COVID-19 was a pandemic that has impacted the world in various ways and forced everyone to quarantine within the confounds of their homes. As studies investigated the effects of the pandemic, it was found that undergraduate students faced severe emotional and psychological difficulties being “at-risk” for greater psychological distress (Mayorga et al., 2021). Undergraduate students are currently made up of Generation Z individuals who are born from 1995 to 2010 (Ang et al., 2021). The present study investigates the relationship between mental health and generational cultural attitudes to explore whether there is a correlation between the stressors from COVID and generation Z’s cultural attitudes. A hypothesis is that generation z college students with more mental health issues due to COVID stressors will be more collectivist and the other is that Generation Z college students are more likely to experience more distress from COVID stressors than previous generations. Participants were given an online survey with the Individualism and Collectivism Scale (Triandis & Gelfand, 1998), Beck’s Depression Inventory-II (Beck et al., 1996), State-Trait Anxiety Inventory (Spielberger, 1983), and the Covid Stress Scale (Taylor et al., 2020). Data collection includes 183 undergraduate students from the University of Central Florida. Pearson correlations were conducted between depression, anxiety, and COVID stress. Also, a Pearson correlation was also made between individualism, collectivism, and COVID stress. Lastly, a paired sample t-test was conducted to compare the means between individualism and collectivism. Overall, results did not show support for the first hypothesis because although there was a significant correlation between depression, anxiety, and COVID stress, it cannot be told how much COVID stress affected mental health. Additionally, there was no significant correlation between collectivism or individualism and COVID stress, indicating that cultural attitudes did not predict the level of COVID distress. However, results did find that students were statistically more collectivistic than individualistic, which supports a part of my hypothesis. Understanding cohort and generational differences in emotional response to the COVID-19 pandemic will help in recognizing and assisting these groups. This would demonstrate a difference in emotional response to the pandemic between generations that could help in mental health resources in any future emergency situations.

No description available.

FKBP5 stellt im Stresssystem der HPA-Achse ein zentrales Gen bei der Regulation der Sensitivität des Glukokortikoidrezeptors und somit der Reaktion auf Stress dar. Zur Adaptation an Umwelteinflüsse ist es selbst in ein komplexes System von Regulationsmechanismen eingebettet, die unter anderem epigenetische Modifikationen in Form von DNA-Methylierung umfassen. Bisherige Studien legen eine starke Assoziation von FKBP5 zu stressinduzierten psychischen Erkrankungen nahe und weisen auf eine Dysregulation der HPA-Achse als möglichen Pathomechanismus hin. Für die enge klinische Interaktion von Depression und Herzinsuffizienz sowie eine ebenfalls vermutete Rolle der HPA-Achse in der Pathogenese letzterer, könnte FKBP5 daher ein entscheidendes Bindeglied darstellen. Gleichzeitig bietet die Identifikation einer über FKBP5 ausgedrückten Dysregulation der HPA-Achse einen biologischen Befund, der als Marker für das Ansprechen einer antidepressiven Therapie herangezogen werden könnte. Ziel dieser Arbeit war daher die Untersuchung eines möglichen Einflusses regulatorischer Parameter von FKBP5 auf die Herzinsuffizienz sowie eine Prüfung dieser als mögliche Biomarker für einen Erfolg der antidepressiven Therapie. Dazu wurden Blutproben von ProbandInnen der GEParD- bzw. DaCFail-Studie mit Depression, Herzinsuffizienz sowie gesunde Kontrollen untersucht. Durch Pyrosequenzierung bisulfitkonvertierter DNA erfolgte die Bestimmung der Methylierung regulatorischer CpGs. Die Messung der relativen mRNA-Expression erfolgte durch den Einsatz einer qPCR. In der Auswertung fand sich keine differentielle mRNA-Expression oder Methylierung zwischen den vier Untersuchungsgruppen. Allerdings reagierten depressive PatientInnen verglichen mit der Kontrollgruppe mit einer geringeren Zunahme der mRNA-Expression als Reaktion auf den mDST. Das Therapieansprechen in der Depressionsgruppe wiederum war mit einer niedrigeren Methylierung auf CpG7 sowie einer höheren mRNA-Expression zu Therapiebeginn assoziiert. Im Behandlungsverlauf führte eine Abnahme der mRNA-Expression bei den Respondern zu einer Annäherung beider Gruppen. Diese Arbeit konnte keine Hinweise für eine Rolle von FKBP5 in der Pathogenese der Herzinsuffizienz finden. Allerdings zeigten die Befunde zur Regulation des Gens bei Glukokortikoidstimulation eine hohe Konstanz zu vorherigen Ergebnissen. In diesen Kontext reihen sich auch die Ergebnisse für das Therapieansprechen ein, die aufgrund einer Herabregulation der HPA-Achse im Therapieverlauf die Idee einer ursächlichen HPA-Dysregulation in der Gruppe der Responder bekräftigen. Für sich allein genommen lassen sich mRNA-Expression und Methylierung aufgrund mangelnder Sensitivität und Spezifität nicht als Biomarker für das Therapieansprechen einsetzen. Die bisherigen Befunde bestärken aber eine mögliche Rolle in einer Batterie unterschiedlicher Biomarker auf verschiedenen Ebenen, wie Klinik, Psychometrie und Physiologie. / FKBP5 represents a central gene in the stress system of the HPA axis in the regulation of the sensitivity of the glucocorticoid receptor and thus the reaction to stress. To adapt to environmental influences, it is itself embedded in a complex system of regulatory mechanisms, including epigenetic modifications in the form of DNA -Methylation. Previous studies suggest a strong association of FKBP5 with stress-induced mental illnesses and point to a dysregulation of the HPA axis as a possible pathomechanism. FKBP5 could therefore represent a crucial link for the close clinical interaction between depression and heart failure as well as a suspected role of the HPA axis in the pathogenesis of the latter. At the same time, the identification of HPA axis dysregulation expressed via FKBP5 provides a biological finding that could be used as a marker for the response to antidepressant therapy. The aim of this work was therefore to investigate a possible influence of regulatory parameters of FKBP5 on heart failure and to examine these as possible biomarkers for the success of the antidepressive therapy. For this purpose, blood samples from subjects of the GEParD or DaCFail study with depression, heart failure and healthy controls were examined. Pyrosequencing of bisulfite-converted DNA was used to determine the methylation of regulatory CpGs. The relative mRNA expression was measured using qPCR. The analysis found no differential mRNA expression or methylation between the four study groups. However, depressed patients responded with a smaller increase in mRNA expression in response to the mDST compared to the control group. The treatment response in the depression group was associated with lower methylation on CpG7 and higher mRNA expression at the start of therapy. Over the course of treatment, a decrease in mRNA expression in responders led to a convergence of both groups. This work did not find any evidence for a role for FKBP5 in the pathogenesis of heart failure. However, the findings on the regulation of the gene during glucocorticoid stimulation showed a high degree of consistency with previous results. The results for the treatment response also fit into this context, which strengthen the idea of a causal HPA dysregulation in the group of responders due to a downregulation of the HPA axis during the course of therapy. Taken alone, mRNA expression and methylation cannot be used as biomarkers of treatment response due to a lack of sensitivity and specificity. However, the findings so far support a possible role in a battery of different biomarkers at different levels, such as clinical, psychometrics and physiology.

Problem background: The voluntary turnover of employees is increasing, the baby boomer generation is retiring and the remaining jobs are to be filled with the workforce left behind, a workforce that is smaller in size. These younger generations (generation Y and Z) have different values and attitudes towards work, and they tend to switch jobs more frequently. This means that companies needs to focus on retaining their personnel. This is particularly true for SMEs since they do not have the same resources to spend on attracting potential workers as larger corporations. Purpose: The purpose of this study is to gain a better understanding of how SMEs use employer branding to retain young employees (18-30 years old) in their organization and how it is perceived. Theoretical framework: Consists of theories regarding employer branding and organizational behaviour. These include signaling theory, functional and symbolic attributes, the seven brand value propositions and organizational reputation. Methodology: The authors has used a deductive qualitative approach where a total of 14 semi structured interviews has been conducted. Seven of the interviews were performed on employees between the age of 18-30 years old from three different companies. The remaining seven were performed on management personnel from the same three companies. The respondents answered a questionnaire at the end of each interview. Empirical results: Contains a summary of each company that were involved as well as what was discussed and uncovered in the interviews. Analysis: It connects the empirical results and the theoretical framework. The found discrepancies and similarities are discussed and analyzed with the seven brand value propositions based on the theoretical framework. Conclusion: It was concluded that there exists a discrepancy between Workers and Management when it comes to the time the Workers are willing to stay. It was also uncovered that development was an important aspect when it came to the young employees turnover intention as well as flexible schedules, support from management, salaries and varying work tasks. The reputation of the companies was also not accurate which in turn could affect the matching potential between organization and individual.

Made available in DSpace on 2015-04-14T14:33:32Z (GMT). No. of bitstreams: 1 381039.pdf: 166940 bytes, checksum: b4f8c3c43d696ecf79f32d065ca1e331 (MD5) Previous issue date: 2006-03-31 / Cuida-se de aprofundamento do estudo sobre o perfil jur?dico-constitucional do direito ? identidade gen?tica da pessoa humana na ordem jur?dico-constitucional p?tria, especialmente fundamentando a consagra??o, ainda que impl?cita, de tal direito na Constitui??o de 1988, como manifesta??o e exig?ncia do princ?pio da dignidade da pessoa humana, da cl?usula geral impl?cita de tutela de todas as manifesta??es essenciais da personalidade humana e do direito fundamental ? vida. Al?m de no??es conceituais preliminares, aportam-se not?cias sobre o projeto genoma humano, d?-se uma breve mirada sobre as principais tecnologias atualmente dispon?veis, analisa-se a evolu??o da prote??o jur?dica do genoma humano no plano internacional e comparado e apresenta-se um estudo cr?tico-comparativo de algumas concep??es filos?ficas de dignidade humana, as concep??es de Kant, Hegel, Dworkin e Habermas, ? guisa da compreens?o da dignidade da pessoa humana como conceito jur?dico. Para al?m da fundamenta??o j? explicitada, estabelece-se o significado do direito fundamental ? identidade gen?tica, analisa-se a sua titularidade, delineia-se o seu ?mbito de prote??o sob o enfoque da multifuncionalidade dos direitos fundamentais, seja como direitos de defesa, seja como direitos a presta??es, enfocando-se especificamente as quest?es relativas ?s tecnologias de clonagem humana, aos testes gen?ticos para conhecer o genoma humano e ?s terapias g?nicas para intervir no genoma humano e, ainda, aborda-se a problem?tica dos limites do direito fundamental ? identidade gen?tica, quando em rota de colis?o com outros direitos fundamentais, bem como a prote??o da reserva legal, do n?cleo essencial e o princ?pio da proporcionalidade, concretizando o problema desses conflitos e tens?es ? luz dos exemplos do direito ? sa?de, liberdade de investiga??o cient?fica e propriedade industrial. Ao final, no que tange ?s atividades do juiz e do legislador, s?o tecidas algumas reflex?es cr?ticas acerca do problema do excesso e da insufici?ncia de prote??o do direito fundamental ? identidade gen?tica da pessoa humana no ordenamento jur?dico-constitucional brasileiro.

Submitted by Caroline Xavier (caroline.xavier@pucrs.br) on 2017-05-04T17:15:51Z No. of bitstreams: 1 TES_HENRIQUE_VIEIRA_FIGUEIRO_COMPLETO.pdf: 4680551 bytes, checksum: 8695b78fe6812f4690586975941c4c31 (MD5) / Made available in DSpace on 2017-05-04T17:15:51Z (GMT). No. of bitstreams: 1 TES_HENRIQUE_VIEIRA_FIGUEIRO_COMPLETO.pdf: 4680551 bytes, checksum: 8695b78fe6812f4690586975941c4c31 (MD5) Previous issue date: 2016-03-11 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Conselho Nacional de Pesquisa e Desenvolvimento Cient?fico e Tecnol?gico - CNPq / In the past 10 years, high throughput sequencing has revolutionized evolutionary biology. With the technical advances that emerged with the genome sequencing of model species, it is now possible to apply these techniques to taxonomic groups without any previously available genetic resources. Complete genome sequencing and reduced representation methods have enabled us to explore deeper evolutionary questions, such as detecting ancient hybridization and signatures of selection on a genomic scale. Among the groups that could benefit from these methods is the Panthera genus. The group is composed by five species (P. onca, P. tigris, P. leo, P. pardus and P. uncia), all of which are large felids that exert important ecological role as apex predators in their habitats. Their low densities, alarming rates of habitat loss and chronic conflict with humans, all of them are threatened with extinction in the wild and thus important targets for conservation. One of the species in this group, the jaguar (P. onca), is the only member of the genus currently present in the Neotropical region, and the focus of our study. The jaguar has a color pattern similar to that of the leopard, but a much more robust constitution, with massive jaws and shorter limbs. The present study aims to characterize for the first time the jaguar genome, and to perform comparative analyses with the genomes from all other Panthera species. In addition, we seek to perform population genomic analyses with Brazilian jaguar populations and search for signatures of divergent selection in different regions. We have sequenced four genomic libraries, with an estimated coverage depth of 84x. The complete genome sequence allowed the annotation of 25,441 genes and the description of other genomic features (e.g. ncRNA, microsatellites, numts). Additionally, we have sequenced the genome of a leopard at low coverage, with an estimated depth of 25x. With the addition of these two genomes, we were able obtain a genomic data set containing all five Panthera species, which was used to perform phylogenetic discordance analyses and to detect signatures of selection using a dataset encompassing 13,143 orthologous genes. We were able to demonstrate the presence of hybridization events during the speciation process of the species, as well as signatures of selection in genes potentially involved in important characteristics of these iconic animals. Among them, the jaguar?s robust build, the social behavior of lions, cold environment adaptations in the snow leopard and the tiger?s stripes. Using an exome capture approach, we performed a population genomics study targeting jaguar populations from different Brazilian biomes. In addition to assessments of genetic diversity and population structure, we detected signals of local adaptation using multiple methods. Among the obtained results is the presence of genes under selection that are related to energetic metabolism in the Amazon, body development in the Pantanal and immunity in the Atlantic Forest. Additionally, we observed several pigmentation-related genes under selection in different biomes. Those genes affect not only pigmentation, but also have pleiotropic effects in development and immunity routes. Overall, these results help to understand the evolutionary processes that have shaped the adaptation of Panthera species, and particularly the jaguar, to the environments where they currently live. / Nos ?ltimos 10 anos, o sequenciamento gen?mico de alto desempenho revolucionou a biologia evolutiva. Com os avan?os gerados pelo sequenciamento do genoma completo de esp?cies modelo, agora ? poss?vel aplicar essas t?cnicas em animais com praticamente nenhum recurso gen?tico dispon?vel. O sequenciamento completo de genomas, bem como o uso de t?cnicas de representa??o reduzida, permitem explorar quest?es evolutivas complexas como, por exemplo, detec??o de hibrida??o e assinaturas de sele??o natural em uma escala gen?mica. Dentre os grupos taxon?micos que podem se beneficiar de tais t?cnicas est? o g?nero Panthera. O grupo ? composto por cinco esp?cies atuais (P. onca, P. tigris, P. leo, P. pardus e P. uncia), todas elas apresentando grande porte e atuando como predadores de topo nos ambientes que ocupam. Devido ?s baixas densidades, alarmante perda de habitat e constantes conflitos com humanos, o n?vel de amea?a em que essas esp?cies se encontram ? preocupante. Dentre as esp?cies do grupo, est? a on?a-pintada (P. onca), ?nica integrante do g?nero na regi?o Neotropical e o principal foco deste trabalho. Nesse sentido, o presente estudo busca caracterizar pela primeira vez o genoma da on?a-pintada, incluindo an?lises comparativas com as outras quatro esp?cies do g?nero. Al?m disso, o trabalho tem como objetivo avaliar as popula??es de on?a no Brasil e buscar assinaturas de sele??o divergente nos biomas que ela ocupa. Para o sequenciamento do genoma da esp?cie, foram utilizadas quatro bibliotecas gen?micas, com uma cobertura estimada de 84x. A sequ?ncia do genoma completo permitiu a anota??o de 25.441 genes e a descri??o de outros componentes do genoma (p.ex. ncRNA, microssat?lites, numts). Adicionalmente, foi sequenciado o genoma de um leopardo (P. pardus) com cobertura estimada de 25x. Com esses dois novos genomas, completou-se um conjunto abrangendo todas as cinco esp?cies do g?nero, permitindo a realiza??o de an?lises de discord?ncia filogen?tica para o grupo e detec??o de sele??o positiva utilizando um conjunto de 13.143 genes ort?logos. Foi poss?vel demonstrar eventos de hibrida??o durante o processo de especia??o das esp?cies do g?nero, bem como sinais de sele??o positiva em genes envolvidos em caracter?sticas que se destacam nos grandes fel?deos. Entre eles, fen?tipos potencialmente afetados por genes sob sele??o incluem o cr?nio e membros robustos da on?a-pintada, o comportamento social no le?o, adapta??o ao frio no leopardo das neves e a presen?a de listras no tigre. Com o uso de captura de exoma, que tem como objetivo o sequenciamento do conjunto de exons da esp?cie, foi poss?vel realizar uma nova avalia??o das caracter?sticas gen?ticas de popula??es de on?a-pintada, bem como a detec??o de assinaturas de adapta??o local. Entre os resultados obtidos est? a presen?a de genes sob sele??o relacionados com metabolismo energ?tico em popula??es da Amaz?nia, adapta??es relacionadas com desenvolvimento corporal no Pantanal e imunidade na Mata Atl?ntica. Adicionalmente, foram observados diversos genes de pigmenta??o com assinaturas de sele??o em diferentes biomas. Esses genes, al?m de afetarem a colora??o dos animais, possuem efeitos pleiotr?picos no desenvolvimento e imunidade da esp?cie. Esses resultados auxiliam no entendimento dos processos evolutivos que moldaram a adapta??o das esp?cies do g?nero, e em especial a on?a pintada, aos ambientes que elas ocupam atualmente.

Submitted by PPG Ci?ncias Criminais (ppgccrim@pucrs.br) on 2017-10-31T11:44:46Z No. of bitstreams: 1 PAULO CONTI - Tese completa.pdf: 2609075 bytes, checksum: 97290ff28a48f55a05a3800950e6fc85 (MD5) / Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2017-11-10T11:50:34Z (GMT) No. of bitstreams: 1 PAULO CONTI - Tese completa.pdf: 2609075 bytes, checksum: 97290ff28a48f55a05a3800950e6fc85 (MD5) / Made available in DSpace on 2017-11-10T11:54:31Z (GMT). No. of bitstreams: 1 PAULO CONTI - Tese completa.pdf: 2609075 bytes, checksum: 97290ff28a48f55a05a3800950e6fc85 (MD5) Previous issue date: 2017-08-21 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / The main purpose of this work is to demonstrate that human genetic diversity constitutes a supraindividual interest, worthy of legal and criminal protection. Thus, in order to achieve this goal, a methodology of a deductive nature is used and a study of an interdisciplinary nature is carried out, encompassing several areas of knowledge: History, Biomedical Sciences, Bioethics and Criminal Sciences, with a special focus on Criminal Law. At first, the work seeks to determine that the use of modern genetic and reproductive technologies applied to the human being, cannot be based on an eugenics ideology of discriminatory character. Subsequently, in the bioethical analysis, the study aims to establish, as a support for the problematic scenario presented, a theoretical model based on the following principles: life, responsibility, and biomedical ethics (hierarchical). In the end, with the support of Constitutional Law and Criminal Law dogmatic, the thesis aims to determine that the sex selection and/or human genetic characteristics, in the non-therapeutic standpoint, violates constitutional principles and grounds the legitimation of legal and criminal intervention for the protection of human genetic diversity. / Este trabajo tiene como objetivo principal demostrar que la diversidad gen?tica humana constituye bien supraindividual, digno de tutela jur?dico-penal. As?, con el fin de alcanzar dicho objetivo, se utiliza una metodolog?a de car?cter deductivo y se realiza un estudio de naturaleza interdisciplinar que engloba diversas ?reas del conocimiento: Historia, Ciencias Biom?dicas, Bio?tica y Ciencias Criminales, con especial enfoque en el Derecho Penal. En un primer momento, el trabajo busca determinar que la utilizaci?n de las modernas tecnolog?as gen?ticas y reproductivas, aplicadas al ser humano, no puede estar fundamentada en una ideolog?a eugen?sica de car?cter discriminatorio. Posteriormente, adentr?ndose en el an?lisis bio?tico, el estudio pretende establecer, como sostenimiento para el escenario problem?tico presentado, un modelo te?rico pautado en los siguientes principios: vida, responsabilidad y ?tica biom?dica (jerarquizada). Al final, con el auxilio del Derecho Constitucional y de la dogm?tica del Derecho Penal, la tesis objetiva determinar que la selecci?n de sexo y/o de caracter?sticas gen?ticas humanas, en la direcci?n no terap?utica, atenta contra principios constitucionales y fundamenta la legitimaci?n de la intervenci?n jur?dico-penal para la tutela de la diversidad gen?tica humana. / Este trabalho possui como objetivo principal demonstrar que a diversidade gen?tica humana constitui bem supraindividual, digno de tutela jur?dico-penal. Assim, no intuito de alcan?ar o referido objetivo, utiliza-se uma metodologia de car?ter dedutivo e realiza-se um estudo de natureza interdisciplinar que engloba diversas ?reas do conhecimento: Hist?ria, Ci?ncias Biom?dicas, Bio?tica e Ci?ncias Criminais, com especial enfoque no Direito Penal. Num primeiro momento, o trabalho procura determinar que a utiliza??o das modernas tecnologias gen?ticas e reprodutivas, aplicadas ao ser humano, n?o pode estar fundamentada numa ideologia eugenista de car?ter discriminat?rio. Posteriormente, adentrando-se na an?lise bio?tica, o estudo visa estabelecer, como sustent?culo para o cen?rio problem?tico apresentado, um modelo te?rico pautado nos seguintes princ?pios: vida, responsabilidade e de ?tica biom?dica (hierarquizada). Ao fim, com o aux?lio do Direito Constitucional e da dogm?tica do Direito Penal, a tese objetiva determinar que a sele??o de sexo e/ou de caracter?sticas gen?ticas humanas, no vi?s n?o terap?utico, atenta contra princ?pios constitucionais e fundamenta a legitima??o da interven??o jur?dico-penal para a tutela da diversidade gen?tica humana.

Made available in DSpace on 2015-04-14T14:51:09Z (GMT). No. of bitstreams: 1 431688.pdf: 567174 bytes, checksum: 5a3c8a6c18361741aa700b9c3a83b24f (MD5) Previous issue date: 2011-03-17 / A artrite reumat?ide ? uma doen?a do sistema auto-imune que atua atrav?s de uma inflama??o nas articula??es tornando-se cr?nica com o passar dos anos, podendo desenvolver uma deformidade e destrui??o destas articula??es devido ? eros?o da cartilagem e do osso. Esta doen?a atinge pessoas de ambos os sexos com idades vari?veis. O diagn?stico da doen?a depende de uma s?rie de combina??es de sintomas cl?nicos, diagn?sticos laboratoriais e radiogr?ficos. A etiologia da AR ? multifatorial, resultando da intera??o de fatores ambientais, hormonais e gen?ticos, que contribuem para sua ocorr?ncia e express?o. Evid?ncias epidemiol?gicas mostram que fatores gen?ticos s?o relatados como risco para o aumento da AR. Acredita-se que v?rios genes possam estar envolvidos com o aparecimento da AR, e um deles ? o gene MBL2, respons?vel pela codifica??o da prote?na Lectina de Liga??o ? Manose. A MBL ? uma prote?na da fam?lia das colectinas importante para o sistema imunol?gico, relacionada com a promo??o de fagocitose de microorganismos, modula??o da resposta inflamat?ria e apoptose. Os baixos n?veis s?ricos de MBL est?o associados com muta??es gen?ticas atrav?s de polimorfismos do gene MBL2. Tr?s polimorfismos de base ?nica (SNPs) foram localizados no ?xon 1 nos c?dons 52 (alelo variante D), 54 (alelo variante B) e 57 (alelo variante C). A presen?a de qualquer uma dessas variantes ? chamada de alelo O, enquanto que a aus?ncia das variantes em qualquer uma das tr?s posi??es ? chamada alelo A. Neste estudo, analisamos o polimorfismo do gene MBL2 em 322 pacientes brasileiros com AR e 343 indiv?duos saud?veis atrav?s da t?cnica de sequenciamento.Quando comparamos indiv?duos saud?veis euro-descendentes e afro-descendentes observamos uma diferen?a significativa nas frequ?ncias genot?picas e al?licas, isto devido a frequ?ncia maior do alelo C (pacientes euro-descendentes 0.0220 vs. Pacientes Afro-descendentes 0.205, controles euro-descendentes 0.029 vs. Controles afro-descendentes 0.144, valores P<0.001). Tamb?m analisamos o gen?tipo MBL em rela??o a manifesta??es extra-articular. Quando consideramos as variantes MBL juntas, n?s encontramos um aumento da frequ?ncia do gen?tipo OO em pacientes com n?dulos reumat?ides (P=0.031). Estes achados sugerem uma associa??o do gen?tipo OO e a severidade da doen?a, entretanto mais estudos s?o necess?rios pra esclarecer a verdadeira fun??o da MBL na AR.

Made available in DSpace on 2015-04-14T14:51:17Z (GMT). No. of bitstreams: 1 438120.pdf: 2337312 bytes, checksum: 3bcbd6b2d333489c6e0cefb866d0b73c (MD5) Previous issue date: 2012-03-30 / Ewing s sarcoma was first described by James Ewing in 1921 and it is the second most common bone tumor in children and young adults. Both chromosomal breakage and translocation occur in this sarcoma. The EWS gene is localized in chromosome 22 and is involved in this translocation. However, little is known about this gene breaking region and what sequences could be involved in higher chromosomal break susceptibility. In this study we aimed to investigate three SNPs in the EWS gene breaking region in a healthy subjects population and in Ewing s sarcoma patients. Genotyping was performed by TaqMan? assay for allelic discrimination using Real-Time PCR System. We conducted analysis of allelic and genotypic frequencies, as well as association and transmission disequilibrium tests. According to our results, the control group showed similar and different genotypes distribution of all SNPs when compared to other populations studied by different projects, which shows how important it is to know the frequencies of our population. To test the hypothesis that some SNP, SNParrangement or haplotype could influence in the susceptibility to develop Ewing s sarcoma, we compared affected with non-affected individuals using association studies. The results showed one significant difference: a higher presence of homozygote T-rs4820804 in Ewing s Sarcoma patients. Transmission Disequilibrium Test (TDT) was performed to compare data from Ewing s Sarcoma patients and from their families but no statistically significant result was found. In conclusion, we find that the TT-rs4820804 EWS genotype can be associate with Ewing s sarcoma and that the rs4820804 SNP can be a candidate to understand the EWS breakage susceptibility. / O sarcoma de Ewing foi primeiramente descrito por James Ewing em 1921 e ? o segundo tumor ?sseo mais frequente em crian?as, adolescente e adultos jovens. Neste sarcoma, ? comum ocorrer a quebra e a transloca??o cromoss?mica. Dentre os genes envolvidos nesta transloca??o est? o gene EWS, localizado no cromossomo 22. Entretanto, pouco se sabe a respeito da regi?o de quebra deste gene e quais sequ?ncias poderiam levar a uma maior susceptibilidade a quebra cromoss?mica. Sendo assim, o objetivo deste trabalho foi investigar tr?s polimorfismos de base ?nica (SNPs) presentes na regi?o de quebra do gene EWS, em uma popula??o de indiv?duos saud?veis e em pacientes afetados pelo Sarcoma de Ewing. A genotipagem para os SNPs selecionados foi realizada usando TaqMan SNP Genotyping Assay pelo sistema de PCR em tempo real. N?s realizamos an?lises de frequ?ncias al?licas e genot?picas, assim como um estudo de associa??o e de desequil?brio de transmiss?o. A compara??o das frequ?ncias al?licas e genot?picas entre as popula??es deste estudo e entre popula??es de projetos j? publicados mostrou particularidades entre as popula??es, revelando a import?ncia de se conhecer tais frequ?ncias na popula??o de estudo. Para testar a hip?tese de que algum SNP, hapl?tipo ou combina??o espec?fica de SNPs poderia influenciar na susceptibilidade ao Sarcoma de Ewing, comparamos afetados com n?o-afetados realizando estudos de associa??o cujos resultados mostraram uma ?nica diferen?a significativa: a maior incid?ncia no gen?tipo TT-rs4820804 entre os afetados pelo Sarcoma de Ewing. O Teste de Desequil?brio de Transmiss?o (TDT) comparou os dados dos pacientes afetados e os dados de seus familiares, mas nenhum resultado significativo foi encontrado. Em conclus?o, o gen?tipo TT-rs4820804 pode estar associado ao Sarcoma de Ewing e o SNP rs4820804 pode ser candidato para aux?lio do entendimento da susceptibilidade de quebra do gene EWS.

Made available in DSpace on 2015-04-14T14:51:17Z (GMT). No. of bitstreams: 1 438127.pdf: 909961 bytes, checksum: 5f9f40febc8291b363b759367f823d98 (MD5) Previous issue date: 2012-03-30 / In this study the SNPs rs640098, rs491714, rs611307 into the FLI1 gene were genotyped in a sample of 201 subjects from southern Brazilian population, in 24 Ewing s sarcoma patients (geographically matched with control group) and 54 of their family members, including parents and siblings. We performed association studies comparing genotypic frequencies of rs640098, rs491714, rs611307 into the FLI1 gene, and all possible genotype combinations between Ewing s Sarcoma patients and control group. Of the three SNPs investigated individually, only one of them showed a significant result when compared to the control group; our non-combined analysis revealed a significantly higher presence of homozygote A-rs497714 among Ewing s Sarcoma patients (p=0.0065; Chi square Test). In all other tested clusters, we always noticed a higher rate of homozygote A-rs497714 among Ewing s Sarcoma patients independent of the other SNP-arrangements and/or haplotype combinations. In addition, we performed transmission disequilibrium tests comparing data from Ewing s Sarcoma patients and from their families (parents and siblings), but no statistically significant result was found. In conclusion, the present study provides evidence statistically founded that the AA-rs497714 FLI1 genotype can associated with Ewing's sarcoma. And that this polymorphism can be clinically useful as a potential genetic marker to the prognostic of risk to develop this cancer or to provide insights into FLI1 chromosome breakage context of tumorigenesis. / Neste estudo, os SNPs rs640098, rs491714, rs611307 no gene FLI1 foram genotipados em uma amostra de 201 indiv?duos da popula??o do sul do Brasil, e em 24 pacientes portadores de Sarcoma Ewing (geograficamente comparado com grupo controle) e 54 de seus familiares, incluindo pais e irm?os. Realizamos estudos de associa??o, comparando as freq??ncias genot?picas do rs640098 e rs491714 e rs611307 no gene FLI1, e todas as combina??es poss?veis entre o gen?tipo de pacientes Sarcoma de Ewing e grupo controle. Dos tr?s SNPs investigados individualmente, apenas um deles apresentou um resultado significativo quando comparado com o grupo controle; nossa an?lise n?o-combinada revelou uma presen?a significativamente maior de homozigoto A-rs497714 entre os pacientes de Sarcoma Ewing (p = 0,0065; Chi quadrado). Em todos os outros grupos testados, foi notada uma maior taxa de homozigoto A-rs497714 entre os pacientes com Sarcoma de Ewing, independentemente dos outros arranjos e / ou combina??es de SNP e hapl?tipos. Al?m disso, foram realizados testes de desequil?brio de transmiss?o, comparando dados de pacientes portadores de Sarcoma de Ewing e de suas fam?lias (pais e irm?os), mas nenhum resultado estatisticamente significativo foi encontrado. Em conclus?o, o presente estudo fornece evid?ncias estatisticamente fundada de que o gen?tipo AA-rs497714 FLI1 pode associado ao sarcoma de Ewing. E que este polimorfismo pode ser clinicamente ?til como um potencial marcador gen?tico para o progn?stico de risco para desenvolver este c?ncer ou para fornecer insights no contexto de quebras cromoss?micas de tumorig?nese no gene FLI1.