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Martinsson, Hanna-Stina. "Single cell analysis of checkpoints in G₁ /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-455-4/.
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Han, Tian. "Flow cell separation in fluctuating g-field." Thesis, Brunel University, 2015. http://bura.brunel.ac.uk/handle/2438/11105.
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Field flow fractionation of particles in rotating coiled column has been investigated in recent year. In contrast to the classical mode of field flow fractionation in narrow channels, the use of rotating coiled columns offers the possibility of large sample loading. In this thesis, the potential for new cell separation methods based on the use of flow fractionation in fluctuating g-fields generated in rotating coil columns is examined. The effects of operational conditions (flow rate and rotational speed – Chapter 3 and Chapter 5); cell properties (cell flexibility – Chapter 4); and column shapes (different inner diameters and coil geometries – Chapter 6) on the flow behaviour of a model system of red blood cells (RBCs) from different species, which differ markedly in size, shape & density, flowing in a single phase of buffered saline have been characterised. Operational Conditions: For a particular rotational speed, there was a minimum flow rate which caused all the cells to be retained in the column and a maximum flow rate at which all cells were eluted. Both the minimum and maximum flow rate were increased when a higher rotational speed was applied. Differences in the behaviour of sheep & hen RBCs have been used to develop a separation method using a continuously increasing flow gradient. This separation could be speeded up by using a step flow gradient. The effects of cell load and rotational direction on the behaviour of RBCs in the column was also studied in this thesis. Cell Properties: The minimum flow rate was found to correlate with cell diameter/cell volume of the RBCs as expected for a sedimentation related process and was partially described by a theoretic equation developed for particles by Fedotov and colleagues (Fedotov et al. 2005). However cell dependent departures from this equation were found which appear to indicate that cell specific surface properties may also be involved for cells (Chapter 3). By contrast the maximum flow rate showed no correlation with cell diameter/cell volume. An effect of cell deformability on the flow separation behaviour of the cells has been demonstrated. Chemical fixation of sheep RBCs with glutaraldehyde rendered the normally deformable RBCs rigid and non-deformable and resulted in the fixed sheep RBCs eluting significantly earlier than unfixed sheep RBCs. This difference was great enough that a mixture of deformable (unfixed) and non-deformable (fixed) sheep RBCs could be separated. Fixed cells tended to show cell aggregation, which could be reduced by the addition of surfactant. Column Geometry: An effect of column shapes on the flow separation behaviour of cells has been demonstrated showing that the optimisation of column design is an important feature of this mode of cell separation. For columns with the same cross sectional area, a “horizontal” rectangular column provided better separation than a circular column and a “vertical” rectangular column gave the least efficient separation. A possible explanation for this behaviour is suggested the thinner sedimentation layer and less secondary flow. Differences in the behaviour of various species of RBCs in the “horizontal” rectangular column have been used to study the efficiency of separation of a mixture of sheep and hen RBCs, and a mixture of rabbit and hen RBCs. This work shows similarities and differences with other reports on cell/particle separations in rotating coiled columns in single phases and also in aqueous two phases systems (ATPS) and these are discussed. Fedotov P.S., Kronrod V.A. & Kasatonova O.N. (2005). Simulation of the motion of solid particles in the carries liquid flow in a rotating coiled column. J. Anal. Chem., 60, 4, 310-316.
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Hölig, Kristina. "G-CSF in Healthy Allogeneic Stem Cell Donors." Karger, 2013. https://tud.qucosa.de/id/qucosa%3A71643.
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Mobilization of peripheral blood stem cells (PBSC) in healthy volunteers with granulocyte colony-stimulating factor (G-CSF) is currently carried out at many institutions worldwide. This report presents the experience of the Dresden center regarding donor evaluation and mobilization schedule. Data regarding efficacy, short- and long-term safety of G-CSF treatment gained from 8290 PBSC collections in healthy donors are outlined. These results are discussed against the background of the available evidence from the literature. Although established as a standard procedure, G-CSF application to allogeneic donors will always be a very delicate procedure and requires the utmost commitment of all staff involved to ensure maximum donor safety. (PBSC) donation does not require hospitalization and is generally assumed to be less physically demanding for the donor. However, application of mobilizing agents is stringently required for successful HSC mobilization. The standard substance, which is almost exclusively used in healthy donors worldwide, is recombinant human granulocyte colony-stimulating factor (rhG-CSF). Two preparations – filgrastim and lenograstim – are available and have been approved for PBSC mobilization for about 15 years in Germany. Currently, more than 20,000 healthy donors worldwide receive rhG-CSF for PBSC mobilization every year [7]. At the Dresden University Hospital, PBSC collections have been performed since 1996. In the two collection facilities associated with the university hospital, 8,290 allogeneic PBSC collections from 8,005 donors (i.e. 285 second collections) have been documented in a database up until May 2012. This paper presents the data of our own group, and summarizes the current knowledge regarding the short- and long-term effects of G-CSF treatment in healthy stem cell donors.
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Mohanty, Snigdha S. "Evaluation of the Imhoflot G-Cell for fine coal cleaning /." Available to subscribers only, 2007. http://proquest.umi.com/pqdweb?did=1400966001&sid=10&Fmt=2&clientId=1509&RQT=309&VName=PQD.
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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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Sharfe, Nigel. "Investigation of G protein expression in human lymphoid cells." Thesis, University of Cambridge, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.308330.
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Mauk, Andrew W. "A new modeling protocol for G-protein coupled receptors : molecular simulation of phospholipid assemblies." Thesis, Georgia Institute of Technology, 1996. http://hdl.handle.net/1853/11033.
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Piva, Tayeme Cristina. "Fibras Gelatinosas em Eriosema (DC.) Desv. (Leguminosae) Distribuição e Caracterização Estrutural e Química /." Botucatu, 2020. http://hdl.handle.net/11449/192250.
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Orientador: Silvia Rodrigues MachadoResumo: Fibras gelatinosas são células especializadas de esclerênquima que possuem uma camada interna altamente modificada de aparência gelatinosa e translúcida, denominada camada-G. Diversas funções são atribuídas as fibras gelatinosas sendo a principal e mais conhecida a sua relação com o lenho de tração. Porém, outras funções de cunho fisiológico e adaptativo, tais como armazenamento de água e manutenção da orientação foliar foram descritas para as fibras gelatinosas. As fibras gelatinosas são reportadas em diversas famílias de angiospermas nos mais diversos ambientes, com isso outras funções podem ser associadas a ocorrência das fibras gelatinosas nos mais diferentes ambientes. O objetivo desse estudo foi analisar as fibras gelatinosas em representantes de Eriosema (DC.) Desv. um gênero de leguminosa comumente encontrado em Cerrado, visando a acessar variações na distribuição e organização das fibras gelatinosas no eixo vegetativo aéreo e subterrâneo, caracterizar a estrutura básica e a histoquímica das paredes celulares. O estudo foi conduzido com 19 táxons coletados em diferentes áreas de Cerrado, sendo amostrados a folha, caule aéreo e órgão subterrâneo. O material foi processado de acordo com técnicas usuais em anatomia e histoquímica vegetal. Uma espécie foi considerada como modelo e foram utilizados os anticorpos LM5 e LM10 marcadores para galactanos e xilanos, respectivamente, nas paredes das fibras gelatinosas. As fibras gelatinosas ocorreram por todo o corpo vegetativo d... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Gelatinous fibers (G-fibers) are specialized sclerenchyma cells that have a highly modified, translucent, gelatinous appearance inner layer called the G-layer. Several functions are attributed to the G-fibers being the main and best known its relation with the tension wood. However, other physiological and adaptive functions, such as water storage and maintenance of leaf orientation, have been described for G-fibers. G-fibers are reported in several angiosperm families in the most diverse environments, so other functions may be associated with the occurrence of G-fibers in the most different environments. The purpose of this study was to analyze the G-fibers in representatives of Eriosema (DC.) Desv. a genus of legumes commonly found in Cerrado, aiming to access variations in the distribution and organization of G-fibers in the aerial and underground vegetative axis, to characterize the basic structure and histochemistry of cell walls. The study was conducted with 19 taxa collected in different areas of Cerrado, being sampled the leaf, aerial stem and underground organ. The material was processed according to usual techniques in plant anatomy and histochemistry. LM5 and LM10 antibodies that mark galactans and xylans, respectively, were used on the G-fibers walls. G-fibers occurred throughout the vegetative body of the studied Eriosema taxa, being extraxylary in regions with primary growth and xylary in regions with secondary growth. As for the organization, in the leaf the G-... (Complete abstract click electronic access below)
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Ghahremani, Mohammad H. "G protein specificity of dopamine D2S receptor signaling in cell growth and proliferation." Thesis, McGill University, 2000. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=36937.
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A wide range of hormonal, developmental and growth factors regulate cellular growth and proliferation events through receptors that couple to heterotrimeric G proteins. Upon activation of the receptor by its ligand the G protein is activated and subsequent dissociation of alpha subunit from betagamma dimer initiates a cascade of intracellular signaling events. Dopamine D2 receptors, short form (D2S) and long form (D2L) have been implicated in diverse physiological functions including the regulation of pituitary cell proliferation. Although in neuro-endocrine cells, the D2 receptor is traditionally known as an inhibitory receptor since it couples to "inhibitory" G proteins (Gi/Go), a stimulatory role of this receptor has been reported in many non-neuronal cell systems involving growth-related signaling pathways. In this thesis, I have investigated the role of the dopamine D2S receptor in cell growth under the hypothesis that "D2S receptor couples specifically to multiple combinations of Gi/o protein subtypes to initiate specific signaling pathways contributing to cellular proliferation".At first I have examined the role of D2S-induced inhibition of adenylyl cyclase (AC). I have shown that D2S receptor activation inhibits cAMP production in Ltk-(LD2S) and Balb/c-3T3 (Balb-D2S) fibroblast cells. This effect is blocked by pertussis toxin, which specifically inactivates Gi/o proteins. Using a series of toxin-insensitive Galphai/o subtypes, I have identified that in LD2S AC inhibition is mediated through Galphai2 when AC is activated by forskolin and through Galphai3 when AC is stimulated by Galphas. In Balb-D2S cells, D2S inhibition of forskolin-inuduced AC is mediated through Galphai2 and Galphai3. Activation of D2S receptor increases Ca+2 mobilization in both cell lines. Unlike inhibition of AC, this action is mediated through Gbetagamma subunits. The D2S receptor induces MAPK activation and increases DNA synthesis in Balb-D2S cells, actions mediated through a combination of G protein subunits. I have shown that MAPK activation is mainly mediated though Galphai2 and Gbetagamma and DNA synthesis is only mediated through Galphai2 and Gbetagamma. Long term activation of D2S receptor in Balb-D2S cells induces cellular transformation and foci formation. I have shown that this effect is mediated through Galphai3, which suggests a different pathway from MAPK activation and DNA synthesis, initiated via specific G proteins, induces cellular transformation.
In conclusion, I have shown that activation of dopamine D2S receptor couples to multiple Gi/o protein subtypes to regulate different growth-related pathways. More over, I have reported that the D2S receptor induces cell growth and transformation in fibroblast cells and that the specificity of D2S receptor signaling in these pathways is dictated by G protein subunit and Galphai/o subtype. Take together, this thesis exhibits different levels of specificity in D2S signaling which provides novel insights for diseases involving alterations in G protein coupling.
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Sambi, Balwinder Singh. "Functional analysis of G-protein coupled receptors expressed in mammalian reporter cell lines." Thesis, University of the West of Scotland, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.247619.
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Lockhart, Brent E. "Expression, Purification, and Characterization of the Mast Cell Proteases Chymase and Cathepsin G." Digital Commons @ East Tennessee State University, 2008. https://dc.etsu.edu/etd/1922.
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Human mast cells have been associated with wound healing, allergies, inflammation, and defense against pathogens and have been detected in tissues close to blood vessels especially in the areas between the inside of the body and the external environment, such as the skin, lungs, digestive tract, mouth, and nose. Previous studies have shown that mast cells contain large granules filled with histamine, heparin, cytokines, eicosanoids, and the serine proteases, tryptase, Chymase, and cathepsin G (CatG). These proteases are stored and released from mast-cell granules upon activation by antigen binding to IgE immunoglobulins on the cell surface or by direct injury. In this study, chymase and CatG were expressed as active enzymes in the yeast Pichia pastoris by homologous recombination of the cDNA coding for the mature active proteases into the Pichia genome. Methanol induction resulted in the secretion of active enzyme into the Pichia growth media and increasing levels of enzyme were detected in the media for 5 days. Cells that secreted the highest levels of activity were selected by kinetic assay. Active chymase was purified from the culture media with a 22% yield of activity by a simple two-step procedure that involved hydrophobic-interaction chromatography followed by affinity chromatography on immobilized heparin. The major peak from the heparin column contained a single band of 30.6 kDa on SDS/PAGE. The purified recombinant human chymase was 96% active and the yield was 2.2 mg/l of growth media. Active CatG was partially purified from culture media using an ultrafiltration. Mass Spectroscopy (Maldi-Tof) data confirmed that the major protein band was CatG, resulting in the first active human CatG to be produced recombinantly. Additionally, the partially purified enzyme was active against both chymotrypsin and trypsin substrates, and its reaction with inhibitors was consistent with CatG. Although the protein yields were low, these results confirm that CatG was recombinantly expressed.
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Malik, Babar. "G (alpha) 12 Is Required For Thromboxane A2 To Regulate Tumor Cell Motility." OpenSIUC, 2011. https://opensiuc.lib.siu.edu/theses/682.
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Thromboxane (TX) A2 is a prostaglandin produced by metabolism of arachidonic acid through cyclooxygenases and thromboxane synthase. TXA2 is biologically active, mainly through activating its cognate, seven transmembrane, G protein coupled receptor. It was previously reported that thromboxane A2 receptor (TP) was expressed in prostate cancer, and further activation of this receptor elicited cell contraction and modulated tumor cell motility through regulating small GTPase RhoA[1]. This study aims to identify G alpha protein(s) involved in thromboxane A2 signaling in tumor cell motility. Methods: The expression of G alpha proteins in the PC3MM cells was studied by real time PCR. Cell contraction assay was performed by staining cells with TRITC phalliodin. Tumor cell motility and invasion were evaluated using wound healing assay and transwell Boyden Chamber assay. To determine the roles of G alpha protein in thromboxane A2 signaling, we expressed different alleles of G alpha proteins (wild type, constitutive active) in PC3MM cells and then the subsequent effects on cell contractions was determined. We also depleted G alpha protein expression by short hairpin RNA and examined subsequent changes in cell contraction and migration after activation of TP. G (alpha) 12 has been reported to play critical role in cell proliferation in vitro and tumor growth in vivo. These findings were validated by performing BrdU Incorporation assay, Cell proliferation assay and cell cycle analysis. Quantitative analysis of the epithelial to mesenchymal transition associated genes was performed by real time PCR. In vivo experiments were performed in order to validate in vitro findings. Results: PC3 MM cell line had the endogenous level of all the G alpha protein (G alpha 12, G alpha i1, G alpha 11, G alpha 13), but not G alpha q. Overexpression of G alpha 12/13 increased cell contraction after activation of thromboxane A2 receptor with U46619. Expression of constitutively active G alpha 12 by itself was sufficient to cause cell contraction, regardless whether TP is activated or not. We have identified two potent shRNAs that can silence the G Alpha 12. Depletion of G alpha 12 via shRNAs reduced cell contraction after TP activation. Tumor cells with depleted G alpha 12 had shown decreased tumor cell motility, invasiveness and cell proliferation. Cell cycle analysis showed that G alpha 12 depleted cells exhibit G1/G0 arrest. Quantitative expression of EMT associated genes was reduced in G alpha 12 depleted cells exhibiting increase in the E cadherin / Vimentin ratio. G alpha 12 depleted cells in comparison to scramble control show reduced rate of cell proliferation reminiscent of in vitro findings. Conclusion: This study presents compelling evidence that G alpha 12 plays a major role in thromboxane A2 regulation of prostate cancer invasion and metastasis. Silencing of G alpha 12 with shRNA may therefore provide a promising therapeutic strategy for prostate cancer patients.
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Chesla, Scott Edward. "Two dimensional (solid phase) kinetic analysis of FCnGamma receptor III (CD16) Interactions with IgG." Diss., Available online, Georgia Institute of Technology, 2005, 2005. http://etd.gatech.edu/theses/available/etd-04042005-154037/.
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Thesis (Ph. D.)--Mechanical Engineering, Georgia Institute of Technology, 2005.Dr. Cheng Zhu, Committee Chair ; Dr. Periasamy Selvaraj, Committee Co-Chair ; Dr. Timothy Wick, Committee Member ; Dr. Lyle Sinor, Committee Member ; Dr. Raymond Vito, Committee Member ; Dr. Robert Nerem, Committee Member.
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Liu, Yu-Tsan. "Regulation of protein trafficking by Ral GTPases and Exocyst in epithelial cells." Thesis, University of Iowa, 2014. https://ir.uiowa.edu/etd/1873.
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In polarized epithelial cells, vectorial protein trafficking is important for transporting specific membrane proteins to generate distinct apical and basolateral membrane protein compositions. The Exocyst is a conserved hetero-octameric protein complex, which regulates different aspects of protein trafficking, including tethering of the Golgi-derived vesicles to target membranes. Two of the Exocyst subunits, Sec5 and Exo84, competitively bind to the small GTPases, RalA and RalB, in a GTP-dependent manner. Although Ral GTPases have been proposed to mediate assembly of Exocyst holocomplexes, we hypothesize that they actually serve to allosterically regulate Exocyst functions by promoting association or disassociation of additional factors. Previous studies have shown that active RalA, but not RalB, accelerated basolateral exocytosis of E-cadherin. In contrast, knockdown of RalB, but not RalA, disrupts endocytosis of E-cadherin. However, mechanisms by which association of Ral GTPases with Sec5 and Exo84 regulate basolateral protein trafficking remain unclear.
Here we investigate roles of Ral GTPases and the Exocyst in regulating basolateral protein trafficking using Madin Darby canine kidney (MDCK) cells and RNA interference (RNAi) technology. We show that RalA, but not RalB, is required for basolateral exocytosis of vesicular stomatitis virus glycoprotein (VSV-G) in the MDCK cells. We combined immunofluorescent labeling and surface biotinylation assays to demonstrate that RalA regulates VSV-G trafficking through the distinct interactions with Sec5 and Exo84. We also show that a Ral-uncoupled Sec5 mutant, but not a Ral-uncoupled Exo84 mutant, inhibits E-cadherin exocytosis. These results suggested that RalA and the Exocyst are required for basolateral exocytosis, and that RalA-Sec5 and RalA-Exo84 interactions play different roles during this process. Our study may provide new insights into mechanisms regulating protein trafficking in epithelial cells, and potentially lead to development of new therapeutic targets for the treatment of diseases in which exocytosis is impaired, such as Polycystic kidney disease and diabetes.
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Xia, Lijin. "Regulators of G-protein Signaling, RGS13 and RGS16, are Associated with CXCL12-mediated CD4+ T Cell Migration." Diss., CLICK HERE for online access, 2008. http://contentdm.lib.byu.edu/ETD/image/etd2588.pdf.
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Lin, Adora A. "The CD4+ T cell response to CNS viral infection." University of Cincinnati / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1235330516.
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Hanson, Ken. "ADP-ribosylation in a murine myelomonocytic cell line and its association with G-CSF induced differentiation." Thesis, University of North Texas, 1993. https://digital.library.unt.edu/ark:/67531/metadc798214/.
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Wilham, Laura Elizabeth. "The role of [beta]-arrestin in agonist-induced down-regulation of the M₁mAChR." CONNECT TO THIS TITLE ONLINE, 2006. http://etd.lib.umt.edu/theses/available/etd-03022007-104437/.
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Ng, Sai-ming. "Characterization of human secretin receptor by the cytosensor microphysiometer system /." Hong Kong : University of Hong Kong, 1998. http://sunzi.lib.hku.hk/hkuto/record.jsp?B19737324.
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Pösel, Claudia. "Effizienz einer Kombinationstherapie aus G-CSF und mononukleären Knochenmarkzellen in einem präklinischen Schlaganfallmodell." Doctoral thesis, Universitätsbibliothek Leipzig, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-175086.
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Eine Vielzahl präklinischer Schlaganfallstudien zeigte die neuroprotektive und neuroregenerative Wirkung des hämatopoetischen Wachstumsfaktors G-CSF (Granulozyten-Kolonie stimulierender Faktor). Ein Wirkungsmechanismus des G-CSF ist die Mobilisation von protektiven Knochen-markzellen in die ischämische Läsion, wobei diese zeitverzögert nach G-CSF-Gabe stattfindet. Eine zusätzliche frühzeitige Transplantation mononukleärer Knochenmarkzellen (BM MNC) könnte diese therapeutische Lücke füllen. Ziel der vorliegenden Studie war es, die Wirksamkeit dieser Kombinations-therapie in einem Schlaganfallmodell der spontan hypertensiven Ratte (SHR) zu testen. Syngene BM MNC wurden aus dem Knochenmark von SHRs durch immunmagnetische Depletion der Granulozyten isoliert. Nach Verschluss der Arteria cerebri media wurde den Tieren über insgesamt 5 Tage G-CSF verabreicht und zusätzlich zu einem frühen (6h nach Schlaganfall) oder späteren (48h nach Schlaganfall) Zeitpunkt BM MNC intravenös appliziert. Unbehandelte Schlaganfalltiere sowie Tiere mit alleiniger G-CSF-Therapie dienten als Kontrolle. Das Infarktvolumen wurde weder durch die alleinige G-CSF-Gabe noch durch die zusätzliche Zelltherapie verändert. Dennoch wiesen Tiere mit G-CSF-Einzeltherapie eine anhaltende funktionelle Verbesserung des sensomotorischen Defizites auf. Während die zusätzliche frühzeitige Zelltransplantation (6h) keinen weiteren Therapieeffekt zeigte, führte die Zelltransplantation nach 48h zu einer Aufhebung des protektiven G-CSF Effektes. Die G-CSF-Therapie bewirkte erwartungsgemäß einen deutlichen Anstieg der zirkulierenden Leukozyten. Interessanterweise wurde der Granulozytengehalt im Blut und in der Milz durch die einmalige Zelltherapie nach 48h signifikant erhöht. Ein Großteil der transplantierten BM MNC (48h) konnte in der Milz nachgewiesen werden und führte dort vermutlich zu einer kompetitiven Hemmung des Granulozytenabbaus. Dies hatte sowohl den Anstieg der zirkulierenden Granulozyten als auch deren vermehrte Infiltration in das ischämische Hirngewebe zur Folge und könnte schließlich den negativen Einfluss auf die funktionelle Verbesserung erklären. Die beobachteten Interaktionsmechanismen werfen ein interessantes Licht auf die mögliche Wirkungsweise von Zelltherapien und unterstreichen die entscheidende Rolle des Immunsystems in der Pathophysiologie des Schlaganfalls.
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Delling, Markus. "Regulation of G-protein-activated inwardly rectifying potassium channels by the neural cell adhesion molecule NCAM." [S.l.] : [s.n.], 2001. http://deposit.ddb.de/cgi-bin/dokserv?idn=963607782.
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Pitt, Samantha Jane. "Potentiation of G protein-coupled receptor signalling by extracellular K⁺ in human platelets and cell lines." Thesis, University of Cambridge, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.613950.
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Volta, Francesco [Verfasser], Gil G. [Akademischer Betreuer] Westmeyer, Gil G. [Gutachter] Westmeyer, Henrik [Gutachter] Semb, and Margret [Gutachter] Schottelius. "Glucose homeostasis is regulated by pancreatic β-cell cilia via endosomal EphA-processing / Francesco Volta ; Gutachter: Gil G. Westmeyer, Henrik Semb, Margret Schottelius ; Betreuer: Gil G. Westmeyer." München : Universitätsbibliothek der TU München, 2021. http://d-nb.info/1232913774/34.
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Hedde, Per Niklas [Verfasser], and G. U. [Akademischer Betreuer] Nienhaus. "Light Microscopy Beyond the Diffraction Barrier for Live Cell Studies / Per Niklas Hedde. Betreuer: G. U. Nienhaus." Karlsruhe : KIT-Bibliothek, 2013. http://d-nb.info/1037776186/34.
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Azarkh, Mykhailo [Verfasser]. "In-cell approaches in electron paramagnetic resonance spectroscopy to study conformations of DNA G-quadruplexes / Mykhailo Azarkh." Konstanz : Bibliothek der Universität Konstanz, 2012. http://d-nb.info/1023650193/34.
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Bornheimer, Scott Joseph. "Spatial and temporal regulation of G-protein signaling elucidated by computational modeling and live cell FRET imaging." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2008. http://wwwlib.umi.com/cr/ucsd/fullcit?p3308008.
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Thesis (Ph. D.)--University of California, San Diego, 2008.Title from first page of PDF file (viewed June 12, 2008). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references.
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Chervyachkova, Elizaveta [Verfasser], and G. Elisabeth [Akademischer Betreuer] Pollerberg. "Light-controlled self-assembly and self-sorting of cell-like compartments / Elizaveta Chervyachkova ; Betreuer: G. Elisabeth Pollerberg." Heidelberg : Universitätsbibliothek Heidelberg, 2018. http://d-nb.info/1177149621/34.
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Brantingson, Skogfält Katarina. "Impact of insulin, glucagon and the I-G complex on cell viability and metabolism in Panc-1." Thesis, Högskolan i Skövde, Institutionen för hälsovetenskaper, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-19918.
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Cancer has been found not only to be a disease of genetic mutations, but also a metabolic state by which insulin and glucagon has an impact on cancer cells. Pancreatic adenocarcinoma (PDAC) is a highly lethal cancer with high risk of recurrence of cancer cells after cancer therapy treatment with a worse outcome. Healthy individuals are reported to have imbalance of blood glucose homeostasis, and an imbalance between secreted insulin and glucagon, which contribute to diabetes onset and might create a new complex between human insulin and glucagon. An increased risk of developing cancer has been seen in patients with type 1 diabetes mellitus (T1D) and type 2 diabetes mellitus (T2D). Investigations were done on human insulin and glucagon and its formation into a new complex. Pancreatic cancer cell lines, Panc-1, were treated with these different peptides, in different concentrations, to find out the impact on cell viability. Lactate-Glo Assay were performed, investigating if there was a change of metabolism within the cells. A complex formation of insulin and glucagon from bovine and porcine, receptively, has previously been shown. Here it is reported of the existence of a new insulin-glucagon (I-G) complex made from human peptides. The I-G complex increase cancer cell viability, change the metabolism within the cells and act differently than from insulin and glucagon alone. The I-G complex interaction in cancer and diabetes, are to be further investigated.
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Ng, Sai-ming Samuel, and 吳世明. "Characterization of human secretin receptor by the cytosensor microphysiometer system." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1998. http://hub.hku.hk/bib/B31219743.
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Lau, Sin-nga, and 劉善雅. "The role of RAB(rat sarcoma-related proteins in brain) Gtpases in regulating testicular junction dynamics." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2004. http://hub.hku.hk/bib/B31245535.
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Nipper, Rick William Jr 1978. "Molecular function of the cell polarity protein partner of inscuteable in Drosophila neuroblasts." Thesis, University of Oregon, 2007. http://hdl.handle.net/1794/6194.
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xiii, 48 p. : (col. ill.) A print copy of this title is available through the UO Libraries under the call number: SCIENCE QL537.D76 N57 2007Asymmetric cell division (ACD) is a unique mechanism employed during development to achieve cellular diversity from a small number of progenitor cells. Cells undergoing ACD distribute factors for self-renewal at the apical cortex and factors for differentiation at the basal cortex. It is critical for proper development that the mitotic spindle be tightly coupled to this axis of polarization such that both sets of proteins are exclusively segregated into the daughter cells. We use ACD in Drosophila neuroblasts as a model system for understanding the molecular mechanisms that govern spindle-cortical coupling. Neuroblasts polarize Partner of Inscuteable (Pins), Gαi and Mushroom Body Defect (Mud) at the apical cell cortex during mitosis. Gαi and Pins are required for establishing cortical polarity while Mud is essential for spindle-cortical alignment. Gαi and Mud interact through Pins GoLoco domains and tetratricopeptide repeats (TPR) respectively, however it is unclear how Mud activity is integrated with Pins and Gαi to link neuroblast cortical polarity to the mitotic spindle. This dissertation describes how Pins interactions with Gαi and Mud regulate Iwo fundamental aspects of neuroblast ACD: cortical polarity and alignment of the spindle with the resulting polarity axis. I demonstrate that Pins is a dynamic scaffolding protein that undergoes a GoLoco-TPR intramolecular interaction, resulting in a conformation of Pins with low Mud and reduced Gαi binding affinity. However, Pins TPR domains fail to completely repress Gαi binding, as a single GoLoco is unaffected by the intramolecular isomerization. Gαi present at the apical cortex specifies Pins localization through binding this "unregulated" GoLoco. Liberation of Pins intramolecularly coupled state occurs through cooperative binding of Gαi and Mud to the other GoLoco and TPR domains, creating a high-affinity Gαi-Pins-Mud complex. This autoregulatory mechanism spatially confines the Pins-Mud interaction to the apical cortex and facilitates proper apical-spindle orientation. In conclusion, these results suggest Gαi induces multiple Pins states to both properly localize Pins and ensure tight coupling between apical polarity and mitotic spindle alignment.
Adviser: Ken Prehoda
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Bucco, Olgatina, and olgatina@gmail com. "Preparing, measuring and capturing G-protein coupled receptor (GPCR) signalling complexes for future development of cell-free assay technologies." Flinders University. medicine, 2006. http://catalogue.flinders.edu.au./local/adt/public/adt-SFU20060703.114912.
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G-protein coupled receptors (GPCRs) are integral membrane proteins which
represent primary cellular targets for intracellular signalling. Many of these receptors
are altered in disease states and hence are the target for over 50% of marketed drugs.
Despite their physiological importance, high-throughput, cell-free assays which
measure functional or signalling activity are only recently being investigated. The
current approach by the pharmaceutical industry to initially screen compounds for
functionality is to use heterologous cell-based assay formats. The aim of this work
was to reconstitute a cell-free GPCR signalling system on an appropriate platform
(surface) as a prototype for future rapid drug screening and other applications. The
proof-of-concept approach involved using the �2A-adrenergic receptor (�2A-AR)
containing cell membrane preparations as the model GPCR, reconstituted with a set
of heterotrimeric G-proteins; G�i1 and �1�2 (the signal transducing complex being
termed a �transductosome�). However, other receptors and G-proteins were also
investigated. Receptors were initially obtained from natural (tissue) sources, however
in the later stages they were expressed in a heterologous system (insect or
mammalian expression system). G-proteins were expressed in Spodoptera
frugiperida (Sf9) insect cells using the baculovirus expression system. Receptor
expression was verified by radioligand binding assays and endogenous G-proteins
were removed from membrane preparations using the chaotropic agent urea to allow
for reconstitution with purified G-proteins. Signal transduction through the
transductosome was measured using the [35S]GTP�S binding assay. Receptor
activated [35S]GTP�S binding was used to determine functional reconstitution and to
validate that the system was working in the normal physiological manner both on and
off a surface (with surface attachment being via histidine attachment on the G�i1
(6xHIS) subunit). Using the captured (surface-attached) transductosomes, the IC50 values for Rauwolscine, Yohimbine (potent �2-AR antagonists), Prazosin (potent �1-
AR antagonist) and Propranolol (�-AR antagonist) displayed the appropriate rank
order for this class of receptor. This cell-free, surface-attached signalling complex
prototype may have use in the future development of drug screening and discovery
assay technologies as well as other applications as an alternative to cell-based assays
which are not readily amendable to miniaturisation, long term storage and therefore
stable robust microarray formats.
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Casadó, Anguera Verònica. "Allosteric interactions between catecholamine receptors and other G protein-coupled receptors: Pharmacological and functional characterization." Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/586262.
Full textAbstract:
Catecholamines, including dopamine (DA) and norepinephrine (NE), are widely distributed in the body and constitute a class of conventional neurotransmitters and hormones that occupy key positions in the regulation of physiological processes and in the development of neurological, psychiatric, endocrine and cardiovascular diseases. There is a linkage between a variety of genes related to DA (e.g. D4 receptor) and NE (e.g. α2A-adrenoceptor) and the vulnerability for developing attention deficit hyperactivity disorder (ADHD), which is characterized by pervasive symptoms of inattention, impulsivity and/or hyperactivity. In addition, adenosine, acting on adenosine receptors (AR), is a modulator of other receptors such as D1-like and D2-like DA receptors (DR). DA and adenosine receptor complexes are involved in the control of the direct and indirect pathway of motor control in basal ganglia, in which adrenergic receptors are also involved.
NE, DA and adenosine receptors belong to the GPCR family, also known as seven transmembrane domain receptors. GPCRs have an enormous biomedical importance. It is estimated that about 35% of approved drugs target GPCRs. Thus, is not surprising that lots of models have been developed in order to explain the pharmacological behavior of these receptors. A large number of GPCRs have been described to form homodimers, heterodimers and higher order oligomers with different pharmacological and functional properties than of its individual components.
The aim of this Thesis has been to study and characterize the molecular interactions at pharmacological and functional level of heterodimers between catecholamine receptors and between catecholamine and adenosine receptors involved in several neurological pathologies related to imbalances in attention, impulsivity and motor control.
For simplicity, for pharmacologically characterize GPCRs, most of the developed models consider them as monomeric entities. Thus, it is not surprising that, when working with receptor dimers but using monomeric models, some parameters obtained may be erroneous. Then, first of all, we went deeper into the study of allosteric interactions within GPCRs using the dimer receptor model, which considers GPCRs as dimers.
Along our study, we have given further evidences that homodimers are the GPCR predominant species, and that allosteric interactions between orthosteric ligands of the different protomers of a GPCR heteromer, have important implications in the field of catecholamine receptor pharmacology. A paradigmatic example of complex allosteric interactions is the A2AR-A2AR-D2R-D2R-Gs-Gi-AC5 heteromer. Moreover, since bivalent ligands are the best example of oligomer selective-ligands that can interact simultaneously with GPCR dimers with high affinity and subtype selectivity, we have developed a precise strategy for developing them. Using computational tools that considered the TM interfaces, distances between orthosteric binding sites and the mode of interaction of the pharmacophore units, we have higher success in affinity results. In particular, the obtained GPCR bivalent ligand had a picomolar binding affinity for the dopamine D2 receptor (D2R) homodimer. However, to obtain oligomer-selective bivalent ligands, the selected pharmacophores must be highly specific. This is not always easy to find. As an example, we have demonstrated that catecholamine receptors constitute a “functional” family of GPCRs. Specifically, in this study we have shown that DA and synthetic DA receptor ligands are able to bind to α2Rs and activate the same signaling pathways as NE. In addition, we have demonstrated the existence of functional D4R-D2SR in vitro and, for the first time, functional D4R-α2AR heteromers in vitro and in rodent brain tissues not only with the D4.4R but also with the D4.7R variant, prevalent in ADHD. Significant different properties of these heteromers were D4R variant-dependent. Finally, given that D2R, D4R and α2AR, are involved in the pathophysiology of ADHD, we suggest that D4R-D2R and α2AR-D4R heteromers could be target for the therapeutic treatment of such neurological disorders.Les catecolamines dopamina (DA) i norepinefrina (NE) tenen una funció clau en la regulació de processos fisiològics i en el desenvolupament de diverses patologies. Existeix una correlació entre gens relacionats amb la DA (com el receptor D4) i amb la NE (com el receptor α2A) i la vulnerabilitat per desenvolupar el trastorn per dèficit d’atenció i hiperactivitat (TDAH). A més, l’adenosina, actuant sobre els receptors d’adenosina (AR), és un modulador dels receptors de DA tipus D1 i D2, que controlen el moviment als ganglis basals, on també es troben implicats els adrenoreceptors. Els receptors de NE, DA i adenosina pertanyen a la família dels GPCR, que té una gran importància biomèdica, essent diana d’un 35% dels fàrmacs aprovats. És conegut que els GPCRs formen homodimers, heterodimers i oligòmers més complexos amb noves propietats farmacològiques i funcionals. En aquesta Tesi hem caracteritzat les interaccions moleculars entre receptors de catecolamines i entre receptors de catecolamines i d’adenosina, involucrats en patologies neurològiques relacionades amb l’atenció, la impulsivitat i el control motor. Concretament, hem donat evidències que els homodimers de GPCRs són les espècies predominants a l’organisme i que les interaccions alostèriques entre lligands ortostèrics dins un heteròmer tenen importants implicacions farmacològiques. També hem generat un protocol de síntesis de lligands bivalents molt eficient. Aquests lligands permeten actuar sobre un oligòmer concret, minimitzant els efectes secundaris en comparació amb fàrmacs dirigits a monomèrs. Hem demostrat que els receptors de catecolamines constitueixen una mateixa família funcional donada la promiscuïtat entre els seus lligands. Finalment, hem descrit l’existència de complexos entre els receptors D4 i D2S i entre D4 i α2A, trobant diferències funcionals segons la variant del receptor D4 involucrada. Donat que els receptors D2R, D4R i α2AR estan involucrats en el TDAH, aquests heteròmers poden ser una nova diana terapèutica per a aquesta patologia.
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Pramod, Hema. "Regulation of stem cell differentiation into cardiomyocytes by lysophosphatidic acid." Thesis, University of Hertfordshire, 2017. http://hdl.handle.net/2299/17561.
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The mechanisms that regulate the differentiation of stem cells (SCs) into cardiomyocytes are still unclear and the role of endogenous molecules on this process remains unexplored. One such molecule is the bioactive phospholipid lysophosphatidic acid (LPA) which accumulates in the myocardium following acute infarction and exerts multiple biological functions, including the regulation of cell growth and differentiation as well as cell survival (Tigyi et al., 2003; Sengupta, et al., 2004). Experiments were therefore carried out in this thesis to reveal whether LPA can induce the differentiation of stem cells into cardiomyocytes and to identify the signalling mechanisms that mediate this effect. All experiments were carried out in the mouse P19 carcinoma stem cell line. Treatments with LPA in the absence and presence of various pharmacological compounds were conducted in embryoid bodies (EBs) formed from the P19 cells in sterile Petri dishes over 4 days. The EBs were subsequently transferred into 6-well cell culture plates and cultured for specific time points. Lysates were generated and subjected to western blotting for expression of cardiac- specific myosin light chain -1v (MLC-1v). To look at the expression of LPA receptors (LPAR1-LPAR5) experiments were carried out by RT-PCR using specific primers for each LPA receptor and the role of the latter in mediated responses to LPA were examined in the presence of the LPAR 1/3 antagonist, Ki16425, or the LPAR 4 receptor blocker suramin. In addition, experiments were carried out investigating the role of Gαi and specific signalling pathways that may be involved in the differentiation of P19 cells. These were carried out using potent inhibitors/antagonists of Gαi inhibitor (Pertussis toxin), PI3K inhibitor (LY294002), Akt inhibitor (Akt inhibitor XIII), PKC inhibitor (Bisindolylmaleimide I BIM-I), ROCK inhibitor (Y-27632), p38-MAPK inhibitor (SB203580) and ERK1/2 inhibitor (PD98059). Further experiments were carried out to establish whether the presence of LPA results in the phosphorylation of the targeted kinases. These studies were however limited to Akt, p38 MAPK and ERK1/2. Incubation of cells with LPA resulted in the differentiation of P19 cells into cardiomyocytes as reflected by the induction of MLC-1v. The latter increased significantly above basal in a time-dependent manner, reaching a maximum 10 days after plating EBs in 6-well plates. The induction of MLC-1v was more pronounced in cells incubated with 5 μM LPA at 6 days but showed little concentration differences at day 12. RT-PCR analysis confirmed the expression of LPA receptors 1 to 4 but not 5. Pre-incubating cells with suramin and Ki16425 concentration-dependently inhibited MLC-1v expression with 0.05 mg/ml and 10 μM respectively, virtually abolishing the expression of MLC-1v. Additionally, inhibitors of LPAR1/3 and LPAR4 receptors and all the signalling inhibitors except SB203580 abolished the phosphorylation of ERK1/2. Similarly, p38 MAPK activation was completely abolished by LPAR1/3 and LPAR4 receptor antagonists, Interestingly, only LY294002 (5 μM) and Y27632 (10 μM) abolished the LPA induced activation of p38 MAPK while SB203580, BIM-I, Akt inhibitor XIII and PD95080 caused no significant changes to the phosphorylation of p38 MAPK. In conclusion, the studies carried out in this thesis have shown that LPA can induce P19 stem cells to differentiate into cardiomyocytes and they are linked to the well characterised LPA receptors (LPAR1/3 and 4). These receptors are coupled to downstream signalling pathways of which those involving the ROCK, PI3K, PKC and/or Akt may be critical, and may converge on ERK1/2. Inhibition of any of these pathways has the potential to suppress differentiation. In contrast, signalling leading to p38 activation may potentially suppress differentiation but this needs further clarification.
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Kin, Nicholas W. "A study of the mechanism by which CD86 regulates IgG1." Columbus, Ohio : Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1174676264.
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Schuster, Susanne [Verfasser], Annette G. [Akademischer Betreuer] Beck-Sickinger, Annette G. [Gutachter] Beck-Sickinger, and Wieland [Gutachter] Kiess. "The NAMPT-mediated NAD salvage pathway in cancer cell metabolism and its regulation by resveratrol / Susanne Schuster ; Gutachter: Annette G. Beck-Sickinger, Wieland Kiess ; Betreuer: Annette G. Beck-Sickinger." Leipzig : Universitätsbibliothek Leipzig, 2015. http://d-nb.info/1239567219/34.
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Gaul, Susanne [Verfasser], Annette G. [Akademischer Betreuer] Beck-Sickinger, Annette G. [Gutachter] Beck-Sickinger, and Wieland [Gutachter] Kiess. "The NAMPT-mediated NAD salvage pathway in cancer cell metabolism and its regulation by resveratrol / Susanne Schuster ; Gutachter: Annette G. Beck-Sickinger, Wieland Kiess ; Betreuer: Annette G. Beck-Sickinger." Leipzig : Universitätsbibliothek Leipzig, 2015. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-173401.
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Yarmishyn, Aliaksandr. "Analysis of the effects of the cyclin encoded by murine g-herpesvirus-68 on mammalian cell cycle control." Thesis, Imperial College London, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.443805.
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Doyle, Lynsey Kerr. "Role of vascular endothelial growth factor (VEGF) in granulosa cell function : involvement of heterotrimeric G-protein signalling pathways." Thesis, University of Edinburgh, 2009. http://hdl.handle.net/1842/4297.
Full textAbstract:
Vascular Endothelial Growth Factor (VEGF) has been shown to be an absolute requirement for ovarian follicle development. Although VEGF is commonly regarded primarily as an angiogenic factor, granulosa cells are a major site of VEGF synthesis in the follicle and they express VEGF receptors (VEGFR1 and VEGFR2). Further, the development of the dominant follicle is characterised by a substantial increase in granulosa cell expression of VEGF and its receptors. In spite of this, potential non-angiogenic effects of VEGF in these follicles have not been elucidated. The objective of the three studies described in this thesis was to use an in vitro bovine granulosa cell model to investigate the roles of VEGF during development of the dominant follicle. In addition, in light of evidence in other cell types, potential interactions between VEGF signalling and heterotrimeric protein signalling in these follicles were also investigated. In the first study, granulosa cells were obtained from healthy follicles with diameters of 4 to 8 mm (corresponding to just before the selection of a dominant follicle during a follicular wave) or 9 to 14 mm (encompassing all developmental stages of a dominant follicle) and exposed to a range of VEGF concentrations (1 to 100 ng/ml) encompassing concentrations found naturally in bovine dominant follicles. VEGF at 1 ng/ml, but not at higher concentrations (P > 0.1), induced significant proliferation of bovine granulosa cells from 4 to 8 mm follicles (P = 0.024) and increased the proliferative response of these cells to FSH (P = 0.045). VEGF also induced a dose-dependent increase in ERK1/2 activation by granulosa cells from 4 to 8 mm follicles (P < 0.03) but did not have any effect on expression of the steroidogenic enzyme, CYP11A1, by these cells (P > 0.1). VEGF, at a dose of 1 ng/ml (P = 0.003), but not at higher doses (P > 0.1), induced an increase in COX-2 expression by granulosa cells from 9 to 14 mm follicles. In addition, LH stimulation of both ERK phosphorylation (P < 0.05) and COX-2 expression (P < 0.05) in granulosa cells from 9 to 14 mm follicles were prevented (P > 0.1) by specific inhibition of VEGFR2, indicating that VEGF may mediate COX-2 responses to LH in these cells. The second study sought to examine the expression of heterotrimeric G-protein á subunits and PLCâ isoforms by real-time PCR and westen blotting in bovine granulosa cells throughout follicle development to identify specific molecular components of heterotrimeric G-protein pathways that may functionally interact with intracellular VEGF signals. Results showed that GNAS, GNA11 and GNAI2 were all expressed at significantly (P < 0.05) higher levels in granulosa cells of pre-ovulatorysize follicles (10.0 to 13.9 mm) than in cells from smaller follicles (2.0 to 5.9 mm and 6.0 to 9.9 mm). In addition, all PLCB isoforms except PLCB2 were expressed in bovine granulosa cells with PLCB3 being more abundant than PLCB1 and -4. Levels of PLCB3 in granulosa cells from pre-ovulatory-size follicles were much higher (>16-fold; P < 0.005) than in smaller follicles. Immunocytochemical analysis revealed that PLCB3 was located primarily in the cytoplasm, whereas PLCB1 was distributed primarily in the nucleus. These results identified Gs, Gq/11, Gi2 and PLCâ3 as candidates for cross-talk between VEGF and heterotrimeric G-protein signalling during the development of the dominant follicle. The potential involvement of these molecules on VEGF-induced responses in granulosa cells from 9-14 mm follicles was investigated in the third study by determining the effects of specific inhibitors of Gi (pertussis toxin, PTX) or Gq/11 (YM-25489) or PLCB3 siRNAs on VEGF-induced p-ERK. Results showed a 2.3 fold mean increase in p-ERK in response to VEGF in the absence of G protein inhibitors (P < 0.0001) but a VEGF response that was completely or partially abolished, respectively, in the presence of PTX (P > 0.8) or YM-25489 (1.6-fold mean increase relative to untreated controls; P = 0.039). LH induced a 1.6 fold increase in p-ERK1/2 (P < 0.02) and this response was prevented by pre-incubation with PTX (P > 0.4) or YM-25489 (P > 0.5). In contrast, similar EGF-induced phosphorylation of ERK (about 5-fold relative to controls) occurred in the absence (P < 0.003) or presence of PTX (P < 0.003) or YM-25489 (P < 0.003). Transfection of granulosa cells with 3 siRNAs targeting PLCB3 that had been previously validated by western blotting and immunocytochemistry had no effect (P = > 0.7) on phosphorylation of ERK in response to VEGF, LH or EGF in granulosa cells. In conclusion, taken together, these results suggest novel roles of VEGF in stimulating granulosa cell proliferation and expression of COX-2 in bovine dominant follicles and implicate VEGF in synergising and/or mediating the effects of gonadotrophins in these cells. In addition, these results indicate a requirement for Gi2 and Gq/11 in VEGF activation of ERK1/2 and induction of the above responses in granulosa cells.
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Dalier, Fabrice. "Stimuli-responsive polymer coatings based on (poly-L-Lysine)-g-poly(N-isopropylacrylamide) to control specific cell adhesion." Thesis, Paris Sciences et Lettres (ComUE), 2016. http://www.theses.fr/2016PSLEE019/document.
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Des revêtements polymères basés sur la physisorption de copolymères en peigne, dérivés du (Poly-L-Lysine)-g-poly(N Isopropylacrylamide) noté PLL-g-PNIPAM, ont été développés afin de contrôler réversiblement l'adhésion cellulaire. La préparation de ces revêtements repose sur l'adsorption spontanée de la poly(lysine) sur la plupart des substrats anioniques usuels en biologie, aisément mis en oeuvre par le non-spécialiste : une simple immersion du substrat dans une solution de PLL-g-PNIPAM donne une monocouche résistante au rinçage et dense en chaines poly(N-Isopropylacrylamide) thermosensibles.L'adsorption de copolymères en peigne dérivés de la PLL et portant des chaînes latérales de natures variées permet d'ajuster à souhait les propriétés du revêtement. Notre attention s'est portée particulièrement sur l'étude de couchesthermosensibles poly(N-Isopropylacrylamide-coligand), où le ligand est soit un groupe biotine, soit un peptide d'adhésion.Une voie de synthèse générique de dérivés PLL-g- PNIPAM est décrite. Elle se fonde sur la polymérisation RAFT du N-acryloxysuccinimide et la post-modification des unités de répétition puis des extrémités de chaînes. Des mesures de la température de transition soluble/insoluble en solution et des caractérisations par AFM et QCM-d de l'extension des chaînes en surface ont permis de démontrer que la transition au sein des revêtements s'opère à une température proche de celle en solution. La stabilité en termes de composition et d'épaisseur des revêtements suite à des cycles de transitions thermiques a été vérifiée. Une étude de l'adsorption de particules décorées par des protéines comme l'avidine a permis de montrer la capacité des couches adsorbée à exposer/masquer la biotine, et à réguler la formation de liaisons spécifiques par simple changement de température. Pour s'assurer de la possibilité d'ajustement du contraste d'accessibilité de ligands, cette étude a été complétée par des mesures sur des couches mixtes contenant des mélanges de chaînes fonctionnelles ou non fonctionnalisées. Enfin, en utilisant un peptide d'adhésion (RGD) comme ligand, il a été montré que l'interaction avec la surface de cellules HeLA peut être réversiblement contrôlée via une variation de température de quelques degrés, moyennant d'optimiser la densité en peptides et la présence de chaînes répulsives en surface.Un control local par stimulation lumineuse a été envisagé. Des poly(N-Isopropylacrylamide) contenant des azobenzenes furent synthétisés mais ne montrent qu'une faible réponse lumineusePolymer coatings based on the physorption of comb-like polymers, (Poly-L-Lysine)-g-poly(NIsopropylacrylamide)derivatives (PLL-g-PNIPAM), have been developed to reversibly modulate specific cell adhesion on demand.This technique of coating relies on the spontaneous adsorption of PLL on typical anionic substrates used in biology: a simple bath application of substrates in solution of PLLg-PNIPAM affords a stable polymer adlayer with dense and thermoresponsive poly(NIsopropylacrylamide) brushes. Adsorption of comb-like polymers with different strands enables to easily modulate properties of the coatings. We focused on thermoresponsive poly(N-Isopropylacrylamide-co-ligand) brusheswhere ligand is Biotin or a peptide of adhesion.A versatile synthesis of PLL-g-PNIPAM is presented. This synthesis is based on RAFT polymerization of N-acryloxysuccinimide and post-modifications of both the backbone and the polymer ends. Detection of the transition soluble/insoluble in solution and AFM/QCM-d studies of PNIPAM adlayers demonstrate that the critical temperature in adlayers are close to the one in solution. Stability in terms of composition and thickness has been checked after temperature cycles. The study of the adsorption of Avidin-coated particles suggests that these adlayers can expose/mask Biotin, and so regulate specific interaction by simple change in temperature. To optimize the thermal contrast of ligand accessibility, this study includes measurements on mixed adlayers with functionalized/unfunctionalized brushes. Finally, specific adhesion of HeLa cells can be thermally modulated on adlayers presenting repellent brushes and with controlled densities of adhesive peptides (RGD).A local control has been considered on such coatings by using light stimulus. In this context, azobenzene-containing Poly(NIsopropylacrylamide) were synthesized but they shown only a weak light-response
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Zhang, Ziwei. "The structural and functional study of GIT1 paxillin binding domain." View the abstract Download the full-text PDF version, 2008. http://etd.utmem.edu/ABSTRACTS/2008-020-ZiweiZhang-index.html.
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Thesis (Ph.D.)--University of Tennessee Health Science Center, 2008.Title from title page screen (viewed on November 5, 2008). Research advisor: Jie Zheng, Ph.D. Document formatted into pages (xiii, 140 p. : ill.). Vita. Abstract. Includes bibliographical references (p. 105-116).
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Jean-Baptiste, Gaël. "Analysis of regulators of G protein signaling (RGS) 5 regulation and lysophosphatidic acid (LPA) signaling in muscle cells." Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=98734.
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G protein-coupled Receptor (GPCR) signalling pathways are essential for all aspects of cell and organ physiology and the involved proteins work together to transmit signals across the plasma membrane. This process is highly regulated by a number of proteins including RGS (Regulators of G protein Signalling) proteins, which serve as GTPase-activating proteins for the Galpha subunit of heterotrimeric G proteins. Previous work in our lab has identified RGS5 as being expressed in the heart as well as being up regulated in the atria but not the ventricules of transgenic (TG4) mice that have a 195-fold cardiac increase in beta2AR levels. To further characterize RGS5 expression, an RGS5 specific antiserum was generated. Western Blot analysis of a panel of rat tissues demonstrated that basal expression of RGS5 protein was confined to the heart and skeletal muscle tissues, as well as the respective cell lines HL-1 and C2C12. Although GPCRs and RGSs are actively being studied in the heart, little is known regarding the role of GPCRs and RGSs in skeletal muscle. Moreover, several conditions such as atrophy, which is characterized by apoptosis of the muscle fibers, are associated with GPCRs in the skeletal muscle. As a prelude to investigating the role of RGS5 in the regulation of GPCR signaling, we identified a number of GPCRs that are able to signal via ERK1/2 in C2C12 skeletal muscle cells. The signalling and responses induced by one GPCR agonist, Lysophosphatidic Acid (LPA), a potent inducer of survival and apoptosis, were analyzed in C2C12 skeletal muscle cells.
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Quesada, López Tania Paloma. "The role of the G-protein coupled receptor 120 (GPR120) on the FGF21 system in white and brown adipose tissues." Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/662931.
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Obesity prevalence has tripled in the last fifty years. For this reason, it is considered the pandemic of the century. It is characterized by the accumulation of metabolic abnormalities triggered by an increase in the size of fat depots in the body. Hence, new therapies to pursue an amelioration of metabolic abnormalities and adipose tissue dysfunction caused by this energy imbalance are being explored. The tissue responsible for the storage of fat is adipose tissue and it was considered just as an energy reservoir until recently. Currently, it is known to be actively involved in energy homeostasis at the same time that it fulfills endocrine functions. Adipose tissue is divided into two main types, white adipose tissue (WAT) and brown adipose tissue (BAT). While energy storage is the main role of WAT, BAT is able to dissipate energy in the form of heat leading to an increased energy expenditure. Surprisingly, it has been reported that WAT has the ability to recruit cells of the brown phenotype and thus increase its energy expenditure in a process denominated as browning. BAT activity and WAT browning are important components of energy expenditure and therefore potential therapeutic targets for the treatment of obesity and its comorbidities. In this work, we show that GPR120 activation, a membrane receptor for polyunsaturated fatty acids (PUFAs), promotes BAT thermogenic activity and WAT browning. The tissue that reported the highest levels of GPR120 expression is BAT, followed by colon and WAT different deposits. In addition, it was discovered that thermal stress (cold exposure) causes an induction in the expression of GPR120 in adipose depots. Likewise, the activation of GPR120 induces an increase in oxygen consumption. Conversely, mice deficient of GPR120 show decreased temperature and UCP1 expression in neonatal BAT and decreased browning after cold exposure in adult WAT. The administration of natural or synthetic agonists of GPR120, such as omega-3 PUFAs or GW9508, induced brown and beige adipocyte differentiation as well as their thermogenic activation and glucose oxidation. This activation by n-3 PUFAs was dependent of GPR120 expression. In addition to these findings, it was revealed that the activation of GPR120 induces the expression and release of fibroblast growth factor-21 (FGF21) by BAT and WAT at the same time that it increases plasma FGF21 levels. FGF21 is a hormonal factor able to induce thermogenic activation of BAT and browning of WAT, both associated with an improvement in metabolic conditions. In the absence of GPR120, the levels of FGF21 under cold stress conditions are decreased. Furthermore, n-3 PUFAs and synthetic agonists do not induce the expression and release of FGF21 in animals and cells deficient of GPR120. Regarding the effects on the activation of BAT, browning of WAT and the increase in glucose oxidation by the activation of GPR120, these are all compromised in mice or adipocytes lacking FGF21. Therefore, it is concluded that GPR120 activation induces BAT thermogenic activity and WAT browning through a mechanism that involves the induction of FGF21.La obesidad es pandemia del siglo XXI y se caracteriza por desencadenar anomalías metabólicas debido al exceso de grasa almacenada en el organismo. Ello urge la exploración de nuevas terapias para su tratamiento. El tejido adiposo (TA) ha pasado de considerarse solo un depósito de energía a ser relacionado con el mantenimiento de la homeostasis energética. Se divide en dos tipos, tejido adiposo blanco (TAB) y tejido adiposo marrón (TAM). El primero sirve como almacén de energía y el segundo produce calor debido al desacoplamiento de la cadena respiratoria resultando en un gasto energético incrementado. El TAB tiene la capacidad de reclutar células del fenotipo marrón en un proceso denominado pardeamiento. La actividad del TAM y el pardeamiento del TAB son componentes importantes del gasto energético y blancos terapéuticos para el tratamiento de la obesidad. GPR120 es un receptor de membrana para ácidos grasos poliinsaturados (PUFAs) que demostró promover la activación del TAM y el pardeamiento del TAB. El TAM es el tejido que expresa GPR120 principalmente y el estrés térmico causa una inducción en la expresión de GPR120 en los depósitos adiposos. Conjuntamente, la activación de GPR120 induce la actividad termogénica del TAM y pardeamiento del TAB. Inversamente, los ratones deficientes de GPR120 muestran una activación de la termogénesis disminuida tras la exposición al frío. Además, la activación de GPR120 ha mostrado inducir la diferenciación de adipocitos marrón y beige así como su activación termogénica. Dicha activación conlleva a la inducción en la expresión y liberación del factor de crecimiento fibroblástico-21 (FGF21) por el TA así como un aumento en los niveles en sangre. FGF21 es un factor hormonal capaz de inducir la termogénesis en el TA y de mejorar las condiciones metabólicas. Los animales deficientes de GPR120 muestran niveles de FGF21 disminuidos tras la exposición a frío mientras que la falta de FGF21 comprometió la inducción de la termogénesis tras la activación de GPR120 en ratones y adipocitos. Se concluyó que la activación de GPR120 induce la actividad termogénica de la grasa marrón y el pardeamiento de la grasa blanca a través de la inducción de FGF21.
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Pösel, Claudia. "Effizienz einer Kombinationstherapie aus G-CSF und mononukleären Knochenmarkzellen in einem präklinischen Schlaganfallmodell." Doctoral thesis, Fraunhofer-Institut für Zelltherapie und Immunologie, 2014. https://ul.qucosa.de/id/qucosa%3A13401.
Full textAbstract:
Eine Vielzahl präklinischer Schlaganfallstudien zeigte die neuroprotektive und neuroregenerative Wirkung des hämatopoetischen Wachstumsfaktors G-CSF (Granulozyten-Kolonie stimulierender Faktor). Ein Wirkungsmechanismus des G-CSF ist die Mobilisation von protektiven Knochen-markzellen in die ischämische Läsion, wobei diese zeitverzögert nach G-CSF-Gabe stattfindet. Eine zusätzliche frühzeitige Transplantation mononukleärer Knochenmarkzellen (BM MNC) könnte diese therapeutische Lücke füllen. Ziel der vorliegenden Studie war es, die Wirksamkeit dieser Kombinations-therapie in einem Schlaganfallmodell der spontan hypertensiven Ratte (SHR) zu testen. Syngene BM MNC wurden aus dem Knochenmark von SHRs durch immunmagnetische Depletion der Granulozyten isoliert. Nach Verschluss der Arteria cerebri media wurde den Tieren über insgesamt 5 Tage G-CSF verabreicht und zusätzlich zu einem frühen (6h nach Schlaganfall) oder späteren (48h nach Schlaganfall) Zeitpunkt BM MNC intravenös appliziert. Unbehandelte Schlaganfalltiere sowie Tiere mit alleiniger G-CSF-Therapie dienten als Kontrolle. Das Infarktvolumen wurde weder durch die alleinige G-CSF-Gabe noch durch die zusätzliche Zelltherapie verändert. Dennoch wiesen Tiere mit G-CSF-Einzeltherapie eine anhaltende funktionelle Verbesserung des sensomotorischen Defizites auf. Während die zusätzliche frühzeitige Zelltransplantation (6h) keinen weiteren Therapieeffekt zeigte, führte die Zelltransplantation nach 48h zu einer Aufhebung des protektiven G-CSF Effektes. Die G-CSF-Therapie bewirkte erwartungsgemäß einen deutlichen Anstieg der zirkulierenden Leukozyten. Interessanterweise wurde der Granulozytengehalt im Blut und in der Milz durch die einmalige Zelltherapie nach 48h signifikant erhöht. Ein Großteil der transplantierten BM MNC (48h) konnte in der Milz nachgewiesen werden und führte dort vermutlich zu einer kompetitiven Hemmung des Granulozytenabbaus. Dies hatte sowohl den Anstieg der zirkulierenden Granulozyten als auch deren vermehrte Infiltration in das ischämische Hirngewebe zur Folge und könnte schließlich den negativen Einfluss auf die funktionelle Verbesserung erklären. Die beobachteten Interaktionsmechanismen werfen ein interessantes Licht auf die mögliche Wirkungsweise von Zelltherapien und unterstreichen die entscheidende Rolle des Immunsystems in der Pathophysiologie des Schlaganfalls.
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Schackel, Thomas [Verfasser], and G. Elisabeth [Akademischer Betreuer] Pollerberg. "Biomaterial implants combined with cell therapy improve axonal regeneration after spinal cord injury / Thomas Schackel ; Betreuer: G. Elisabeth Pollerberg." Heidelberg : Universitätsbibliothek Heidelberg, 2020. http://d-nb.info/1220290173/34.
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Sadideen, Doraid, and Doraid Sadideen. "Exploring G-Protein-Coupled Receptors Regulation, Specificity and Controllability of Exosomes Release in the Neuronal Cell Line SH-SY5Y." Thesis, The University of Arizona, 2016. http://hdl.handle.net/10150/621166.
Full textAbstract:
Parkinson's disease is a neurodegenerative disease characterized by the buildup of aggregated and spread of misfolded alpha-synuclein. How the misfolded alpha-synuclein contributing to the toxicity and death of neuronal cells has been the focal point of research. The spread of alpha-synuclein has been attributed to many mechanisms, one of which is via cell-derived vesicles called exosomes. This project aims to examine the controllability of exosome release. SH-SY5Y, MCF-7 and CHO-K1 cells were transfected with dopamine receptor 3-green fluorescent protein, G-protein receptor 143 or green fluorescent protein and treated with either dopamine or L-DOPA. Medium was harvested and subjected to ultracentrifugation and a silver stain and western blot were performed. There was no significant difference in the total protein in the exosome fraction lanes between the treatment groups or within them. Another aim was to test the specificity of exosomes. Exosomes isolated from SH-SY5Y or MCF-7 were labeled with Exo-Red dye and introduced to wells containing SH-SY5Y, MCF-7 and CHO-K1 cells at room temperature and -4C. At room temperature, exosomes were observed intercellular in all of the cell lines, however, they did not deliver their content. At -4C exosome uptake was halted and they remained on the surface of the cells. Exo-Red labeled SH-SY5Y exosomes were treated with proteinase K and were introduced to CHO-K1 cells at -4C and room temperature. CHO-K1 did not take up exosomes, suggesting exosomes contain one or more necessary proteins needed to interact with the cellular membrane to initiate internalization. CHO-K1 cells were treated with versene to examine the involvement of integrin proteins. Exo-Red labeled SH-SY5Y exosomes were trapped on the surface of CHO-K1 after versene treatment. Lastly, Exo-Red labeled SH-SY5Y exosomes were biotinylated and magnetically captured then introduced to SH-SY5Y and MCF-7 cells and a silver stain and a biotinylated blot were performed. MCF-7 bound more Exo-Red labeled SH-SY5Y exosomes.
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Doi, Keiko. "Crucial role of the Rap G protein signal in Notch activation and leukemogenicity of T-cell acute lymphoblastic leukemia." Kyoto University, 2015. http://hdl.handle.net/2433/199214.
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Rendon, Maria Auxilio. "Commensal and pathogenic Escherichia coli use a common pilus for epithelial cell colonization. G-quadruplex interactive compounds as broad spectrum antimicrobials." Diss., The University of Arizona, 2009. http://hdl.handle.net/10150/194441.
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Diarrheagenic Escherichia coli (E. coli) and Neisseria sp. are Gram-negative pathogens that cause high disease burden, especially in low-income countries.Enterohemorrhagic E. coli (EHEC) and enteropathogenic E. coli (EPEC) are a subset of E. coli that can cause disease. The sequence of E. coli genomes revealed the presence of at least 16 putative pili operons, it is still unknown if they encode functional pili. Several adhesins have been described in EPEC; however it is still an enigma if EHEC produces pili. In this dissertation the identification and characterization of a new pilus in EHEC is described. The main pilin subunit is encoded in the yagZ gene (renamed ecpA) and is present in all E. coli. We demonstrate ECP production in 137 (70%) of a total of 197 ecpA+ strains representing different categories of E. coli. Isogenic ecpA mutants of EHEC O157:H7 and fecal commensal E. coli showed significant reduction in adherence to cultured epithelial cells. Adherence levels were not hampered after single mutation of ecpA in EPEC. Only after the removal of the known EPEC adhesins such as BFP and intimin we were able to see significant reduction in adherence levels. In sum, ECP is the first pilus of EHEC O157:H7 with a potential role in host epithelial cell colonization. However, EPEC-ECP plays a secondary role in adherence.Since 2007 the CDC recommends only third generation cephalosporins as the elected treatment for Neisseria gonorrhoeae infections. There is an urgent need to search for new drug targets and to development new drugs. Regions rich in guanine in the DNA are able to form secondary structures known as G-quadruplexes. It has been shown that G-quadruplexes are involved in control of transcription, translation and telomere elongation in mammalian cells. G-quadruplex interactive compounds are being developed for cancer therapy. G-quadruplex motifs are also present in bacteria. The fact that G-quadruplex interactive compounds can impair cancer development leads us to hypothesize that these drugs can be used as antimicrobials. This work presents evidence for the potential of G-quadruplex interactive compounds as broad-spectrum antimicrobials.
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Schmiedel, Yvonne Verfasser], and Peter [Akademischer Betreuer] [Kremsner. "Pronounced regulatory T cell activity in human schistosomiasis : differences in T cell proliferation and cytokine responses before and after treatment with Praziquantel / Yvonne Schmiedel ; Betreuer: Peter G. Kremsner." Tübingen : Universitätsbibliothek Tübingen, 2012. http://d-nb.info/1160683689/34.
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