Thesis (Ph. D.)--Rutgers University, 2007. / "Graduate Program in Biomedical Engineering." Includes bibliographical references (p. 45-48).

Thesis (Ph.D.)--University of Alabama at Birmingham, 2007. / Title from PDF title page (viewed on Sept. 16, 2009). Includes bibliographical references.

Thesis (M. Phil.)--University of Hong Kong, 2010. / Includes bibliographical references (leaves 95-117). Also available in print.

Thesis (M.S.)--Uniformed Services University of the Health Sciences, 2006 / Typescript (photocopy)

Thesis (Ph. D. in Cancer Biology)--Vanderbilt University, Aug. 2007. / Title from title screen. Includes bibliographical references.

Thesis (Ph. D.)--Ohio State University, 2007. / Full text release at OhioLINK's ETD Center delayed at author's request

Thesis (Ph. D.)--University of Oregon, 2006. / Typescript. Includes vita and abstract. Includes bibliographical references (leaves 88-100). Also available for download via the World Wide Web; free to University of Oregon users.

Thesis (Ph. D.)--University of Washington, 2000. / Vita. Includes bibliographical references (leaves 121-136).

Thesis (MSc)--University of Stellenbosch, 2003. / ENGLISH ABSTRACT: Yeasts, like most organisms, have to survive in highly variable and hostile environments. Survival therefore requires adaptation to the changing external conditions. On the molecular level, specific adaptation to specific environmental conditions requires the yeast to be able: (i) to sense all relevant environmental parameters; (ii) to relay the perceived signals to the interior of the cell via signal transduction networks; and (iii) to implement a specific molecular response by modifying enzyme activities and by regulating transcription of the appropriate genes. The availability of nutrients is one of the major trophic factors for all unicellular organisms, including yeast. Saccharomyces cerevisiae senses the nutritional composition of the media and implements a specific developmental choice in response to the level of essential nutrients. In conditions in which ample nutrients are available, S. cerevisiae will divide mitotically and populate the growth environment. If the nutrients are exhausted, diploid S. cerevisiae cells can undergo meiosis, which produces four ascospores encased in an ascus. These ascospores are robust and provide the yeast with a means to survive adverse environmental conditions. The ascospores can lie dormant for extended periods of time until the onset of favourable growth conditions, upon which the spores will germinate, mate and give rise to a new yeast population. However, S. cerevisiae has a third developmental option, referred to as pseudohyphal and invasive growth. In growth conditions in which nutrients are limited, but not exhausted, the yeast can undergo a morphological switch, altering its budding pattern and forming chains of elongated cells that can penetrate the growth substrate to forage for nutrients. The focus of this study was on elements of the signal transduction networks regulating invasive growth in S. cerevisiae. Some components of the signal transduction pathways are well characterised, while several transcription factors that are regulated via these pathways remain poorly studied. In this study, the RMEt gene was identified for its ability to enhance starch degradation and invasive growth when present on a multiple copy plasmid. Rme1 p had previously been identified as a repressor of meiosis and, for this reason, the literature review focuses on the regulation of the meiotic process. In particular, the review focuses on the factors governing entry into meiosis in response to nutrient starvation and ploidy. Also, the transcriptional regulation of the master initiator of meiosis, IMEt, and the action of Ime1 p are included in the review. The experimental part of the study entailed a genetic analysis of the role of Rme1 p in invasive growth and starch metabolism. Epistasis analysis was conducted of Rme1 p and elements of the MAP Kinase module, as well as of the transcription factors, Mss11p, Msn1p/Mss10p, Tec1p, Phd1p and F108p. Rme1p is known to bind to the promoter of CLN2, a G1-cyclin, and enhances its expression. Therefore, the cell cyclins CLN1 and CLN2 were included in the study. The study revealed that Rme1 p functions independently or downstream of the MAP Kinase cascade and does not require Cln1 p or Cln2p to induce invasive growth. FL011/MUC1 encodes a cell wall protein that is required for invasive growth. Like the above-mentioned factors, Rme1 p requires FL011 to induce invasive growth. We identified an Rme1 p binding site in the promoter of FL011. Overexpression of Rme1p was able to induce FL01t expression, despite deletions of mss11, msn1, ttos, tee1 and phd1. In the inverse experiment, these factors were able to induce FL011 expression in an rme1 deleted strain. This would indicate that Rme1 p does not function in a hierarchical signalling system with these factors, but could function in a more general role to modify transcription. / AFRIKAANSE OPSOMMING: Die natuur is hoogs veranderlik en alle organismes, insluitende gis, moet by die omgewing kan aanpas om te kan oorleef. Baie eksterne faktore beïnvloed die ontwikkeling van die gissel. Vir die gis om by spesifieke omgewingstoestande aan te pas, moet die gis op 'n molekulêre vlak: (i) al die omgewingsparameters waarneem; (ii) die waargenome omgewingsparameters as seine na die selkern deur middel van seintransduksieweë gelei; en (iii) transkripsie van gene aktiveer of onderdruk en ensiemaktiwiteit reguleer om sodoende die gepaste molekulêre respons te implementeer. Die beskikbaarheid van voedingstowwe in die omgewing is een van die belangrikste omgewingseine wat eensellige organismes moet kan waarneem. Saccharomyces cerevisiae kan spesifieke ontwikkelingsopsies, na gelang van die voedingstowwe wat beskikbaar is, uitoefen. In groeiomstandighede waar daar 'n oorvloed van voedingstowwe is, verdeel S. cerevisiae d.m.v. mitose en vesprei dit deur die omgewing. Sodra die voedingstowwe uitgeput is, word mitose onderdruk. Diploïede S. cerevisiae inisieer meiose, wat aanleiding tot die vorming van vier spore gee. Hierdie spore bevat slegs die helfte van die ouer se chromosome en kan gevolglik met 'n ander spoor paar om weer 'n diploïede gissel te vorm. Die spore is bestand teen strawwe omgewingstoestande en kan vir lang tye oorleef. Wanneer die spoor aan gunstige groeitoestande blootgestel word, ontkiem dit om aan 'n nuwe giskolonie oorsprong te gee. S. cerevisiae het egter 'n derde ontwikkelingsopsie, naamlik pseudohife-differensiëring. Wanneer die beskikbaarheid van voedingstowwe in die omgewing afneem, maar nog nie uitgeput is nie, ondergaan die gis 'n morfologiese verandering. Hierdie verandering word gekenmerk deur selverlenging, nl. botselle wat slegs aan die een punt van die gissel vorm en dogterselle wat aan die moerderselle geheg bly. Dit lei tot die vorming van kettings van selle wat van die giskolonie af weggroei. Voorts kan die selkettings ook die groeisubstraat binnedring. Dit staan as penetrasie-groei bekend en laat die gis toe om na nuwe voedingsbronne te soek. Hierdie studie het op die elemente van seintransduksieweë, wat by penetrasiegroei betrokke is, gefokus. Sekere komponente van die seintransduksieweë is reeds goed gekarakteriseer, terwyl ander komponente nog grootliks onbekend is. In hierdie studie, word 'n rol vir RME1 in die verbetering van styselafbraak en penetrasiegroei geïdentifiseer. Aangesien Rme1 p voorheen as 'n onderdrukker van meiose geïdentifiseer is, is 'n litetaruurstudie oor die inisiasie van meiose saamgestel. Die faktore wat meiose induseer, naamlik 'n gebrek aan voedingstowwe en die sel se ploïedie, word bespreek. Die regulering van die meester inisieerder van meiosie, IME1, asook die proteïene waarmee Ime1p reageer, is ook in die studie ingesluit. Die eksperimentele deel van die studie behels die genetiese analise van Rme1 p tydens penetrasiegroei en styselhidroliese. 'n Epistase-analise tussen Rme1 p en elemente van die MAP-Kinasemodule, asook van die transkripsie faktore Mss11 p, Msn1p/Mss10p, Tec1p, Phd1p en F108p, is onderneem. Rme1p is bekend om aan die promotor van CLN2 te bind en transkripsie te induseer. Daarom is die selsikliene CLN1 en CLN2 in die studie ingesluit. Die studie dui daarop dat Rme1 ponafhanklik van die MAP-Kinasemodule funksioneer en nie Cln1 p en Cln2p benodig om penetrasiegroei te induseer nie. FL011/MUC1 kodeer vir 'n selwandproteïen wat noodsaaklik vir pentrasiegroei is. Soos in die geval van die bogenoemde faktore, benodig Rme1 p FL011 om penetrasiegroei te kan induseer. Ten spyte van mss11-, msn1-, ttos-, tec1- en phd1- delesies, kan ooruitdrukking van Rme1p die transkripsie van FL011 induseer. In die omgekeerde eksperiment kon die bogenoemde faktore FL011-transkripsie ten spyte van 'n rme1 delesie induseer. Die resultate dui daarop dat Rme1 p nie in 'n hiërargiese pad funksioneer nie, maar dat dit waarskynlik 'n meer algemene rol deur transkripsiemodifisering vervul.

O titânio comercialmente puro (Ti-Cp) e suas ligas destacam-se como biomateriais metálicos devido a sua biocompatibilidade sendo amplamente utilizados. Buscando aprimorar o sucesso clínico dos implantes de Ti-Cp em longo prazo, é necessário revestir a sua superfície, proporcionando uma eficiente ancoragem mecânica do implante com o tecido ósseo. Dentre os diversos revestimentos superficiais destacam-se os revestimentos híbridos orgânicos-inorgânicos à base de precursores alcóxidos de silício, obtidos via processo sol-gel. Para que ocorra uma satisfatória adesão do revestimento no substrato, precisa-se levar em consideração a natureza e a preparação da superfície metálica antes da aplicação deste revestimento. Na etapa inicial do trabalho, pré-tratamentos superficiais foram propostos previamente à aplicação dos revestimentos buscando aumentar a aderência entre o titânio e este revestimento híbrido. Utilizou-se três diferentes pré-tratamentos na superfície do Ti-Cp: o "piranha" (ácido sulfúrico e peróxido de hidrogênio), o "kroll" (ácido fluorídrico, ácido nítrico e água) e o "hidróxido de sódio". Em sequência, aplicou-se por processo de dip-coating sobre as superfícies tratadas, um revestimento híbrido produzido a partir dos precursores alcóxidos de silício tetraetoxisilano (TEOS) e metiltrietoxisilano (MTES), obtido pelo processo de sol-gel. Em uma segunda etapa, sobre a superfície do Ti-Cp com o pré-tratamento superficial que proporcionou uma maior aderência do revestimento híbrido ao titânio, aplicou-se por dip-coating, um revestimento híbrido à base de precursores alcóxidos de silício TEOS e MTES com adição de partículas de hidroxiapatita buscando aprimorar a diferenciação celular sobre o revestimento híbrido. O pré-tratamento com o hidróxido de sódio promove o melhor resultado dentre os pré-tratamentos, pois o revestimento híbrido aplicado posteriormente apresenta recobrimento regular e adesão ao substrato de Ti-Cp. Os resultados morfológicos por MEV-FEG mostraram um revestimento híbrido com boa dispersão da hidroxiapatita e um recobrimento regular e adesão ao substrato de Ti-Cp. Nos resultados biológicos Ti-Cp revestido com TEOS/MTES com a presença de partículas de hidroxiapatita obteve uma adesão celular semelhante ao Ti-Cp sem tratamento. Porém este mesmo revestimento não propiciou a proliferação e diferenciação celular. Os resultados indicaram que a combinação de fatores como a sua superfície hidrofóbica (91°) e a presença da hidroxiapatita no revestimento tornou a superfície desorganizada, acarretando em uma superfície com comportamento desfavorável para o desenvolvimento das células-tronco mesenquimais. / Commercially pure titanium (cp-Ti) and its alloys stand out among the metallic materials due to their biocompatibility being widely used in biomaterials. In order to improve the clinical success of cp-Ti implants in the long term, it is necessary to coat the surface, providing an efficient mechanical anchoring of the implant with the bone tissue. Among the various surface coatings are the hybrid coatings based on silicon alkoxide precursors, obtained by the sol-gel process, however, considering the nature and the preparation of the metal surface prior to the application of this coating. In the initial stage of the work, surface pre-treatments were proposed prior to the application of the coatings seeking to increase the adhesion between the titanium and this hybrid coating. Three different pretreatments were used on the cp-Ti surface: "piranha" (sulfuric acid and hydrogen peroxide), "kroll "(hydrofluoric acid, nitric acid and water) and "sodium hydroxide". Subsequently, a hybrid coating produced by the tetraethoxysilane silicon (TEOS) and methyltriethoxysilane (MTES) precursors obtained by the sol-gel process was applied by the dip-coating process onto the treated surfaces. In a second step, on the surface of the cp-Ti with the surface pretreatment that gave a greater adhesion of the hybrid coating to the titanium, dip-coating, a hybrid coating based on precursors silicon alkoxides TEOS and MTES with the addition of hydroxyapatite particles to enhance cell differentiation on the hybrid coating. Pretreatment with sodium hydroxide promotes the best result among the pre-treatments, since the hybrid coating applied afterwards presents regular coating and adhesion to the cp-Ti substrate. The morphological results by SEM-FEG showed a hybrid coating with good dispersion of the hydroxyapatite and a regular coating and adhesion to the cp-Ti substrate. In the biological results Ti-Cp coated with TEOS / MTES with the presence of hydroxyapatite particles obtained a cell adhesion similar to Ti-Cp without treatment. However, this same coating did not promote cell proliferation and differentiation. The results indicated that the combination of factors such as its hydrophobic surface (91°) and the presence of the hydroxyapatite encapsulated in the coating rendering the surface disorganized led to a surface with unfavorable behavior for the development of mesenchymal stem cells.