Thesis (Ph. D.)--University of Alabama at Birmingham, 2009. / Title from PDF title page (viewed Sept. 2, 2009). Additional advisors: Uday Vaidya, Burton Patterson, Susan Bellis, Mark Weaver, Vinoy Thomas. Includes bibliographical references.

Thesis (M.Med.Sc.)--University of Hong Kong, 2003. / Includes bibliographical references (leaves 84-92). Also available in print.

Thesis (Ph. D.)--Ohio State University, 2006. / Available online via OhioLINK's ETD Center; full text release delayed at author's request until 2007 Mar 21

Thesis (Ph.D. in Immunology) -- University of Colorado at Denver and Health Sciences Center, 2005. / Typescript. Includes bibliographical references (leaves 91-100). Free to UCDHSC affiliates. Online version available via ProQuest Digital Dissertations;

Thesis (Ph.D.)--Kent State University, 2006. / Title from PDF t.p. (viewed Sept. 20, 2006). Advisor: Gary Meszaros. Keywords: cardiac fibroblasts; myofibroblasts; extracellular matrix; collagen VI; post-myocardial infarction remodeling. Includes bibliographical references (p. 135-152).

Thesis (M.S.) -- Worcester Polytechnic Institute. / Keywords: histology; implant; biomaterials; MRI. Includes bibliographical references (p.80-86).

abstract: Skeletal diseases related to reduced bone strength, like osteoporosis, vary in frequency and severity among human populations due in part to underlying genetic differentiation. With >600 disease-associated mutations (DAMs), COL1a1, which encodes the primary subunit of type I collagen, the main structural protein in bone, is most commonly associated with this phenotypic variation. Although numerous studies have explored genotype-phenotype relationships with COL1a1, surprisingly, no study has undertaken an evolutionary approach to determine how changes in constraint over time can be modeled to help predict bone-related disease factors. Here, molecular population and comparative species genetic analyses were conducted to characterize the evolutionary history of COL1a1. First, nucleotide and protein sequences of COL1a1 in 14 taxa representing ~450 million years of vertebrate evolution were used to investigate constraint across gene regions. Protein residues of historically high conservation are significantly correlated with disease severity today, providing a highly accurate model for disease prediction, yet interestingly, intron composition also exhibits high conservation suggesting strong historical purifying selection. Second, a human population genetic analysis of 192 COL1a1 nucleotide sequences representing 10 ethnically and geographically diverse samples was conducted. This random sample of the population shows surprisingly high numbers of amino acid polymorphisms (albeit rare in frequency), suggesting that not all protein variants today are highly deleterious. Further, an unusual haplotype structure was identified across populations, but which is only associated with noncoding variation in the 5' region of COL1a1 where gene expression alteration is most likely. Finally, a population genetic analysis of 40 chimpanzee COL1a1 sequences shows no amino acid polymorphism, yet does reveal an unusual haplotype structure with significantly extended linkage disequilibrium >30 kilobases away, as well as a surprisingly common exon duplication that is generally highly deleterious in humans. Altogether, these analyses indicate a history of temporally and spatially varying purifying selection on not only coding, but noncoding COL1a1 regions that is also reflected in population differentiation. In contrast to clinical studies, this approach reveals potentially functional variation, which in future analyses could explain the observed bone strength variation not only seen within humans, but other closely related primates. / Dissertation/Thesis / Ph.D. Biology 2010

Made available in DSpace on 2015-07-22T20:50:56Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-07-27. Added 1 bitstream(s) on 2015-08-11T03:07:21Z : No. of bitstreams: 1 Publico-12807.pdf: 1925667 bytes, checksum: 40f94a2382fcb5e9e0c7155532f0079a (MD5) / Objetivo: Apresentar e avaliar os resultados histológicos, anatômicos e funcionais do procedimento de McIndoe modificado, utilizando a celulose oxidada (Surgicel®). Métodos: Onze mulheres com agenesia vaginal se submeteram à neovaginoplastia com ou sem canalização útero-vaginal utilizando um molde revestido com celulose oxidada. As cirurgias foram realizadas entre janeiro de 2009 e dezembro de 2010. Oito dessas pacientes tiveram o diagnóstico de Síndrome de Mayer-Rokitansky-Kuster-Hauser (MRKH), e as outras três tiveram o diagnóstico de Agenesia Cervico-vaginal (CVA). O tempo médio de seguimento foi 14 meses (variando de 6 a 24 meses), e incluiu exame físico e avaliação do questionário sexual (Female Sexual Function Index-FSFI). Amostras teciduais foram obtidas no momento da cirurgia e 1 a 12 meses após o procedimento. Biópsias vaginais para controle foram obtidas de um grupo de pacientes com doenças ginecológicas benignas. Avaliou-se a epitelização escamosa do tecido da neovagina, e a quantidade total de colágeno das neovaginas, e comparou-se com o grupo controle. Para análise estatística utilizou-se o teste ANOVA e o t-test. Resultados: Seis meses após a cirurgia, o sucesso anatômico foi encontrado em 100% das pacientes com síndrome MRKH (comprimento vaginal > 6 cm), e sucesso funcional em todas as pacientes que iniciaram atividade sexual (Score FSFI > 30). As biópsias mostraram epitelização da neovagina após 6 meses em todas as amostras, e o conteúdo total de colágeno foi comparável ao de uma vagina normal. Uma complicação maior ocorreu em uma paciente com CVA, que culminou em morte. O procedimento de canalização útero vaginal não foi bem sucedido em criar um pertuito para menstruações regulares mensais em nenhum dos casos. Nenhuma das pacientes com CVA obtiveram sucesso anatômico ou funcional. Conclusão: A neovaginoplastia com a técnica de McIndoe modificada, utilizando a celulose oxidada (Surgicel®), procedimento simples e de baixo custo, permite a formação de canal vaginal com epitelização e conteúdo de colágeno similar ao de uma vagina normal. É uma potencial alternativa terapêutica para síndrome de MRKH. / Objective: To present and evaluate the histological, anatomical and functional results of the McIndoe procedure, as modified by the application of oxidized cellulose (SurgicelTM) in women with vaginal agenesis. Study design: Eleven patients with vaginal agenesis underwent vaginoplasty with or without uterovaginal cannulation using a mold that had been wrapped with oxidized cellulose. The surgeries were performed between January 2009 and January 2010. Eight of the patients had been diagnosed with Mayer-Rokitansky- Kuster-Hauser (MRKH) syndrome, and the remaining three had been diagnosed with cervicovaginal agenesis (CVA). The mean follow-up time was 14 months (range, 6-24 months), and it included clinical examinations and evaluation of the Female Sexual Function Index (FSFI). Neovaginal biopsies were taken from the patients with MRKH syndrome at the time of surgery and 1-12 months after surgery. Control tissues were taken from a group of patients without vaginal disease. The histology of the samples was evaluated to determine squamous epithelialization of the neovaginal tissue over time, and the total collagen content of the neovaginas were compared with normal control subjects. For statistical analysis we employed the ANOVA test and the t-test. Results: At 6 months, anatomical success was achieved in 100% of the MRKH syndrome patients (neovaginal length . 6 cm), and functional success was achieved in 100% of the patients who started their sexual life (FSFI score . 30). Biopsy results showed complete epithelialization of the neovagina after 5 monthsin all samples, and the amount of collagen content in the neovaginas progressively increased. After 6 months, the collagen content was comparable to that of a normal vagina. One major postoperative complication occurred in a patient with CVA, which culminated in death. The uterovaginal canalization procedure was unsuccessful at creating an outflow tract for regular menses in all cases. None of patients with CVA achieved anatomical or functional success. Conclusions: The procedure described here offers patients a functional vagina by means of a simple and low-cost procedure that elicits squamous epithelialization of the neovaginal vault, with total collagen content similar to that of normal vaginal tissue. It is a potential alternative therapeutic approach for MRKH syndrome but not applicable to cases of CVA. / TEDE

Adipose tissue is an organ that plays an important role in energy storage, nutritional balance and thermogenesis. White and brown adipose tissues have distinct cell morphology and metabolic functions. White adipose tissue (WAT) with unilocular lipid droplets serves as a major site of energy storage, while brown adipose tissue (BAT) with multilocular lipid droplets plays an important role in thermogenesis via a mitochondrial protein, uncoupling protein 1 (UCP1). These cells are derived from mesenchymal stem cells (MSCs). Newly discovered beige adipocytes are derived from the same MSC precursors as WAT but resemble BAT due to expression of UCP1. Due to side effects of drugs for treating obesity, activation of UCP1 positive beige adipocytes in WAT has become a new therapeutic target. The interaction of extracellular matrix (ECM) with integrin was found to regulate cell specification of mesenchymal stem cells (MSCs) via intracellular signaling. However, the role of individual ECM proteins in beige adipogenesis in WAT remains unknown. Therefore, we established a system for culturing stromal vascular fraction (SVF) cells from inguinal WAT on ECM protein coated plates and differentiating the cells into either white or beige adipocytes. We found that cells cultured on type I collagen had more round cell morphology and higher mRNA expression of thermogenic genes, UCP1 and type II iodothyronine deiodinase (DIO2),which was further enhanced in myocardin-related transcription factor A (MRTFA) knockout SVF cells. MRTFA has been reported to regulate beige adipogenesis in BMP-ROCK signaling pathway. Based on our data, we found that type I collagen-integrin signaling regulates beige adipogenesis by controlling the activity of MRTFA in MSCs. Our study has provided an insight into developing therapeutic drugs to enhance beige adipocytes formation in WAT for reducing obesity in the future.

Submitted by Jos? Henrique Henrique (jose.neves@ufvjm.edu.br) on 2017-09-21T19:51:20Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) tarciane_silva_pinto.pdf: 4051834 bytes, checksum: d6525c9152e47311a8695bf3eed5c6e6 (MD5) / Approved for entry into archive by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2017-10-09T13:37:54Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) tarciane_silva_pinto.pdf: 4051834 bytes, checksum: d6525c9152e47311a8695bf3eed5c6e6 (MD5) / Made available in DSpace on 2017-10-09T13:37:54Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) tarciane_silva_pinto.pdf: 4051834 bytes, checksum: d6525c9152e47311a8695bf3eed5c6e6 (MD5) Previous issue date: 2017 / Neste trabalho, Carbon Dots (CDs) obtidos a partir de celulose de algod?o e contendo 4,5 mmol.g-1 de grupos funcionais ?cidos, dos quais 63 % exibiam pKas t?picos de ?cidos carbox?licos foram usados na prepara??o de filmes automontados com os biopol?meros quitosana (QT) e col?geno (CL) a fim de verificar a morfologia, espessura e intera??es moleculares entre os componentes. A quitosana usada apresentou um total de 4,2 mmolg-1 de grupos funcionais -NH2, correspondente a um grau de desacetila??o de ~70 %. Por outro lado, o col?geno hidrolisado apresentou diferentes grupos funcionais com acidez de Br?nsted, t?picos da presen?a de diferentes amino?cidos na estrutura. Todos os filmes finos foram preparados com a t?cnica de deposi??o camada por camada (do ingl?s: Layer-by-layer (LbL)) por meio de imers?o do substrato nas diferentes solu??es. Os materiais foram caracterizados por diferentes t?cnicas, incluindo Microscopia de For?a At?mica, Espectroscopia na regi?o do UV-Vis, Espectroscopia de Resson?ncia de Plasma de Superf?cie e Titula??o Calorim?trica. Em todas as condi??es experimentais utilizadas para o crescimento dos filmes, observou-se um crescimento linear da quantidade de material depositado com o n?mero de imers?es realizadas. No entanto, diferentes condi??es das solu??es dos biopol?meros e da suspens?o de Carbon Dots produziram filmes com espessura e morfologia diferentes. Nos filmes de QT/CDs a quantidade de nanopart?culas depositadas por bicamada, com solu??o de quitosana em pH = 3,5, pH = 5 e pH = 3,5 na presen?a de 0,1 mol/L de NaCl, foram, respectivamente, 11 mg.m-2, 16 mg.m-2 e 24 mg.m-2 sendo as espessuras dos filmes, com 20 bicamadas, correspondentes a estas quantidades foram de 60, 150 e 200 nm. Este resultado ? atribu?do ao aumento da flexibilidade das cadeias polim?ricas dos biopol?meros, as quais est?o menos carregadas. Dessa forma, as cadeias podem apresentar conforma??es mais adequadas para recobrir eficientemente a estrutura das nanopart?culas quase esf?ricas. Al?m disso, o aumento da for?a i?nica da solu??o de Carbon Dots tamb?m contribui para o aumento de material depositado devido ? forma??o de aglomerados sob estas condi??es. Nos filmes de CL/CDs, a quantidade de nanopart?culas depositadas, com solu??o de col?geno em pH = 3,16, pH = 5 e pH = 3,16 na presen?a de 0,1 mol/L de NaCl, foram 2,3 mg.m-2, 6,46 mg.m-2 e 6,41 mg.m-2, respectivamente. No entanto, a energia de intera??o, obtida por calorimetria isot?rmica, ? maior em pH baixo. Em geral, a quantidade de material depositado nos filmes de col?geno ? bem inferior ?s observadas para os filmes de QT/CDs e, consequentemente, filmes com espessuras entre 40 e 50 nm. Al?m disso, n?o foi observada varia??o significativa entre as massas depositadas nestes filmes com o aumento do pH e for?a i?nica. Estes resultados podem estar relacionados ? menor ?carga parcial positiva? sobre as cadeias da prote?na em rela??o a quitosana, observada pelos potenciais zeta nestas condi??es. Por fim, os resultados aqui apresentados sugerem que as estruturas dos filmes, isto ?, morfologia e espessura, podem ser facilmente controladas e reproduzidas manipulando-se as condi??es das solu??es dos biopol?meros, al?m do tradicional n?mero de imers?es. Em adi??o, o estudo pode contribuir para o desenvolvimento de uma nova classe de dispositivos de alto desempenho, como sensores e superf?cies fotoativas. / Disserta??o (Mestrado) ? Programa de P?s-Gradua??o em Qu?mica, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2017. / In the present work, Carbon Dots (CDs), obtained from cotton cellulose and containing 4.5 mmol g-1 of acid functional groups, of which 63% exhibited typical pKa?s compared to carboxylic acids, were used in the preparation of self-assembled films with the biopolymers Chitosan (QT) and Collagen (CL) in order to verify the morphology, thickness and molecular interactions among the components. The chitosan used in this work had a total of 4.2 mmol g-1 of functional groups ?NH2, corresponding to a deacetylation degree of ~70%. On the other hand, the hydrolyzed collagen showed different functional groups with Br?nsted acidity typical to the presence of different amino acids in the structure. All the thin films were prepared using the Layer-by-layer method (LbL) by immersing the substrate in different solutions. The materials were characterized by several techniques, such as Atomic Force Microscopy, UV-Vis Spectroscopy, Surface Plasmon Resonance and Calorimetric Titration. It was observed, in all experimental conditions for the growth of the films, a linear increase in the amount of deposited material with the number of immersions performed. However, different conditions of the biopolymer solutions produced films with different thickness and morphology. In the films QT/CDs the amount of nanoparticles deposited per bilayer, with the chitosan solution at pH = 3.5, pH = 5 and pH = 3.5 with the presence of 0.1 mol L-1 of NaCl, were, respectively, 11 mg m-2, 16 mg m-2 and 24 mg m-2 with the thickness of the film, at 20 bilayers, at 60, 150 and 200 nm. This result is associated to the increase in the flexibility of the polymeric chains of the biopolymers, which are less charged. Thus, the chains can present conformations that are proper to cover more efficiently the structure of the almost spherical nanoparticles. Furthermore, the increase of the ionic strength of the Carbon Dots solution also contributes to the increase of the material deposited due to the formation of agglomerates in these conditions. In the films CL/CDs, the amount of nanoparticles deposited, with the collagen solution at pH = 3.16, pH = 5 and pH3.16 in the presence of 0.1 mol L-1 of NaCl, were 2.3 mg m-2, 6.46 mg m-2 and 6.41 mg m-2, respectively. However, the interaction energy, obtained by isothermal calorimetry, is higher in low pH. In general, the amount of material deposited on the collagen films is much lower than that observed for the QT/CDs films and, consequently, films thickness are 40 and 50 nm. Besides that, it was not observed any significant variation between the masses deposited in these films with the increase of the pH and the ionic strength. These results may be associated to the lower ?partial positive charge? on the protein chains in relation to the chitosan, observed by the zeta potentials in these conditions. The presented results suggest that the structures of the films, i.e. morphology and thickness, can be easily controlled and reproduced manipulating the conditions of the biopolymer solutions and the number of immersions. Additionally, the study may contribute to the development of a new class of high performance devices, such as sensors and photoactive surfaces.