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Decker, Kimberly Jean. "Gata6 regulates pancreatic branching morphogenesis and endocrine differentiation /." Connect to full text via ProQuest. Limited to UCD Anschutz Medical Campus, 2007.
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Thesis (Ph.D. in Molecular Biology) -- University of Colorado Denver, 2007.Typescript. Includes bibliographical references (leaves 160-175). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;
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Liljeström, E. (Emmi). "Transcription factor GATA6 in ductal metaplasia of hepatocytes." Bachelor's thesis, University of Oulu, 2019. http://jultika.oulu.fi/Record/nbnfioulu-201902051147.
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Abstract. GATA6 is evolutionary highly conserved transcription factor and a newish indicator and possible causer of ductal metaplasia in biliary atresia (BA). BA is a rare neonatal cholestatic liver disease caused by fibroinflammatory obstruction of bile ducts. BA causes proliferation of bile ducts which is also called ductal metaplasia. In ductal metaplasia hepatocytes phenotype starts resembling more cholangiocytes. When bile gathers inside the liver it (liver) starts to create new bile ducts. This reaction is called ductal reaction what is a consequence of ductal metaplasia.
In this thesis work we, study the role of GATA6 in ductal metaplasia. We have two different kinds of mice: control mouse (ctrl) and knock out mouse (cKO). Both mice were operated with bile duct ligation (BDL) to resemble the BA-like condition. Our control (Ctrl) mouse only went over BDL and cKO mouse’s GATA6 gene was silenced in addition of the BDL.
Missing of GATA6 has shown histology changes in liver tissue — there is no clear bile duct structure like in normal BA-like tissue. Post-mortem tells also a bad condition of the liver of cKO mouse. Similarly, gene expression studies supports hypothesis that ductal reaction hardly ever happens when GATA6 is missing.
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Patil, Shilpa [Verfasser]. "EZH2-GATA6 axis in Pancreatic ductal adenocarcinoma / Shilpa Patil." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2020. http://d-nb.info/1218780746/34.
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Rodrigues, Patricia. "Regulation of lipid metabolism by GATA6 : an integrated 'omics' approach." Thesis, Cardiff University, 2019. http://orca.cf.ac.uk/120173/.
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The transcription factor GATA6 was recently recognised as a master regulator of the phenotype and function of peritoneal resident macrophages (pResMf), whose deficiency results in dysregulated proliferative renewal during homeostasis and altered inflammatory responses, associated with delays in resolution. Herein, I show using microarray analysis that mice with a myeloid deficiency of Gata6 (Gata6-KOmye mice) have significant changes in genes associated with lipid metabolism, in particular sphingolipids (SL). Three of the most notable alterations were the downregulation of genes responsible for the degradation of glucosylceramides (GlcCer) and sphingomyelins (SM) (Gba2 and Smpd1), as well as a gene involved in the regulation of lysosomal pH, and consequently, lysosomal function. To characterise the metabolic defect, I compared the lipidome of Gata6-KOmye and wild-type (WT) pResMf using a high-resolution LC-MS based global lipidomics approach and replicated my findings using targeted LC-MS/MS. SL showed a high percentage of changes (25% of all lipids levels were altered significantly) with a marked increase in Gata6-KOmye pResMf. SL are important constituents of the plasma membrane in eukaryotes and, as second messengers, modulate apoptosis, cell proliferation and differentiation. Targeted lipidomics by LC-MS/MS showed that the most significantly-increased molecular species were long chain GlcCer and SM. This linked with downregulation of Gba2, Ctse and Smpd1, observed during the microarray analysis, and was confirmed by supressing these pathways, in RAW 264.7 cells, using knockdown (shRNA) approaches. Accumulation of SL metabolites in tissues is implicated in a plethora of patho-physiological complications such as development of neurological dysfunctions, atherosclerosis, diabetes, and heart failure, whilst in cells it correlates with defects in cell migration, cholesterol traffic and efflux, lipid transport, cell activation, proliferation and apoptosis. Overall, I concluded that GATA6 regulates lipid metabolism in pResMf, on both a transcriptional and metabolic level, with particular focus on SL levels. Furthermore,there is indication that this regulation may at least in part control phenotype and function in pResMf through altering SL signalling. Thus, my studies propose GATA6 as a new lipid-regulating transcription factor and highlight the importance of lipid regulation in pResMf biology.
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Gharibeh, Lara. "Gata6 Haploinsufficiency Leads to Aortic Valve, Conduction System and Limbs Defects." Thesis, Université d'Ottawa / University of Ottawa, 2018. http://hdl.handle.net/10393/37584.
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Cardiovascular diseases are the leading cause of morbidity and mortality worldwide. Congenital heart disease (CHD) is a risk factor for premature cardiovascular complications. Great advances have occurred in the past years leading to the identification of several genes essential for proper cardiac formation such as GATA4/5/6 mutated in some individuals with CHD. GATA6 is a zinc finger transcription factor whose presence is crucial for early embryonic development. GATA6 is expressed in many cell types of the heart including myocardial, endocardial, neural crest, and vascular smooth muscle. In human, mutations in GATA6 result in variable cardiac phenotypes. The objective of this thesis was to determine the roles that GATA6 play in the different cell types of the heart and to elucidate the molecular basis of the cardiac defects associated with Gata6 haploinsufficiency. For this, a combination of cell and molecular techniques were used in vitro and in vivo. First, we show that Gata6 heterozygozity leads to RL-type bicuspid aortic valve (BAV)- the most common CHD affecting 2% of the population. GATA6-dependent BAV is the result of disruption of valve remodeling and extracellular matrix composition in Gata6 haploinsufficient mice. Cell-specific inactivation of one Gata6 allele from Isl-1 positive cells, but not from endothelial or neural crest cells, recapitulates the phenotype of Gata6 heterozygous mice revealing an essential role for GATA6 in secondary heart field myocytes during valvulogenesis. We further uncovered a role for GATA6 as an important regulator of the cardiac conduction system and revealed that GATA6 expression regulates the activity of the cardiac pacemaker. GATA6 exerts its role via regulation of the cross-talk among the different cell types of the SAN. Lastly, some CHDs are characterized by abnormalities of both the limbs and the heart such as the Holt Oram syndrome (caused by mutation in TBX5 transcription factor). The molecular basis for limb-heart defects remain poorly understood. In the course of this work, we discovered that Gata6 haploinsufficiency resulted in a partially penetrant polysyndactyly (extra digits fused together) phenotype. Together, the data provide novel molecular and cellular insight into GATA6 role in normal and pathologic heat development. Our results also suggest that GATA6 should be added to the list of genes whose mutations are potentially associated with heart and limb abnormalities. Better knowledge of the molecular basis of CHD is a prerequisite for the development of diagnostic and therapeutic strategies to improve care of individuals with congenital heart disease.
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Chia, Crystal Ying. "The role of transcription factor GATA6 in the development of the human pancreas." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/271836.
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While there has been an opulence of data and studies surrounding the study of the developing pancreas in mammals and other vertebrates, the focus has largely been in mice. The paucity of research in the development of the human pancreas has led to diminished knowledge in the area, compared to other species. Recent discoveries provide growing evidence for discrepancies between mouse and human pancreatic development and diseases and highlight the fact that developmental studies of the pancreas in humans are imperative. The need to develop therapies for diabetes, a growing and one of the leading health problems worldwide, further compels more exploration in this area to deepen our understanding in the different aspects of diabetes in humans and its underlying causes. Research involving modelling human diseases in vitro enables the investigation of the cellular and molecular mechanisms underlying these diseases as well as the development of therapies for treating them. The availability of hPSCs brings with it the advantage of overcoming the limitations of animal models for certain disorders such as pancreatic agenesis, the focus of my project. The use of site-specific nucleases such as TALENs for such a purpose represents a paradigm shift in disease modelling, where TALENs are capable of directly correcting disease-causing mutations, therefore permanently eliminating the symptoms with precise genome modifications. Alternatively, TALENs can also be used to inactivate specific genes by inducing site-specific mutations. Using these tools, I found that GATA6 is required for the formation of the definitive endoderm (DE) and pancreas in humans; hPSCs harbouring homozygous GATA6 mutations fail to form the definitive endoderm, and consequently the pancreas, whereas hPSCs harbouring heterozygous GATA6 mutations exhibited impairment in definitive endoderm development, although it remains unclear if this is a protocol dependent defect. At the pancreatic stage, heterozygous GATA6 mutations consistently compromised pancreas formation regardless of protocol used. I also found that GATA6 transcriptionally activates the development of the definitive endoderm and pancreatic endoderm, and possibly represses the development of mesoderm. Furthermore, I also established that GATA6 directly interacts with key definitive endoderm markers CXCR4 and SOX17, and pancreatic marker PDX1. Taken together, the work herein demonstrates the successful use of hPSCs coupled with the TALEN genome editing technology as a unique in vitro system for disease modelling. These findings also establish two developmental windows, the DE and pancreatic progenitor stages, where GATA6 haploinsufficiency can result in the impairment of pancreatic development leading to pancreatic hypoplasia observed in human GATA6 heterozygous patients. Lastly, my work also provides the molecular mechanism by which GATA6 regulates pancreatic development. Overall, this study provided new insights in the role of GATA6 during development of the human pancreas. These results will be important in developing new methods of differentiation for hPSCs and understanding the interconnection between early organogenesis and late onset of diabetes.
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Montagni, Elisa 1984. "Transcription factor GATA6 and ISC gene SMOC2 in the regulation of BMP pathway in intestinal adenoma." Doctoral thesis, Universitat Pompeu Fabra, 2015. http://hdl.handle.net/10803/523489.
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The first chapter identifies the transcription factor GATA6 as negative regulator of a transcriptional circuit dedicated to prevent the expansion of Adenoma Stem Cells (AdSCs) during the onset of colorectal cancer (CRC). In particular, we show that GATA6 directly activates the expression of the WNT pathway component LGR5 and represses BMP levels in adenoma by competing with the β-catenin/TCF4 complex for the binding to BMP4 enhancer regions. As a result of this mechanism, two compartments are established within an adenoma: a BMP positive differentiated cell zone and a BMP negative undifferentiated cell zone, where AdSCs reside. Genetic deletion of Gata6 increases BMP levels in the AdSC compartment, inhibiting self-renewal and intestinal tumorigenesis. These findings represent a key contribution to understand the mechanisms that regulate tumor hierarchy and reveal for the first time the existence of a niche that protects AdSCs from BMP signals.
The second chapter focuses on the functional characterization of Smoc2, a novel Intestinal Stem Cell (ISC) gene. We generated genetic mouse models in order to overexpress or ablate Smoc2 in the intestine. We found that SMOC2 acts as a BMP inhibitor in the intestine and that it is not only restricted to epithelial Stem Cells (SCs) but it is also expressed by the stroma. Although it is dispensable for normal ISC maintenance and intestinal homeostasis, high levels of SMOC2 are required for tumorigenesis. Indeed, Smoc2 overexpression leads to spontaneous development of hamartomas and enhances adenoma formation in mice with an Apc mutant background; inversely, Smoc2 deficiency decreases tumorigenesis and prolongs survival of Apc mutant mice. In particular, we observed that SMOC2-mediated BMP inhibition positively affects Insulin-like Growth Factor (Igf1) expression in adenoma endothelial cells (ECs). Our data suggest that SMOC2 could enhance tumor-associated inflammation through BMP-mediated Igf1 regulation in the stroma.El primer capítulo describe la identificación del factor de transcripción GATA6 como regulador negativo de un circuito transcripcional fisiológico dedicado a reprimir la expansión de las células madre de los adenomas (Adenoma Stem Cells o AdSCs) en el inicio de la tumorogénesis colorrectal. De manera específica, mostramos como el factor GATA6 activa directamente la expresión del componente de la ruta de WNT, LGR5, y también directamente reprime niveles de hormona BMP (Bone Morphogenetic Protein) a través de la competición directa con el complejo beta-catenina-TCF4 por la unión a regiones enhancer del gen BMP4. Como resultado de este circuito transcripcional que hemos descubierto, en los adenomas se generan dos compartimentos, una zona positiva para la señalización mediada por BMP que contiene las células diferenciadas de los adenomas, y un área negativa para BMP, donde residen y se expanden las AdSCs. La ablación genética de Gata6 incrementa los niveles de BMPs en el compartimento de las AdSCs, inhibiendo la autorenovación de las mismas y por ende la tumorogénesis. Este descubrimiento representa una aportación clave para entender los mecanismos que regulan la jerarquía tumoral y revelan por primera vez la existencia de un nicho que protege las AdSCs de las señales de BMP. El segundo capítulo describe la caracterización funcional de Smoc2, uno de los genes identificados en el laboratorio dentro del programa genético específico de las células madre del intestino (Intestinal Stem Cells o ISCs). Durante el transcurso de la tesis
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Fletcher, Georgina Clare. "A role for GATA6 in mediating anterior mesendoderm migration in the Xenopus laevis gastrula." Thesis, King's College London (University of London), 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.416041.
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Whissell, Gavin 1978. "WNT signaling, hypoxia and GATA6 : their role in colorectal cancer, stem cells and disease progression." Doctoral thesis, Universitat Pompeu Fabra, 2013. http://hdl.handle.net/10803/295581.
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The recent discovery that intestinal adenomas are built on a stem cell hierarchy has raised great interest in understanding the signals that maintain tumor stem cells. We unveiled the existence of a transcriptional circuit dedicated to prevent the expansion of adenoma stem cells during the onset of CRC. This circuit was found to be controlled by the transcription factor GATA6, which directly activated the expression of the WNT pathway component LGR5 and repressed BMP levels in adenomas. As a result of this mechanism, two cell compartments were established in adenomas: a BMP positive zone that comprises differentiated tumor cells and a BMP negative niche that hosts adenoma stem cells. Genetic deletion of Gata6 elevated BMP levels in tumors, which in turn inhibited adenoma stem cell self-renewal and intestinal tumorigenesis. These findings represent a key contribution to understand the mechanisms that regulate the tumor stem cell hierarchy and reveal for first time the existence of a niche that protects AdSCs from BMP signals.
In subsequent studies, we further explore the role of GATA factors in EMT both in Drosophila and mammalian models. During the formation of the Drosophila endoderm relatively static epithelial cells have to convert to highly migratory cells to form a large part of the intestinal tract. We showed that the Drosophila GATA factor Srp is necessary to induce EMT, which resulted in relocalization of E-cadherin protein without altering its expression. Mammalian GATA4 and GATA6 also induced an EMT when ectopically expressed in culture. GATA factor Srp and GATA6 both transcriptionally inhibited Crumbs orthologues, delocalized E-cadherin and activated mesenchymal genes. This work has uncovered a novel evolutionarily conserved alternative route to EMT that is Snail independent. This discovery could have important clinical implications in pathogenesis, namely in cancer progression.
Further studies aimed to characterize WNT signaling during CRC progression. WNT signaling is required for the maintenance of colorectal cancer stem cells (CRC-SCs) but paradoxically low levels of WNT genes associate with a higher risk of disease relapse. We identified a core expression program driven by beta-catenin/TCF in CRC-SCs, which was shown to be a strict indicator of the dependency on WNT signaling for growth. We showed that during disease progression, a subset of WNT genes is downregulated as a consequence of tumor hypoxia. This response characterized a group of patients displaying very high risk of cancer recurrence after therapy. Hypoxia-induced genes were prominently expressed at invasion fronts coinciding with lower expression of the WNT program. Therefore, hypoxia refines the WNT program in CRC-SCs during the acquisition of a malignant phenotype. This finding has important implications in CRC progression, as it explains how some CRC-SC genes (like EPHB2) are shut down during the progression of the disease and directly challenges recent high impact work in the field that points to methylation as the mechanism responsible for the refinement of WNT signaling. Moreover it identifies hypoxia as a culprit in this invasive cell phenotype. These findings may have important clinical implications in treatment of CRC.El reciente descubrimiento de que los adenomas intestinales mantienen una jerarquía similar a la del epitelio intestinal normal, ha despertado gran interés por entender las señales que especifican y mantienen a las células madre tumorales. En este trabajo, damos a conocer la existencia de un circuito transcripcional dedicado a prevenir la expansión de células madre de adenoma durante el inicio del cáncer colorectal (CCR). Este circuito está controlado por el factor de transcripción GATA6, el cual activa directamente el componente de la vía de señalización WNT LGR5, y reprime los niveles de BMP en adenomas. Como resultado de este mecanismo, se establecen dos compartimentos celulares en los adenomas: una zona BMP positiva que contiene células tumorales diferenciadas y un nicho BMP negativo que aloja células madre de adenoma. La deleción genética de Gata6 eleva los niveles de BMP en tumores, lo que a su vez inhibe la auto-renovación de células madre de adenoma y la tumorigénesis intestinal. Estos hallazgos representan una contribución fundamental para comprender los mecanismos que regulan la jerarquía de las células madre tumorales y revelan por primera vez la existencia de un nicho que protege a las células madre de adenoma de señales BMP. En estudios posteriores, continuamos explorando el rol de los factores GATA en la transición epitelio-mesénquima tanto en modelos de Drosophila como de mamífero. Durante el desarrollo del endodermo en Drosophila, células epiteliales relativamente estáticas se convierten en células migratorias para formar una gran parte del tracto intestinal a través del proceso de transición epitelio-mesénquima. Hemos demostrado que el factor GATA -en Drosophila denominado Srp- es necesario para inducir una transición epitelio-mesénquima que da lugar a la relocalización de la proteína E-cadherina sin alterar su expresión. Los factores GATA4 y GATA6 de mamífero también inducen transición epitelio-mesénquima cuando son expresados de forma ectópica en cultivos celulares. Tanto el factor GATA Srp como GATA6 inhiben la transcripción de ortólogos de Crumbs, deslocalizan la E-cadherina y activan genes mesenquimales. Nuestro trabajo ha dado a conocer una nueva ruta alternativa para la transición epitelio-mesénquima que se encuentra conservada evolutivamente y que es independiente de Snail. Este descubrimiento podría tener importantes implicaciones clínicas en patogenia, y más específicamente en la progresión del cáncer. Un tercer aspecto del trabajo presentado se centra en la caracterización de la vía de señalización WNT durante la progresión del CCR. La señalización WNT es necesaria para el mantenimiento de las células madre de cáncer colorectal (CM-CCR), aunque paradójicamente, bajos niveles de genes WNT se asocian con un mayor riesgo de recaída de la enfermedad. Hemos identificado un programa básico de expresión impulsado por beta-catenina/TCF en CM-CCR, que se ha demostrado ser un indicador estricto de la dependencia de señalización WNT para el crecimiento. Hemos demostrado que durante la progresión de la enfermedad, se suprime la expresión de un subconjunto de genes WNT como consecuencia de hipoxia tumoral. Esta respuesta caracteriza a un grupo de pacientes con un muy alto riesgo de reincidencia del cáncer después de la terapia. Los genes inducidos por hipoxia se expresan de manera prominente en frentes de invasión coincidiendo con una menor actividad de la vía del programa WNT. Por lo tanto, la hipoxia refina el programa WNT en CM-CCR durante la adquisición de un fenotipo maligno. Este hallazgo tiene implicaciones importantes para la progresión del CCR, porque explica cómo algunos genes de CM-CCR (como receptores EPHB2) se apagan durante la progresión de la enfermedad y directamente desafía trabajos de alto impacto recientemente reportados en el área, que apuestan por la metilación como mecanismo responsable del refinamiento del programa WNT. Por otra parte, identifica a la hipoxia como un culpable de este fenotipo de células invasivas. Estos hallazgos podrían tener importantes implicaciones clínicas en el tratamiento del cáncer colorectal.
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Bessonnard, Sylvain. "Régulations génétiques contrôlant l'engagement cellulaire au cours du développement murin : différenciation de l'épiblaste versus l'endoderme primitif." Thesis, Clermont-Ferrand 1, 2012. http://www.theses.fr/2012CLF1MM06.
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A 3.5 jours de développement (J3.5), l'embryon de souris est constitué d'un épithélium externe, le trophectoderme, et d'une masse cellulaire interne (MCI). La MCI est hétérogène, constituée des précurseurs de l'épiblaste (Epi) et de l'endoderme primitif (EPr), représentée par l'expression exclusive de Nanog et de Gata6 respectivement. Lors de l'implantation à E4.5, l'EPr forme un épithélium à la surface de la MCI, en regard de la cavité blastocoelique. L'Epi donnera tous les tissus du nouveau-né. L'EPr permet les premiers échanges nutritionnels entre l'embryon et la mère. Je m'intéresse au rôle de Nanog et de Gata6 dans la détermination et la différenciation de l'Epi et de l'EPr. De plus, je m'intéresse à l'implication de la signalisation RTK dans l'expression de ces deux gènes. Enfin, je cherche à comprendre les interrelations entre Gata6 et Nanog. A l'aide des modèles de souris KO, des modèles in vitro ainsi que des techniques innovantes développées au sein du laboratoire, nous avons mis en évidence que la modulation de l'expression de Nanog, Gata6, Fgf4 et Fgfr2 semble suffisante pour l'engagement des cellules vers un devenir Epi ou EPr. De plus, ces résultats permettent de proposer un nouveau modèle expliquant le rôle de Gata6 et de Nanog dans la spécification des cellules Epi et EPrAt 3.5 days of development (E3.5), the mouse embryo consists of an outer epithelium, the trophectoderm, and an inner cell mass (ICM). The ICM is heterogeneous, composed of the precursors of the epiblast (Epi) and the primitive endoderm (PrE), expressing either Nanog or Gata6 respectively. Upon implantation at E4.5 the EPr forms an epithelium on the surface of the ICM, facing the blastocoelic cavity. The Epi give rise all tissues of the newborn. The PrE allows the first nutritional exchanges between the embryo and the mother. I focus on the role of Nanog and Gata6 in the determination and differentiation of Epi and PrE. In addition I am interested in the involvement of RTK signaling in the expression of both genes. Finally, I seek to understand the relationships between Gata6 and Nanog. Using the transgenic mouse models, in vitro models as well as innovative techniques developed in the laboratory, we have demonstrated that modulating the expression of Nanog, Gata6, FGF4 and FGFR2 seems sufficient for commitment of cells to become an Epi or EPr. Furthermore, these results allow proposing a new model explaining the role of Gata6 and Nanog in the determination and differentiation of Epi and PrE cells
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Wang, Xue [Verfasser], and Jörg [Akademischer Betreuer] Heineke. "Specific deletion of the transcription factors GATA4 and GATA6 in fibroblasts triggers cardiac dysfunction during pressure overload / Xue Wang ; Akademischer Betreuer: Jörg Heineke ; Klinik für Kardiologie und Angiologie." Hannover : Bibliothek der Medizinischen Hochschule Hannover, 2018. http://d-nb.info/1167246586/34.
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Tardif, Derek. "Implication du facteur de transcription GATA-6 dans la régénération musculaire." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=112311.
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Efficient muscle regeneration is essential in mammals in order to overcome daily stress such as wounds, exercise and pathologic processes. This regeneration relies on muscle stem cells, the satellite cells. After a lesion, satellite cells are activated, proliferate and differentiate in fonctionnal muscle fibers. Our laboratory has previously shown that the transcription factor GATA-6 is expressed in the satellite cells. The present thesis confirms the expression of this factor in this cell type. Also, it seems that GATA-6 could be implicated in the maintaining of quiescence of these cells. The GATA-6 heterozygous mouse muscle is characterized by an increase level of Myf5 and Pax7+ cells. Moreover, suppression of one copy of the GATA-6 gene in a muscular dystrophy model mouse, the mdx mice, alleviates its phenotype. Further experiments on a muscle-specific GATA-6 null mouse will allow a better understanding of the role of GATA-6 in muscle regeneration.Keywords. GATA-6, muscle regeneration, mdx, satellite cells
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Singh, Indrabahadur [Verfasser]. "HMGA2-mediated epigenetic regulation of Gata6 controls epithelial canonical WNT signaling during lung development and homeostasis / Indrabahadur Singh." Gießen : Universitätsbibliothek, 2015. http://d-nb.info/107435513X/34.
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Nakajima, Naoki. "GATA6-positive lung adenocarcinomas are associated with invasive mucinous adenocarcinoma morphology, hepatocyte nuclear factor 4α expression, and KRAS mutations." Kyoto University, 2020. http://hdl.handle.net/2433/253168.
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Bassalert, Cécilia. "Influence des voies de signalisation IGF et MAPK sur la spécification des lignages de l'embryon de souris préimplantatoire." Thesis, Université Clermont Auvergne (2017-2020), 2018. http://www.theses.fr/2018CLFAC029.
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Au cours de la préimplantation, l'embryon de souris produit deux lignages cellulaires, le trophectoderme (TE), et la masse cellulaire interne (MCI) qui elle-même se différencie en épiblaste (Epi) et en endoderme primitif (EPr), caractérisés respectivement par l'expression exclusive de Nanog et de Gata6. La voie FGF/MAPK joue un rôle critique dans l’acquisition de l’identité EPr. J’ai examiné l’expression de pERK, DUSP4 et ETV5 qui permettent de visualiser l'activité des MAPK. Ces analyses ont été effectuées en activant ou inhibant la voie FGF/MAPK, ainsi que dans des embryons mutants pour Nanog et/ou Gata6. Ceci a permis d’observer l’activation de la voie FGF/MAPK dès E3,25. Un autre volet de mon travail a été d'analyser la voie de l’IGF dans les embryons préimplantatoires afin de comprendre l’influence de cette voie dans les différents lignages. J’ai montré que le récepteur activé pIGF1R est exprimé de manière différentielle dans le TE, l’EPr et l’Epi au cours du développement. Une supplémentation d’IGF1 induit une augmentation du nombre de cellules en deux phases, d'abord de l’Epi puis de l’EPr. A l’inverse, une perte de fonction d’IGF1R induit une diminution du nombre de cellules entre E3,75 et E4,25During preimplantation, mouse embryo produces two cellular lineages, the trophectoderm (TE), and the inner cell mass (ICM), which differentiates in epiblast (Epi) and primitive endoderm (PrE), characterized respectively by the complementary expression of Nanog and Gata6. FGF/MAPK pathway plays a critical role in the acquisition of a PrE identity. I examined the expression of the markers of MAPK activity pERK, DUSP4 and ETV5. The analyze was performed with activation or inhibition of FGF/MAPK pathway and in mutant embryos for Nanog or Gata6. This showed that FGF/MAPK pathway is activated as soon as E3,25. I have also analyzed the IGF pathway in preimplantation embryos in order to understand the role of this pathway in embryonic lineages. I showed that active receptor pIGF1R is differentially expressed in TE, PrE and Epi during embryonic development. Supplementation with IGF1 induces an increase in cell number in two phases, first in Epi then in PrE. Conversely, loss of function of IGF1R induces a decrease in cell number between E3,75 and E4,25
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Chauveau, Sabine. "Etude des embryons doubles mutants Nanog-/- ; Gata6-/- durant la spécification de la masse cellulaire interne. Mise en évidence d'une nouvelle hétérogénéité." Thesis, Clermont-Ferrand 1, 2016. http://www.theses.fr/2016CLF1MM29/document.
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Lors de la formation du blastocyste, l'embryon de souris est constitué d'un épithélium externe, le trophectoderme (TE), et d'une masse cellulaire interne (MCI). L’épiblaste (EPI) et l’endoderme primitif (EPr) se spécifient au sein de la MCI sous un patron de « sel et poivre » caractérisé par l’expression complémentaire de NANOG, marqueur de l’EPI et de GATA6, marqueur de l’EPr. Nanog est nécessaire pour l’acquisition d’une identité EPI et Gata6 induit le devenir en EPr. La voie FGF/MAPK joue un rôle critique dans l’acquisition de l’identité EPr et la perturbation de son activité impacte directement sur le ratio EPr/EPI dans la MCI. Je recherche des facteurs qui serait exprimés de manière hétérogène avant la spécification des cellules internes et pourraient faire pencher la balance vers un destin ou l’autre. Pour cela, j’ai disséqué l’évolution des cellules de la MCI au sein des embryons Nanog-/- et Gata6-/-. Ces embryons forment correctement le TE et la MCI qui ne se spécifie ni en EPI ni en EPr. En effet, les cellules internes des embryons Nanog-/- ; Gata6-/- restent bloquées autour du stade E3.25. De manière étonnante, dans les cellules de la MCI, le facteur de transcription SOX2 est présent et ce, de manière hétérogène. De plus, grâce à des traitements inhibiteurs de la voie FGF/MAPK, je montre que cette voie n’est pas responsable de l’hétérogénéité d’expression de SOX2. Ainsi, l’expression hétérogène de SOX2 dans les cellules internes des embryons est donc indépendante de Nanog, de Gata6 et de la voie FGF/MAPKDuring mouse blastocyst formation, the embryo consists of an outer epithelium, the trophectoderm (TE), and the inner cell mass (ICM). The epiblast (EPI) and the primitive endoderm (PrE) are specified within the MCI in a "salt and pepper" pattern characterized by the complementary expression of NANOG, marker of EPI and gata6, marker of PrE. Nanog is mandatory to acquire an EPI identity and Gata6 induces the PrE identity. FGF /MAPK pathway plays a critical role in the acquisition of a PrE identity and disruption of its activity directly impacts the PrE/Epi ratio within the ICM. I’m looking for factors that would be expressed heterogeneously before the specification of internal cells and might tilt the balance towards one fate or the other. For this, I dissected the evolution of ICM cells within Nanog-/- ; Gata6-/- embryos. These embryos form properly the TE and MCI that specifies neither EPI nor PrE. Indeed, the internal cells of Nanog-/- ; Gata6-/- embryos remain stuck around the stage of E3.25. Surprisingly, in the MCI cells, the transcription factor SOX2 is present and this, heterogeneously. Moreover, using inhibitors treatments of the FGF/MAPK pathway, I show that this pathway is not responsible for the heterogeneity of expression of SOX2. Thus, the heterogeneous expression of SOX2 in the inner cells of the embryos is therefore independent of Nanog, Gata6 and the FGF/MAPK pathway
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Tan, Yu Yin Nicole Medical Sciences Faculty of Medicine UNSW. "Gene expression during activation of smooth muscle cells." Publisher:University of New South Wales. Medical Sciences, 2009. http://handle.unsw.edu.au/1959.4/43615.
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Cardiovascular disease, which involves the cardiac, cerebrovascular and peripheral vascular system, is the major cause of morbidity and mortality in the western world. Changes in the vascular microenvironment trigger cascades of molecular events involving altered signaling, transcription and translation of a gene. The aim of this thesis was to increase our understanding on the molecular regulation of activated vascular smooth muscle cells. The first study looking at PDGF-D expression provides new insights into the regulatory mechanisms controlling the phosphorylation of Sp1. Studies performed identified three amino acids in Sp1 (Thr668, Ser670 and Thr681) that is phosphorylated by PKC-zeta activated by AngII. In the second study, the translational regulatory role of a novel gene YrdC induced by injury was investigated. Current knowledge of translational regulators controlling altered gene expression is little and studies in this thesis shows a splice variant of YrdC playing an important role in controlling mRNA translation and thus protein synthesis in the context of injury. The final study investigated in this study was the increased expression of the apoptotic FasL by the activation of GATA6. Although FasL has been extensively studied over the years, this is the first study linking a GATA factor with FasL in any cell type and provides key insights into the transcriptional events underpinning FasL-dependent SMC apoptosis following exposure to AngII.
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Elatmani, Habiba. "Caractérisation du rôle d'Unr, une protéine de liaison à l'ARN, dans les cellules souches embryonnaires murines." Thesis, Bordeaux 2, 2009. http://www.theses.fr/2009BOR21681/document.
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Le gène unr (upstream of N-ras) code une protéine de liaison à l’ARN, Unr, qui régule la stabilité et la traduction d’ARN messagers cibles. L’invalidation du gène unr chez la souris conduit à une létalité embryonnaire à mi-gestation (10,5 jours post-coitum, jpc). Unr est donc essentielle pour le développement de la souris. Le phénotype le plus frappant des embryons unr-/- est leur petite taille qui est déjà visible à 8,5jpc. Ce phénotype pourrait refléter un problème précoce de prolifération/différenciation au cours du développement qu’il est possible d’étudier dans les cellules souches embryonnaires (ES). Les cellules ES sont dérivées des cellules pluripotentes des embryons au stade blastocyste (3,5jpc). Les cellules ES peuvent s’auto-renouveler c’est à dire proliférer indéfiniment sous forme non différenciée ce qui correspond à leur état pluripotent ou différencier en tous les types cellulaires (lignages) adultes dérivés des feuillets primordiaux (endoderme définitif, mésoderme et ectoderme) ce que défini la pluripotence. Ces deux propriétés des cellules ES conditionnent leur devenir et définissent leur identité. Nous avons remarqué que les cellules ES unr-/- ont tendance à différencier spontanément alors qu’elles sont cultivées dans des conditions qui les maintiennent dans un état non différencié et prolifératif (état pluripotent). En routine, les cultures de cellules ES unr-/- contiennent environ 25% de cellules morphologiquement différenciées. Nos travaux montrent en effet, qu’elles différencient en endoderme primitif. Nous avons reproduit ce phénotype dans une autre lignée des cellules ES de fond génétique différent par déplétion stable d’Unr. La restauration de l’expression d’Unr dans les cellules ES unr-/- limite fortement leur engagement en différenciation. Unr contribue donc au maintient de l’état pluripotent des cellules ES en prévenant leur différenciation spontanée vers le lignage endodermique primitif (Epr). Ce tissu au cours du développement va former l’épithélium de la poche embryonnaire ou sac vitellin. Nos données préliminaires montrent que les cellules ES en absence d’Unr maintiennent tout de même leur capacité de différenciation multi-lignages (endoderme définitif, mésoderme et ectoderme) quand celle-ci est induite. Ensuite, nous nous sommes intéressés au(x) mécanisme(s) d’action d’Unr. Nous avons fait l’hypothèse qu’Unr pourrait directement agir en régulant positivement des gènes qui inhibent la différenciation des cellules ES en Epr ou en régulant négativement des gènes qui l’induisent. Nous avons identifié le gène gata6 comme cible potentielle d’Unr. Une augmentation modérée de l’expression du facteur de transcription Gata6 dans les cellules ES conduit à une autorégulation positive du gène gata6 et induit la différenciation des cellules ES en Epr. Nos données suggèrent qu’Unr pourrait directement déstabiliser les ARNms Gata6 dans les cellules ES afin de prévenir leur différenciation spontanée en Endoderme primitifUnr (upstream of N-ras) is a cytoplasmic RNA-binding protein with cold shock domains, involved in regulation of messenger RNA stability and translation. Unr is essential to mouse development since Embryos deficient for Unr die at mid-gestation. Here we report that unr knockout ES cells maintained under growth conditions that sustain self-renewal spontaneously differentiate toward the primitive endoderm (PrE) lineage. This phenotype was reproduced in another ES line (E14tg2a) after shRNA-induced Unr depletion. Moreover, Unr rescue in Unr-deficient ES cells limits their PrE differentiation engagement. However, Unr is dispensable for multilineage differentiation, as shown by knockout ES cells capacity to produce differentiated teratomas. We further investigated the molecular mechanisms underlying the differentiation of unr-/- ES to primitive endoderm, and found that Unr acts downstream of Nanog. Our data also show Gata6 mRNAs are more stable in Unr-deficient ES cells as compared to wild-type ES cells. We propose that the possible repression by Unr of this key inducer of PrE differentiation at a post-transcriptional level may contributes to the stabilization of ES cells pluripotent state
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Tarradas, Pou Anna. "Els factors GATA4 i GATA5 en la regulació transcripcional del gen que codifica pel canal de sodi cardíac (SCN5A)." Doctoral thesis, Universitat de Girona, 2017. http://hdl.handle.net/10803/405732.
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The SCN5A gene encodes the alpha subunit of the cardiac sodium channel (NaV1.5), which is responsible for the influx of sodium ions through membrane of cardiomyocytes. Different evidences suggest that an aberrant expression of the SCN5A gene may cause cardiac arrhythmias. However, the mechanisms that control SCN5A expression regulation are largely unknown. This thesis proposes a new mechanism of SCN5A transcriptional regulation in the adult human heart: transcription factors GATA4 and GATA5 synergize in the activation of the SCN5A expression. In addition, it has been proposed that GATA4 activity on the SCN5A is regulated by acetylation/deacetylation via the acetyltransferase p300 and the deacetylase HDAC2. It has been identified three lysines of GATA4 that are targets of p300 and HDAC2. In summary, this study contributes to further understand the molecular basis of the cardiac arrhythmias associated with alteration of sodium currentsEl gen SCN5A codifica per la subunitat alfa del canal de sodi cardíac dependent de voltatge (NaV1.5), el qual permet l’entrada de ions sodi a través de la membrana dels cardiomiòcits. Diverses evidències suggereixen que una expressió anòmala del gen SCN5A pot donar lloc a arítmies cardíaques. Malauradament, els mecanismes que regulen l’expressió d’SCN5A són molt poc coneguts. Aquesta tesi proposa un nou mecanisme de regulació transcripcional del gen SCN5A en el cor humà adult: els factors de transcripció GATA4 i GATA5 activen sinèrgicament l’expressió del gen SCN5A. També s’ha proposat que l’activitat de GATA4 sobre SCN5A està regulada per un mecanisme d’acetilació/desacetilació a on hi participen l’acetiltransferasa p300 i la desacetilasa HDAC2. S’han identificat tres residus de lisines de GATA4 que són dianes de p300 i HDAC2. En resum, aquest estudi permet entendre millor les bases moleculars de les arítmies cardíaques associades amb alteracions del corrent de sodi
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Bouchard, Marie-France. "Fonctions aberrantes des facteurs de transcription GATA chez l'humain : régulation de l'expression ectopique du gène CYP19A1 par GATA3/4 dans les cellules de cancer du sein et effet des mutations ponctuelles de GATA4 sur la régulation de ses gènes cibles gonadiques." Thesis, Université Laval, 2009. http://www.theses.ulaval.ca/2009/26555/26555.pdf.
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Roth, Eva-Maria [Verfasser]. "Die GATA binding protein 4 (GATA4) Sequenzvariation S377G bei Patienten mit isoliertem Vorhofseptumdefekt im Herzen – Determination eines Phänotyps? / Eva-Maria Roth." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2009. http://d-nb.info/1023956977/34.
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Yürek, Markus. "GATA-Assistenten – En konceptvalidering av röststyrning i GATA." Thesis, Mittuniversitetet, Institutionen för informationssystem och –teknologi, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:miun:diva-36453.
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GATA is a web-application used by truckdrivers transporting timber from assigned pick-up places in the forest to specific receiving locations. GATA is used to facilitate and ease the navigation, communication and planning behind each delivery. This create situations where GATA needs to be used while driving, this is both dangerous and illegal. To solve this problem a voice-controlled proof-of-concept application for the most common features used during driving was developed and given the name GATA-Assistenten. The application was designed with a concept of having a few basic features built upon a stable platform. Dialogflow was chosen as tool to create the AI-voice control and to get it integrated with Google Assistant. Two tracks were created, one for drivers to change the estimated time of arrival and one to get the status on the receiving sites. According to statics at least 0,5% of all traffic related accidents can be directly contributed to interacting with communication devices, this is without taking the unrecorded cases into account. The conclusion based on these statistics is that GATA-Assistenten can not only help avoid accidents but also save lives. If a company wants to invest in safety, it is paramount to use voice-control, however it is also important to do research and development on new technologies to find out and fix the causes behind accidents.GATA är en webbapplikation som används av lastbilschaufförer vid frakt av timmer från skogarna till mottagningsplatser för att lättare navigera, kommunicera och planera körningar på uppdrag av SCA. Det innebär att chaufförerna ibland behöver använda GATA under färd, något som inte bara kan vara en trafikfara utan även är olagligt. För att lösa detta problem skall ett proof-of-concept på röststyrning utvecklas för några av de vanligaste funktionerna som används under färd i GATA. Röststyrningsapplikationen som fick namnet GATA-Assistenten designades utifrån ett koncept om att ha få grundläggande funktioner byggt på en stabil plattform. Dialogflow valdes som verktyg för att skapa en AI-baserad röststyrning med integration via Google Assistant. GATA- Assistenten bestod slutligen av två huvudspår, det ena för att ändra den av chauffören angivna ankomsttiden till mottagningsplatsen och det andra för att ta reda på aviseringsläge på mottagningsplatserna. Enligt statistik är minst 0,5% av alla olyckor direkt orsakade av en förares interaktion med någon form av kommunikationsutrustning, detta utan att ta mörkertalet i beaktande. Slutsatsen som kan tas av detta är att GATA-Assistenten kan hjälpa till att undvika olyckor och rädda liv. Vill ett företag satsa på säkerhet är röststyrning ett måste, om det finns en nollvision kring olyckor i trafiken måste dock mer forskning och utveckling läggas på ny teknik för att ta reda på samt åtgärda orsakerna bakom alla olyckor.
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Duncan, Jeremy Shane. "Cochlear neurosensory specification and competence: you gata have Gata." Diss., University of Iowa, 2012. https://ir.uiowa.edu/etd/2864.
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Early prosensory specification to develop competence in the otic epithelium is disrupted by mutations of Eya1, Pax2, Sox2, Jag1, and Gata3. Mutations in these genes apparently disrupt sensory competence and may affect Atoh1 upregulation, a gene known to be necessary for sensory cell differentiation within the ear. How these genes interact with each other and other factors within the genetic network of the ear to refine and restrict sensory specification and impart competence to the developing organ of Corti is not known. These genes also interact with other factors expressed adjacent to or within the developing organ of Corti and provide the context to allow prosensory cells, after cell cycle exit, to appropriately respond to Atoh1 expression and differentiate as hair cells. Gata3 is expressed throughout the early placode. As ear development continues Gata3 is restricted to all prosensory areas except that of the saccule. In addition, it is expressed in a subset of delaminating neuroblasts. Gata3 continues to be highly expressed in the cochlear sensory epithelia as cells differentiate, and is expressed in all cells of the organ of Corti through adult. The human disorder caused by haploinsufficiency of Gata3 is known as Hypoparathyriodism, Deafness, and Renal dysplasia syndrome, and has been linked in mice to early hair cell death. I investigated the role of Gata3 in cochlear neurosensory specification utilizing a mouse Gata3 knockout model and a conditionally deleted Gata3 line combined with two cre driver lines (Foxg1cre and Pax2cre). Although both cre lines are expressed in the inner ear with only a slight difference in onset of expression there are major phenotypic differences. While the Foxg1cre:Gata3f/f deletion resulted in an ear closely matching that of the null mutant with a cochlear duct devoid of neurosensory cells, the Pax2cre:Gata3f/f cochlear duct contained patches of partially differentiated hair cells. Through the use of qRT-PCR and in situ hybridization of both mutants I was able to paint a picture of how Gata3 interacts with other prosensory genes to upregulate downstream genes. In particular, Atoh1, was downregulated but not absent with the loss of Gata3. Indicating that Gata3 is one of a set of factors necessary for the proper upregulation of Atoh1 in the cochlea.
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Hamlet, Isla. "GATA1 protein partners in megakaryocytes." Thesis, University of Oxford, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.442463.
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Lane, Jonathan. "Gatan som rum & system." Thesis, Blekinge Tekniska Högskola, Institutionen för fysisk planering, 2019. http://urn.kb.se/resolve?urn=urn:nbn:se:bth-18393.
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The streets are one of the most commonly used spaces of a city and most people would probably say that they know what a street is. However, at a second glance, streets could be quite complex spaces hosting sometimes co-existing and sometimes contradicting uses. To start with, there is both an inherent relation between staying and moving as well as between space and network in the concept of streets. Relations that is reflected in the global goals for sustainable development and that can´t be treated separated from each other if the streets are going to work as both a network of transportation, public spaces and as individual spaces. This study aims to investigate these inherent relations in the concept of streets between space and networks, staying and moving to describe the inherent complexity in the concept of streets these relations causes. Through the reasearh survey of this essay it is discovered that different parts of important litterature about urban planing treats this complexity in the concept of streets differently. This essay is therefore carried out through a observational study where different streets in Gothenburg, Sweden is observed. Thereafter the streets are described and analyzed in the light of the inherent complexity in the concept streets to examine if differents streets treats this complexity differently.
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Bouchard, Marie France. "Fonctions aberrantes des facteurs de transcription GATA chez l'humain : régulation de l'expression ectopique du gène CYP19A1 par GATA 3/4 dans les cellules de cancer du sein et effet des mutations ponctuelle de GATA4 sur la régulation de ses gènes cibles gonadiques." Doctoral thesis, Université Laval, 2009. http://hdl.handle.net/20.500.11794/21206.
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Plusieurs pathologies humaines sont associées à l'altération de l'expression ou de la fonction de facteurs de transcription GATA. L'hyperméthylation, l'hypoacétylation ou la surexpression des gènes GALA sont observées dans plusieurs types de cancers. Des mutations ponctuelles des gènes GATA sont aussi à l'origine de graves maladies congénitales. Plus de 60% des tumeurs du sein sont dépendantes des estrogènes et produisent elles-mêmes les hormones nécessaires à leur croissance. Cette production aberrante d'estrogènes est causée par la surexpression de l'enzyme aromatase, codée par le gène CYP19A1. L'utilisation ectopique dans les tumeurs du sein du promoteur PII du gène CYP19A1, normalement spécifique à l'ovaire et régulé par la voie de signalisation AMPc/PKA, est reconnue comme étant responsable de la surexpression de l'enzyme et de la production inappropriée d'estrogènes par les tumeurs. Les facteurs GATA sont impliqués dans la régulation du promoteur PII de CYP19A1 dans les gonades. J'ai démontré que GATA3 et/ou GATA4 sont exprimés dans plusieurs lignées cellulaires de cancer du sein. En réponse à l'activation de la voie de signalisation AMPc/PKA, GATA3/4 et le récepteur nucléaire LRH1 coopèrent de façon synergique pour moduler l'activité du promoteur PII dans les cellules de cancer du sein MCF-7. Ces résultats fournissent un nouveau mécanisme dépendant de GATA pour expliquer l'expression aberrante de l'enzyme aromatase dans les tumeurs du sein. Les mutations hétérozygotes connues de GATA4 ségrègent avec de graves défauts cardiaques congénitaux. GATA4 est un important régulateur du développement cardiaque mais aussi un marqueur précoce du développement gonadique. Toutefois, aucune des mutations connues de GATA4 n'affecte le développement ou la fonction gonadique des individus porteurs. L'effet des différentes mutations de ce facteur sur la régulation de l'expression de ses cibles gonadiques demeurait par contre inconnu. J'ai étudié cinq mutations différentes du facteur GATA4. J'ai démontré que certaines de ces mutations affectent significativement la fonction de GATA4 dans un contexte de régulation de l'expression de gènes gonadiques. Mes résultats démontrent que malgré l'absence d'un phénotype observable, la plupart des mutations de GATA4 réduisent significativement sa capacité d'activer l'expression de ses gènes cibles sans affecter sa capacité à se lier à l'ADN ou celle de recruter ses co-activateurs transcriptionnels. Dans l'ensemble, les résultats présentés dans ma thèse démontrent comment les facteurs GATA exprimés dans un contexte tumoral contribuent à l'expression aberrante de CYP19A1 dans les cellules cancéreuses du sein selon un mécanisme rappelant celui menant à l'expression gonadique de ce gène et d'autre part comment l'altération de la séquence peptidique du facteur GATA4, telle qu'observée dans de nombreuses malformations cardiaques congénitales, affecte la fonction de ce facteur de transcription dans la régulation de l'expression de ses cibles gonadiques.
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Ekstål, Simon. "Kommunikationslösning för GATA-systemet." Thesis, Mittuniversitetet, Avdelningen för informationssystem och -teknologi, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:miun:diva-30995.
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Sogeti is an IT-consulting company active in many countries. It has many different assignments and develops systems for companies in different industries. One of these assignments and systems is a system called GATA made for the company SCA's business-branch SCA SKOG. GATA stands for GPS Assisted Transport Announcement and is a comprehensive solution for timber transport from forest to industry. At this point in time, messages that do not belong to the system's main data must be sent and received outside the system. The purpose of this project has been to create a communication solution that addresses this for the system. The basic objective of the solution has been to create a local communication solution and then integrate this solution with the system. This was supposed to be done in a structured manner during sprints and with a proof-of-concept model. A local communication solution has been created consisting of a server with a message-component, a console application for creating and sending messages and a website for receiving and presenting messages. The result of the local communication solution has been proven to be consistent with the basic objective. Thereafter the local communication solution was integrated with the GATA-system. The integration resulted in a message- component being created on the system server, a console application was created within the system and a component on the system's website was created. This integrated communication solution imitates and can perform the same operations as the local communication solution and has been adapted to the GATA-system. The result of the integration and thus the entire project have been proven to be successful according to the basic target objective.Sogeti är ett IT-konsultföretag aktivt inom många länder. Det innehar många olika uppdrag och utvecklar system till företag inom olika branscher. Ett av dessa uppdrag och system är ett system vid namn GATA skapat för företaget SCAs verksamhet SCA SKOG. GATA står för GPS Assisted Transport Announcement och är en helhetslösning för transport av timmer från skog till industri. I dagens skede måste meddelanden som inte tillhör systemets huvudsakliga data skickas och tas emot utanför systemet. Syftet med detta projekt har varit att skapa en kommunikationslösning som åtgärdar detta för systemet. Den grundläggande målbilden för lösningen har bestått av att skapa en lokal kommunikationslösning och därefter integrera denna lösning med systemet. Detta skulle göras på ett strukturerat sätt under sprinter och med en proof-of-concept modell. En lokal kommunikationslösning har skapats bestående av en server med meddelande-komponent, en konsol-applikation för att skapa och skicka meddelanden och en webbplats för att motta och presentera meddelanden. Resultatet av den lokala kommunikationslösningen har bevisats stämma överens med den grundläggande målbilden. Därefter integrerades den lokala kommunikationslösningen med GATA-systemet. Integrationen resulterade i att en meddelande-komponent skapades på systemets server, en konsol-applikation skapades inom systemet och en komponent på systemets webbplats skapades. Denna integrerade kommunikationslösning imiterar och kan utföra samma operationer som den lokala kommunikationslösningen och har anpassats till GATA-systemet. Resultatet av integrationen och därigenom hela projektet har enligt den grundläggande målbilden bevisats vara framgångsrikt.
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Sanner, Malin. "Saab Qlean : en fyrhjuling för gatan." Thesis, Konstfack, Industridesign, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:konstfack:diva-2838.
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Examensarbetet har syftat till att ta fram ett koncept för en fyrhjuling för Saab att köra på allmän väg. Projektet har drivits i samarbete med Caran och Saab Automobile. Arbetet har dessutom varit ett unikt samarbete med två andra examensarbeten från andra högskolor som behandlat konstruktion och brukar- och marknadsanalys för fyrhjulingen. Konceptet är en miljövänlig hybridfyrhjuling som går att lägga ner i kurvorna.Examensarbetet har syftat till att ta fram ett koncept för en fyrhjuling för Saab att köra på allmän väg.
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Yamak, Fatimah Abir. "GATA4 Partners in Cardiac Cell Proliferation." Thèse, Université d'Ottawa / University of Ottawa, 2013. http://hdl.handle.net/10393/23802.
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Cardiovascular diseases are the leading cause of death in humans throughout the world and “congenital heart defects” (CHDs) are the major cause of infant mortality and morbidity. GATA4 is one of the most critical and intensely studied cardiac transcription factor. It is important for proliferation of cardiomyocytes as well as their survival and adaptive response. The focus of the following thesis was to identify GATA4 mediators and cofactors in cardiac growth. The first part focused on cyclin D2 (CycD2), a growth inducible cell cycle protein. We identified Ccnd2 (gene encoding CycD2) as a direct transcriptional target of GATA4 in postnatal cardiomyocytes and Ccnd2 cardiomyocyte specific overexpression in Gata4 heterozygote mice was able to rescue their heart size and function. We further uncovered a novel regulatory loop between GATA4 and CycD2. CycD2 enhanced GATA4 activation of its target promoters. GATA4 was able to physically interact with CycD2 and its cyclin dependent kinase CDK4 suggesting that GATA4 recruits CycD2/CDK4 to its target promoters. Together, our data uncover a role of CycD2 in the developing and postnatal heart and provide novel insight for the potential of targeting the cell cycle in cardiac therapy. The second part of the project focused on KLF13, a cell specific cofactor of GATA4. KLF13 is a member of the Krϋppel-like transcription factors that are important regulators of cell proliferation and differentiation. Klf13 is highly enriched in the developing heart where it is found in both myocardial and endocardial cells. To determine its role in the mammalian heart, we deleted the Klf13 gene in transgenic mice. Klf13-/- mice were born at 50% reduced frequency and presented with variable cardiac phenotypes. Epithelial-mesenchymal transformation (EMT) was affected in these mice and reduced cell proliferation was evident in the AV cushion. These data uncover a role for a new class of transcription factors in heart formation and point to KLF13 as a regulator of endocardial cell proliferation and a potential CHD causing gene. Future discovery of more cardiac regulators and understanding the molecular basis of CHDs is essential for preventions of these defects and possible development of therapeutic approaches for myocardial repair.
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Lawall, Thaíse. "Ovário-histerectomia minilaparoscópica em gatas hígidas." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2015. http://hdl.handle.net/10183/116275.
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A ovário-histerectomia (OVH) é um procedimento cirúrgico realizado de maneira rotineira na clínica de pequenos animais, com objetivo terapêutico ou de promover a esterilização reprodutiva nas fêmeas. Muitas abordagens pela técnica convencional aberta já foram descritas e com viabilidade comprovada. No segmento da cirurgia de invasão mínima dentro da Medicina Veterinária, diversos métodos vêm sendo propostos variando entre si em relação ao posicionamento, quantidade e tamanho dos trocartes e método de hemostasia. Assim sendo, o objetivo deste estudo foi avaliar e descrever a viabilidade de realização da OVH em felinas com até 5 kg de peso corporal através de abordagem minilaparoscópica com uso de eltrocoagulação bipolar como método hemostático. A minilaparoscopia (MINI) não é uma modalidade recente na cirurgia laparoscópica humana. Considerada a evolução mais sofisticada da cirurgia laparoscopia, a MINI apresenta muitos outros benefícios além do estético; visto que a lesão relacionada ao dano cirúrgico não se resume as somas das incisões realizadas. A técnica reina pela delicadeza e precisão dos movimentos, sem perda da triangulação, essencial ao padrão laparoscópico. Foram avaliados os procedimentos de 15 felinas quanto à viabilidade e dificuldades do acesso minilaparoscópico, uso do cautério bipolar, o tamanho das incisões e a necessidade de ampliá-las, complicações trans e pós-operatórias assim como a dor demonstrada por esses pacientes. A avaliação da dor foi feita através de tabela específica para espécie felina com diretrizes estabelecidas e confiabilidade comprovada, auxiliada a outras duas tabelas de avaliação da dor. A conversão de minilaparoscopia à cirurgia aberta foi necessária em um dos quinze pacientes operados nesse estudo. Conclui-se que a realização da técnica de OVH por abordagem minilaparoscópica em gatas é factível.Ovariohysterectomy (OHE) is a surgical procedure routinely performed in small animals practice, with therapeutic purpose or to promote reproductive sterilization in females. Numerous approaches have been described using conventional open technique and had their viability proven. In the segment of minimally invasive surgery in the Veterinary Medicine, several methods have been proposed, differing from each other in position, number and size of trocars and hemostasis method used. Thus, the goal of this study was to evaluate and describe the practicability of performing OHE in cats with up to 5 kg of body weight through minilaparoscopic approach, using bipolar eltrocoagulation as hemostatic method. The minilaparoscopy (MINI) is not a new modality in human laparoscopic surgery. Considered the most sophisticated evolution of laparoscopic surgery, the MINI has many other benefits beyond the aesthetic; since the injury caused by the damage of surgery is not just the sum of the incisions. The technique stands out for the delicacy and accuracy of the movement without loss of triangulation, essential for the laparoscopic model. The procedures of 15 female cats were evaluated for the viability and difficulties of minilaparoscopic approach, use of bipolar cautery, incision size and the need to enlarge it, trans and postoperative complications and pain demonstrated in these patients. Pain assessment was done through specific table for feline species with established guidelines and proven reliability, helped by other two pain assessment tables. The conversion from minilaparoscopy to open surgery was required in one of the fifteen patients operated on in this study. Therefore, the implementation minilaparoscopic approach for OHE technique is feasible in cats.
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Pinto, Rita Mafalda Marques de Oliveira. "Neoplasias mamárias em cadelas e gatas." Bachelor's thesis, Universidade Técnica de Lisboa. Faculdade de Medicina Veterinária, 2009. http://hdl.handle.net/10400.5/1159.
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Dissertação de Mestrado Integrado em Medicina VeterináriaO estudo das neoplasias mamárias tem um elevado interesse clínico e científico pois além de constituírem uma das neoplasias mais frequentes nas cadelas e nas gatas, muitos dos resultados obtidos são extrapoláveis para a espécie humana. A presente dissertação teve como objectivo caracterizar uma amostra de cadelas e gatas com neoplasias mamárias, apresentadas à consulta no ano de 2008, no Hospital Veterinário de Almada. De seguida procedeu-se à análise estatística da amostra populacional, de modo a descrever os animais afectados e a relacionar as características morfológicas e histopatológicas recolhidas com a informação presente nas referências bibliográficas pesquisadas. A caracterização foi feita com base na espécie, raça, idade, apresentação clínica, factores ambientais, classificação histológica, metastização regional e à distância e na sobrevivência após mastectomia. Na amostra investigada foram identificadas 19 neoplasias mamárias: 13 em cadelas; 6 em gatas. Este estudo identificou os tumores mamários como as neoplasias mais comuns ( 50%) em ambas as espécies e calculou uma prevalência de 4 tumores mamários em cada 100 fêmeas em risco, quer em cadelas quer em gatas da amostra populacional estudada. O incentivo à castração precoce das fêmeas e à sensibilização dos proprietários para os riscos envolvidos e para as possibilidades terapêuticas desta patologia são fundamentais e urgentes.
ABSTRACT - MAMMARY NEOPLASIAS IN BITCHES AND QUEENS - The study of mammary gland neoplasias has a high clinical and scientific interest, since it represents one of the most common neoplasias in bitches and queens. Moreover many results can be extrapolated to the human species. The aim of this dissertation was to characterize a sample of bitches and queens with mammary tumours, presented to consultation in 2008 at the Hospital Veterinário de Almada. A statistic analysis was done to describe the affected animals and to compare the tumour’s morphological and histological characteristics with published information The characterization of the sample was made for species, breed, age, clinical presentation, environmental factors, histological classification, regional and distant metastasis and post mastectomy survival. Nineteen mammary gland neoplasias were identified: 13 in bitches; 6 in queens. This study found that the mammary gland tumours were the most common neoplasias ( 50%) in both species. A similar annual prevalence of 4 per 100 females in risk, either for bitches or for queens was estimated on the studied sample. The incentive for early neutering the females and owners education about the risks involved and the treatment potential are essential and a pressing need.
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Whyatt, David John. "Erythroid development and GATA-1." Thesis, Open University, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.239713.
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Kuhl, Christiane. "Structure / function analysis of GATA1 in megakaryocytes." Thesis, University of Oxford, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.418523.
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Magnusson, Simon. "Jämställda gatan : Personbaserade gatunamn och ideologierna bakom." Thesis, Uppsala universitet, Institutionen för nordiska språk, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-216881.
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Uppsatsen undersöker könsfördelningen bland ideologiska personbaserade gatunamn i Uppsala och Gävle. Den utgår från teorier om att gatunamn vidmakthåller sociopolitiska maktstrukturer och har en normerande effekt på historieskrivningen. För att undersöka om tidens mer jämställda samhälle påverkat namngivningen indelas det totala gatunamnsbeståndet i två perioder med brytåret 2000 där den tidigare perioden jämförs med den senare när jämställdhets- medvetenheten förväntats ökat.Uppsala som under 2000-talet debatterat frågan uppvisar en ökad andel kvinnonamn på 30 procentenheter mot Gävles ökning på 16 procentenheter där man heller inte har några jämställdhetsstadgar vid namngivningen.Namnberedningarnas sammanträdesprotokoll granskas i syfte att undersöka genusanknytande resonemang där fallet Fadimes plats belyser en äldre och uteslutande kulturvårdande politik som format namnbeståndet. En enkät- undersökning där 193 kommuner ingår visar att 67 kommuner jobbar efter stadgar vid namngivningen varav 5 kommuner rapporterar jämställdhetsstadgar. Resultatet tyder på att de inriktningsmål som visat sig effektiva i Uppsala nationellt sett är ovanliga.
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Özel, Deniz. "Allt lugnt efter Lugna Gatan? : En kvalitativ studie om upplevelser av Fittjaområdet efter nedläggningen av Lugna Gatan i Fittja." Thesis, Uppsala universitet, Sociologiska institutionen, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-336074.
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Fittja är en av Sveriges mest brottsutsatta förorter och därför har organisationen Lugna Gatan arbetat som trygghetsvärdar i området. Efter många år lades Lugna Gatans verksamhet ner och det påverkade många i området. Men hur påverkades de? Denna studie besvarar frågeställningen om hur de verksamma personerna i Fittjaområdet upplevde tiden med Lugna Gatan och tiden efter att de lämnat. Intervjuer gjordes med verksamma inom området och slutsatsen var att Lugna Gatans arbete skapade en trygghet i området som saknas med den nya aktören Skyddsvärnet, men Skyddsvärnet har däremot lyckats med att förbättra arbetet inom skolan till skillnad från Lugna Gatan.
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Borges, Gustavo. "Mutações no gene GATA2 em pacientes com síndromes de falência medular." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/17/17154/tde-07062017-103827/.
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Citopenia é um importante sinal de falência medular, sendo um achado comum de várias doenças, dentre as quais se destacam as mielodisplasias e a anemia aplástica. As mielodisplasias correspondem a um grupo de alterações hematopoéticas de natureza clonal, cuja principal característica é a hematopoese ineficaz, clinicamente manifesta como uma medula óssea celular, porém associada a citopenias. Já a anemia aplástica apresenta uma medula hipo ou acelular sem evidência de infiltração neoplásica, sendo substituída por tecido gorduroso. O gene GATA2 é um fator regulador da hematopoese, atuando também na manutenção e proliferação do pool de células-tronco e progenitoras hematopoéticas. Recentemente, mutações constitucionais no gene GATA2 foram descritas na síndrome de monocitopenia e infecção micobacteriana (MonoMac), que eventualmente cursa com outras citopenias, medula hipocelular ou mesmo mielodisplasia. Entretanto, a contribuição de mutações no gene GATA2 para o desenvolvimento de anemia aplástica adquirida e síndrome mielodisplásica não é conhecida. Neste trabalho, propomos pesquisar mutações no gene GATA2 em pacientes com anemia aplástica adquirida e síndrome mielodisplásica, por meio de sequenciamento direto do DNA. Adicionalmente, também avaliaremos as subpopulações linfocitárias no sangue periférico e níveis de citocinas plasmáticas no intuito de correlacionar a presença de mutação do GATA2 a um perfil imunológico.Cytopenia is an important signal of marrow failure, being commom to various diseases, among them myelodysplasia and aplastic anemia. Myelodysplasia is a group of hematopoietic clonal disorders, with inneficient hematopoiesis, cellular bone marrow with associated cytopenias. The aplastic anemia presents a hypo or even acellular bone marrow without any evidence of neoplastic infiltration with the stem cells being substituted by fat. The GATA2 gene is a key regulator of hematopoiesis, also acting on the maintenance and proliferation of stem and progenitor cells. Recently, constitutional mutations in the GATA2 gene were described in MonoMAC syndrome, which eventually presents cytopenias, hypocellular marrow or even myelodysplasia. However, the contribution of GATA2 mutations for the development of acquired aplastic anemia or myelodysplasia is not known. In this work we aim to search for GATA2 gene mutations in patients with acquired aplastic anemia and myelodysplasia through Sanger sequencing. Also, we will evaluate the levels of subpopulations of lymphocytes and the plasmatic levels of cytokines to establish a correlation between the presence of mutation in the GATA2 and a specific immune profile
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Kurek, Dorota Malgorzata. "Studies on the role of Gata3 during development." [S.l.] : Rotterdam : [The Author] ; Erasmus University [Host], 2008. http://hdl.handle.net/1765/11127.
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Price, Lynn. "Microarray analysis of TBX5 and GATA4 transcriptional targets." Thesis, University of Nottingham, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.442255.
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Gonçalves, Liudimila Passos. "Autotransplante ortotópico de córtex ovariano de gatas domésticas." reponame:Repositório Institucional da UnB, 2017. http://repositorio.unb.br/handle/10482/31134.
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Dissertação (mestrado)—Universidade de Brasília, Centro de Desenvolvimento Sustentável, Programa de Pós-Graduação em Desenvolvimento Sustentável, 2017.Submitted by Raquel Almeida (raquel.df13@gmail.com) on 2017-11-28T19:53:54Z No. of bitstreams: 1 2017_LiudimilaPassosGonçalves.pdf: 1010541 bytes, checksum: 2a11599e92fb4d18d72613c36acd6b49 (MD5)
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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq).
Este trabalho objetivou realizar o autotransplante ortotópico de córtex ovariano em gatas domésticas. Foi padronizada a espessura de corte (1 mm) do fragmento cortical e o método de implante ortotópico diretamente sobre a medula remanescente, deixando o lado contralateral apenas com a região medular como controle. Foi observado desenvolvimento folicular em ambos os lados, porém com valores inferiores no lado onde tinha apenas a medula remanescente. Apesar de ter sido constatado que os folículos primordiais se encontram a uma profundidade máxima de 200 µm, mesmo com a retirada de fatias de 1000µm (ou 1 mm) de espessura ainda resta tecido cortical com folículos ovarianos capazes de se desenvolver. Dessa forma, foi realizada uma nova etapa de implante ortotópico diretamente sobre a medula remanescente (acentuando a profundidade do corte após a retirada dos fragmentos) e foi comparado, com os implantes na bolsa peritoneal próxima ao ovário, também considerado ortotópico. Foi encontrado um bom desenvolvimento folicular nos implantes na bolsa peritoneal, muitas vezes superior ao da região medular. Ainda houve desenvolvimento de folículos antrais na região medular remanescente. Como o objetivo a longo prazo da técnica de transplante ortotópico de tecido ovariano em felinos é utilizar a gata doméstica como receptora de implantes de felinos ameaçados de extinção, é indispensável que os folículos em desenvolvimento sejam exclusivamente do transplante. Com este trabalho, pode-se concluir que a retirada de fragmentos de 1 mm de espessura da camada cortical do ovário de gatas é suficiente para recuperar a maioria dos folículos ovarianos pré-antrais, porém não a deixa estéril; o implante dos fragmentos sobre a medula remanescente não nos dá certeza de que os folículos desenvolvidos são do implante; e o implante em bolsa peritoneal (região ortotópica) é capaz de promover condições favoráveis ao bom desenvolvimento folicular em gatas. Sendo assim, o peritônio é sugerido como o melhor local para o implante ortotópico, e pode ser explorado para o xenotransplante em felinos até o momento.
The aim of this study was to perform ortotopic autotransplantation of ovarian cortex in domestic cats. On a pilot study, the thickness of the cortex slices (1mm) and the method of grafting were standardized. Then, five cats were used for the ovarian grafting. The ovarian cortex was completely removed from both ovaries, and cortex slices from one ovary were grafted on the remainder medulla of the contralateral ovary, while the other ovary was kept with only the medullar region as a control. Follicular development was observed on both ovaries, with lower number of follicles on the side with only the remainder medulla than on the side that received the cortex grafts. Primordial follicles were on a 200 µm maximum depth, but removing slices of 1000 µm (1 mm) still left cortex material enough to allow follicular development. This way, a second experiment was performed to compare the orthotopic implant directly on the medullar region with implants on peritoneal pockets (also considered orthotopic). Follicular development was observed on grafts on peritoneal pockets. However, antral follicles development still occurred on the medullar region. Since the main objective of stablishing the technique of orthotopic transplantation of ovarian tissue in cats is to use de domestic cat as the surrogate for wild felines’ ovarian tissue, it is essential that the development of follicles are exclusively from the graft. With this work we concluded that: removing 1 mm thick slices of ovarian cortex is enough to recover most primordial follicles, but not enough to render the queen infertile; grafting the cortex slices on the remainder medullar tissue does not guarantee that developing follicles are from the grafted tissue, and the implant on peritoneal pockets allow good conditions for follicular development in cats. This way, for now, the peritoneum is the best local for the orthotopic transplant of ovarian tissue, and may be a suitable site for the xenotransplantation of wild felines’ ovarian tissue to domestic cats.
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Taniguchi, Hiroaki. "Regulation of GATA4 transcriptional activity in the gonads." Thesis, Université Laval, 2007. http://www.theses.ulaval.ca/2007/24610/24610.pdf.
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Gilli, Simone Cristina Olenscki. "Regulação do gene gata3 humano pelo virus HTLVI." [s.n.], 2004. http://repositorio.unicamp.br/jspui/handle/REPOSIP/311958.
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Orientador: Sara T. O. SaadTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: A infecção pelo vírus linfotrópico de células T tipo I (HTLV I) tem sido associada à leucemia/linfoma T do adulto (LLTA), à paraparesia espástica tropical! mielopatia associada ao HTLV I (PET/MAH), à uveíte e, recentemente, à Síndrome de Sjõgren e outras doenças do sistema conjuntivo. Os fatores que detenninam a evolução para essas doenças relacionadas à infecção são desconhecidos, mas podem estar ligados à predisposição genética e à resposta imune do hospedeiro. Camundongos com ausência do gene GATA3 demonstram várias e graves anormalidades morfológicas e fisiológicas no sistema nervoso central e periférico, além de comprometimento da hematopoese durante o desenvolvimento embrionário. Há, portanto, semelhanças entre os sistemas comprometidos na ausência do gene GATA3 e aqueles alterados secundariamente à infecção pelo HTLV I. Vários estudos sugerem que uma fosfoproteína viral presente no HTLVI, denominada Tax, ative a transcrição de vários genes envolvidos na produção de citocinas ou na resposta e na proliferação celular, como c-fos, c-myc, erg-I, IL-I, IL-2, GM-CSF. Entretanto, a crelação entre a infecção pelo vírus HTLV I e o fator de transcrição GATA3 ainda não havia sido determinada. Os objetivos do presente trabalho foram caracterizar a relação entre o fator de transcrição GATA3 e o vírus HTLV I, utilizando-se, para tanto, a técnica de RT-PCR semiquantitativo; analisar a relação entre o fator de transcrição GATA3 e o vírus HTLV I, por meio de estudos de interação DNA/proteína; e demonstrar, por estudos funcionais em modelos celulares in vitro, a resposta das regiões de controle transcricional do gene GATA3 à proteína Tax. Demonstramos, através do RT-PCR semi-quantitativo que ocorre uma evidente redução na expressão do gene GATA3 em portadores saudávies da infecção pelo HTLVI, e também de forma mais acentuada nos portadores de Leucemia Linfoma T do Adulto e Paraparesia Espástica Tropical/Mielopatia associada ao HTLVI. Estudos in vitro, que utilizaram construções com o gene reporter CAT direcionado pelo promotor e silenciador do gene GATA3 co-transfectados com vetores de expressão da proteína Tax e seu mutante, revelaram que Tax exerce atividade discreta no promotor de gene GATA3, mas reprime de modo marcante a atividade do promotor na presença de seu silenciador. Essa repressão provavelmente ocorre através da interação de tax com o fator de trans.crição ZEB, o silenciador do promotor do gene GATA3, uma vez que interação deste com a proteína Tax foi demonstrada no estudo de retardamento em gel. O estudo demonstrou, pela primeira vez, a regulação do gene GATA3 pelo vírus HTLVI. Essa regulação pode estar envolvida na fisiopatologia das doenças relacionadas à infecção pelo HTLVI
Abstract: The HTLV-I nonstructural protein Tax plays a crucial role in cellular transformation. It activates the transcription factors of various cellular genes and interacts with cellular proteins. Limited data are available on the interaction between specific T cell transcription factor GATA3 and Tax. hnplication for the significance ofGATA3 on T-cell development and function, (Th2) differentiation, and a role ofGATA3 during immune response has been reported. To determine the effect of the Tax protein on GATA3 gene expression, we investigated the interaction between this protein and the GATA3 promoter and repressor regions. The semi quantitative RT-PCR demonstrated a considerable decrease in the expression of the GATA 3 cDNA all subjects infected by HTLV I and no expression of GATA 3 mRNA was observed in one subject with ATLL and another with HAM/TSP. Results demonstrated an interaction between Tax and GATA3 gene and a role ofTax in the negative regulation of GATA3 expression, through its interaction with the repressor, ZEB. This interaction may be involved in the pathophysiology of adult T cell leukemiallymphoma and tropical spastic paraparesis/HTLV-I-associated myelophathy
Doutorado
Clinica Medica
Doutor em Clínica Médica
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Oikonomopoulos, Spyridon. "Inferring structural properties of protein-DNA binding using high-throughput sequencing : the paradigm of GATA1, KLF1 and their complexes GATA1/FOG1 and GATA1/KLF1 : insights into the transcriptional regulation of the erythroid cell lineage." Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:72b92906-4ef6-4c1d-9155-484521027e2e.
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GATA1 and KLF1 are transcription factors that regulate genes which are important for the development of erythroid cells. The GATA1 transcriptional co-factor FOG1 has been shown to be essential in a wide range of GATA1 dependent cellular functions. Here we tried to understand the diverse mechanisms by which GATA1 and KLF1 recognize their binding sites, how the GATA1 recognition mechanisms are affected by complexation with either FOG1 or KLF1 and how the GATA1 recognition mechanisms affect the transcriptional regulation of the erythroid differentiation. We profiled the DNA binding specificities/affinities of a GATA1 fragment (mGATA1NC), that contains only the two DNA binding domains (N-terminal and C-terminal Zn finger), and the DNA binding specificities/affinities of a KLF1 fragment (mKLF1257-358), that contains the three DNA binding domains, using a novel methodology that combines EMSA with high throughput sequencing (EMSA-seq (Wong et al., 2011a)). We also profiled the DNA binding specificities of the C-terminal Zn finger of GATA1 alone (mGATA1C), the wt-mGATA1, the wt-mGATA1/wt-mFOG1 complex and the mGATA1NC/mKLF1257-358 complex. At first, we confirmed that the N-terminal Zn finger of GATA1 has a strong preference for the “GATC” motif, whereas the C-terminal Zn finger of GATA1 has a strong preference for the “GATA” motif. Next, we found that in the mGATA1NC, both DNA binding domains can bind simultaneously a wide range of different positional combinations of the co-occurring “GATA” and “GATC” motifs, on the same DNA sequence. The wt-mGATA1 did not show the ability to bind in the same co-occurring motifs implying an effect of the non-DNA binding domains of the protein in the regulation of its DNA binding specificities. On the contrary, complexation of wt-mGATA1 with the wt-mFOG1 partially restored its ability to bind in a now limited range of different positional combinations of the co-occurring “GATA” and “GATC” motifs, on the same DNA sequence. Similar observations were made for other pairs of GATA1 N-terminal and C-terminal Zn finger specific motifs. We then projected the GATA1 DNA binding specificities/affinities in vivo and we classified the GATA1 ChIP-seq peaks in low, medium or high affinity based on the number of the GATA1 motifs. We noticed that high affinity GATA1 ChIP-seq peaks tend to appear in regions with low nucleosome occupancy. We also noticed that GATA1 ChIP-seq peaks in the enhancer regions are usually high affinity whereas GATA1 ChIP-seq peaks in the proximal promoter regions are usually low affinity. Additionally, we observed that high affinity GATA1 ChIP-seq peaks are usually found in regions with increased levels of H3K4me2 and are associated with a higher decrease in the H3K4me3 levels on the TSS of the nearby genes. None of these GATA1 related in vivo observations were found for the KLF1 ChIP-seq positions. These findings significantly advance our understanding of the DNA binding properties of GATA1, KLF1 and their complexes and give an insight on the importance of the GATA1 DNA binding affinities in the regulation of the erythroid transcriptional program. Overall the work establishes an experimental and analytical framework to investigate how transcriptional co-factors can change the DNA binding specificities of specific transcription factors and how integration of the transcription factor DNA binding affinities with in vivo data can give novel insights into the transcriptional regulation.
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Joyce, Tobias Andrew. "Functional genomics of Arabidopsis thaliana GATA factors." Thesis, University of Leeds, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.434621.
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Gillis, William Joseph. "The evolution of metazoan GATA transcription factors /." Connect to title online (Scholars' Bank) Connect to title online (ProQuest), 2008. http://hdl.handle.net/1794/8568.
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Thesis (Ph. D.)--University of Oregon, 2008.Typescript. Includes vita and abstract. "This dissertation includes both ... previously published and unpublished co-authored material"--P. v. Includes bibliographical references (leaves 120-135). Also available online in Scholars' Bank; and in ProQuest, free to University of Oregon users.
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Gillis, William Joseph 1981. "The evolution of metazoan GATA transcription factors." Thesis, University of Oregon, 2008. http://hdl.handle.net/1794/8568.
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xiii, 135 p. ; ill. (some col.) A print copy of this title is available through the UO Libraries. Search the library catalog for the location and call number.This thesis explores the origin and evolution of animal germ layers via evolutionary-developmental analyses of the GATA family of transcription factors. GATA factors identified via a conserved dual zinc-finger domain direct early germ layer specification across a wide variety of animals. However, most of these developmental roles are characterized in invertebrate models, whose rapidly evolved sequences make it difficult to reconstruct evolutionary relationships. This study reconstructs the stepwise evolution of metazoan GATA transcription factors, defining homologous developmental roles based upon clear orthology assignments. We identified two GATA transcription factors ( PdGATA123 and PdGATA456 ) from the marine annelid Platynereis dumerilii to aid comparison of protostome and deuterostome GATA factors. Our phylogenetic analyses defined these as protostome orthologs of GATA1/2/3 and GATA4/5/6 vertebrate subfamilies, while the mRNA localization of the Platynereis GATAs showed ectodermal versus endomesodermal germ layer restrictions, similar to their vertebrate orthologs. To define the phylogenetic relationships of more divergent genes in the invertebrate models, we identified GATA homologs from recently sequenced protostome genomes. Molecular phylogenetic analyses, comparisons of intron/exon structure, and conserved synteny confirm all protostome GATA transcription factor genes are members of either the GATA123 or GATA456 class. These data allowed us to identify multiple protostome-specific duplications of GATA456 homologs and reconstruct the origin and relationships of all arthropod GATA genes. To probe GATA transcription factor evolution in deuterostomes, including vertebrates, we identified GATA factors in basal deuterostomes, including the cephalochordate Branchiostoma floridae and the hemichordate Saccoglossus kowalevskii. Phylogenetic analyses of these data independently confirmed that the ancestral deuterostome and chordate--like the bilaterian ancestor--possessed only two GATA transcription factors. This work was facilitated by a bioinformatics platform we are developing to identify gene families from preassembled genomic sequence. We generated anti- PdGATA antibodies to further explore the role of Platynereis GATAs in germ layer formation. We identified multiple presumptive endomesodermal cells in which nuclear localization of PdGATA456 protein first occurs and utilized PdGATA456 protein localization to follow endomesodermal cell populations throughout development. These analyses represent some of the first cellular and molecular analyses of Platynereis germ layer formation. This dissertation includes both my previously published and unpublished co-authored material.
Adviser: Stephan Q. Schneider
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Lee, Pei Yun Bronner-Fraser Marianne. "Function and regulation of the Strongylocentrotus purpuratus gatae gene /." Diss., Pasadena, Calif. : California Institute of Technology, 2007. http://resolver.caltech.edu/CaltechETD:etd-04072007-221302.
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Conceição, Maria Eduarda Bastos Andrade Moutinho da. "Miniligadura pré-montada (miniloop) na ovariectomia laparoscópica em gatas /." Jaboticabal, 2017. http://hdl.handle.net/11449/150690.
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Orientador: Luis Gustavo Gosuen Gonçalves DiasCoorientador: Pedro Paulo Maia Teixeira
Banca: Annelise Carla Camplesi dos Santos
Banca: Felipe Farias Pereira da Câmara Barros
Resumo: O objetivo deste trabalho foi descrever e avaliar a aplicabilidade e exequibilidade da técnica de miniligadura pré-montada, passada por punção abdominal percutânea (Miniloop), para hemostasia preventiva do complexo arteriovenoso ovariano (CAVO) em ovariectomia laparoscópica em gatas. Comparou-se a técnica em tela frente à técnica aberta minimamente invasiva para hemostasia do CAVO. Foram utilizadas 20 gatas saudáveis distribuídas em dois grupos contendo 10 pacientes em cada um. No grupo controle (GC) a cirurgia foi realizada com auxílio do gancho de Snook e ligadura do CAVO com polidiaxanona 2-0. O grupo miniloop (GM) foi operado por técnica videolaparoscópica com dois portais e miniligadura pré-montada passada por punção percutânea de 2 mm, utilizando o mesmo fio. No transoperatório, frequência cardíaca (FC) e respiratória (FR), EtCO2 (gás carbônico expirado) e temperatura corporal foram monitorados constantemente com monitor multiparamétrico. Avaliou-se dor por meio de escalas de avaliação subjetiva nos períodos pré-operatório, 1, 12, 24, 48, 72 horas e 10 dias após o início do retorno anestésico. Por venopunção da jugular externa, amostra de sangue foi coletada para determinação de proteínas de fase aguda (APP) e leucograma no pré-operatório, 1, 12, 24, 48, 72 horas e 10 dias após o início do retorno anestésico e, para determinar inflamação pós-operatória e comparar as duas técnicas cirúrgicas. O tempo de cirurgia e anestesia foi maior no GM, já o tempo de recuperação foi... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: The aim of this study was to evaluate the applicability and feasibility of percutaneous pre-tied miniligature (miniloop) for ovarian vasculature hemostasis in laparoscopic ovariectomy in queens. It was compared to open minimally invasive technique on post-operative pain and inflammation. It was used 20 cats, female, health, distributed in two groups, each one containing 10 animals. On control group (GC) the surgery was performed by laparotomy with Snook hook aid and ovarian vasculature ligation using polidiaxianone, 2-0. On Miniloop Group (GM) was performed videolaparoscopy with two-portal access and percutaneous miniloop with same surgical wire. During the surgery, cardiac frequency (FC) and breath frequency (FR), etCO2 and temperature were monitored with multiparameter monitor. It was performed pain evaluation by subjective scales at preoperative, 1, 6, 24 and 48 hours after anestesic recuperation. Blood was taken in jugular to measure APPs and leucogram at preoperative, 1, 24, 48, 72 hours and 10 days after anesthetic return, to determine inflammation and compare two techniques. Duration of anesthesia and surgery was longer on GM, but recuperation time was similar in two groups. FR and etCO2 were taller on GM, except at incision moment, although FC and temperature were taller on GC during all surgery. No difference between groups or moments was observed in pain evaluation. Segmented neutrophil were similar at all times on GC, but on GM had a pic at 48 and 72 hours. To APP... (Complete abstract click electronic access below)
Mestre
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Pregernig, Gabriela. "Determinants of GATA1-mediated gene regulation during erythroid maturation." Thesis, Massachusetts Institute of Technology, 2017. http://hdl.handle.net/1721.1/112505.
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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biological Engineering, 2017.Cataloged from PDF version of thesis.
Includes bibliographical references (pages 151-171).
Hematopoiesis has long been used as a model system to study development and lineage decision-making. Within this branch of development, erythropoiesis is the process through which mature red blood cells arise from progenitor cells. In this context, GATA1 is widely considered to be the master transcription factor for erythropoiesis, controlling the expression of a vast majority of the genes involved in red blood cell maturation. GATA1 dysfunction has been shown to cause several human disorders, including anemias and thalassemias, and has been linked to the onset of various types of leukemia. GATA1 has been shown to function as both a gene activator and repressor, posing the question of how it distinguishes between various categories of genes and regulates them. In this thesis, we apply a combination of systems and molecular biology approaches in order to gain a better understanding of various regulatory mechanisms centered around GATA1. In the main study of this thesis, we uncover a new physical interaction between GATA1 and the cohesin complex, which has previously been involved in establishing three-dimensional chromatin architecture in the nucleus. We collected chromatin interaction data in a murine cell line model for erythropoiesis, and identified tens of thousands of DNA looping events in both progenitor and differentiated cells. Integration of these chromatin interaction maps with gene expression and transcription factor occupancy datasets revealed new principles underlying gene regulation, and suggests that GATA1 plays a major role in orchestrating the 3D organization of the differentiating erythroid cell. In a second study, we identify a new feedback mechanism which facilitates the replacement of GATA2, a transcription factor expressed at earlier stages of hematopoiesis, by GATA1. We show that Fbw7, an ubiquitin ligase protein trans-activated by GATA1, targets GATA2 for proteosomal degradation, thus reducing its halflife and leading to more efficient GATA factor switching. Finally, in a last section, we characterize the GATA1 -interacting transcription factors zfp281 and zfp148, and show that they play functionally redundant roles in erythroid development. Altogether, this thesis presents new insights into GATA1 various aspects of GATA1 biology, which will contribute to our understanding of mechanisms of gene regulation.
by Gabriela Pregernig.
Ph. D.
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Zaidan, Nada Mousa O. "The role of Gata3 in blood stem cell emergence." Thesis, University of Cambridge, 2018. https://www.repository.cam.ac.uk/handle/1810/274544.
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The first definitive haematopoietic stem cells (HSCs) produced during embryonic development are generated from a specialised subset of endothelial cells known as haemogenic endothelium. Recently, it was reported that Gata3 plays a dual role in the development of sympathetic nervous system and haematopoietic system. In fact, Gata3 has proven to be crucial for the production of HSCs through regulation of catecholamine production from the co-developing sympathetic nervous system. Also, it was recently shown that Gata3 is expressed in the haemogenic endothelium and haematopoietic progenitor cells. Here, I will specifically examine the role of Gata3 in the production of HSCs; if it is expressed and plays a role in the precursors from which HSCs arise. Using a Gata3-GFP reporter mouse line, we found that Gata3 is expressed in various cell types in the HSCs microenvironment, including mesenchymal cells, endothelial cells, haematopoietic cells and sympathetic nervous system, and this expression was stage dependant. In the endothelial cells, we have found that the haemogenic endothelium activity is enriched in Gata3 expressing cells. Within the haematopoietic cells, we have found that Gata3 marks a specific stage along the developmental pathway towards the generation of definitive haematopoietic stem cells, and that Gata3 expressing haematopoietic cells are enriched for the most immature and stem cell like progenitors. Moreover, Gata3 will be specifically knocked out in haemogenic endothelial cells to determine whether it plays an essential role in the production of HSCs from the endothelium using the Vec-Cre system. We found that Gata3 within the haemogenic endothelium plays a major role in haematopoietic progenitors formation, and possibly haematopoietic stem cell formation. Finally, we used molecular assay (RNA seq) to identify the role of Gata3 in the haematopoietic stem cell microenvironment and found that Gata3 plays a major role in the development and differentiation of various cells and systems, and implicated Gata3 as cell cycle regulator. In summary, we found that Gata3 expressing cells is enriched for haemogenic endothelium, crucial for the haematopoietic progenitors formation, plays and important role in endothelial to haematopoietic transition, and plays a key developmental role in both haematopoietic stem cell and its microenvironment.
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Theodoridou, Elisabeth, and Marina Mikuljan. "Gatan som aldrig sover - gatuprostitutionen på Agneslundsvägen i Malmö." Thesis, Malmö universitet, Fakulteten för hälsa och samhälle (HS), 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:mau:diva-25386.
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Gatuprostitution är ett komplext fenomen och för övrigt väldigt känsligt attundersöka. Följande arbete sker i samarbete med Polisen i Malmö och syftar tillatt beskriva området Sorgenfri i Malmö. Studien kommer inrikta sig påAgneslundsvägen och dess fysiska konstruktion som har förutsatt attgatuprostitutionen har kunnat etableras på gatan. Dessutom redogör studien för deattribut som ofta återfinns på geografiska platser där det förekommergatuprostitution. Vidare omnämner uppsatsen de förändringar ochombyggnationer som bidragit till att gatuprostitutionen i Malmö under åren harförflyttats från diverse gator i området Sorgenfri. Metoden som använts kanbeskrivas som en litteraturstudie som kompletterats med intervjuer samt enobservation. I dagsläget är gatuprostitutionen mest aktiv på Agneslundsvägen,men då området är ett utvecklingsprojekt för Malmö stad påvisar uppsatsensresultat att det utifrån tidigare historik och forskning kan antas att den återigenkommer att förflyttas. Agneslundsvägen lär få en mer naturlig rörelse avmänniskor och trafik, något som är väldigt missgynnande för gatuprostitution.Street prostitution is a complex phenomenon and, moreover, very sensitive toinvestigate. The following work is done in cooperation with the Police in Malmöand aims to describe the area named Sorgenfri in Malmö. The study will focus onAgneslundsvägen and its physical structure, which has given street prostitutionthe prerequisites to establish on the street. In addition, the work describes theattributes that are often found in geographic locations where street prostitutionoccurs. Furthermore, the paper mentions the changes and rebuildings that havecontributed to the fact that the street prostitution in Malmö over the years hasbeen moved from various streets in the Sorgenfri area. The method used can bedescribed as a literature study complemented with interviews and an observation.As things stands, street prostitution is most active on Agneslundsvägen, but as thearea is a development project for Malmö city the essay's findings show that, basedon previous history and research, it can be assumed that it will again be moved.Agneslundsvägen will get a more natural movement of people and traffic,something that is very disadvantageous for street prostitution.