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Submitted by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2016-04-04T15:05:19Z No. of bitstreams: 1 SAMARA MARQUES DOS REIS .pdf: 1152921 bytes, checksum: 30f5b5e9c3afbab29666da7f6e7c9033 (MD5) / Made available in DSpace on 2016-04-04T15:05:19Z (GMT). No. of bitstreams: 1 SAMARA MARQUES DOS REIS .pdf: 1152921 bytes, checksum: 30f5b5e9c3afbab29666da7f6e7c9033 (MD5) Previous issue date: 2015-03-04 / Estudos de associação gene-doença mostraram uma relação entre TPH2 e a depressão em diferentes populações, estudos, no entanto, têm sido produzidos resultados contraditórios, sendo a Triptofano hidroxilase-2 (TPH2) uma enzima limitante da taxa na via sintética para a serotonina do cérebro, vários estudos relatam os polimorfismos da enzima TPH2. Dois grandes projetos, o HapMap e o 1000 genomas, organizaram a maioria dos polimorfismos a partir do estudo de várias populações disponibilizando estes dados. Este trabalho tem como objetivo desenvolver um método de estudo para obtenção de possíveis marcadores de predisposição a doença a partir da correlação entre os dados epidemiológicos e frequências populacionais de polimorfismos, baseado na hipótese de que se numa população existe maior frequência de uma determinada patologia determinada geneticamente, então as variantes envolvidas deveriam estar em maior frequência e vice-versa. O modelo usado foi o envolvimento de variantes do gene TPH2 na predisposição à depressão. Os dados obtidos com correlação positiva em um dos genótipos homozigotos e também no alelo deste homozigoto sugeriram a presença de 10 polimorfismos (14,49% do total) possivelmente envolvidos no desenvolvimento do processo depressivo. Estes dados foram comparados com dados da literatura envolvendo estudos do tipo caso controle. Nestes trabalhos foram estudados 20 dos 69 polimorfismos descritos para o gene TPH2. Com exceção de um único polimorfismo, todos os dados obtidos com a nossa estratégia apresentaram-se iguais aos dados da literatura, inclusive quanto ao alelo que determinaria predisposição à depressão quando demonstrada associação. Portanto, propomos esta estratégia como uma forma alternativa de se realizar estudos do tipo Genome-Wide Association sem a necessidade de estudos caso-controle, apenas usando dados epidemiológicos da doença, diminuindo o tempo e custo destes estudos. / Disease-gene association studies reported a relation between the TPH2 and depression in different populations, however some studies have produced contradictory results, being the tryptophan hydroxylase-2 (TPH2) a limiting enzyme in the rate of synthetic route of serotonin in the brain, many studies reported the polymorphisms of the TPH2 enzyme. Two big projects, HapMap and 1000 genomes, organized the major part of these polymorphisms from the study of several populations becoming these data available. This work is aimed to develop a system to obtain possible predisposition markers of a disease from the correlation between epidemiological data and population frequencies of polymorphism, based in the hypothesis that if in a population there is more frequency of a certain kind of pathology genetically determined, the variables involved should be more frequent and vice-versa. The model used was the involvement of variables of the TPH2 gene in the predisposition of depression. The data obtained with positive correlation in one of homozygous genotypes and in the allele of this homozygous suggested the presence of 10 polymorphisms (total 14,49%) possibly related to the development of depression. These data were compared to literature data involving case control studies. In these work were studied 20 from 69 polymorphisms described to the TPH2 gene. With the exception of only one polymorphism, all the data obtained through the strategy proposed in this work have been equals to the literature data, including the allele that is determinant to the predisposition of depression when it is demonstrated the association. Therefore, it is proposed this strategy as an alternative to realize this kind of Genome-Wide Association studies without the necessity of a case control study, only using the epidemiological data from the disease, decreasing the time and the cost of this study.

O presente trabalho avaliou através de um questionário e entrevistas pessoais no período de maio a setembro de 2004, cinqüenta participantes voluntários sujeitos de pesquisas envolvendo seres humanos, nas unidades de saúde do âmbito da Secretaria Municipal de Saúde – SMS, espalhadas pelo município de São Paulo e na Faculdade de Odontologia da Universidade de São Paulo – FOUSP. Colheu a opinião destes, sobre a experiência da voluntariedade nos experimentos de que participaram nestes locais, abordando questões como: o motivo de terem contribuído, grau de conhecimento do Termo de Consentimento Livre e Esclarecido -TCLE e a importância dispensada a este documento, com que concordaram e autorizaram a participação, de acordo com a determinação da Resolução 196/96, diretriz nacional que regulamenta as pesquisas envolvendo seres humanos. O estudo observou que, passados oito anos da entrada em vigor da Resolução 196/96, o processo de obtenção do consentimento livre e esclarecido ainda carece de cuidados. Participantes efetivamente não são esclarecidos ou não entendem o que lhes foi proposto. Consideramos a necessidade de uma maior difusão, através de ações educativas, do assunto “experimentação com seres humanos", para um maior entendimento dos voluntários de pesquisas dos seus direitos e deveres, no sentido de manter as pesquisas num elevado padrão ético. O presente estudo pretende contribuir com a hermenêutica desta Resolução e suscitar maiores discussões e reflexões sobre o assunto / The present assignment evaluated through a questionnaire and personal interviews in the period within May and September 2004, fifty volunteered participants subjects of researches involving human beings, in the units of health SMS) in São Paulo city and at Odontology University of São Paulo - FOUSP. It collected the opinion of these volunteers about the experience of voluntariness in the experiments that took part in these locals, tackling matters as: their reason of having contributed, knowledge degree of free consent form – TCLE and the dispensed importance of this document, to which they agreed and authorized the participation, according to the determination of the Resolution 196/96, national guideline that regulates the researches involving human beings. The study observed that eight years after the Resolution 196/96 was put into effect, the obtainment process of the informed consent still lacks of cares. Participants are not clear or do not understand what they were proposed. We consider the need of a larger diffusion through educational actions, of the subject experimentation with human beings, for volunteers larger understanding of their right and duties, in the sense to maintaining the researches in an elevated ethical standard. The present study intends to contribute with the hermeneutics of this Resolution and to raise larger discussions and reflections on the subject

Theoretical research has demonstrated that ecological interactions in sympatry or parapatry can generate disruptive selection that in concert with assortative mating can lead to speciation. However, empirical examples are few and restricted to terrestrial and lacustrine systems. New Zealand triplefin fishes (Family Tripterygiidae) are an ideal model system to study speciation in the sea, as they conform to the criteria of an adaptive radiation, being philopatric, speciose and abundant, and having largely sympatric distributions. This thesis investigates two key aspects of the New Zealand triplefin radiation: 1) which ecological traits are under selection?; and 2) which traits are potentially available for the development of assortative mating? Habitat use was identified as a possible key trait for selection and investigated in detail in this thesis. Habitat use of the majority of New Zealand triplefin species was censused quantitatively throughout most of their latitudinal range and analysed using novel statistical methods. Analyses showed that habitat use was highly divergent between species and thus diversification in habitat may have been a major component in the evolution of this clade. The phylogenetic analysis of habitat characters confirmed that there has been rapid evolution in habitat use among species. Habitat selection at settlement was highly species-specific, indicating that interspecific differences in adult habitat use may be the outcome of active habitat choice established at settlement. These species-specific habitat associations showed no evidence for geographic variation in habitat use. Laboratory trials and field observations of the sister-species pair Ruanoho decemdigitatus and R. whero showed that competition was linked with body size, with R. decemdigitatus being the larger and consequently dominant species. The second part of this thesis investigated which traits may have contributed to prezygotic isolation, and thus to assortative mating. Little evidence was found for divergence in breeding season or male colour patterns. However, divergence in habitat affected breeding habitat choice, as triplefins court and mate in the same territory as that occupied year round. This suggests that assortative mating in New Zealand triplefin species could be the by-product of adaptation to habitat resources. Body size affected mate choice and time at first maturity in the Ruanoho sister-species pair, suggesting that size is important in the maintenance of reproductive isolation in these species. Differences in body size may have also lead to assortative mating in other New Zealand triplefin sister-species pairs, as all sister-species pairs differ in maximum body size. The findings of this thesis invoke a strong role for ecologically-based selection in speciation, and support the hypothesis that adaptation to habitat has been a major factor in speciation in this system. / This PhD was funded by the New Zealand Royal Society (Marsden Fund 02-UOA-005 to Kendall Clements), the Tertiary Education Commission (Top Achiever Doctoral Scholarship), and the University of Auckland (University of Auckland Doctoral Scholarship.

Theoretical research has demonstrated that ecological interactions in sympatry or parapatry can generate disruptive selection that in concert with assortative mating can lead to speciation. However, empirical examples are few and restricted to terrestrial and lacustrine systems. New Zealand triplefin fishes (Family Tripterygiidae) are an ideal model system to study speciation in the sea, as they conform to the criteria of an adaptive radiation, being philopatric, speciose and abundant, and having largely sympatric distributions. This thesis investigates two key aspects of the New Zealand triplefin radiation: 1) which ecological traits are under selection?; and 2) which traits are potentially available for the development of assortative mating? Habitat use was identified as a possible key trait for selection and investigated in detail in this thesis. Habitat use of the majority of New Zealand triplefin species was censused quantitatively throughout most of their latitudinal range and analysed using novel statistical methods. Analyses showed that habitat use was highly divergent between species and thus diversification in habitat may have been a major component in the evolution of this clade. The phylogenetic analysis of habitat characters confirmed that there has been rapid evolution in habitat use among species. Habitat selection at settlement was highly species-specific, indicating that interspecific differences in adult habitat use may be the outcome of active habitat choice established at settlement. These species-specific habitat associations showed no evidence for geographic variation in habitat use. Laboratory trials and field observations of the sister-species pair Ruanoho decemdigitatus and R. whero showed that competition was linked with body size, with R. decemdigitatus being the larger and consequently dominant species. The second part of this thesis investigated which traits may have contributed to prezygotic isolation, and thus to assortative mating. Little evidence was found for divergence in breeding season or male colour patterns. However, divergence in habitat affected breeding habitat choice, as triplefins court and mate in the same territory as that occupied year round. This suggests that assortative mating in New Zealand triplefin species could be the by-product of adaptation to habitat resources. Body size affected mate choice and time at first maturity in the Ruanoho sister-species pair, suggesting that size is important in the maintenance of reproductive isolation in these species. Differences in body size may have also lead to assortative mating in other New Zealand triplefin sister-species pairs, as all sister-species pairs differ in maximum body size. The findings of this thesis invoke a strong role for ecologically-based selection in speciation, and support the hypothesis that adaptation to habitat has been a major factor in speciation in this system. / This PhD was funded by the New Zealand Royal Society (Marsden Fund 02-UOA-005 to Kendall Clements), the Tertiary Education Commission (Top Achiever Doctoral Scholarship), and the University of Auckland (University of Auckland Doctoral Scholarship.

Theoretical research has demonstrated that ecological interactions in sympatry or parapatry can generate disruptive selection that in concert with assortative mating can lead to speciation. However, empirical examples are few and restricted to terrestrial and lacustrine systems. New Zealand triplefin fishes (Family Tripterygiidae) are an ideal model system to study speciation in the sea, as they conform to the criteria of an adaptive radiation, being philopatric, speciose and abundant, and having largely sympatric distributions. This thesis investigates two key aspects of the New Zealand triplefin radiation: 1) which ecological traits are under selection?; and 2) which traits are potentially available for the development of assortative mating? Habitat use was identified as a possible key trait for selection and investigated in detail in this thesis. Habitat use of the majority of New Zealand triplefin species was censused quantitatively throughout most of their latitudinal range and analysed using novel statistical methods. Analyses showed that habitat use was highly divergent between species and thus diversification in habitat may have been a major component in the evolution of this clade. The phylogenetic analysis of habitat characters confirmed that there has been rapid evolution in habitat use among species. Habitat selection at settlement was highly species-specific, indicating that interspecific differences in adult habitat use may be the outcome of active habitat choice established at settlement. These species-specific habitat associations showed no evidence for geographic variation in habitat use. Laboratory trials and field observations of the sister-species pair Ruanoho decemdigitatus and R. whero showed that competition was linked with body size, with R. decemdigitatus being the larger and consequently dominant species. The second part of this thesis investigated which traits may have contributed to prezygotic isolation, and thus to assortative mating. Little evidence was found for divergence in breeding season or male colour patterns. However, divergence in habitat affected breeding habitat choice, as triplefins court and mate in the same territory as that occupied year round. This suggests that assortative mating in New Zealand triplefin species could be the by-product of adaptation to habitat resources. Body size affected mate choice and time at first maturity in the Ruanoho sister-species pair, suggesting that size is important in the maintenance of reproductive isolation in these species. Differences in body size may have also lead to assortative mating in other New Zealand triplefin sister-species pairs, as all sister-species pairs differ in maximum body size. The findings of this thesis invoke a strong role for ecologically-based selection in speciation, and support the hypothesis that adaptation to habitat has been a major factor in speciation in this system. / This PhD was funded by the New Zealand Royal Society (Marsden Fund 02-UOA-005 to Kendall Clements), the Tertiary Education Commission (Top Achiever Doctoral Scholarship), and the University of Auckland (University of Auckland Doctoral Scholarship.

Theoretical research has demonstrated that ecological interactions in sympatry or parapatry can generate disruptive selection that in concert with assortative mating can lead to speciation. However, empirical examples are few and restricted to terrestrial and lacustrine systems. New Zealand triplefin fishes (Family Tripterygiidae) are an ideal model system to study speciation in the sea, as they conform to the criteria of an adaptive radiation, being philopatric, speciose and abundant, and having largely sympatric distributions. This thesis investigates two key aspects of the New Zealand triplefin radiation: 1) which ecological traits are under selection?; and 2) which traits are potentially available for the development of assortative mating? Habitat use was identified as a possible key trait for selection and investigated in detail in this thesis. Habitat use of the majority of New Zealand triplefin species was censused quantitatively throughout most of their latitudinal range and analysed using novel statistical methods. Analyses showed that habitat use was highly divergent between species and thus diversification in habitat may have been a major component in the evolution of this clade. The phylogenetic analysis of habitat characters confirmed that there has been rapid evolution in habitat use among species. Habitat selection at settlement was highly species-specific, indicating that interspecific differences in adult habitat use may be the outcome of active habitat choice established at settlement. These species-specific habitat associations showed no evidence for geographic variation in habitat use. Laboratory trials and field observations of the sister-species pair Ruanoho decemdigitatus and R. whero showed that competition was linked with body size, with R. decemdigitatus being the larger and consequently dominant species. The second part of this thesis investigated which traits may have contributed to prezygotic isolation, and thus to assortative mating. Little evidence was found for divergence in breeding season or male colour patterns. However, divergence in habitat affected breeding habitat choice, as triplefins court and mate in the same territory as that occupied year round. This suggests that assortative mating in New Zealand triplefin species could be the by-product of adaptation to habitat resources. Body size affected mate choice and time at first maturity in the Ruanoho sister-species pair, suggesting that size is important in the maintenance of reproductive isolation in these species. Differences in body size may have also lead to assortative mating in other New Zealand triplefin sister-species pairs, as all sister-species pairs differ in maximum body size. The findings of this thesis invoke a strong role for ecologically-based selection in speciation, and support the hypothesis that adaptation to habitat has been a major factor in speciation in this system. / This PhD was funded by the New Zealand Royal Society (Marsden Fund 02-UOA-005 to Kendall Clements), the Tertiary Education Commission (Top Achiever Doctoral Scholarship), and the University of Auckland (University of Auckland Doctoral Scholarship.

O presente trabalho avaliou através de um questionário e entrevistas pessoais no período de maio a setembro de 2004, cinqüenta participantes voluntários sujeitos de pesquisas envolvendo seres humanos, nas unidades de saúde do âmbito da Secretaria Municipal de Saúde – SMS, espalhadas pelo município de São Paulo e na Faculdade de Odontologia da Universidade de São Paulo – FOUSP. Colheu a opinião destes, sobre a experiência da voluntariedade nos experimentos de que participaram nestes locais, abordando questões como: o motivo de terem contribuído, grau de conhecimento do Termo de Consentimento Livre e Esclarecido -TCLE e a importância dispensada a este documento, com que concordaram e autorizaram a participação, de acordo com a determinação da Resolução 196/96, diretriz nacional que regulamenta as pesquisas envolvendo seres humanos. O estudo observou que, passados oito anos da entrada em vigor da Resolução 196/96, o processo de obtenção do consentimento livre e esclarecido ainda carece de cuidados. Participantes efetivamente não são esclarecidos ou não entendem o que lhes foi proposto. Consideramos a necessidade de uma maior difusão, através de ações educativas, do assunto “experimentação com seres humanos”, para um maior entendimento dos voluntários de pesquisas dos seus direitos e deveres, no sentido de manter as pesquisas num elevado padrão ético. O presente estudo pretende contribuir com a hermenêutica desta Resolução e suscitar maiores discussões e reflexões sobre o assunto / The present assignment evaluated through a questionnaire and personal interviews in the period within May and September 2004, fifty volunteered participants subjects of researches involving human beings, in the units of health SMS) in São Paulo city and at Odontology University of São Paulo - FOUSP. It collected the opinion of these volunteers about the experience of voluntariness in the experiments that took part in these locals, tackling matters as: their reason of having contributed, knowledge degree of free consent form – TCLE and the dispensed importance of this document, to which they agreed and authorized the participation, according to the determination of the Resolution 196/96, national guideline that regulates the researches involving human beings. The study observed that eight years after the Resolution 196/96 was put into effect, the obtainment process of the informed consent still lacks of cares. Participants are not clear or do not understand what they were proposed. We consider the need of a larger diffusion through educational actions, of the subject experimentation with human beings, for volunteers larger understanding of their right and duties, in the sense to maintaining the researches in an elevated ethical standard. The present study intends to contribute with the hermeneutics of this Resolution and to raise larger discussions and reflections on the subject

The study aims to review the regulatory powers exercised by the South African Revenue Services (SARS) with regard to the issuing, decline or revocation of a taxpayer’s tax clearance certificate, to highlight any remedial measures and procedures available to the aggrieved taxpayer in order to protect the right of taxpayers to fair administrative action in their dealings with SARS. Previously, a tax clearance certificate was not issued in terms of any statute or provision of any Tax Act. However, since the introduction of the Tax Administration Act, as amended (TAA), the issuing of the tax clearance certificates are more efficiently regulated. The issuing of tax clearance certificate’s must conform to the values and principles prescribed for under current legislation, and more particularly, as espoused under the Constitution of South Africa, 1996 (the Constitution). However, it has been reported some taxpayer were experiencing unreasonable and incomprehensible delays in obtaining responses to the objections lodged with SARS for assessment. Taxpayers seeking resolution of their disputes with SARS, currently opt to incur litigation costs in order to obtain appropriate relief from the High Courts. Taxpayers must take note that there is nothing in Promotion of Administrative Justice Act (PAJA) or the common law, which empowers a Court to order an administrator to take action, including the making of a decision which the administrator is not lawfully allowed to make. The study highlights remedial measures and procedures available to the aggrieved taxpayer to prevent the misapplication of fiscal power by SARS in the issuing of the taxpayer’s compliance status, thus protecting the right to fair administrative action in their dealings with SARS. Taxpayers who are aggrieved by a decision taken by the Revenue Authority are encouraged to timeously address their grievances, commencing with the internal dispute resolution remedies provided for within the TAA. / Taxation