Submitted by JULIANA TEODORA DE ASSIS REGES null (juliana.teodora@bol.com.br) on 2016-10-21T00:48:25Z No. of bitstreams: 1 Reges-Tese-DR.pdf: 2852424 bytes, checksum: e86c4e7420b8cf40a8dcc1e723431082 (MD5) / Approved for entry into archive by Juliano Benedito Ferreira (julianoferreira@reitoria.unesp.br) on 2016-10-27T16:48:41Z (GMT) No. of bitstreams: 1 reges_jta_dr_jabo.pdf: 2852424 bytes, checksum: e86c4e7420b8cf40a8dcc1e723431082 (MD5) / Made available in DSpace on 2016-10-27T16:48:41Z (GMT). No. of bitstreams: 1 reges_jta_dr_jabo.pdf: 2852424 bytes, checksum: e86c4e7420b8cf40a8dcc1e723431082 (MD5) Previous issue date: 2016-08-23 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Na primeira parte de nosso estudo descrevemos a associação de Pyricularia pennisetigena e P. zingibericola a gramíneas invasoras de áreas de trigo no centro-sul do Brasil. Desconhece-se, entretanto, qual o potencial de P. pennisetigena e P. zingibericola como patógenos de poáceas de interesse econômico para a agricultura brasileira. Dessa forma, objetivamos caracterizar o espectro de patogenicidade de P. pennisetigena e P. zingibericola a braquiária, cevada e trigo e compará-lo com P. grisea e com a espécie até recentemente descrita como P. oryzae patotipo Triticum, de ocorrência generalizada no agroecossistema brasileiro. Foram testados 20 isolados de Pyricularia spp. obtidos de amostras de folhas infectadas de plantas invasoras de campos de trigo. A classificação dos isolados em espécies distintas de Pyricularia foi efetuada usando-se filogenia molecular baseada nas sequencias parciais dos genes actina e calmodulina. Pyricularia pennisetigena e P. zingibericola inoculadas em folhas, foram patogênicas a braquiária, cevada e trigo, com diferenças na agressividade entre as espécies. Pyricularia zingibericola foi a espécie mais agressiva a braquiária e cevada, enquanto P. pennisetigena foi a espécie mais agressiva em plantas jovens de trigo. Por outro lado, P. grisea isolada de Digitaria sanguinalis ou de Urochloa spp. não infectou trigo. A análise filogenética das regiões ACT e CAL concatenadas reproduziu as relações filogenéticas e a magnitude das diferenças descritas entre Pyricularia zingibericola, P. pennisetigena, P. oryzae patotipo Triticum e P. grisea. Urochloa spp. provavelmente representam fonte permanente de inóculo inicial dos patógenos da brusone do trigo entre as épocas de cultivo. Na segunda parte desta pesquisa, foi estudado a estrutura genética de populações do patógeno da brusone do trigo, o fungo Ascomiceto Pyricularia graminis-tritici sp. nov., no centro-sul do Brasil. Os objetivos foram responder às seguintes perguntas: As populações geograficamente distintas de P. graminis-tritici do trigo eram geneticamente subdivididas? Como se distribuía a diversidade gênica e genotípica entre as populações regionais de P. graminis-tritici, cerca de 30 anos após as primeiras epidemias de brusone no Brasil? Qual o sistema reprodutivo predominante de P. graminis-tritici no país? Conclui-se que não houve subdivisão na maioria das populações geográficas contemporâneas de P. graminis-tritici do trigo, indicando mecanismo eficiente de fluxo gênico. A magnitude e a extensão do fluxo gênico entre populações geográficas de P. graminis-tritici do trigo, o sistema reprodutivo predominantemente sexual, aliados a alta diversidade genética do fungo, indicam um patógeno com alto potencial evolutivo no agroecossistema brasileiro. Outras espécies de poáceas hospedeiras com ampla distribuição geográfica no Brasil, como por exemplo, o capim-braquiária (Urochloa brizantha), podem ter importante papel no ciclo de vida e na biologia reprodutiva, na sobrevivência e na dispersão do inóculo de P. graministritici a curta e longa distâncias, mantendo as populações geográficas do patógeno conectadas. Os padrões de fluxo gênico e genotípico entre populações hospedeiro-distintas do patógeno reforçam a hipótese de que a brusone do trigo pode ter tido origem de novo a partir de populações endêmicas de P. graminis-tritici que infectam outras espécies de poáceas (nativas ou invasoras de áreas de trigo) no país. / In the first part of our study we described the association of Pyricularia pennisetigena and P. zingibericola with invasive grasses from wheat cropping areas in South-Central Brazil. However, the potential of P. pennisetigena and P. zingibericola as pathogens to poaceous plants of economic interest for Brazilian agriculture is still unknown. Therefore, this study aimed to characterize the pathogenicity spectrum of P. pennisetigena and P. zingibericola to signal grass, barley and wheat and compare with P. grisea and with the species until recently described as P. oryzae pathotype Triticum, of widespread occurrence in the Brazilian agroecosystem. Twenty isolates of Pyricularia spp. obtained from samples of infected leaves of weed species in wheat fields were tested. Classification of isolates into different species of Pyricularia was performed using molecular phylogeny based on the partial actin and calmodulin gene sequences. Pyricularia pennisetigena and P. zingibericola inoculated on leaves were pathogenic to signal grass, barley and wheat, with differences in aggressiveness between species. Pyricularia zingibericola was the most aggressive species to signal grass and barley, while P. pennisetigena was the most aggressive species to young plants of wheat. On the other hand, P. grisea isolated from Digitaria sanguinalis or Urochloa spp. did not infect wheat. Phylogenetic analysis of the concatenated regions ACT and CAL reproduced the phylogenetic relationships and the magnitude of the differences reported between Pyricularia zingibericola, P. pennisetigena, P. oryzae pathotype Triticum and P. grisea. Urochloa spp. probably represents a permanent source of initial inoculum of the wheat blast pathogens between growing seasons. In the second part of this research, we studied the genetic structure of populations of the wheat blast pathogen, the Ascomycete fungus Pyricularia graminis - tritici sp. nov., in the South-Central Brazil. The objectives were to answer the following questions: The geographically distinct populations of P. graminis-triticiwheat were genetically subdivided? How gene and genotypic diversity were distributed among regional populations of P. graminis-tritici about 30 years after the first outbreaks of wheat blast in Brazil? What is the predominant reproductive system of P. graminis-tritici in the country? We concluded that there was no subdivision among most of the contemporary geographical populations of Pyricularia graminis- tritici from wheat fields, indicating an efficient mechanism of gene flow. The magnitude and extent of gene flow among geographical populations of P. graminis-tritici, the predominantly sexual reproductive system, coupled with high genetic diversity of the fungus, indicated a pathogen with high evolutionary potential in the Brazilian agro-ecosystem. Other species of poaceous hosts with wide geographic distribution in Brazil, for example, signal grass (Urochloa brizantha) can play an important role in the life cycle and reproductive biology, survival and spread of inoculum of P. graminis- tritici at short and long distances, keeping the geographical populations of the pathogen connected. The patterns of gene and genotypic flow between host-distinct populations of the pathogen reinforce the hypothesis that the wheat blast may had a de novo origin from endemic populations of P. graminis-tritici infecting other poaceous species (native or invasive WRwheat areas) in the country.

MSCAGR ( Plant Production) / Department of Plant Production / See the attached abstract below

Orientador: Agnes Cristina Fett Conte / Banca: Roseli Maria Zechi Ceide / Banca: Luiz Carlos de Mattos / Resumo: Os defeitos congênitos resultam de causas genéticas e não genéticas, afetam cerca de 3 a 5% dos recém-nascidos e são reconhecidos como uma das maiores causas de morbidade e mortalidade no primeiro ano de vida, além de serem a causa de muitas mortes embrionárias e fetais. Possuem etiologia e fatores de risco variados, muitos ainda desconhecidos. Dados epidemiológicos brasileiros são escassos. O estudo dos fatores epidemiológicos pode ampliar o conhecimento sobre tais defeitos e propiciar estratégias de prevenção, além do Aconselhamento Genético adequado para as famílias envolvidas. O presente trabalho realizou um estudo genético clínico prospectivo de todos os recém-nascidos e natimortos com defeitos congênitos atendidos no período de um ano no Hospital de Base de São José do Rio Preto/SP (HB), com o objetivo de estimar a prevalência, caracterizar em tipos de doenças, diagnósticos ou categorias diagnósticas, verificar as possíveis causas e consequências dos defeitos. Para cada criança foi realizada a análise cariotípica (nos casos indicados), a avaliação física, o registro fotográfico, análise de dados de prontuário médico e coleta de informações complementares com a família. Foram estudados 110 indivíduos, 103 recém-nascidos e sete natimortos. A prevalência foi de 2,8%. Em 82% dos casos o diagnóstico específico pode ser sugerido. Os defeitos congênitos de etiologia genética foram mais frequentes que os de etiologia não genética. Os de herança multifatorial foram os mais freqüentes (29%), seguidos dos de etiologia heterogênea (22%), monogênica (19%), desconhecida (13,5%), cromossômica (12%) e ambiental (4,5%). A idade materna, a consangüinidade parental e a predisposição familial (presença de defeitos congênitos na família) foram alguns fatores de risco identificados. A maioria dos afetados eram prematuros e a hospitalização... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Birth defects, resulting from genetic and non-genetic causes, affect about 3 to 5% of newborns and are recognized as a major cause of morbidity and mortality within the first year of life, as well as being the cause of many embryonic and fetal deaths. Not infrequently the varied etiology and risk factors remain unknown. Brazilian epidemiological data are scarce. The study of epidemiological factors may increase knowledge about these defects and make prevention strategies and genetic counseling possible for affected families. This work constitutes a prospective clinical genetic study of all newborn and stillborn infants with birth defects seen over one year in Hospital de Base in São José do Rio Preto, Sao Paulo, in order to estimate the prevalence, characterize the disease types, diagnoses or diagnostic categories and evaluate possible causes and consequences of the defects. Karyotypic analysis, a physical assessment, photographic records, an analysis of the patients' medical records and the collection of additional information with the family was performed for each infant. The study assessed 103 newborn and 7 stillborn subjects. The prevalence of birth defects was of 2.8%. A specific diagnosis was suggested in 82% of cases. Genetically-related birth defects were more prevalent than those with non-genetic etiology. Infants with multifactorial inheritance patterns were the most common (29%), followed by heterogeneous etiology (22%), monogenic inheritance patterns (19%), unknown (13,5%), chromosomal etiologies (12%) and environmental factors (4.5%). Maternal age, parental consanguinity and family susceptibility (the presence of defects in the family) were some of the identified risk factors. Most affected infants were premature and the most commonly observed consequences were prolonged hospital stays and death. Hence, birth defects are frequent in the population; several causes are... (Complete abstract click electronic access below) / Mestre

Cystic fibrosis (CF) is a single gene Mendelian disorder characterized by pulmonary disease and pancreatic insufficiency. Pulmonary disease is the major cause of death in CF patients. Although some cystic fibrosis transmembrane conductance regulator (CFTR) genotypes are associated with less severe disease, patients possessing the same genotype show great variation in pulmonary disease severity and progression. Genes involved in modulating the inflammatory response and genes increasing susceptibility to infection are proposed as modifiers of pulmonary disease severity. Polymorphisms selected for based on evidence that they affect the function of the gene and prevalence of the putative risk allele: 1) antiprotease gene alpha-1-antitrypsin (alpha-1-AT), 2) innate immunity genes: mannose binding lectin (MBL2) (promoter [G→C] at -221 and codon 52 (Arg52Cys, D allele), 54 (Gly54Asp, B allele), and 57 (Gly57Glu, C allele), and pulmonary surfactant genes SPA-1 (Arg219Trp), SPA-2 (Thr9Asn, Lys223Gln) and SPD (Thr11Met), 3) antioxidant genes GSTM1 and T1 (gene deletion polymorphisms), GSTP1 (Ile105Val) and GCLC repeats, 4) mucin genes (MUC2 and MUC5B). Pulmonary disease progression and survival in patients with chronic Burkholderia cepacia complex (BCC) infection were also investigated controlling for genomovar and RAPD type of the organism. BCC infection was associated with more severe pulmonary disease progression and worse survival. Alpha-1-AT genotype was not a major contributor to variability of pulmonary disease severity, but the results suggest that alpha-1-AT plasma levels during pulmonary infections may be affected by poor nutritional status. We showed similar pulmonary disease progression and MBL2 genotype. Contrary to the previous literature, wild-type MBL2 genotype was associated with steeper decline in pulmonary disease over time following chronic infection with BCC, but genotype was not associated with increased susceptibility to BCC infection. We showed inconsistant results for the pulmonary surfactant gene polymorphisms, GSTM1, T1 and GSTP1 polymorphisms, and number of repeats for GCLC and MUC5B depending on the phenotype investigated. We conclude that some of the variability in pulmonary disease severity and progression in CF is explained by polymorphisms in secondary genes.

Cystic fibrosis (CF) is a single gene Mendelian disorder characterized by pulmonary disease and pancreatic insufficiency. Pulmonary disease is the major cause of death in CF patients. Although some cystic fibrosis transmembrane conductance regulator (CFTR) genotypes are associated with less severe disease, patients possessing the same genotype show great variation in pulmonary disease severity and progression. Genes involved in modulating the inflammatory response and genes increasing susceptibility to infection are proposed as modifiers of pulmonary disease severity. Polymorphisms selected for based on evidence that they affect the function of the gene and prevalence of the putative risk allele: 1) antiprotease gene alpha-1-antitrypsin (alpha-1-AT), 2) innate immunity genes: mannose binding lectin (MBL2) (promoter [G→C] at -221 and codon 52 (Arg52Cys, D allele), 54 (Gly54Asp, B allele), and 57 (Gly57Glu, C allele), and pulmonary surfactant genes SPA-1 (Arg219Trp), SPA-2 (Thr9Asn, Lys223Gln) and SPD (Thr11Met), 3) antioxidant genes GSTM1 and T1 (gene deletion polymorphisms), GSTP1 (Ile105Val) and GCLC repeats, 4) mucin genes (MUC2 and MUC5B). Pulmonary disease progression and survival in patients with chronic Burkholderia cepacia complex (BCC) infection were also investigated controlling for genomovar and RAPD type of the organism. BCC infection was associated with more severe pulmonary disease progression and worse survival. Alpha-1-AT genotype was not a major contributor to variability of pulmonary disease severity, but the results suggest that alpha-1-AT plasma levels during pulmonary infections may be affected by poor nutritional status. We showed similar pulmonary disease progression and MBL2 genotype. Contrary to the previous literature, wild-type MBL2 genotype was associated with steeper decline in pulmonary disease over time following chronic infection with BCC, but genotype was not associated with increased susceptibility to BCC infection. We showed inconsistant results for the pulmonary surfactant gene polymorphisms, GSTM1, T1 and GSTP1 polymorphisms, and number of repeats for GCLC and MUC5B depending on the phenotype investigated. We conclude that some of the variability in pulmonary disease severity and progression in CF is explained by polymorphisms in secondary genes.

Made available in DSpace on 2014-06-11T19:26:04Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-02-26Bitstream added on 2014-06-13T19:53:57Z : No. of bitstreams: 1 oliveira_cif_me_sjrp.pdf: 1431703 bytes, checksum: 19bdfb08ccbb18b978cdc957759cb23d (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Os defeitos congênitos resultam de causas genéticas e não genéticas, afetam cerca de 3 a 5% dos recém-nascidos e são reconhecidos como uma das maiores causas de morbidade e mortalidade no primeiro ano de vida, além de serem a causa de muitas mortes embrionárias e fetais. Possuem etiologia e fatores de risco variados, muitos ainda desconhecidos. Dados epidemiológicos brasileiros são escassos. O estudo dos fatores epidemiológicos pode ampliar o conhecimento sobre tais defeitos e propiciar estratégias de prevenção, além do Aconselhamento Genético adequado para as famílias envolvidas. O presente trabalho realizou um estudo genético clínico prospectivo de todos os recém-nascidos e natimortos com defeitos congênitos atendidos no período de um ano no Hospital de Base de São José do Rio Preto/SP (HB), com o objetivo de estimar a prevalência, caracterizar em tipos de doenças, diagnósticos ou categorias diagnósticas, verificar as possíveis causas e consequências dos defeitos. Para cada criança foi realizada a análise cariotípica (nos casos indicados), a avaliação física, o registro fotográfico, análise de dados de prontuário médico e coleta de informações complementares com a família. Foram estudados 110 indivíduos, 103 recém-nascidos e sete natimortos. A prevalência foi de 2,8%. Em 82% dos casos o diagnóstico específico pode ser sugerido. Os defeitos congênitos de etiologia genética foram mais frequentes que os de etiologia não genética. Os de herança multifatorial foram os mais freqüentes (29%), seguidos dos de etiologia heterogênea (22%), monogênica (19%), desconhecida (13,5%), cromossômica (12%) e ambiental (4,5%). A idade materna, a consangüinidade parental e a predisposição familial (presença de defeitos congênitos na família) foram alguns fatores de risco identificados. A maioria dos afetados eram prematuros e a hospitalização... / Birth defects, resulting from genetic and non-genetic causes, affect about 3 to 5% of newborns and are recognized as a major cause of morbidity and mortality within the first year of life, as well as being the cause of many embryonic and fetal deaths. Not infrequently the varied etiology and risk factors remain unknown. Brazilian epidemiological data are scarce. The study of epidemiological factors may increase knowledge about these defects and make prevention strategies and genetic counseling possible for affected families. This work constitutes a prospective clinical genetic study of all newborn and stillborn infants with birth defects seen over one year in Hospital de Base in São José do Rio Preto, Sao Paulo, in order to estimate the prevalence, characterize the disease types, diagnoses or diagnostic categories and evaluate possible causes and consequences of the defects. Karyotypic analysis, a physical assessment, photographic records, an analysis of the patients’ medical records and the collection of additional information with the family was performed for each infant. The study assessed 103 newborn and 7 stillborn subjects. The prevalence of birth defects was of 2.8%. A specific diagnosis was suggested in 82% of cases. Genetically-related birth defects were more prevalent than those with non-genetic etiology. Infants with multifactorial inheritance patterns were the most common (29%), followed by heterogeneous etiology (22%), monogenic inheritance patterns (19%), unknown (13,5%), chromosomal etiologies (12%) and environmental factors (4.5%). Maternal age, parental consanguinity and family susceptibility (the presence of defects in the family) were some of the identified risk factors. Most affected infants were premature and the most commonly observed consequences were prolonged hospital stays and death. Hence, birth defects are frequent in the population; several causes are... (Complete abstract click electronic access below)

Cystic fibrosis (CF) is a single gene Mendelian disorder characterized by pulmonary disease and pancreatic insufficiency. Pulmonary disease is the major cause of death in CF patients. Although some cystic fibrosis transmembrane conductance regulator (CFTR) genotypes are associated with less severe disease, patients possessing the same genotype show great variation in pulmonary disease severity and progression. Genes involved in modulating the inflammatory response and genes increasing susceptibility to infection are proposed as modifiers of pulmonary disease severity. Polymorphisms selected for based on evidence that they affect the function of the gene and prevalence of the putative risk allele: 1) antiprotease gene alpha-1-antitrypsin (alpha-1-AT), 2) innate immunity genes: mannose binding lectin (MBL2) (promoter [G→C] at -221 and codon 52 (Arg52Cys, D allele), 54 (Gly54Asp, B allele), and 57 (Gly57Glu, C allele), and pulmonary surfactant genes SPA-1 (Arg219Trp), SPA-2 (Thr9Asn, Lys223Gln) and SPD (Thr11Met), 3) antioxidant genes GSTM1 and T1 (gene deletion polymorphisms), GSTP1 (Ile105Val) and GCLC repeats, 4) mucin genes (MUC2 and MUC5B). Pulmonary disease progression and survival in patients with chronic Burkholderia cepacia complex (BCC) infection were also investigated controlling for genomovar and RAPD type of the organism. BCC infection was associated with more severe pulmonary disease progression and worse survival. Alpha-1-AT genotype was not a major contributor to variability of pulmonary disease severity, but the results suggest that alpha-1-AT plasma levels during pulmonary infections may be affected by poor nutritional status. We showed similar pulmonary disease progression and MBL2 genotype. Contrary to the previous literature, wild-type MBL2 genotype was associated with steeper decline in pulmonary disease over time following chronic infection with BCC, but genotype was not associated with increased susceptibility to BCC infection. We showed inconsistant results for the pulmonary surfactant gene polymorphisms, GSTM1, T1 and GSTP1 polymorphisms, and number of repeats for GCLC and MUC5B depending on the phenotype investigated. We conclude that some of the variability in pulmonary disease severity and progression in CF is explained by polymorphisms in secondary genes. / Medicine, Faculty of / Medicine, Department of / Experimental Medicine, Division of / Graduate

科学研究費補助金 研究種目:基盤研究(C) 課題番号:15520248 研究代表者:松沢 和宏 研究期間:2003-2005年度

The doctoral thesis MD. Liubov Kastnerova (previous name Kyrpychova) is focused on the histomorphological and molecular biologic features of selected cutaneous epithelial and nonepithelial tumors and is structured as a commentary to the 20 articles published during four years, representing the completed scientific projects in the Ph.D. course. In eight papers, the author of the thesis is the first author, whereas she coauthored in the remaining 12 papers. The thesis is composed of the commented files of authors own publications and it is divided into cutaneous epithelial and nonepithelial tumors. The first section, «Cutaneous epithelial tumors», includes 14 articles that are subdivided into two parts: adnexal tumors (9 articles) and lesions of anogenital mammary-like glands (5 articles). Of the nine articles on adnexal tumors, there are 5 articles focused on various benign and malignant adnexal lesions with apocrine or eccrine differentiation. Novel findings in this part include the identification of hitherto unreported alterations of the MYBL1 gene in adenoid cystic carcinoma of the skin and lack of deletion of the 1p36 locus in this neoplasm; the lack of a correlation between cellular composition and the presence CRTC1-MAML2 fusions in hidradenoma, the absence of CRTC3-MAML2 fusions in this tumor,...