Submitted by Danielle Karla Martins Silva (danielle.martins@ufpe.br) on 2015-03-12T13:01:25Z No. of bitstreams: 2 DISSERTAÇÃO FINAL - SADRAQUE ENEAS DE FIGUEIREDO LUCENA.pdf: 1824920 bytes, checksum: 893382afbc1ec6488124ee05b213f03e (MD5) license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) / Made available in DSpace on 2015-03-12T13:01:25Z (GMT). No. of bitstreams: 2 DISSERTAÇÃO FINAL - SADRAQUE ENEAS DE FIGUEIREDO LUCENA.pdf: 1824920 bytes, checksum: 893382afbc1ec6488124ee05b213f03e (MD5) license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Previous issue date: 2013 / CAPES / Em determinados estudos, a modelagem de dados por meio de regressão pode levar a dois ou mais modelos com ajustes semelhantes, mas com especificações distintas. Se qualquer um dos modelos avaliados não pode ser obtido do outro por meio de restrições sobre os parâmetros que os indexam, estes são ditos não-encaixados. Em se tratando de modelos de regressão beta, que são adequados a dados cuja variável resposta varia no intervalo (0;1), os mesmos são não encaixados quando os modelos diferem nos regressores e/ou nos casos em que há distinção na função de ligação associada ao preditor linear utilizado no submodelo da média ou da precisão. Nessas situações, os testes propostos para avaliar qual dos modelos está corretamente especificado não podem ser aplicados, pois são adequados apenas a modelos lineares de regressão. Neste sentido, a presente dissertação tem por objetivo apresentar uma adaptação no teste J – o mais utilizado em regressões na avaliação de hipóteses não-encaixadas – e em sua modificação, o teste MJ. Foram avaliados cenários em que os modelos diferem nos regressores e nas funções de ligação considerando-se pequenos tamanhos de amostra, uma vez que em amostras grandes as aproximações assintóticas são válidas. A avaliação foi baseada nas taxas de rejeição nula dos testes, sendo comparados os resultados dos testes com suas versões bootstrap. De acordo com os resultados, as taxas de rejeição dos testes tenderam aos valores desejados de acordo com o aumento do tamanho da amostra e a utilização de uma esquema bootstrap reduziu consideravelmente as distorções de tamanho.

Orientador: Altair Antoninha Del Bel Cury / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-07-31T15:14:31Z (GMT). No. of bitstreams: 1 Oliveira_PauloAntoniode_D.pdf: 6996623 bytes, checksum: c54fe9e3e6e9361a6e5856b4bdcf51d5 (MD5) Previous issue date: 2001 / Resumo: Foi propósito deste trabalho avaliar a prevalência de distúrbios da Articulação Têmporo Mandibular (DATM), em jovens universitários em uma amostra padronizada (n = 178) e relacionar prováveis agentes etiológicos. A metodologia utilizada para obtenção de dados foi questionário, exame clínico e eletrovibratografia computadorizada. A prevalência de distúrbios de ATM foi de 42,70% (76) sendo 31,46% (56) do sexo feminino e 11,24% (20) do sexo masculino; para dor 16,29% (29) sendo 9,55% (17) do sexo feminino e 6,74% (12) do sexo masculino; ruídos articulares 17,98% (32) sendo 14,61% (26) do sexo feminino e 3,37% (6) do sexo masculino; dor e ruído articular foi de 8,43% (15) sendo 7,30% (13) do sexo feminino e 1,12% (2) do sexo masculino. Para a etiologia dos distúrbios foram encontrados hipermobilidade articular sistêmica, apertamento dental, correção ortodôntica anterior e tensão emocional. A prevalência de portadores de hipermobilidade na amostra foi de 44,94% (80) sendo 31,46% (56) do sexo feminino e 13,48% (24) do sexo masculino. Destes apresentaram DATM 21,91% (39) sendo 17,42% (31) do sexo feminino e 4,49% (8) do sexo masculino; quanto ao apertamento 44,94% (80) apertavam dentes sendo 35,96% (64) do sexo feminino e 8,99% (16) do sexo masculino. Dentre estes apresentaram DATM 26,03% (41) sendo 20,22% (36) do sexo feminino e 2,81% (5) do sexo masculino; quanto a correção ortodôntica anterior, encontrou-se 64,04% (114) sendo 41,57% (74) do sexo feminino e 22,47% (40) do sexo masculino. Dentre estes apresentaram DATM 30,90% (55) sendo 21,91% (39) do sexo feminino e 8,99% (16) do sexo masculino. Relataram ser portadores de tensão emocional 62,92% (112) sendo 47,19%(84) do sexo feminino e 15,73% (28) do sexo masculino. Dentre estes apresentaram DATM 29,21% (52) sendo 24,16% (43) do sexo feminino e 5,06% (9) do sexo masculino. Os resultados sugeriram que a prevalência de DATM na amostra examinada foi relativamente alta sendo o sexo feminino o mais susceptivel. Não se encontrou um agente etiológico predominante no estudo, concluindo-se que DA TM tem etiologia multifatorial / Abstract: The purpose of this work was to evaluate the TMJs of young high school students, in a custom sample (# = 178) with the objective of acquiring a prevalence of signs and symptoms. The studies were also re1ated to probable etiological agents. The methods used in the data acquirement was questionnaire, c1inica1 examination and computerized eletrovibratography. The prevalence for TMJ disorders in the sample was 42,70% (76 young people) being 3],46% (56) female and 11,24% (20) male. The prevalence of pain was ]6,29% (29) being 9,55% (17) female and 6,74% (12) male. The prevalence of TMJ sounds was ]7,98% (32) being 14,6]% (26) female and 3,37% (6) male. The prevalence of pain and TMJ sounds was 8,43% (15) being 7,30% (13) female and 1,12% (2) male. About probable etiological agents: general joint hypermobility, dental compress, former orthodontic correction and emotional tension were studied. People with hypermobility represented 44,94% (80) being 31,46% (56) female and 13,48% (24) male. Between then 2],91% (39) had TMJ disorders, being 17,42% (31) female and 4,49% (8) male. In the sampke 44,94% (80) had dental compress, being 35,96% (64) female and 8,99% (16) male. Between then 26,03% (41) had TMJ disorders being 20,22% (36) female and 2,81% (5) male. The prevalence of young people with former orthodontic correction in the sample was 64,04% (114) being 41,57% (74) female and 22,47% (40) male. Between then 30,90% (55) being 21,21% (39) female and 8,99% (16) male. Reported to have emotional tension 62,92% (112) in the sample, being 47,19% (84) female and 15,73% (28) Was concluded that the prevatence of TMJ disorders in the sample is relatively high mate. Between then 29,21% (52) had TMJ disorders, being 24,16% (43) femate and 5,06% (9) mate and the femate sex is, for sure, most susceptible. No predominant etiological agent was found with this study, witch makes us conclude that TMJ disorders has multifactoriat etiology / Doutorado / Protese Dental / Doutor em Clínica Odontológica

The guanosine monophosphate synthetase (GMPS) is a class I glutamine amidotransferase, involved in the de-novo purine nucleotide biosynthesis. The enzyme catalyzes the biochemical transformation of xantosine (XMP) into guanosine monophosphate (GMP) in presence of ATP, Mg2+ and glutamine. All GMPSs consist of two catalytic sites 1) for GATase activity 2) for the ATPPase activity. The two catalytic sites may be housed in the same polypeptide (two-domain-type) or in separate polypeptides (two-subunit-type). Most of the studies have been performed on two-domain-type GMPSs, while only one study has been reported from two-subunit-type GMPS (Maruoka et al. 2009). The two-subunit-type GMPS presents an example where the component reactions of a single enzymatic reaction are carried out by two distinct subunits. In order to get better understanding of structural aspects and mechanistic principle that governs the GMPS activity in two-subunit-type GMPSs, we initiated the study by taking GMPS of Methanocaldococcus jannaschii as a model system. The GMPS of M. jannaschii (Mj) is a two-subunit-type protein. The GATase subunit catalyzes the hydrolysis of glutamine to produce glutamate and ammonia. The ATPPase subunit catalyses the amination of XMP to produce GMP using the ammonia generated in GATase subunit. Since the two component reactions are catalysed by two separate subunits and are coupled in the way that product of one reaction (ammonia) acts as a nucleophile in the second reaction. The cross-talk between these two subunits in order to maximise the efficiency of overall GMPS warrants investigation. The GATase activity is tightly regulated by the interaction with ATPPase domain/subunit, in all GMPS except in the case of P. falciparum. This interaction is facilitated by substrate binding to the ATPPase domain/subunit. Though, the conditions for the interaction between two subunits is known in a two-subunit-type GMP synthetase from P. horikoshii, the structural basis of substrate dependent interaction is not known. As a first step to understand the structural basis of interaction between the Mj GATase and Mj ATPPase subunits, we have determined the structure of Mj GATase (21 kDa) subunit using high resolution, multinuclear, multidimensional NMR spectroscopy. Sequence specific resonance assignments were obtained through analysis of various 2D and 3D hetero-nuclear multidimensional NMR experiments. NMR based distance restraints were obtained from assignment of correlations observed in NOE based experiments. Data were acquired on isotopically enriched samples of Mj GATase. The structure of Mj GATase (2lxn) was solved by using cyana-3.0 using NMR based restraints as input for the structure calculation. The ensemble of 20 lowest-energy structures showed root-mean-square deviations of 0.35±0.06 Å for backbone atoms and 0.8±0.06 Å for all heavy atoms. Attempts were also made to obtain assignments for the 69.6 kDa dimeric ATPPase subunit. Partial assignments have been obtained for this subunit. The GATase subunit is catalytically inactive. So far, there has been only one published report on a two-subunit-type GMPS from P. horikashii. The study has shown that the catalytic activity of GATase is regulated by the GATase-ATPPase interaction which is facilitated by the substrate binding to the ATPPase subunit. For the first time, we have provided the structural basis of interaction between GATase-ATPPase (112 kDa) in a two-subunit-type GMPS. Observed line width changes were used to identify residues in GATase residues that are involved in the Mj GATase-ATPPase interaction. Our data provides a possible explanation for conformational changes observed in the Mj GATase subunit upon GATase-ATPPase interaction that lead to GATase activation. Ammonia is generated in GATase subunit and is very reactive and labile. Thus, the faithful transportation of ammonia from GATase to ATPPase subunit is very crucial for optimal GMPS activity. Till date, a PDB query for GMPS retrieves only one structure which belongs to two-subunit-type GMPS, where authors have determined the structures of GATase and ATPPase subunits separately. However, the structure of holo-GMPS is not determined yet. Using interface information from experimental data and HADDOCK, we have constructed a model for the holo-GMPS from M. jannaschii. A possible ammonia channel has been deduced using the programs MOLE 2.0 and CAVER 2.0. This ammonia channel has a length of 46 Å, which is well within the range of the lengths calculated for similar channels in other glutamine amidotransferase. It had been suggested earlier that in addition to the magnesium required for charge stabilization of ATP, additional binding sites were present on GMPS. The effect of excess Mg2+ requirement on the GMPS activity has been studied in two-domain-type GMPS. However, the interaction between GATase and Mg2+ has been not investigated in any GMPS. This prompted us to investigate the effect of MgCl2 on Mj GATase subunit. For the first time, using chemical shift perturbation, we have established interaction between Mj GATase and Mg2+. The dissociation constant (Kd) of the Mj GATase-Mg2+ interaction was determined. The Kd value was found to be 1 mM, which indicates a very weak interaction. The substrate of the GATase subunit is glutamine. The condition of the hydrolysis of the glutamine is known in GMPS. However, the binding of the glutamine and associated conformational changes in GATase have been not studied in GMPS. Furthermore, till date there is no structure available for the glutamine bound GMPS/GATase. Using isotope edited one dimensional and two-dimensional NMR spectroscopy; we have shown that the Mj GATase catalytic residues are not in a compatible conformation to bind with glutamine. Thus, a conformational change in Mj GATase subunit is a pre-requisite condition for the binding of glutamine. These conformational changes are brought by the Mj GATase-ATPPase interaction.

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