Дисертації з теми "Negative regulators"
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Lively, Julie C. (Julie Christina) 1971. "Beta 3 integrins : negative regulators of angiogenesis." Thesis, Massachusetts Institute of Technology, 2002. http://hdl.handle.net/1721.1/8386.
Повний текст джерелаIncludes bibliographical references (leaves 199-219).
A method was developed to isolate and purify primary murine endothelial cells from lung tissue (MLEC). The cells generated by this method were characterized by immuno-fluorescence detection and FACS analysis and expressed specific antigens including PECAM-1, ICAM-1, ICAM-2, VCAM-1 and VE-cadherin. Using this method, cells from wild-type and beta 3-integrin-deficient animals were purified and used to determine the specificity of a novel potential anti-angiogenic drug. This study shows that tumstatin, a fragment of the alpha 3 chain of collagen IV, inhibits proliferation, inhibits total protein synthesis and specifically inhibits CAP-dependent protein synthesis in MLEC. These effects do not occur when beta 3-null MLEC are treated with tumstatin or any of its derivatives. Nor do they occur in mouse embryonic fibroblasts which do express beta 3 integrin. The inhibition by tumstatin also occurs in in vivo angiogenesis assayed using a Matrigel plug insert. Similarly to in vitro assays, tumstatin failed to inhibit angiogenesis in beta 3 integrin-deficient animals. These results suggest that avf33 integrin is necessary but not sufficient for the activity of tumstatin. Further studies are required to identify avf33 integrin-associated factors in endothelial cells which determine tumstatin's endothelial cell specificity. Matrigel plug assays were also used to demonstrate that the loss of beta-3 integrin enhanced VEGF-induced angiogenesis. Results also show that VEGF-induced angiogenesis was enhanced in aortic ring explants from beta 3-null animals. These data suggest a new role for beta 3 integrin as a negative regulator of angiogenesis, both as a receptor for an endogenous inhibitory molecule and as an inhibitor of VEGF-induced angiogenesis.
by Julie C. Lively.
Ph.D.
Kearns, Jeffrey D. "Distinct functions of negative regulators of NF-kappaB." Diss., [La Jolla] : University of California, San Diego, 2009. http://wwwlib.umi.com/cr/ucsd/fullcit?p3360060.
Повний текст джерелаTitle from first page of PDF file (viewed August 11, 2009). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references (p. 197-205).
Datar, Ila. "Positive and negative regulators of tumorigenesis and/or metastasis." University of Toledo Health Science Campus / OhioLINK, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=mco1438962728.
Повний текст джерелаSubedee, Ashim. "Molecular Determinants and Transcriptional Regulators in Triple Negative Breast Cancer." Thesis, Harvard University, 2015. http://nrs.harvard.edu/urn-3:HUL.InstRepos:23845415.
Повний текст джерелаMedical Sciences
Carlsson, Emil Karl Viktor. "Biochemical, molecular and cellular studies on negative regulators of TLR-signalling." Thesis, Imperial College London, 2015. http://hdl.handle.net/10044/1/38528.
Повний текст джерелаSpencer, William John. "Negative regulators of chromosome replication in the dimorphic bacterium Caulobacter crescentus." Thesis, McGill University, 2006. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=103183.
Повний текст джерелаIn Caulobacter, chromosome replication is repressed, in part, by the binding of the response regulator CtrA to five binding sites (a-e) within the Caulobacter origin of replication (Cori ). Periodic phosphorylation of CtrA stimulates binding to the consensus sequence TTAA-N7-TTAA (N= any nucleotide) found in Cori and many cell-cycle regulated genes. This thesis presents an alternate mode of CtrA binding, namely, that phosphorylation does not stimulate binding to a specific class of CtrA-regulated promoters. This work shows that CtrA and CtrA-phosphate bind to two ctrA promoters with equal and weak affinity. As well, in vivo binding assays reveal that a non-proteolyzable CtrA allele (CtrADelta3) can occupy the ctrA promoters continuously without altering the temporal regulation of these promoters. The data suggest phosphorylation, while not increasing affinity for weak CtrA binding sites, provides allosteric signals that permit the recruitment of components required for transcription.
The proposed allosteric mechanism of CtrA-regulated transcription may also be important for CtrA-mediated repression of chromosome replication. Chromatin Immunoprecipitation assays (ChIP) allow for the sensitive detection of specific protein/DNA complexes in vivo. ChIP reveals that CtrA binds to Cori in swarmers but not in stalk cells when chromosome replication commences. The protein chaperone, ClpX, was recruited to Cori prior to the start of S-phase and correlates with the loss of CtrA binding to Cori. Expression of a non-proteolyzable CtrADelta3 allele showed increased affinity for Cori DNA. The increase in CtrADelta3 binding stimulated a corresponding increase in C1pX binding to Cori. This evidence suggests that C1pX recruitment to Cori is likely CtrA-dependant. The absence of CtrA binding in stalk cells suggests other mechanisms may be required to prevent re-replication in stalk cells.
An analysis of the Caulobacter genome identifies two DnaA-like genes. The first, cdl-1, is a homolog of the E. coli hda gene, a protein essential for regulated inactivation of DnaA (RIDA). The second, cdl-2, is a novel gene restricted to the alpha-proteobacteria group and whose function is unknown. Overexpression of either gene in Caulobacter produced filamentous cells that could not divide. DNA synthesis in these cells is also impaired and suggests the intracellular concentrations of these two proteins are important for coordinating proper cell cycle progression.
Hooker, Erika. "Negative regulators of the Src family kinases in renal epithelial cells." Thesis, McGill University, 2013. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=116932.
Повний текст джерелаLes kinases Src sont des tyrosine-kinases cytosoliques qui sont impliquées dans multiples processus dans les cellules épithéliales et autres. Originalement identifiée comme un oncogène viral, la kinase Src est maintenant caractérisée comme une régulatrice de la prolifération, la différenciation et la motilité cellulaire. Nous avons précédemment montré que les kinases Src sont capables de modifier l'expression génique dans les tubules des reins durant le domage rénal par ischémie et réperfusion. Cependant, les mécanismes de signalisation qui contrôle la réponse transcriptionelle des kinases Src ne sont pas bien compris. La présente thèse décrit deux nouveaux inhibiteurs endogènes de la famille de kinases Src dans les cellules rénale épithéliales.Les deux premiers manuscrits établissent que la protéine adaptatrice Dok-4 fonctionne comme un inhibiteur des kinases Src. Contrairement à la plus part de protéines adaptatrices, la famille Dok est caractérisée par des actions inhibitrices durant la signalisation par les tyrosines kinases. Malgré que Dok-4 soit le membre de la famille Dok exprimé de manière la plus ubiquitaire, sa fonction est encore mal connue. Le premier manuscrit que je présente (Manuscrit I) décrit le domaine PTB de Dok-4. On y a démontré que le domaine PTB contient une extension C-terminal consistant probablement en une hélice alpha et que celle-ci est essentielle pour les interactions canoniques du domaine PTB de Dok-4. De plus, nous avons identifié la phosphatase lipidique Ship1 comme un nouveau partenaire de ce domaine PTB redéfini. Cette interaction est augmentée quand les kinases Src sont actives et elle implique un motif NPXpY dans la région C-terminale de Ship1. Contrairement à l'interaction entre Dok-4 et Ship1, l'interaction décrite dans le deuxième manuscrit (Manuscrit II) entre Dok-4 et le facteur de transcription, Elk4, implique le domaine PTB, mais se fait dans une manière atypique. L'interaction entre Dok-4 et Elk4 induit la relocalisation d'Elk4 du noyau au cytoplasme et cause la dégradation de la protéine Elk4. Dans les cellules rénales, Dok-4 inhibe l'activation d'Elk4 par les kinases Src et réprime l'expression des gènes de réponse précoce ("immediate early genes"), comme egr-1 et fos, et quelques cibles transcriptionelles de ces gènes. En accord avec ces données, suppression de Dok-4 est associée avec une augmentation de prolifération. En utilisant un modèle in vivo d'ischémie-reperfusion rénale, où la surexpression de gène de réponse précoce a déjà été démontrée, nous avons détecté une forte activation des kinases Src suivie d'une augmentation retardée de l'expression d'Elk4 dans les lysates de reins. Ces données suggèrent que dans ce modèle Dok-4 pourrait être critique pour limiter les dommages aux reins causé par l'induction des gènes de réponse précoce par Elk4. En plus d'activer l'expression des gènes de réponse précoce, nous avons précédemment montré que les kinases Src sont impliquées dans l'induction transcriptionnelle du récepteur tyrosine-kinase, EphA2, durant l'ischémie-reperfusion rénale. Dans le manuscrit préliminaire que je présente, nous avons noté que dans un modèle de déplétion et réplétion d'ATP, les kinases Src sont activées et les protéines Stat, des effecteurs des kinases Jak, sont déphsophorylés et inactives. Comme corollaire de cette observation, la surexpression de trois membres de de la famille Jak inhibent l'activation du promoteur d'EphA2 par les Src kinases. En plus, l'inhibition des kinases Jak endogènes par traitement aux siRNA ou par un inhibiteur pharmacologique, Jak Inhibitor I, active le promoteur d'EphA2. Étonnement, l'inhibition de l'expression d'EphA2 par les kinases Jak se fait indépendamment des protéines Stat et les récepteurs à cytokines. Mises ensemble, les données de cette thèse démontrent deux nouveaux inhibiteurs de la famille Src dans les cellules rénales épithéliales, la protéine adaptatrice, Dok-4 et les kinases, Jak1 et Jak2.
Evans, Abigail Alexandra. "An analysis of selected negative regulators of growth in breast cancer." Thesis, Queen Mary, University of London, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.287979.
Повний текст джерелаGadbois, Ellen L. (Ellen Louise) 1968. "Functional antagonism of the RNA polymerase II holoenzyme by negative regulators." Thesis, Massachusetts Institute of Technology, 1997. http://hdl.handle.net/1721.1/43553.
Повний текст джерелаMiller, Allan. "Negative regulators of gene expression in yeast : a1/α2 and SIR". Thesis, University of Cambridge, 1987. https://www.repository.cam.ac.uk/handle/1810/270426.
Повний текст джерелаDierdorf, Nina [Verfasser]. "Identification of negative regulators of integrin-mediated cell adhesion / Nina Dierdorf." Konstanz : Bibliothek der Universität Konstanz, 2015. http://d-nb.info/1142113876/34.
Повний текст джерелаBlack, Markaisa. "FOX proteins as novel negative regulators of lung fibrosis and mitochondrial respiration." University of Cincinnati / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1530270199796482.
Повний текст джерелаWilson, Robert. "Characterisation of XId2 and XId4, putative negative regulators of HLH genes in Xenopus laevis." Thesis, Open University, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.357135.
Повний текст джерелаMaehr, Tanja. "Cloning and expression analysis of putative negative regulators of immune responses in rainbow trout Oncorhynchus mykiss." Thesis, University of Aberdeen, 2013. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=201702.
Повний текст джерелаAmin, Parth Hitenbhai, and Parth Amin. "Adducins are Negative Regulators of Migration and Invasion of Normal Lung Epithelial Cells and Lung Cancer Cells." VCU Scholars Compass, 2016. http://scholarscompass.vcu.edu/etd/4401.
Повний текст джерелаJameson, Katie H. "Structural and biophysical investigations of two negative regulators of DNA replication initiation in Bacillus subtilis, YabA and SirA." Thesis, University of York, 2015. http://etheses.whiterose.ac.uk/13168/.
Повний текст джерелаLi, Zhi. "Insights on type I IFN signaling and regulation : studies of disease-associated TYK2 variants and of the negative regulators USP18/ISG15." Thesis, Paris 6, 2017. http://www.theses.fr/2017PA066437/document.
Повний текст джерелаToday, the pervasive action of type I IFN (IFN-alpha/beta, here IFN) in human physiology and pathology has become evident. Dysregulated IFN response can lead to interferonopathies and auto-immune diseases (AID). My thesis work has focused on the study of three elements of the IFN response pathway, aiming to understand how dysregulation occurs. TYK2 belongs to the Janus tyrosine kinase family and is involved in signaling of several immunoregulatory cytokines, such as type I IFN, IL-10, IL-12 and IL-23. Depending on the receptor complex, TYK2 is co-activated with either JAK1 or JAK2. A detailed molecular characterization of the interplay between the two juxtaposed enzymes is missing. In my study, I characterized two rare AID-associated human variants TYK2 I684S and TYK2 P1104A. I found that both variants are catalytically impaired but rescue signaling in response to IFN in fibroblasts. My results support a model of reciprocal activation of Janus kinases. Through signaling studies I showed that TYK2 P1104A homozygosity has a cytokine-specific impact in EBV-B cells. My studies of two other AID-associated TYK2 SNPs (rs12720270 and rs2304256) suggest that they promote Exon 8 retention and increase TYK2 expression. In the second part of my thesis work, I contributed to dissecting the molecular mechanism that tunes down IFN response in cells from rare USP18- and ISG15-deficient patients that suffered of interferonopathies. This work substantiated the essential role of USP18 in downregulating the IFN response and highlighted ISG15 as a novel IFN inhibitor in humans, but not in mice
Nilsson, Jonas. "The LRIG-family : identification of novel regulators of ErbB signaling with clinical implications in astrocytoma /." Doctoral thesis, Umeå : Department of Radiation Sciences, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-783.
Повний текст джерелаNunes, de Miranda Susana Marina Verfasser], Michael [Akademischer Betreuer] Huber, and Ralph [Akademischer Betreuer] [Panstruga. "Influence of the two negative regulators SHIP1 and Lyn on the antigen-induced mast cell phenotype / Susana Marina Nunes de Miranda ; Michael Huber, Ralph Panstruga." Aachen : Universitätsbibliothek der RWTH Aachen, 2018. http://d-nb.info/1171993285/34.
Повний текст джерелаNunes, de Miranda Susana Marina [Verfasser], Michael Akademischer Betreuer] Huber, and Ralph [Akademischer Betreuer] [Panstruga. "Influence of the two negative regulators SHIP1 and Lyn on the antigen-induced mast cell phenotype / Susana Marina Nunes de Miranda ; Michael Huber, Ralph Panstruga." Aachen : Universitätsbibliothek der RWTH Aachen, 2018. http://d-nb.info/1171993285/34.
Повний текст джерелаNeubauer, Svetlana. "Untersuchungen von inter- und intramolekularen Interaktionen des globalen Regulators AbrB und dessen Antirepressors AbbA." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2014. http://dx.doi.org/10.18452/16887.
Повний текст джерелаIn previous binding studies it could be demonstrated that a global regulator AbrB and the extensive phyC promoter region of Bacillus amyloliquefaciens FZB45 interact in a complex manner. AbrB binding is a multistep cooperative process. The integrity of both binding sites, ABS1 and ABS2, which are separated by 162 bp, is crucial for the AbrB-mediated repression of phyC. This work presents the first real-time binding kinetics of the AbrB-DNA interaction using surface plasmon resonance (SPR). AbrB exhibited high affinities to all analyzed 40-bp oligonucleotides that were derived from the ABSs of phyC. All parts of the ABS2, but only a small region within ABS1, were bound cooperatively to AbrB with a stoichiometry of 2 DNA to 1 AbrB tetramer and with 2
Lei, Ernest. "Cascaded Linear Regulator with Negative Voltage Tracking Switching Regulator." DigitalCommons@CalPoly, 2020. https://digitalcommons.calpoly.edu/theses/2176.
Повний текст джерелаAndersson, Anton, and Dexter Wolffsohn. "Regulatory Focus and Penalty Taking in Handball." Thesis, Högskolan i Halmstad, Hälsa och idrott, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:hh:diva-41613.
Повний текст джерелаStraffläggnings prestation i handboll inom ett själv-regulatoriskt fokus-ramverk undersöktes. I en två-oberoende grupps design, regulatorisk inramning (antingen promotion eller prevention) gavs till deltagarna (N = 25) innan straffläggning. Mer exakt, svenska manliga (n = 15) och kvinnliga (n = 10) spelare från den manliga tredje och kvinnliga andra svenska divisionen var slumpmässigt tilldelade att skjuta tre straffar under antingen en promotion-inramad (n = 13; Målder = 20.77, SD = 3.77 år) eller prevention-inramad (n = 12; Målder = 19.25, SD = 2.09 år) straffsituation. Mätningar av positiva och negativa affekter bedömde pre-prestation emotionella tillstånd. Resultaten visade att promotions-fokuserade individer presterade bättre i en promotion-inramning straffsituation (fit) än i en prevention-inramning straffsituation (mismatch). Dessutom när i regulatoriskt-fit, rapporterades positiva emotioner högre än i mismatch. Resultaten är diskuterade i förhållande till rollen av fit och emotionella tillstånd i prestation-under-press kritiska situationer
Giesen, Kay. "Die tramtrack-Gengruppe - negative Regulatoren zellulärer Differenzierung?" [S.l. : s.n.], 2000. http://deposit.ddb.de/cgi-bin/dokserv?idn=95981227X.
Повний текст джерелаFarrah, Jennifer. "CEACAMI as a negative regulator of T cell functions." Thesis, McGill University, 2003. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=81247.
Повний текст джерелаDoughty, Phillip Andrew. "Protein engineering of the ferric uptake regulator from Pseudomonas aeruginosa." Thesis, University of East Anglia, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.390637.
Повний текст джерелаLi, Grace T. Y. "C/EBPbeta is a Negative Regulator of Skeletal Muscle Differentiation." Thèse, Université d'Ottawa / University of Ottawa, 2011. http://hdl.handle.net/10393/20110.
Повний текст джерелаGour, Naina. "Dectin-1 is a critical negative regulator of allergic asthma." University of Cincinnati / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1413472037.
Повний текст джерелаPradhan, Madhura. "Ship : a negative regulator of RAS Pathway in B Lymphocytes /." The Ohio State University, 2000. http://rave.ohiolink.edu/etdc/view?acc_num=osu1488194825666984.
Повний текст джерелаSturrock, Marc. "Spatio-temporal modelling of gene regulatory networks containing negative feedback loops." Thesis, University of Dundee, 2013. https://discovery.dundee.ac.uk/en/studentTheses/b824506e-d515-442a-b9dc-ff82568f3c09.
Повний текст джерелаStephenson, Natalie. "Mechanotransduction of the Notch signalling pathway via the negative regulatory region." Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/mechanotransduction-of-the-notch-signalling-pathway-via-the-negative-regulatory-region(c13c0f01-3095-4895-a536-1dfc324d9899).html.
Повний текст джерелаLiu, Jinqi. "Characterization of negative regulatory proteins involved in tissue specific MMTV expression /." Digital version accessible at:, 1998. http://wwwlib.umi.com/cr/utexas/main.
Повний текст джерелаSong, Xiaozheng. "Estrogen Receptor Beta Is A Negative Regulator Of Mammary Cell Proliferation." ScholarWorks @ UVM, 2014. http://scholarworks.uvm.edu/graddis/259.
Повний текст джерелаWee, Hee-Jun. "Serine phosphorylation of RUNX2 with novel potential functions as negative regulatory mechanisms." Kyoto University, 2003. http://hdl.handle.net/2433/149370.
Повний текст джерелаCentuori, Sara Mozelle. "NEGATIVE REGULATION OF REGULATORY T CELLS BY MYELOID-DERIVED SUPPRESSOR CELLS IN CANCER." Diss., The University of Arizona, 2011. http://hdl.handle.net/10150/145099.
Повний текст джерелаChan, James Yi-Hsin. "The isolation and characterisation of the CD164 gene, a negative regulator of haematopoiesis." Thesis, University of Oxford, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.301889.
Повний текст джерелаKingsbury, Joanne Maree. "Characterisation of a negative regulator of hydrophobic amino acid transport in Saccharomyces cerevisiae." Thesis, University of Canterbury. Plant and Microbial Sciences, 2000. http://hdl.handle.net/10092/5737.
Повний текст джерелаChan, Sze-lai Celine, and 陳思例. "Sclerostin: a negative regulator of bone formation and a target for osteoporosis therapy." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B4189702X.
Повний текст джерелаBaggott, Rhiannon Rebecca. "Role of the plasma membrane calcium ATPase as a negative regulator of angiogenesis." Thesis, University of Wolverhampton, 2014. http://hdl.handle.net/2436/332139.
Повний текст джерелаJung, Joo-Yong. "INTERLEUKIN-10 AS A NEGATIVE REGULATOR OF INTERFERON-MEDIATED IMMUNITY IN CHLAMYDIAL INFECTIONS." Miami University / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=miami1196971379.
Повний текст джерелаMitton, Bryan A. "Protein Phosphatase Inhibitor-1 as a Positive Or Negative Regulator of Cardiac Contractility." University of Cincinnati / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1195325467.
Повний текст джерелаChan, Sze-lai Celine. "Sclerostin a negative regulator of bone formation and a target for osteoporosis therapy /." Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B4189702X.
Повний текст джерелаTews, Martha [Verfasser]. "Cholesterol als negativer post-transkriptioneller Regulator der Selenoprotein-Expression / Martha Tews." Mainz : Universitätsbibliothek Mainz, 2019. http://d-nb.info/1194189547/34.
Повний текст джерелаWilson, Maria Elizabeth. "Characterisation of hormone responsive and negative regulatory elements in the human insulin gene enhancer." Thesis, University of Aberdeen, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295586.
Повний текст джерелаBelloc, Rocasalbas Eulàlia. "Identification of a new deadenylation negative feedback loop that regulates meiotic progression." Doctoral thesis, Universitat Pompeu Fabra, 2008. http://hdl.handle.net/10803/7179.
Повний текст джерелаCampbell, Charles. "Sortilin is a Negative Regulator of Sonic Hedgehog Processing and Anterograde Trafficking in Neurons." Thesis, Université d'Ottawa / University of Ottawa, 2016. http://hdl.handle.net/10393/34560.
Повний текст джерелаBaril, Caroline. "The PP2C phosphatase Alphabet is a general negative regulator of MAPK signaling in Drosophila." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=18415.
Повний текст джерелаLes voies de signalisation de type MAPK ont été hautement conservées au cours de l'évolution et sont principalement impliquées dans la transmission de signaux extracellulaires vers les compartiments intracellulaires. Les voies ERK, JNK et p38 sont les cascades de type MAPK les mieux décrites et reposent sur l'activation d'un module de trois kinases par phosphorylation séquentielle. En effet, lorsqu'un signal mitogénique, proinflammatoire ou de stress est perçu par la cellule, une MAPK Kinase Kinase (MAPKKK) phosphorylera une MAPK kinase (MAPKK) qui phosphorylera ensuite une MAPK. Ces modules sont utilisés dans une multitude de contextes développementaux ainsi que pour le maintien de l'homéostasie chez les organismes adultes. Bien que la majorité des constituants de base des modules MAPK soient connus, nous possédons peu d'information concernant les mécanismes moléculaires impliqués dans le contrôle de la force, la durée, la localisation et la terminaison du signal. Par le biais de cribles génétiques chez la Drosophile, notre équipe a identifié plusieurs nouveaux loci potentiellement impliqués dans la régulation de la voie de signalisation ERK/MAPK. Par conséquent, l'objectif principal de mes recherches doctorales a porté sur la caractérisation d'un de ces nouveaux loci, que nous avons renommé alphabet (alph). Le gene alph encode une Ser/Thr phosphatase ayant une forte homologie de séquence avec PP2Ca/ß de mammifère. Dans un premier temps, j'ai démontré que l'activité phosphatase d'Alph était requise pour l'inhibition de la voie ERK/MAPK en aval de Ras et possiblement en amont de ERK/MAPK. Chez les levures, les plantes et les mammifères, les phosphatases de type PP2C sont principalement impliquées dans l'inactivation des voies JNK et p38. De façon similaire, j'ai démontré dans un deuxième temps qu'Alph agit aussi comme régulateur négatif de ces deux voies chez la Drosophile, possiblement en aval de Rac1 et en amont des M
Chan, Wilson. "Studies on the molecular mechanisms of Fibulin-5 as a negative Regulator of Angiogenesis." Thesis, McGill University, 2011. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=96718.
Повний текст джерелаL'angiogenèse est un processus finement régulé par lequel de nouveaux vaisseaux sanguins se forment dans les vaisseaux sanguins préexistants. Il s'agit d'un processus complexe modulé par une multitude de facteurs pro-et anti-angiogéniques, qui incluent naturellement les membres de la matrice extracellulaire (MEC) en raison du degré élevé de remodelage tissulaire nécessaire dans l'angiogenèse. La Fibulin-5 (DANCE, EVEC) est une protéine de la MEC liant les intégrines et l'élastine. Elle est fortement exprimée dans les vaisseaux sanguins au cours du développement, est régulée à la hausse lors de lésion vasculaire et est impliquée dans la régulation de la transition des cellules musculaires lisses (CML) vasculaires d'un état de repos à un état de prolifération. Récemment, les souris Fbln5 -/- ont montré une augmentation de vaisseaux sanguins cutanés, une augmentation de la migration et de la prolifération des cellules endothéliales (CEs) et une augmentation de 30 fois de l'expression de l'angiopoïétine-1 (Ang-1) dans les CML vasculaires, un promoteur puissant de l'angiogenèse. Dans la présente étude, nous avons étudié le(s) mécanisme(s) moléculaire(s), par le(s)quel(s) la fibuline-5 pourrait agir comme un régulateur négatif de l'angiogenèse, plus précisément, sur la modulation de l'activité Ang-1 dans les CEs. Nous avons utilisé des essais de liaison en phase solide afin de déterminer les interactions physiques directes que la fibuline-5 pourrait avoir avec l'Ang-1 et son récepteur Tie-2. Nous avons également utilisé des essais de liaison en phase solide pour enquêter sur les molécules de surface cellulaire pouvant lier la fibuline-5 et nous avons confirmé que le motif RGD de la fibuline-5 sert à la liaison aux intégrines. De plus, la fibuline-5 a une grande affinité pour l'héparine, suggérant une interaction potentielle avec la surface cellulaire par les protéoglycanes héparane-sulfate. Nous avons également cherché à comprendre le mécanisme de signalisation en aval de la fibuline-5 et nous avons établi une nouvelle voie dépendante d'Akt dans laquelle la fibuline-5 agit comme une molécule anti-angiogénique.
McCrindle, Tyronne K. "Characterisation of the AT4G11100 gene, a negative regulator of disease resistance in Arabidopsis thaliana." Master's thesis, University of Cape Town, 2015. http://hdl.handle.net/11427/15728.
Повний текст джерелаGomes, Nuno Miguel Araújo da Cunha. "NDT80 transcription factor as a negative regulator for Candida parapsilosis adhesion and biofilm formation." Master's thesis, Universidade de Aveiro, 2014. http://hdl.handle.net/10773/14925.
Повний текст джерелаC. parapsilosis infections incidence has been increasing for the past 20 years. Its caracteristics of adhering and forming biofilms are a critical factor for infection caused by this organism, affecting from immunocompromised or transplanted patients to low-birth-weight neonates. The health-care workers are a major transmission vehicle of this fungus. The azoles class of antifungal drugs are the first and most common line of defense to treat infections by this type of yeast species. Its mode of action on the yeast cell works by inhibiting the lanoststerol 14α-demethylase, an enzyme belonging to the ergosterol biosyntethic pathway.. On a recent study it has become clear that C. parapsilosis antifungal azole resistance may display similar resistance mechanisms that the ones described for C. albicans. A resistant strain obtained after exposure to posaconazole has shown an upregulation of two transcriptional factors, Upc2 and Ndt80. The aim of this work was to assess the role of these two transcriptional factors on C. parapsilosis azole resistance. For that, it was intended to knockout both genes using the SAT1-flipper cassette. The strain obtained after disruption of one copy of NDT80 gene displayed an unexpected phenotype, concerning adhesion and biofilm formation, comparatively to the wild-type BC014 strain. It were also made susceptibility tests although with no evident changes. These results demonstrate that NDT80 gene may be a negative regulator of C. parapsilosis adherence to abiotic and biotic substrates, impairing also biofilm formation.
As infecções por C. parapsilosis têm vindo a aumentar nos últimos 20 anos. As suas características intrínsecas de adesão e capacidade de formação de biofilmes são um factor critíco de infecção, sendo os pacientes transplantados ou com o sistema imunitário comprometido ou mesmo os neonatos de baixo peso o grupo de risco mais afectado. Os prestadores de cuidados de saúde são o meio de transmissão mais comum para a infecção por esta levedura. A classe dos antifúngicos azóis são a primeira linha de defesa para tratamento de infecções por este tipo de leveduras. Estes actuam inibindo a enzima lanosterol 14α-demethylase, enzima constituinte da via biossintética do ergosterol. Um estudo recente demonstrontrou que a resistência aos azoles em C. parapsilosis poderá ter os mesmos mecanismos observados e estudados em C. albicans. Uma estirpe resistente obtida após exposição a Posaconazole revelou uma sobre-expressão de 13 genes envolvidos na biossíntese do ergosterol, entre eles dois factores de transcrição, Upc2 e Ndt80. Com vista a avaliar o papel destes factores de transcrição na resistência aos azoles em C. parapsilosis, pretendeu-se efectuar a delecção dos dois genes usando a ferramenta molecular SAT1-flipper cassette. Apenas um alelo do gene NDT80 foi deletado, originando um fenótipo distinto em comparação com a estirpe original BC014, em particular na sua capacidade de adesão e de formação de biofilmes. Foram realizados testes de susceptibilidade embora sem qualquer diferença evidente entre fenótipos. Estes resultados demonstram que o gene NDT80 pode ser um regulador negativo da capacidade de adesão de C. parapsilosis, afectando também o seu potencial de formação de biofilmes.