Дисертації з теми "RXRs"
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Marceau, Geoffroy. "Facteurs de transcription nucléaires (RARs, RXRs, LXRs) et membranes amniotiques : métabolisme des rétinoïdes et stratégies d'identification de nouveaux gènes cibles des rétinoïdes." Clermont-Ferrand 1, 2007. http://www.theses.fr/2007CLF1MM01.
Повний текст джерелаQuintas, Ameixa Maria Clara. "Regulation of RXRa gene expression in embryonic cells." Thesis, University College London (University of London), 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.391704.
Повний текст джерелаGuzmán, Alerie. "RXR signalling in oligodendrocyte lineage cells." Thesis, University of Cambridge, 2015. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708611.
Повний текст джерелаDi, Canio Ludovica. "Regulation of oligodendrocyte lineage cell function by the RXRγ nuclear receptor". Thesis, University of Cambridge, 2019. https://www.repository.cam.ac.uk/handle/1810/289129.
Повний текст джерелаKrezel, Wojciech. "Fonction du recepteur nucleaire rxr chez la souris." Université Louis Pasteur (Strasbourg) (1971-2008), 1997. http://www.theses.fr/1997STR13090.
Повний текст джерелаHalftermeyer, Juliane. "Rôle de RXR sur la transformation par PML-RARα". Paris 7, 2011. http://www.theses.fr/2011PA077194.
Повний текст джерелаAcute promyelocytic leukemia (APL) is induced in 99% of cases by a translocation t(15-17) leading to the PML-RARa fusion oncoprotein. PML-RARa acts as a transcriptional repressor, thus inducing a characteristic differentiation block of myeloid cells. In vivo, PML-RARa is always found in association with the nuclear receptor RXR (Retinoid X Receptor). Actually, RXR is an essential protein for PML-RARa driven transformation. During my thesis, I developed in vivo and ex vivo models to study the functional role of RXR in APL, both models using conditional excision of RXR in RXRaf/f, RXRbf/f, RXRg-/- mice and the Cre-ERT2/Lox System inducible by 4-OHT. In primary bone marrow cells transformed with PML-RARa, excision of RXRs induces a dramatic loss of clonogenicity and growth arrest ex vivo. I also constructed a transgenic model of PML-RARa mice, with RXRaf/f, RXRbf/f, RXRg-/-. After introduction of a constitutively active FLT3 and Cre-ERT2,1 obtained a murine APL in which I was able to excise RXRs. In vivo, loss of RXRs results in a prolongation of mice survival and elicits full differentiation of leukemic cells, similar to that induced by treatment with retinoic acid (RA), but does not degrade PML-RARa. RA treatment was previously thought to activate transcription of target genes and thus promote differentiation by converting PML-RARa from a repressor to an activator protein. However, my results support an other model in which treatment-induced differentiation is promoted by the mere derepression of PML-RARa target genes. Further studies are needed to evaluate the DNA binding of PML-RARa in presence or absence of RXR in order to verify this hypothesis
Ma, Xingjie. "Identification d'un nouveau régulateur et d'une nouvelle fonction de la sénescence cellulaire." Thesis, Lyon, 2018. http://www.theses.fr/2018LYSE1138.
Повний текст джерелаCellular senescence is a stable proliferation arrest accompanied with senescence-associated secretory phenotype (SASP). Senescence is induced by diverse stimuli such as telomere shortening and oncogene activation and plays key roles in many physiopathological contexts like embryonic development, cancer and aging. However the molecular mechanisms regulating senescence remain partially understood. Our laboratory recently identified a new senescence regulator: the inositol 1,4,5-trisphosphate receptor type 2 (ITPR2), an ER calcium release channel. ITPR2 is repressed in many cancers, but its transcriptional regulation is barely known. Therefore, the first aim of my thesis was to characterize new ITPR2 regulators. Through siRNA screen and Nanostring analysis, we identified the nuclear receptor RXRA as a transcriptional repressor of ITPR2. We found that in primary human fibroblasts, RXRA knockdown induces ITPR2 expression and thereby calcium signaling, reactive oxygen species (ROS) production, DNA damage and ultimately senescence through p53-p21 axis. Conversely, RXRA overexpression delays replicative senescence. SASP has been described to induce/reinforce senescence, and most of the SASP factors are able to regulate calcium signaling through their receptors. The second aim of my thesis was to investigate the role of the SASP and the participation of calcium signaling in it. We observed that the SASP induces senescence accompanied with a neuroendocrine differentiation (NED) in some breast cancer cells. Interestingly, SASP triggers calcium accumulation in the cytoplasm which seems to be involved in the regulation of NED. We then analyzed human breast tumor datasets and observed that NED-positive samples display some senescence marks: functional p53, low proliferation level and Sprouty 2 expression. Altogether, my work identified RXRA as a new senescence regulator and showed calcium signaling is involved in SASP-induced NED in breast cancer cells
Dias, Sandra Martha Gomes. "Estudos estruturais dos receptores nucleares humanos para os hormônios tireoidianos Isoforma ß1 (hTRß1) e para o ácido retinóico 9-cis Isoforma a (hRXRa)." Universidade de São Paulo, 2004. http://www.teses.usp.br/teses/disponiveis/76/76132/tde-21092007-141432/.
Повний текст джерелаIn eukaryotes, nuclear receptors are of major importance for intercellular signaling because they join different intra and extracellular signals during regulation of genetic programs. The great majority of these proteins function as ligand activated transcription factors providing a direct link between signaling molecules and the transcriptional responses elicited by them. The genetic programs that these receptors establish or modify affect virtually all aspects of the multicellular organisms? life, such as embryogenesis, homeostasis, reproduction, cell growth, and death. Their gene-regulatory power and selectivity has prompted intense research which is now starting to decipher the complex network of molecular events involved in transcription regulation. The future challenge will be to uncover the molecular rules that define spatial and temporal control of gene expression. Such knowledge would be essential to the development of more efficient drugs with better therapeutic values. Therefore, the main purpose in this study was to extend the understanding on the behavior and the structure of human thyroid receptor, isoform ?1 (hTRβ1), and human retinoic acid X receptor, isoform ? (hRXRα). It was applied the small angle X-ray scattering technique to determine, in solution, the envelop of both receptors containing DNA and ligand binding domains. Beside this, several crystallization conditions were tried for both receptors. The results made possible to define the spatial localization of the domains and the quaternary structure of the homodimers and homotetramers. Consequently, we were able to propose the first structural models for nuclear receptors containing the DNA and ligand binding domains. The oligomeric behavior of the hTRβ1, in solution, was also analyzed qualitatively. We verified that it was influenced by the presence of T3 hormone, the protein concentration, the presence of both DNA and ligand binding domains, and by specific mutations. Based on these results, we were able to hypothesize that the hTRβ1 has the capacity of autorepression. Up to now, only the hRXRα, in the whole nuclear receptor superfamily, had been described to behave similarly. Finally, we crystallized the ligand binding domain of the hTRβ1 in the presence of the ligands T3, Triac, and GC-1. The objective was to solve crystallographic structures essential for the future development of tiromimetics with isoform-selective action.
Alsudais, Hamood. "Activation of the Retinoid X Receptor Augments the Expression of Akt2 to Enhance Myogenic Differentiation." Thesis, Université d'Ottawa / University of Ottawa, 2015. http://hdl.handle.net/10393/33395.
Повний текст джерелаDelman, Emily. "Effects of Synthetic Ligands onHeterodimer Pairs Regarding Full-Length Human PPARa, RXRa and LXRa." Wright State University / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=wright1472204976.
Повний текст джерелаCastaneda, Saucedo Eduardo. "Role of the retinoid X receptor α (RXRα) and its heterodimetric partners during skin carcinogenesis". Université Louis Pasteur (Strasbourg) (1971-2008), 2004. https://publication-theses.unistra.fr/public/theses_doctorat/2004/CASTANEDA_SAUCEDO_Eduardo_2004.pdf.
Повний текст джерелаFinney, Emily Q. "Using Radio Relics to Constrain the Dynamics of 1 RXS J0603.3+4214." Scholarship @ Claremont, 2014. http://scholarship.claremont.edu/scripps_theses/321.
Повний текст джерелаKovalevich, Jane. "Cocaine-Mediated Disruption of RXR-gamma Signaling: The Role of TNF-alpha." Diss., Temple University Libraries, 2014. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/242911.
Повний текст джерелаPh.D.
Cocaine abuse poses a substantial health and economic burden for which no effective treatment currently exists. Exposure to cocaine results in altered signaling in a number of central nervous system (CNS) pathways. Previous studies have primarily focused on neurotransmitter systems, such as the dopaminergic and glutamatergic systems, as well as on drug-induced neuroplasticity within the mesolimbic system, which is believed to contribute to reward, addiction, and relapse following withdrawal. Furthermore, cocaine exerts a number of effects on gene regulation that contribute to many pathological conditions commonly afflicting users such as mood disturbances, psychotic symptoms, and long-term cognitive dysfunction. While some mechanisms by which cocaine regulates gene expression have been well-characterized, a large gap in our understanding regarding its downstream actions still exists and must be elucidated in order to develop effective treatment strategies. One pathway we have discovered to be disrupted in an animal model of chronic cocaine abuse is the retinoid X receptor (RXR) signaling pathway. Retinoid X receptors serve as obligate heterodimer partners for a number of nuclear receptor transcription factors, including the thyroid hormone receptor (TR), retinoic acid receptor, vitamin D receptor, and peroxisome proliferator activated receptor. Heterodimeric complexes bind to specific recognition sequences in or around the promoter of target genes to activate, or in some cases, repress, transcriptional activity. Therefore, alterations in the levels and function of RXRs can potentially disrupt numerous signaling cascades. In this context, we observed a significant down-regulation in mRNA and protein levels of RXR-y, an isoform predominantly expressed in the CNS that is involved in dopaminergic signaling, in brains of cocaine-administered mice. Additionally, we observed significantly decreased levels of the neuroplasticity protein, neurogranin, which is regulated transcriptionally by TR/RXR heterodimers. Mechanisms underlying regulation of RXR levels in cells of the CNS are vastly unexplored. Studies in other organ systems, including liver and cardiac systems, demonstrate pro-inflammatory cytokines and cellular stress pathways exert repressive effects on RXR signaling, although these studies solely investigated regulation of the RXR-a isoform. Recently, studies have highlighted the role of the immune system during chronic drug abuse, and demonstrate that significant amounts of proinflammatory factors are produced in the brains of chronic cocaine abusers. Therefore, we hypothesized that cocaine-mediated induction of inflammatory cytokines, such as tumor necrosis factor (TNF)-a may contribute to decreased RXR-y expression within the CNS. Utilizing in vitro neuronal systems, we have demonstrated that cocaine exposure induces neuronal expression of TNF-a and that this contributes to decreased levels of RXR-y, as inhibition of TNF-a or its downstream effector c-Jun-NH2-terminal kinase (JNK) prevents cocaine-mediated reductions in RXR-y protein levels. Furthermore, treatment of neurons with TNF-a alone mimics the effects on RXR-y levels observed in cocaine-treated cells. Additionally, we show that proteasome-dependent protein degradation likely plays a role, as inhibition of the 26 S proteasome with Bortezomib during cocaine or TNF-a exposure blocks the down-regulation of RXR-y levels. Degradation of RXR-y in response to cocaine and TNF-a may involve nuclear export, as our results show an increased level of RXR-y in the cytoplasmic compartment shortly after treatment, and inhibiting nuclear export during treatment with Leptomycin B prevents decreases in whole cell protein levels of RXR-y. In addition to the effects of chronic cocaine abuse on neurons, other CNS cell types such as oligodendrocytes may be negatively impacted by exposure to cocaine. Imaging studies and post-mortem microarray data from human cocaine abuse patients reveal loss of myelin and down-regulated expression of myelin-related genes in the nucleus accumbens and frontal cortex. Altered myelin integrity likely contributes to cognitive deficits that present in many chronic cocaine abuse patients and may also exacerbate damage to neurons. However, limited investigation has been performed to evaluate the effects of cocaine on oligodendrocyte health and function. We have employed an in vivo murine model of chronic cocaine administration to evaluate the impact of cocaine on white matter protein levels. Our data reveal that cocaine induces a significant decrease in white matter protein levels, even following an extended period of withdrawal, in the nucleus accumbens. One potential mechanism for cocaine-mediated white matter damage involves perturbations of glutamate homeostasis, as glutamatergic signaling can induce excitotoxicity in CNS cells, including oligodendrocytes. In this context, we found that administration of the B-lactam antibiotic, ceftriaxone, during cocaine withdrawal ameliorates loss of white matter proteins. Ceftriaxone has previously been shown to upregulate expression and activity of the glial glutamate transporter GLT-1, lending support to the theory that cocaine-mediated myelin loss may be due, in part, to disruption of glutamatergic signaling. Ceftriaxone treatment also decreased expression of cleaved caspase-3, a pro-apoptotic signaling molecule activated during excitotoxic cell death, in cocaine-administered mice. Taken together, our studies characterize two novel consequences of cocaine exposure: (1) decreased neuronal RXR-y expression and down-regulation of RXR-target genes, such as neurogranin, and (2) loss of myelin proteins in the nucleus accumbens which can be attenuated by administration of ceftriaxone. These findings yield insight into mechanisms underlying cocaine-mediated CNS cell death, and highlight potential treatment avenues for restoring brain health. Additionally, as inflammatory processes were identified as key mediators in some of these observations, our findings likely extend to a number of neurodegenerative diseases which are characterized by a neuroinflammatory component.
Temple University--Theses
Podlesny-Drabiniok, Anna. "Role of RXR signaling in control of neuroinflammation : relevance for research into depression." Thesis, Strasbourg, 2018. http://www.theses.fr/2018STRAJ042.
Повний текст джерелаDepression is severe mental disorder that is a second leading contributor to diseases burden. Recently, retinoid X receptor signaling and chronic inflammation have been identified as genetic and environmental factors. However, a cross-talk between these two factors was poorly understood. During my PhD I have studied how retinoid X receptor gamma (RXRg) controls neuroinflammation in two pre-clinical models of depression. I have shown that RXRg controls age-specific signal that drives microglial senescence and hypoactivity. The latter, impacts also microglial phagocytosis and contribute to neuronal hypertrophy in the striatum that previously was associated with depressive symptoms. Additionally, I showed antidepressant activity and cellular mechanism of rexinoids and fibrates in chronic social defeat stress. Obtained data have strong therapeutic potential that may allow for development of new antidepressant therapies
Бондар, О. В. "Розробка клієнтського застосування веб-програми «дозвіл» з використанням підходів реверс-інженерінгу". Thesis, Чернігів, 2020. http://ir.stu.cn.ua/123456789/23436.
Повний текст джерелаОб'єктом розробки дипломної роботи є веб-клієнт для клієнт-серверного застосунку «Дозвіл», мета якого – облік екологічних дозволів. Клієнт був розроблений за допомогою програмного каркасу Angular, який може бути запущений на будь якій ОС з підтримкою Node.js. Angular – це легкий і багатофункціональний інструмент для створення клієнтських і односторінкових застосунків з підтримкою двохстороннього зв’язування. Метою розробки було створення зручного веб-клієнта для запису, організації, збору, групування і опрацьовування екологічних дозволів на викиди шкідливих речовин для підприємств. Основним методом проектування було обране структурне моделювання із використанням UML-діaгрaм. В ході виконання кваліфікаційної роботи був реалізований веб-клієнт, який взаємодіє з REST-сервером по HTTP протоколу. Для реалізації веб-клієнту системи обліку «Дозвіл» були використані технології Angular 9, RxJS 6.5.4, CORS 2.8.5, Bootstrap 4.4.1, а також редактор Visual Studio Code 1.45. Для розгортання веб-клієнту даного застосунку необхідно Node.js версії 13.13 або вище, та Angular CLI 9.1.2. Подальша розробка веб-клієнту «Дозвіл» можлива в сторону покращення механізму авторизації, автентифікації та отримання даних з API-серверу, підвищення зручності користування і удосконалення автоматизації введення даних.
The object of development is the web client for client-server application “Dozvil”, the purpose of which is accounting for environmental permits for enterprises. The client was developed on Angular framework and can be run on any machine which supports Node.js. The Angular is easy and multifunctional tool for creating client and one-page applications with two-way data binding. The purpose of the development was to create a ready-made comfortable client of system for recording, keeping, collecting, organizing, grouping and processing environmental permissions for enterprises. The main design method was structural modeling with using the UML diagrams. During performance of the qualification work was realized web client which communicates with REST-server over HTTP protocol. To implement the web client "Dozvil" were used technologies Angular 9, RxJS 6.5.4, CORS 2.8.5, Bootstrap 4.4.1, together with streamlined code editor Visual Studio Code 1.45. To deploy the web-client of this application are required Node.js 13.13 or higher and Angular CLI 9.1.2. Further development of the web-client "Dozvil" is possible in the direction of improving of authorization and authentication process, increasing convenience of using and improvement automatization of a data entry.
Hennuyer, Nathalie. "Recepteurs nucleaires et metabolisme lipidique : effets des ppar et de rxr (doctorat : sciences pharmaceutiques)." Lille 2, 1999. http://www.theses.fr/1999LIL2P006.
Повний текст джерелаMASCREZ, BENEDICTE. "Etude des fonctions activatrices af 1 et af 2 de rxr chez la souris." Université Louis Pasteur (Strasbourg) (1971-2008), 1998. http://www.theses.fr/1998STR13247.
Повний текст джерелаChiang, Ming-Yi. "Reverse genetic analysis of nuclear receptors, RXR[gamma], RAR[beta] and Tlx in mice /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 1997. http://wwwlib.umi.com/cr/ucsd/fullcit?p9814539.
Повний текст джерелаGirardi, Carolina Saibro. "Papéis das isoformas de RXR na diferenciação neuronal mediada pelo ácido retinoico em SH-SY5Y." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2018. http://hdl.handle.net/10183/187266.
Повний текст джерелаDeveloping and optimizing therapies aiming at restoring neuronal function depend on better understanding the molecular mechanisms behind differentiation of neurogenic cells into mature neurons. Retinoic acid (RA) promotes neuronal differentiation in multiple cell types through gene reprogramming and cytosolic signaling pathways. The nuclear RXR receptors are main molecular mediators of RA cellular effects. However, little is known about specific roles of distinct RXR isoforms in neuronal differentiation. In view of this, the RA-mediated differentiation of SH-SY5Y neuroblastoma cell line was investigated. Analysis of RA-induced parameters in SH-SY5Y cells showed cell cycle arrest and adoption of neuronal hallmarks. The expression profiles of RXR isoforms detected in SH-SY5Y cells, RXRα e RXRβ, were found varyingly modulated along neuronal differentiation both at transcript and protein levels. Finally, transitory silencing of RXRα and RXRβ single isoforms during the first stages of RA-mediated differentiation distinctly affected cellular phenomena induced by RA: whereas RXRα is required for genomic and non-genomic effects during differentiation, RXRβ negatively regulate neurite extension in SH-SY5Y cells. Results thus indicate distinct functions for RXR isoforms during the first stages of RA-dependent neuronal differentiation of neuroblastoma, and reveal new perspectives for studying RXRs as molecular targets in neuronal replacement therapies.
Lalloyer, Fanny. "Facteurs de risque de l'athérosclérose : modulation et régulation par les récepteurs nucléaires PPARα et RXR". Lille 2, 2006. http://www.theses.fr/2006LIL2S028.
Повний текст джерелаMetabolic syndrome associates a set of symptoms predisposing to the development of atherosclerosis such as dyslipoproteinemia, glucose intolerance, decreased insulin sensitivity, high blood pressure and overweight. Many studies have demonstrated the physiopathological implication of the nuclear receptors in the modulation of some of these metabolic abnormalities particularly associated with dysregulated expressions of target genes implicated in lipoprotein and glucose metabolism. Our work has focused more particularly on two nuclear recpetors, PPARα and RXR, and their implication in insulin resistance and dyslipoproteinemias. First, we investigated the role of PPARα in glucose metabolism and insulin resistance. Therefore, we used leptin-deficient mice (ob/ob) (model of insulin resistance and obesity) which were deficient or not in PPARα and showed an essential and beneficial role of PPARα in the adaptative response of pancreas to insulin resistance. Secondly, we aimed to analyse the implication of PPARα in dyslipidemia and atherosclerosis by studying the effect of a lack of PPARα in a murine model of dyslipidemia and atherosclerosis, the human apolipoprotein E2-knock-in (apoE2-KI) mouse. We demonstrated that PPARα itself does not influence atherosclerosis progression under high fat diet but is necessary to mediate the atheroprotective effect of fenofibrate, a hypolipidemic drug widely used in humans. Finally, by using the model of apoE2-KI mice, we confirmed and precised the atheroprotective effect of rexinoids. We used LG1069 (Bexarotene*, Targretin*), RXR agonist widely used in clinical practice as an antitumoral agent. Despite the induction of hypertriglyceridemia which we demonstrated to be LXR-dependent, LG1069 protects against lesion development, in part by decreasing intestinal cholesterol absorption. To conclude, thanks to the use of suitable murine models, our studies have shown a beneficial implication of the nuclear receptors PPARα and RXR in insulin resistance and dyslipidemias, two risks factors predisposing to atherosclerosis
Salek, Pawel. "Wave packet theory of resonant X-ray scattering." Doctoral thesis, KTH, Bioteknologi, 2001. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-3188.
Повний текст джерелаJuntunen, K. (Kari). "Functional and structural characterization of nuclear vitamin D receptor and its ligand binding domain." Doctoral thesis, University of Oulu, 2002. http://urn.fi/urn:isbn:9514268784.
Повний текст джерелаKanda, Hiroshi. "A nuclear complex containing PPARα/RXRα is markedly downregulated in the hypertrophied rat left ventricular myocardium with normal systolic function". Kyoto University, 2001. http://hdl.handle.net/2433/150585.
Повний текст джерелаStonehouse, Timothy James. "Analysis of the role of RXR in monocyte-macrophage differentiation and function using U937 monoblastoid cells." Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.321988.
Повний текст джерелаFlora, Gagan Deep. "Non-genomic effects of the Pregnane X Receptor (PXR) and Retinoid X Receptor (RXR) in platelets." Thesis, University of Reading, 2018. http://centaur.reading.ac.uk/80709/.
Повний текст джерелаGrave, Nathália. "Influência de polimorfismos em genes da rota da vitamina D em parâmetros antropométricos e bioquímicos." reponame:Repositório Institucional da UNIVATES, 2015. http://hdl.handle.net/10737/1079.
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Introdução: Muitos estudos tem relacionado a deficiência de vitamina D com o risco para as doenças crônicas, principalmente obesidade e dislipidemia. A vitamina D age através da ligação ao receptor de vitamina D (VDR), o qual forma heterodímeros com o receptor do retinoide X gama (RXRG). O gene GC codifica a proteína de ligação da vitamina D (DBP), a qual é responsável pelo transporte da vitamina D na corrente sanguínea. Considerando que a genética desempenha um papel importante na etiologia destas doenças, poucos estudos analisam a associação de variantes em genes da rota da vitamina D com parâmetros antropométricos e bioquímicos relacionados a estes desfechos. Objetivo: Investigar a associação entre polimorfismos de genes relacionados à rota da vitamina D, rs2228570 (gene VDR), rs2134095 (gene RXRG), rs7041 (gene GC), e parâmetros antropométricos e bioquímicos em uma amostra de adultos. Métodos: Medidas antropométricas e bioquímicas foram avaliadas em 542 indivíduos adultos de ambos os gêneros em uma amostra de base populacional. O DNA genômico foi extraído a partir de amostra de sangue e os polimorfismos foram genotipados pela reação em cadeia da polimerase (PCR) através de discriminação alélica TaqMan (Applied Biosystems, Foster City, CA). As comparações dos desfechos entre os genótipos foram feitas usando ANOVA, Kruskal-Wallis, qui-quadrado de Pearson ou teste exato de Fisher, e as interações gene-gene foram avaliadas usando modelo linear geral. Resultados: Não identificamos nenhum efeito principal dos polimorfismos nos parâmetros avaliados. No entanto, ao analisarmos as interações gene-gene, detectamos uma interação significativa entre os genes RXRG e GC sobre os níveis de colesterol LDL. Conclusões: Nossos achados evidenciaram uma interação significativa entre polimorfismos de dois genes da rota da vitamina D, rs2134095 (RXRG) e rs7041 (GC) sobre os níveis de colesterol LDL, corroborando os achados da literatura que tem consistentemente relacionado a vitamina D com o perfil lipídico.
Introduction: Many studies have related vitamin D deficiency with the risk for chronic diseases, especially obesity and dyslipidemia. Vitamin D acts by binding to the vitamin D receptor (VDR), which form heterodimers with the retinoid X receptor gamma (RXRG). The GC gene encoding the binding protein Vitamin D (BPD), which is responsible for the vitamin D transport in the bloodstream. Considering that genetics play a significant role in the etiology of these diseases, few studies have analyzed the association of variants in genes of vitamin D route anthropometric and biochemical parameters related to these outcomes. Objective: To investigate the association between gene polymorphisms related to vitamin D route, rs2228570 (VDR gene), rs2134095 (RXRG gene), rs7041 (GC gene), and anthropometric and biochemical parameters in a sample of adults. Methods: anthropometric and biochemical measures were assessed in 542 adults of both genders in a population-based sample. Genomic DNA was extracted from blood sample and polymorphisms were genotyped by polymerase chain reaction (PCR) using the TaqMan allelic discrimination (Applied Biosystems, Foster City, CA). Comparisons of outcomes between genotypes were performed using ANOVA, Kruskal-Wallis test, chi-square test or Fisher's exact test, and gene-gene interactions were assessed using general linear model. Results: We have not identified any major effect of polymorphisms in the evaluated parameters. However, when we analyze the gene-gene interactions, we detected a significant interaction between RXRG and GC genes on LDL cholesterol levels. Conclusions: Our findings showed a significant interaction between polymorphisms in two genes of vitamin D route, rs2134095 (RXRG) and rs7041 (GC) on the levels of LDL cholesterol, corroborating literature findings that have consistently related to vitamin D with the profile lipid.
Бондар, О. В. "Розробка інформаційної системи клієнт-сервер для організації робочої комунікації". Thesis, Чернігів, 2021. http://ir.stu.cn.ua/123456789/24991.
Повний текст джерелаОб’єктом розробки кваліфікаційної роботи є клієнт-серверна система для організації робочої комунікації. Серверна частина системи була розроблена з використанням програмної платформи ExpressJS, а в основі веб- клієнта лежить фреймворк Angular, що дозволяє компонентам системи бути запущеними на будь якій операційній системі. Метою розробки було створення системи, яка дозволить працівникам розділяти кожну ітерацію унікалього запиту клієнта на окрему задачу для обговорення та подальшого вирішення. Для проектування був обраний методом структурного моделювання із використанням діаграм UML. В ході виконання кваліфікаційної роботи було розроблено серверну частину, використовуючи середовище виконання Node.js, фреймворк ExpressJS та базу даних MуSQL та клієнтську, на основі програмної платформи Angular та бібліотеки RxJS. Сервер надає АРІ, та взаємодіє з клієнтом за допомогою HTTP протоколу. Для реалізації системи були використані такі технології, як база даних MySQL 8.0, Angular 12, RxJS 7.4.0, NodeJS та ExpressJS 4.17. Для розгортки сервера необхідно Node.js 14.0 або вище та MySQL 8.0, для клієнта достатньо будь якого веб-сервера. Подальше покращення системи можливе в сторону розширення АРІ, додавання нотифікацій та чатів на основі вебсокетів, покращення користувацкього інтерфейсу та досвіду.
The object of development in this qualification work is a client-server system for the organization of work communication. The server part was developed based on ExpressJS framework, and the web client is based on the framework Angular, which allows the components of the system to be launched on any OS. The purpose of the development was to create a system that would allow employees to divide each iteration of a unique customer request into a separate task for discussion and further solution. Method of structural modeling using UML diagrams was chosen for the design. While performing the qualification work, the server part was developed using the Node.js runtime environment, the ExpressJS framework and the MySQL database, based on the Angular software platform and the RxJS library. The server provides APIs and communicates with the client using the HTTP protocol. Technologies such as MySQL 8.0, Angular 12, RxJS 7.4.0, NodeJS and ExpressJS 4.17 were used to implement the system. Node.js 14.0 or higher and MySQL 8.0 are required to deploy the server, any web server is enough for the client. Further improvement of the system is possible by expanding API, adding notifications and chats based on web sockets, improving user interface (UI) and experience (UX).
Eberhardt, Jérôme. "Etude de la dynamique structurale du domaine de liaison au ligand de RXRα et implication de la phosphorylation dans la transcription". Thesis, Strasbourg, 2016. http://www.theses.fr/2016STRAJ118/document.
Повний текст джерелаMany studies reveal that the ligand binding domain of RXRα is very dynamic, still even in a presence of an agonist ligand. Therefore, the availability of experimental data (HDX, NMR and X-ray) on the domain was used as a leverage in order to set up a protocol, based on accelerated molecular dynamics, to explore its conformational dynamic and to validate it. This protocol was applied to understand the influence of the pSer260 phosphorylation, closed to the binding surface of coactivator proteins and implied in the hepatocellular carcinoma growth, on its structure and its dynamic. At the same time, a dimensional reduction method was developed to analyse long molecular dynamic trajectories. Thus, with this approach, we identified a couple of new alternative and stable conformations of the ligand binding domain of RXRα
ADAM, STITAH SYLVIE. "Phosphorylation des recepteurs des retinoides rar et rxr. Consequences sur la transcription, la differenciation et la proliferation." Université Louis Pasteur (Strasbourg) (1971-2008), 1999. http://www.theses.fr/1999STR13165.
Повний текст джерелаGhbeish, Nora Jamaleddin. "Analyzing nuclear receptor activation and repression : the role of ultraspiracle, the Drosophila RXR, in Drosophila eye development /." Diss., Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2001. http://wwwlib.umi.com/cr/ucsd/fullcit?p9993987.
Повний текст джерелаLeung, Kin-yue. "Involvement of NF-kB subunit p65 and retinoic acid receptors RARæ and RXRæ in the transcriptional regulation of the human GnRH II gene." Click to view the E-thesis via HKUTO, 2005. http://sunzi.lib.hku.hk/hkuto/record/B36367035.
Повний текст джерелаLeung, Kin-yue, and 梁建裕. "Involvement of NF-kB subunit p65 and retinoic acid receptors RARæ and RXRæ in the transcriptional regulation of the human GnRH II gene." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B36367035.
Повний текст джерелаGiovanelli, Martina. "Reactive programming: un caso di studio." Bachelor's thesis, Alma Mater Studiorum - Università di Bologna, 2016. http://amslaurea.unibo.it/10451/.
Повний текст джерелаBocanegra, Atoche Alessandra. "Detección y expresión de los receptores X retinoicos (RXR) en la mucosa yeyunal de crías de alpacas (Vicugna pacos)." Bachelor's thesis, Universidad Nacional Mayor de San Marcos, 2019. https://hdl.handle.net/20.500.12672/10964.
Повний текст джерелаTesis
Orlov, Igor. "Structural study of nuclear receptor RXR/VDR complex with its target DNA by cryo-electron microscopy and 3D reconstruction." Strasbourg, 2010. http://www.theses.fr/2010STRA6047.
Повний текст джерелаNuclear receptors are ligand-dependant transcription regulators that bind directly to the DNA in the promoter region of a target gene. Their regulation occurs through steroid hormones and vitamin A and D derivatives. Structural studies of different kinds of complexes of nuclear receptors with a DNA can provide a basis for the investigation of molecular mechanisms of the ligand-dependant transcription regulation by steroid hormones and vitamins. Until now, structural studies of nuclear receptors have focused mainly on their two individual core domains, the ligand-binding domain (LBD) and the DNA-binding domain (DBD). Here we present the architecture of the full nuclear receptor heterodimeric complex of the ligand-bound vitamin D receptor (VDR) and retinoid X receptor (RXR) bound to a consensus DNA response element forming a direct repeat (DR3). The structure of the RXR/VDR/DNA complex has been determined by single particle cryo-electron microscopy whilst overcoming technical challenges related to the 100kDa molecular weight of the object. The structure reveals an open conformation with the DBD and LBD parts connected through well-resolved hinges. The DBDs are bound side-on to the DNA partially facing the LBDs while keeping the area of transactivation helix H12 accessible for recruiting chromatin-modifying co-regulator proteins on the side oriented downstream of the DNA
Etter, Guillaume. "Role of retinoid X receptor gamma and dopamine receptor D2 in hippocampal and memory functions." Thesis, Strasbourg, 2013. http://www.theses.fr/2013STRAJ055.
Повний текст джерелаThe present thesis work is an attempt to understand the mechanisms of Rxrγ control of memory functions, as well as the potential involvement of dopaminergic signaling in these mecanisms. In this context, I focused my research on hippocampal functions at several distinct levels. The first part of my work (1) aimed at defining the hippocampal cell populations expressing Rxrγ using various histological techniques (immunohistochemistry, in situhybridization) in order to (2) study the electrophysiological functions of these cells using invitro patch-clamp.To identify the role of Rxrγ in the control of cell autonomous functions, as well as the consequences on the surrounding network, I have studied the effects of its loss of function in Rxrγ/mice.As the different subregions of the hippocampus are implicated indistinct aspects of learning and memory, and in particular the dentate gyrus being associated with pattern separation (Leutgeb et al., 2007), I have also tried to dissect the mnemonic processes that rely on Rxrγ activity by performing behavioral analyses of Rxrγ/mice. Considering the transcriptional activities of Rxrγ on Drd2, I have also (4) studied dopaminergic signaling in the hippocampus of wild type and Rxrγ null mutant mice. Finally, to demonstrate the neuroanatomical and homeostatic specificity of Rxrγ control on memory, I performed (5) specific inactivations of Rxrγ in hippocampi of conditional mutant mice that possessed floxed Rxrγ, using AAV vectors expressing recombinase Cre
Daury, Laetitia. "Etude de l'implication de c-jun dans la régulation de la différenciation des myoblastes aviaires par la T3." Montpellier, ENSA, 2001. http://www.theses.fr/2001ENSA0023.
Повний текст джерелаIn this study, we have studied the implication of c-Jun in the T3 myogenic pathway. We describe the occurence of a functional interaction involving c-Jun, c-ErbAal (T3Ral) and CMDl (avian MyoD) in proliferative quail myoblasts, preserving transcription of T3 target genes. We found also that RXRg expression abrogates this positive interaction. These data suggest that T3 target genes expression involves different interactions with the T3 nuclear receptor during proliferation (no RXR expression) and differentiation (induction of RXR expression). Ln addition, we observed that, independently of the hormone presence, c-ErbAal inhibits CMDl and Myogenin. Furthermore, this influence involves two basic sequences of the hinge domain of the T3 receptor, probably inducing a physical interaction with similar sequences occurring in the myogenic factor. We found also that coexpression of RXR and c-Jun abrogates this influence. All these data suggest that sequestration of CMDl in a c-Erb/c-Jun/CMDl complex suggested by our previous data could preserve the duration of myoblast proliferation. RXR expression, in association to the increase in c-Jun protein levels observed in this study, could restore CMDl activity at the induction of differentiation. This study brings also evidence that c-Jun/ATF2 cooperation is increased at cell confluence versus c-Jun/c-Fos or c-Jun/Fra2 cooperation. In addition, we found that whereas c-Jun/c-Fos and c-
Wallén, Åsa. "Some aspects of nuclear receptor function in the CNS : novel roles of Nurr1 and RXR in developing and mature neurons /." Stockholm, 2002.
Знайти повний текст джерелаEGEA, PASCAL. "Etudes structurales des recepteurs nucleaires des retinoides : rxr et rar par diffusion aux petits angles et cristallographie des rayons x." Université Louis Pasteur (Strasbourg) (1971-2008), 1999. http://www.theses.fr/1999STR13131.
Повний текст джерелаBrocard, Jacques. "Mutagenese somatique conditionnelle chez la souris et controle spatio-temporel de l'inactivation du gene codant le recepteur des retinoides rxr alpha." Université Louis Pasteur (Strasbourg) (1971-2008), 1998. http://www.theses.fr/1998STR13235.
Повний текст джерелаKhilji, Saadia. "Dissecting the Epigenetic Signaling Underlying Early Myogenic Differentiation." Thesis, Université d'Ottawa / University of Ottawa, 2021. http://hdl.handle.net/10393/42092.
Повний текст джерелаSavage, Julie C. "Nuclear Receptors License Phagocytosis in Mouse Models of Alzheimer's Disease." Case Western Reserve University School of Graduate Studies / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=case1430907654.
Повний текст джерелаHamed, Munerah. "Characterization of the Epigenetic Signature Underlying Early Myogenic Differentiation." Thesis, Université d'Ottawa / University of Ottawa, 2019. http://hdl.handle.net/10393/39559.
Повний текст джерелаDubuquoy, Laurent. "Rôle de l'hétérodimère récepteur activé par les proliférateurs de peroxysomes gamma (PPARγ) / récepteur X des rétinoi͏̈des (RXR) au cours de l'inflammation intestinale". Lille 2, 2002. http://www.theses.fr/2002LIL2MT14.
Повний текст джерелаThe peroxisome proliferator-activated receptor g (PPARg) is a nuclear receptor which is highly expressed in adipose tissue where it has a crucial role in adipogenesis. Recently, new sites of PPARg expression have been described especially in colon mucosa and new functions have been attributed in the regulation of inflammation. To activate transcription, PPARg requires heterodimerization with the retinoid X receptor (RXR). Proof of a role for the RXR/PPARg heterodimer in intestinal inflammation was limited to pharmacological studies demonstrating the efficacy of PPARg agonists. In a first study, we evaluated the involvement of both RXR and PPARg in intestinal inflammation. To this aim, colitis was induced by intra-rectal administration of trinitrobenzene sulfonic acid (TNBS) in mice. The intensity of colitis was evaluated in PPARg +/- and RXRa +/- mice and also after administration of selective RXR (rexinoid) and PPARg agonists. The intensity of colitis was evaluated by macroscopic and histologic scores and quantification of inflammatory mediators and the signaling pathway activation. Those experiments revealed that PPARg +/- and RXRa +/- mice both displayed an increased susceptibility to TNBS-induced colitis compared to WT mice. Colitis was significantly reduced by the administration of both PPARg and RXR agonists, reflected by increased survival rates and an improvement of the different biological parameters. When co-administered, a synergistic effect of PPARg and RXR ligands was observed. This first demonstration that RXR plays a role in intestinal homeostasis, as well as PPARg, opens a new field of investigation in a therapeutic point of view. Since PPARg is mainly expressed in the colon where bacteria are numerous, we hypothesized that intestinal flora and more particularly the major LPS receptor TLR-4 may modulate PPARg expression by colon epithelial cells. PPARg expression and gene were studied in patients with Crohn's disease (CD) and ulcerative colitis (UC), two inflammatory bowel diseases (IBD) resulting from an abnormal immune response against bacteria. Intestinal flora and TLR-4 induced PPARg expression in colon epithelial cells. While PPARg levels appeared normal in CD and controls, UC patients displayed an impaired expression of PPARg confined to colon epithelial cells without mutation in the PPARg gene. These data suggest that PPARg could be a new marker to diagnose UC and fueled speculations about the roles of this nuclear receptor in the physiopathology of UC
Blumentrath, Jörg. "Wirkung von RAR- und RXR-Agonisten (Retinoiden) und einem PPAR[gamma]-Agonisten (Rosiglitazon) auf die Insulinsekretion, Proliferation und GLUT2 von INS-1-Zellen /." [S.l.] : [s.n.], 1999. http://www.gbv.de/dms/bs/toc/305260308.pdf.
Повний текст джерелаLobato, Maria Inês Rodrigues. "Estudo de marcadores moleculares relacionados a cadeia dos retinóides (TTR e RXR[beta] e suas relações com endofenótipos clínicos e dismórficos em esquizofrenia)." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2004. http://hdl.handle.net/10183/5554.
Повний текст джерелаSolomin, Ludmila. "Nuclear hormone receptor signaling in the developing CNS : studies on the retinoid receptors RAR and RXR, and the orphan receptors NURR1, NOR1 and NGFI-B /." Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3663-3/.
Повний текст джерелаOuadah-Boussouf, Nafia. "Analyse in vivo de la dynamique du tissu adipeux blanc après exposition à des polluants chimiques ou à des molécules pharmacologiques chez le poisson zèbre." Thesis, Bordeaux 1, 2012. http://www.theses.fr/2012BOR14755/document.
Повний текст джерелаAn unbalanced diet and / or the presence of exogenous compounds contaminants mayalter endocrine signaling and lipid homeostasis and induce obesity. The work done in thisthesis have, at first, developed a simple and rapid method, called "zebrafish obesogenic (ZO)test" to identify in vivo by using the zebrafish larva, the factors that may increase or decreasethe size of the white adipocyte and therefore modulate the level of adiposity (Tingaud-Sequeira, Ouadah, Babin, J. Lipid Res. 52, 1765-1772, 2011). This test helps to identifycompounds and mixtures of obesogenic and anti-obesogenic molecules and providesinformation relevant to the risk assessment of their presence but also to elucidate themechanisms involved. Work in a second time allowed to answer as to how the action oftributyltin chloride, a powerful obesogenic contaminant found widely in the environment.This molecule acts in vivo on white adipocytes in a concentration of the order of nano molarvia nuclear receptors LXR and RXR, and not via the PPARgamma isoforms / delta (Ouadahand Babin, manuscript in preparation)
Beyer, Christine. "Der Einfluss von all-trans-Retinol, 13-cis-Retinsäure, Methanol und TSH unter verschiedenen Kulturbedingungen auf den 125I-Stoffwechsel von kultivierten Thyreozyten und deren RAR alpha- und RXR alpha- Rezeptoren." [S.l. : s.n.], 2004. http://www.bsz-bw.de/cgi-bin/xvms.cgi?SWB11312764.
Повний текст джерелаTaylor, Jennifer. "Engineering and improving a molecular switch system for gene therapy applications." Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/39501.
Повний текст джерела