Dissertations / Theses on the topic 'Barhl1'
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Pöschl, Julia. "The role of the transcription factor BARHL1 in medulloblastoma." Diss., lmu, 2011. http://nbn-resolving.de/urn:nbn:de:bvb:19-137752.
Full textPöschl, Julia [Verfasser], and Ulrich [Akademischer Betreuer] Schüller. "The role of the transcription factor BARHL1 in medulloblastoma / Julia Pöschl. Betreuer: Ulrich Schüller." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2011. http://d-nb.info/1018615717/34.
Full textBou-Rouphaël, Johnny. "A new role for Barhl1 in a cerebellar germinative zone as inhibitor of T-cell factors transcriptional activity." Electronic Thesis or Diss., Sorbonne université, 2023. http://www.theses.fr/2023SORUS009.
Full textThe human cerebellum hosts more than 50% of all brain neurons. Cerebellar granule neurons are the smallest and most abundant neurons. atonal homologue 1 (Atoh1)-expressing granule neuron progenitors (GNPs) emerge from the upper rhombic lip (URL), a germinative zone located in the cerebellar primordium and displaying features of a niche of neural stem cells. GNPs proliferate, migrate, and differentiate to settle into the internal granule layer. These processes are tightly regulated by a number of transcription factors and signaling pathways. T-Cell Factor/Lymphoid Enhancer-binding Factor (Tcf/Lef) are transcriptional effectors acting downstream of Wnt/β-catenin signaling. Although Tcf is transcriptionally active in the URL, neither its function(s) nor its developmental regulator(s) have been addressed in this area. The transcription factor BarH-like 1 (Barhl1) is expressed in committed GNPs located in areas devoid of Tcf transcriptional activity. The aims of this thesis were to investigate the functions of Tcf and of Barhl1 as regulators of GNPs development using amphibian as experimental model. The data presented in this work encompass a thorough analysis of the spatial and temporal expressions of key markers involved in GNP development in amphibian, and an investigation of Barhl1 and Tcf functions in this developmental process. Our gain and loss of function experiments, together with the transcriptomic analysis of Barhl1 depletion in the rhombomere 1 validate a key role for Tcf as a transcriptional activator of atoh1 and as an inducer of the URL territory, and for Barhl1 as a developmental inhibitor of Tcf activity allowing GNPs to exit the URL. We identified key genes inhibited by Barhl1 and involved in the maintenance of URL germinative zone
Betin, Cansu. "Barely Transitive Groups." Phd thesis, METU, 2007. http://etd.lib.metu.edu.tr/upload/3/12608605/index.pdf.
Full textSena, Elena. "The Transcription Factor Barhl2 Inhibits Wnt Canonical Signaling during Xenopus Embryogenesis." Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS090/document.
Full textEmbryonic development is a highly controlled process where different signaling pathways participate into the elaboration of an organism. One of the main signaling pathways is the Wnt canonical pathway. The long-lasting search to understand Wnt/β-catenin transduction cascade revealed that the net transcriptional read out of Wnt/β-catenin signaling is highly dependent on the cellular context. In X. laevis embryos Wnt/β-catenin signaling is the informative signal for the Spemann Organizer induction. However little is known on what limits Wnt activity in this territory and consequently the size of the Spemann Organizer. The results presented in this manuscript provide evidence that the evolutionarily conserved transcription factor Barhl2 limits the development of the Spemann organizer. In this territory Barhl2 inhibits Wnt activity via its interaction with the co-repressor Groucho and the transcription factor Tcf. It participates to the recruitment of the chromatin remodeling enzyme, Hdac1 that represses the expression of Spemann organizer genes. Using a Xenopus tropicalis Tcf reporter line we demonstrate that Barhl2 inhibitory effect on Groucho-Tcf activities is maintained during embryogenesis and plays a role in the confinement of neural progenitors in the brain. Together, our results provide a new and important mechanism for the control of Wnt transcriptional activity
Kuzucuoglu, M. "Barely transitive permutation groups." Thesis, University of Manchester, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.233097.
Full textParish, Elisa Victoria. "Interactions between Pax6, Barhl2 and Shh in the early patterning of the mammalian diencephalon." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/23387.
Full textJuraver-Geslin, Hugo. "Barhl2, un inhibiteur prolifératif des progéniteurs neuraux dans le développement du diencéphale caudal." Paris 6, 2013. http://www.theses.fr/2013PA066101.
Full textOur team focuses on the development of the caudal forebrain that generates the thalamus, a processor of information to the cortex, and its organizing center, the zona limitans intrathalamica (ZLI). ZLI, through the secretion of Sonic Hedgehog (Shh) and Wnt ligands controls the acquisition of identity and the growth of the entire caudal forebrain. Shh and Wnt are the main pahways that controls the survival and proliferation of neural progenitors during development. In amphibians and rodents, the homeodomain containing gene Barhl2 is expressed with Shh and Wnt ligands in the forebrain neuroepithelium. In Xenopus, Barhl2 limit the proliferation of diencephalic neural progenitors and controls the neuroepithelium architecture. Barhl2 acts through an unconventional function of Caspase-3, the major effector of apoptosis, which inhibits the accumulation and activation of βcaténine. My work also showed that Barhl2 is crucial in the development of the histogenic field that generates the ZLI and thalamus. A dynamic network involving barhl2, iroquois (irx), otx and pax6 is at play in establishing the presumptive territories. My work, and studies in zebrafish, shows that barhl2, otx2 and irx3 are masters prepatterning genes of the ZLI and this role is conserved in vertebrates
Olivesi, Dominique. "Virgile Barel : 1889-1979 /." Nice : Serre, 1996. http://catalogue.bnf.fr/ark:/12148/cb36688081n.
Full textLewis, Colin A. "Barkly East bells and the British Empire." The Ringing World, 2002. http://www.ringingworld.co.uk.
Full textShi, Yibing. "Barely visible impact damage in polymer composite laminates." Thesis, University of Cambridge, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.334270.
Full textCárdenas, Bunsen José Alejandro. "Mercedes López-Baralt, Guamán Poma, autor y artista." Pontificia Universidad Católica del Perú, 2013. http://repositorio.pucp.edu.pe/index/handle/123456789/100915.
Full textHarrison, Paul. "Being barely there : thinking through the break-up of idealism." Thesis, University of Bristol, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.340438.
Full textLi, Lin. "L'expression de BARD1 et sa fonction potentielle dans le cancer = (Expression of BARD1 isoforms and possible function in cancer) /." Genève : [s.n.], 2007. http://www.unige.ch/cyberdocuments/theses2007/LiL/these.pdf.
Full textAvec des articles de l'auteur parus dans la presse professionnelle. Contient un résumé (1 p.) et une introduction (5 p.) en français. A paru également en version électronique. Bibliogr.
Savage, Darryl B. "Nutritional influences on reproductive performance of beef cattle in the Barkly Tableland /." St. Lucia, Qld, 2004. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe17977.pdf.
Full textKane, Wendi. "Working Hard and Barely Making it: Ideological Contradictions and the Working Poor." Master's thesis, University of Central Florida, 2009. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/4049.
Full textM.A.
Department of Sociology
Sciences
Applied Sociology MA
Kane, Wendi Belinda. "Working hard and barely making it ideological contradictions and the working poor /." Orlando, Fla. : University of Central Florida, 2009. http://purl.fcla.edu/fcla/etd/CFE0002518.
Full textAdu-Tutu, K. O., W. B. McCloskey, S. H. Husman, P. Clay, M. J. Ottman, E. C. Martin, and T. Teegerstrom. "Weed Management and Agronomic Performance of a Cotton-Barely Double Crop Rotation." College of Agriculture, University of Arizona (Tucson, AZ), 2005. http://hdl.handle.net/10150/198166.
Full textYbos, Cynthia. "Barely There Tales: A Phenomenological Study of Stories Told by Pre-service Teachers." ScholarWorks@UNO, 2010. http://scholarworks.uno.edu/td/1240.
Full textBaril, Lisa Marie. "Change in deciduous woody vegetation, implications of increased willow (Salix spp.) growth for bird species diversity, and willow species composition in and around Yellowstone National Park's Northern range." Thesis, Montana State University, 2009. http://etd.lib.montana.edu/etd/2009/baril/BarilL1209.pdf.
Full textLiu, Xuan. "BARF1 sequence analysis and functional significance in EBV-Related disorders." Click to view the E-thesis via HKUTO, 2005. http://sunzi.lib.hku.hk/hkuto/record/B36190445.
Full textBartl, Guido [Verfasser], and A. [Akademischer Betreuer] Hangleiter. "Interferometrische Bestimmung von absoluten Kugelradiustopografien / Guido Bartl ; Betreuer: A. Hangleiter." Braunschweig : Technische Universität Braunschweig, 2010. http://d-nb.info/117582898X/34.
Full textLiu, Xuan, and 劉絢. "BARF1 sequence analysis and functional significance in EBV-Related disorders." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2005. http://hub.hku.hk/bib/B36190445.
Full textBartl, Daniel [Verfasser]. "Robust techniques for utility maximization and related problems / Daniel Bartl." Konstanz : KOPS Universität Konstanz, 2019. http://d-nb.info/1192665627/34.
Full textLu, Chi-Sheng. "The role of BRCA1/BARD1 in breast cancer a dissertation /." San Antonio : UTHSC, 2008. http://proquest.umi.com.libproxy.uthscsa.edu/pqdweb?did=1605126591&sid=11&Fmt=2&clientId=70986&RQT=309&VName=PQD.
Full textMARTORELLI, DEBORA. "BARF1 AS A NEW THERAPEUTIC TARGET FOR EBV-ASSOCIATED MALIGNANCIES." Doctoral thesis, Università degli studi di Ferrara, 2010. http://hdl.handle.net/11392/2389347.
Full textTurrini, Riccardo. "Targeting BARF1 for the therapeutic control of EBV-associated malignancies." Doctoral thesis, Università degli studi di Padova, 2010. http://hdl.handle.net/11577/3427092.
Full textIl virus di Epstein-Barr è un γ-herpesvirus che infetta preferenzialmente i linfociti B umani. Si stima che il 95% della popolazione mondiale sia infettata, ma normalmente tale infezione avviene nell’infanzia ed è asintomatica. Oltre ad essere l'agente causale di una malattia linfoproliferativa autolimitante, la mononucleosi infettiva, la presenza del virus è associata ad alcune neoplasie umane, caratterizzate da diversi pattern di espressione genetica. Alcune delle neoplasie EBV-associate sono il linfoma di Burkitt (BL) e alcune forme di carcinoma gastrico (GC), il linfoma di Hodgkin (HL) e il carcinoma nasofaringeo (NPC), e infine le malattie linfoproliferative post-trapianto (PTLD). Oltre ai geni di latenza, è nota l’espressione di diversi RNA non poliadenilati (EBER) e, soprattutto nei casi di NPC e di GC, l’espressione da parte delle cellule infettate di una proteina transmembrana del ciclo litico, BARF1. BARF1 è una proteina di 221 aminoacidi, con una porzione transmembrana al C-terminale. Solo recentemente ne è stato dimostrato il ruolo trasformante ed immortalizzante in cellule umane. Inoltre, il dominio extracellulare può essere tagliato, ed è in grado di agire in modo paracrino come fattore di crescita per le cellule adiacenti, possedendo infatti attività mitogena. In generale, tuttavia, le attività mitogene e mutagene non sono state ancora completamente elucidate, ma l’importanza di questa proteina nei pathway di progressione neoplastica e la sua espressione unicamente nelle cellule infettate (o in quelle che ne legano la forma secreta) la rendono un ottimo candidato come bersaglio per un approccio terapeutico delle neoplasie EBV-correlate. Esistono diversi orientamenti terapeutici nei confronti delle neoplasie EBV-relate; alcune strategie prevedono la riduzione del regime di immunosoppressione, soprattutto per il trattamento di PTLD, la somministrazione di farmaci antivirali, la terapia genica, l’uso di chemioterapici e approcci di immunoterapia. L’uso di linfociti T citotossici (CTL) autologhi o da donatori compatibili si è dimostrata efficace e generalmente priva di effetti collaterali, soprattutto in pazienti affetti da PTLD. Un altro aspetto dell’immunoterapia prevede l’utilizzo di anticorpi monoclonali (mAb), come già dimostrato in ambito clinico dall'utilizzo di rituximab. In questo progetto di Dottorato viene descritta la generazione e la valutazione in vitro di diversi anticorpi monoclonali specifici per BARF1. Inoltre, una volta dimostratane l'attività su colture cellulari in vitro, si è traslato l'approccio ad alcuni modelli pre-clinici sfruttando topi immunodeficienti portatori di tumore EBV-positivo. Anche in questi esperimenti è stato possibile dimostrare l'efficacia terapeutica degli anticorpi prodotti. Da un lato, l’utilizzo di mAb sia nella diagnosi che nella cura di neoplasie sta assumendo un’importanza crescente in ambito clinico, grazie alla specificità di azione di queste molecole e alla loro relativa facilità d’uso, soprattutto se paragonati all’immunoterapia cellulare adottiva. Dall’altro, BARF1, benchè non ne siano ancora state completamente studiate le funzioni e le interconnessioni con altre molecole o cellule, è sicuramente un target promettente per i tumori EBV-relati, in quanto, nonostante sia una proteina espressa durante il ciclo litico, è presente soprattutto nei casi di NPC e di GC, e possiede importanti funzioni trasformanti, anche con azione paracrina.
Adamovich, Aleksandra Igorevna. "Functional Analysis of BARD1 and BRCA1 Variants of Uncertain Significance in Homology-Directed Repair." The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1563316267936516.
Full textErrera, Reagan Michelle. "Inhibition and success of prymnesium parvum invasion on plankton communities in Texas, USA and prymnesium parvum pigment dynamics." Thesis, Texas A&M University, 2003. http://hdl.handle.net/1969.1/5985.
Full textFeki, Anis. "Rôle de BARD1 comme suppresseur de tumeur dans un modèle animal /." Genève : [s.n.], 2004. http://www.unige.ch/cyberdocuments/theses2004/FekiA/these.pdf.
Full textChristensen, Devin Eugene. "Identifying substrate and E2 interactions of the BRCA1/BARD1 ubiquitin ligase /." Thesis, Connect to this title online; UW restricted, 2007. http://hdl.handle.net/1773/9222.
Full textMadgett, Elizabeth Bryony. "Checkpoint function and replication dynamics in brca1 and bard1 DT40 cells." Thesis, University of Cambridge, 2007. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.613163.
Full textBelliveau, Tammie. "Barely a whisper in the system, parents' perspectives on the prevention of foster care placement." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/mq21874.pdf.
Full textWelter, John T. "Oblique angle pulse-echo ultrasound characterization of barely visible impact damage in polymer matrix composites." University of Dayton / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=dayton1575295152635788.
Full textBartl, Alexander [Verfasser], Achim [Akademischer Betreuer] Schwenk, and Segovia Almudena [Akademischer Betreuer] Arcones. "Neutrino Interactions with Supernova Matter / Alexander Bartl ; Achim Schwenk, Almudena Arcones Segovia." Darmstadt : Universitäts- und Landesbibliothek Darmstadt, 2016. http://d-nb.info/1117797171/34.
Full textKaufmann, Aisling. "The role of the BARD1 BRCT domains in the DNA damage response." Thesis, University of Dundee, 2014. https://discovery.dundee.ac.uk/en/studentTheses/8c8c745f-8b73-420f-b264-2b12334195e7.
Full textLelièvre, Jean. "Problématique d'incohérence des registres d'inventaire chez Marcel Baril Ltee : diagnostic et recommandations /." Thèse, Chicoutimi : Université du Québec à Chicoutimi, 1986. http://theses.uqac.ca.
Full textCe mémoire a été réalisé à l'Université du Québec en Abitibi-Témiscamingue dans le cadre du programme de maîtrise en gestion des petites et moyennes organisations extensionné de l'UQAC à l'UQAT. CaQCU Document électronique également accessible en format PDF. CaQCU
Bartl, Bettina Uta [Verfasser]. "Der Einfluss der Lagerung von Erythrozytenkonzentraten auf die Komplementaktivierung / Bettina Uta Bartl." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2017. http://d-nb.info/1133492800/34.
Full textTimofejeva, Oksana. "Formation of Barely Soluble Compounds in the CuSO4 – K4P2O7 – H2O and CuSO4 – (NH4)4P2O7 – H2O Systems." Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2009. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2009~D_20090526_111121-30909.
Full textNaudojant IR-spektrometrijos, rentgenofazinės analizės, atominės absorbcinės spektroskopijos, kolorimetrijos analizės metodus buvo ištirta sistemose CuSO4 – K4P2O7 – H2O ir CuSO4 – (NH4)4P2O7 – H2O susidarančių mažai tirpių junginių sudėtis, jų susidarymo dėsningumai ir vykstančios reakcijos, įvairių veiksnių įtaką nuosėdų sudėčiai ir struktūrai. Nustatyta, kad sistemoje CuSO4 – K4P2O7 – H2O, be jau žinomų mažai tirpių junginių (paprastosios druskos Cu2P2O7 ∙ 5H2O ir dvigubosios druskos Cu3K2(P2O7)2 ∙ 3H2O), susidaro ir naujas mokslinėje literatūroje neaprašytas junginys (Dimorfas B), dvigubajai druskai patiriant polimorfinį perėjimą. Polimorfinio perėjimo trukmė labai priklauso nuo pH ir reaguojančių jonų koncentracijų. FTIR duomenų analizė parodė, kad difosfato jonų energetinė būsena Cu – K ir Cu – NH4 Dimorfuose B panaši. Jų rentgenogramos yra panašios, tikėtina, kad šie junginiai – izostruktūriniai, jų kristalinės gardelės tipas – monoklininis. Naudojant Lazarevo lygtį, bei Rulmonto priklausomybę buvo apskaičiuoti Cu – K ir Cu – NH4 Dimorfų A ir B bei paprastosios druskos P – O – P kampai, gauta, kad jie mažai keičiasi siaurame 123,1 – 127,1 º intervale. Nustatyta, kad dviguboji druska susidaro iš paprastosios, vykstant heterogeninei reakcijai: 3Cu2P2O7 ∙ 5H2O↓ + H2P2O72– + 4K+ → 2Cu3K2(P2O7)2∙ 3H2O↓ + 2H++ 9H2O. Mokslinėje literatūroje tokia reakcija neaprašyta jokiai difosfatų sistemai, jos tyrimo duomenys yra nauji. Taip pat nustatyta, kad heterogeninės reakcijos... [toliau žr. visą tekstą]
Rice, Ian S. "Honors Thesis: BRCA1 Interactions with BACH1, BARD1, and CHK2: Recent Evidence and Potential Developments in the Diagnosis, Treatment, and Prevention of Human Breast Cancer." Miami University Honors Theses / OhioLINK, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=muhonors1114185039.
Full textPartorp, David. "Att gestalta nordisk mytologi genom berättarteknik : Berättarteknik i spel." Thesis, University of Skövde, School of Humanities and Informatics, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-3363.
Full textDenna rapport avser verket Norse som jag – David Partorp – och min andra gruppmedlem – Jesper Flarup – har skapat. Norse är en modul till The Elder Scrolls IV: Oblivion (2006) med nordisk mytologi som tema. Norse följer en berättelse från mytologin vid namn Gudarnas skatter vars innehåll syftar till att två dvärgar ska tillverka tre skatter till gudarna. Berättelsen är hämtad från böckerna Nordens gudar och myter skriven av H R Ellis Davidson (1964/1984) samt Snorres Edda översatt av Björn Collinder (1970). Till detta huvuduppdrag tillkommer egenskrivna sidouppdrag.
Den frågeställning som ligger som grund för rapporten är:
- Hur kan jag förmedla en bild av den nordiska mytologin genom mitt spel?
- Vilken händelse lämpar sig för att gestalta mytologin?
- Hur ska händelsen gestaltas?
Den första delfrågan behandlar alltså vad som ska berättas och den andra hur händelsen ska berättas.
För att besvara dessa frågor så används dels andra liknande spel; Rune (2000), Age of Mythology (2002) och World of Warcraft: Wrath of the Lich King (2008). Den litteratur som används är Game Design - Theory & Practice (Rouse III, 2005), Andrew Rollings and Ernest Adams on Game Design (Rollings & Adams, 2003), Nordisk mytologisk kosmologi som spelvärld - Vilka källor bör användas i skapandet av en spelvärld baserad på nordisk mytologi? (Nilsson, 2006) samt Fruktan, medkänsla och kritisk distans (Tjäder, 2000).
Huvudsakligen i Andrew Rollings and Ernest Adams on Game Design (Rollings & Adams, 2003) används Christopher Voglers The Hero’s Journey (1993, i Rollings & Adams, 2003) som definierar hur en berättelse är uppbyggd utifrån tolv steg.
Svar på första frågeställningen blev således historien Gudarnas skatter som återfinns i boken Nordens gudar och myter (Davidson, 1964/1984). Valet av just denna historia har bl.a. sin bakgrund i Aristoteles definitioner av ett drama.
Svar på andra frågeställningen med användandet av Voglers The Hero’s Journey (1993, i Rollings & Adams, 2003) resulterade i ett icke-linjärt strukturerat uppdrag som följer nio av de tolv steg som beskrivs. De resterande tre stegen används först och främst till längre spel som har en djupare bakgrundshistoria (Rollings & Adams, 2003).
Norse
Marklund, Sanna, and Max Dyrhage. "Spel som rekryteringsverktyg inom IT." Thesis, KTH, Skolan för datavetenskap och kommunikation (CSC), 2015. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-168969.
Full textThe purpose of this study was to find out where and how a game can be used in the recruitment process within the IT industry. To investigate this studies were made of the recruitment process Swedish companies in the IT industry, research and theories of game design and the relationship between general personality traits and the gaming behavior. Qualitative interviews with recruiters and game researcher and a study of the relationship between personality traits and the game's personality has been implemented. This has been combined with the literature in recruitment and games to identify recommendations on the continuation of game design for a game aimed towards recruitment.The study shows that a game should be adjusted to where in the recruitment process you aim to use it. The study showed two parts od the recruitment process where a game could be in use, for one a game could fit in the collection of candidates for a recruitment process to attract candidates or brand the company and for second to assess a candidate's technical skills. The test group surveyed consists mostly of people who like to explore in a game and the study therefore proposes a game to attract candidates in a recruitment process should be designed. When it comes to assessing technical skills the study suggests a game the candidate can play in different ways. Based on the player's behavior different personality traits can be demonstrated.
Wietek, Jonas [Verfasser], Hegemann [Gutachter] Peter, Bartl [Gutachter] Franz, and J. Simon [Gutachter] Wiegert. "Anion Conducting Channelrhodopsins / Jonas Wietek ; Gutachter: Hegemann Peter, Bartl Franz, J. Simon Wiegert." Berlin : Humboldt-Universität zu Berlin, 2018. http://d-nb.info/1185579125/34.
Full textBartl, Jasmin [Verfasser], and Edna [Akademischer Betreuer] Grünblatt. "Impairment of insulin signaling pathway in Alzheimer’s disease / Jasmin Bartl. Betreuer: Edna Grünblatt." Würzburg : Universitätsbibliothek der Universität Würzburg, 2012. http://d-nb.info/1029426759/34.
Full textAndrade, Simone Caixeta de 1977. "Investigação do papel da homeoproteína BARX1 na morfogênese do dente molar em camundongos." [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/290038.
Full textTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
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Resumo: A dentição não é somente o maior componente do complexo crânio facial dos mamíferos, mas um modelo útil de desenvolvimento, combinado em um sistema de um único órgão, onde ocorrem fenômenos de organização espacial, simetria, aquisição de formas complexas e citodiferenciação órgão-específica. Durante os primeiros estágios do desenvolvimento do dente ocorre uma série de interações entre o epitélio oral e mesênquima, por meio de diferentes moléculas sinalizadoras ao longo do futuro processo alveolar. Bmp4 atua ativando Msx1 na região de incisivos e molares e restringe a ação de Barx1 apenas na região dos molares. A interação entre o sinal mesenquimal Bmp4 e o sinal epitelial Shh faz parte dos primeiros eventos da formação do germe dentário no estágio botão. As fases seguintes são os estágios capuz e sino. Mutações nos genes Msx1 e Barx1 impedem o desenvolvimento do germe dentário além do estágio botão. Para o gene Msx1 essa condição é permanente, enquanto para Barx1 é temporal e o crescimento do germe dentário é retomado após o estágio E14.5 em camundongos. O objetivo desse trabalho é investigar a interação genética entre Msx1 e Barx1 no desenvolvimento do primeiro molar inferior na fase sino (E16.5) e qual a influência da ausência do gene Msx1 na dimensão das estruturas vestigiais MS, R2 e do primeiro molar inferior nas fases botão (E13.5) e sino (E16.5). Esse estudo também se propôs a avaliar se genes Barx2, Barhl1 e Barhl2 estariam expressos em botões de molares inferiores (E13.5). Os resultados indicaram que na ausência completa de Barx1, um único alelo de Msx1 não é suficiente para promover a evolução do botão dentário a capuz em camundongos E16.5 Barx1;Msx1 e não houve expressão de Bmp4 nesses camundongos. A expressão nula dos genes Barx2, Barhl1 e Barhl2 em botões de molares inferiores em camundongos wild-type E13.5 indica que genes da família Bar não possuem nenhum papel no desenvolvimento de molares inferiores. Ainda, dados alométricos de Msx1-/- (E13.5 e E16.5) indicam que a mutação no gene Msx1 e consequente ausência de expressão de Smad1-5-8 e Shh não impede o crescimento no sentido proximal-distal. Conclui-se que existe interação entre Barx1 e Msx1. Barx1 é necessário para controlar os níveis de expressão de Bmp4. Barx2 possivelmente desempenha um papel importante na morfogênese de pré-molares e incisivos inferiores. O atraso no desenvolvimento dos molares inferiores de camundongos Msx1-/- é permanente ao estágio botão, contudo, os botões dentários destes camundongos continuam a exibir um crescimento no sentido proximal-distal no estágio E16.5
Abstract: The dentition is not only the largest component of the craniofacial complex of mammals, but a useful model of development, combined in a single organ system, where phenomena of spatial organization, symmetry, complex shape acquisition and organ-specific cytodifferentiation occur. During the early stages of tooth development, series interactions take place between oral epithelial and mesenchyme by different signalling molecules along the future alveolar process. Bmp4 acts by activating Msx1 in the region of incisors and molars and it restricts the action of Barx1 only to the molars' region. The interaction between mesenchymal Bmp4 signal and Shh epithelial signal is part of the first events of tooth germ formation at the bud stage. The next stages are cap and bell. Mutations in Msx1 and Barx1 genes inhibit the development of the tooth germ beyond the bud stage. For the Msx1 gene, this condition is permanent, while for Barx1 is temporal and the growth of tooth germ is retaken after stage E14.5 in mice. This study investigates the genetic interaction between Msx1 and Barx1 in the first lower molar development at the bell stage (E16.5), the effect of the absence of Msx1 gene in the size of the vestigial structures MS, R2 and first lower molar bud (E13.5) and bell (E16.5). This study also aimed to assess whether Barx2, Barhl1 and Barhl2 genes were expressed in lower molars buds (E13.5). The results indicated that in the complete absence of Barx1, a single allele of Msx1 is not sufficient to promote the development of tooth bud to cap in E16.5 Barx1;Msx1 mice, and there was no expression of Bmp4 in these mice. The null expression of Barx2, Barhl1 and Barhl2 genes in lower molar buds in E13.5 wild-type mice indicates that genes of the Bar family do not exert any role in the development of lower molars. Still, allometric data on Msx1-/- (E13.5 and E16.5) indicates that Msx1 gene mutation and consequently the absence of Shh and SMAD1-5-8 expression do not prevent growth towards proximal-distal. It is concluded that there is interaction between Barx1 and Msx1. Barx1 is necessary to control the expression levels of Bmp4. Barx2 might play a role in the lower premolars and incisors morphogenesis. The delayed development of Msx1-/- lower molars is permanent at the bud stage, however, the tooth buds of these mice continue to exhibit growth towards proximal-distal at E16.5 stage
Doutorado
Histologia e Embriologia
Doutor em Biologia Buco-Dental
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Full textBARF1, an oncogene encoded by Epstein-Barr virus expressed in 90% of NPC, possess immortalizing and transforming activity in various cell types. We focus our first part of work to study the effect and localization of p29 protein encoded by BARF1 in human epithelial HaCaT culture medium. The p29 protein showed its mitogenic activity resulting in cell cycle progression G1 to S phase. Expression de BARF in HaCaT cells induced malignant transformation in nude mice. Confocal and immunoelectron mcroscopy analysis showed its cytoplasmic and nuclear localization. In the second part of work, the efect of deletion and substitution mutants of BARB-1 was studied in rodent fibroblast Balb/c3T3. Its amino acid sequence between 31 and 56th was responsible to malignant transformation