of fish renin-angiotensin systems". Thesis, University of Exeter, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.248168.
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Chen, Changfeng. "Retinoic acid receptors and mouse epidermal tumorigenesis and development". Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=84492.
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Retinoic acid (RA), the major biologically active form of vitamin A, plays important roles in regulating a broad range of biological processes.Progressive loss of RARs is associated with skin carcinogenesis both in human and animals. Despite such observations, the biological significance of RAR loss in skin carcinogenesis has not yet been clarified. To this end, we established keratinocyte cell lines deficient in RARalpha, RARgamma, or both and employed a well-established tumorigenesis model to investigate whether loss of RARs is causally related to skin tumorigenesis. We found that RARgamma is the major RAR subtype mediating the growth and AP-1 inhibitory effects of RA on keratinocytes in vitro. Consistent with this observation, loss of RARgamma, but not RARalpha, predisposed keratinocytes to tumor formation, suggesting that RARgamma may act as a tumor suppressor. Reconstitution of RARs in the RARalphagamma-/- keratinocytes inhibited their tumorigenic potential, further proving that RARs have tumor suppressive effects.
As expected, expression of dnRARalpha resulted in profound epidermal defects. Intriguingly, dnRAalphaDBD caused a virtually identical skin phenotype, suggesting that dnRARalpha acts to affect epidermal development via a DNA-binding-independent mechanism. The epidermal phenotype of these transgenic mice is reminiscent of that seen in the p63-/- mice, and p63 expression was indeed significantly reduced in the epidermis expressing dnRARalpha or dnRARalphaDBD, suggesting that downregulation of p63 by dnRARalpha may be attributable to the epidermal phenotypes associated with the transgenic mice. These observations also suggest that DNA-binding is not required for dnRARalpha to attenuate p63 expression in the epidermis. Consistent with these observations, I also found that p63 is indeed not a RAR-target, as no overt changes in p63 expression were observed in the RARalphagamma-/- epidermis, which appeared normal. (Abstract shortened by UMI.)
43
Lundström, Linda. "Subtype selective activation and molecular characterization of galanin receptors". Doctoral thesis, Stockholms universitet, Institutionen för neurokemi, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-1344.
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Showing an extensive distribution in the nervous system, and often in co-localization with the classical neurotransmitters, neuropeptides are functioning as important modulators of neuronal signaling. Subsequently, compelling evidence has implicated a modulatory role for the neuropeptide galanin in several physiological functions. The effect of galanin is trancduced intracellularly by three different receptors, and defining the explicit effect from these receptor subtypes is of outmost interest, and likely to result in future therapeutic utilization of the galanin system. The main aim of this thesis was to improve the development of subtype selective ligands utilized to differentiate between the galanin receptor subtypes. To achieve this, we have designed and developed novel galanin receptor ligands and characterized the molecular interactions necessary for ligand bindig at the GalR2 subtype. The major findings include the introduction and characterization of two galanin receptor ligands, selectively activating GalR1 or inhibiting GalR2. Although having moderate selectivity, the two ligands have been utilized in a number of studies, pursuing their initial presentation, in order to differentiate between the galanin receptors and to establish their specific function. Further optimization is likely to improve the selectivity and utilization of these ligands. By identifying the major pharmacophores in the Gal(2-11) ligand and the residues in the GalR2 subtype participating in ligand binding, we have been able to characterize the binding site in this receptor subtype and interactions that are of significance for recognition of subtype specific ligands. Together, these findings on GalR2 and Gal(2-11) are of importance for future design of ligands acting on this receptor.
44
Meyer, Annika Kristin [Verfasser]. "Molecular Receptors Based on Bridged Corannulenes / Annika Kristin Meyer". Berlin : Freie Universität Berlin, 2016. http://d-nb.info/1119810906/34.
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Lundström, Linda. "Subtype selective activation and molecular characterization of galanin receptors /". Stockholm : Department of Neurochemistry, Stockholm University, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-1344.
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Ishimaru, Hiroshi. "Molecular biology of novel glutamate receptors in Xenopus laevis". Thesis, University of Cambridge, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.309048.
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Maughfling, Edward John Rosewarne. "Molecular basis for the ligand selectivity of bombesin receptors". Thesis, University of Cambridge, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.625098.
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Hadingham, Karen Louise. "Molecular and genetic analysis of cellular receptors for enteroviruses". Thesis, University of Reading, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.278055.
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Kirwan, Michael Joseph. "Molecular cloning and characterisation of insect nicotinic acetylcholine receptors". Thesis, University College London (University of London), 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.408548.
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Purohit, Prasad G. "Molecular determinants of pharmacological distinctions among nicotinic acetylcholine receptors". Thesis, University of Strathclyde, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.424352.
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