Made available in DSpace on 2014-06-11T19:32:53Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-08-10Bitstream added on 2014-06-13T19:22:41Z : No. of bitstreams: 1 morais_ats_dr_sjrp.pdf: 1276143 bytes, checksum: 62a89d8b555ac92b5faf4baa19e4db2f (MD5) / O vírus da Febre Amarela (YFV) pertence ao gênero Flavivirus e causa uma importante doença. Nos últimos anos, uma alarmante ressurgência da circulação viral e expansão do vírus em áreas endêmicas têm sido detectadas na África e América do Sul. NS5 é uma proteína viral não estrutural com duas atividades essenciais para a replicação viral, uma de metiltransferase e outra de RNA Polimerase dependente de RNA (RdRp). Para o melhor entendimento dos mecanismos de replicação viral, interações entre NS5 e proteínas celulares têm sido amplamente estudadas. Assim, os objetivos desse estudo foram caracterizar a interação da proteína NS5 e eIF3L, avaliar a função de eIF3L na replicação do vírus da febre amarela, e caracterizar estruturalmente a proteína eIF3L. Métodos. Para identificar a interação de NS5 YFV com eIF3L, foi realizado ensaios em sistema duplo-híbrido usando RdRp NS5 YFV contra eIF3L. Para o mapeamento da interação, foram construídos mutantes deletantes de RNApol e analisados em sistema duplo-híbrido. A região de interação de RNApol foi segmentada em três fragmentos e analisada na presença de eIF3L. Para mapear os resíduos de NS5 críticos para a interação, foi realizada mutagênese sítio-dirigida no segmento 3 de ID. A interação foi analisada em ensaios in vitro e em cultura de células de mamíferos. A significância de eIF3L para a replicação do YFV foi investigada usando superexpressão de eIF3L em células BHK21-RepYF17D LucNeoIres. A proteína eIF3L foi purificada usando uma combinação de cromatografia de afinidade e de exclusão molecular para subsequente caracterização estrutural. Resultados. Nesse estudo, foi caracterizada a interação de NS5 com o fator eucariótico de início de tradução... / Yellow fever virus (YFV) belongs to the Flavivirus genus and causes an important disease. An alarming resurgence of viral circulation and expansion of the YFV endemic zones have been detected in Africa and South America in recent years. NS5 is a viral protein that contains the methyltransferase and RNA-dependent RNA polymerase domains, which are essential during viral replication. Interactions among NS5 and cellular proteins have been studied for the understanding of viral replication. The aim of this study was to characterize the interaction of NS5 protein with EIF3L and evaluate the role of EIF3L in yellow fever replication. Methods. To identify the interaction of YFV NS5 with cellular proteins, we performed a two-hybrid screen using YFV NS5 RdRp domain as bait and a human cDNA library. For mapping the interaction, RNApol deletions mutants were performed and analyses in two-hybrid system. The RNApol region of interaction was segmented in three fragments and analyses into yeast containing eIF3L. To map residues of NS5 that are critical for its interaction, we performed a site-direct mutagenesis in segment 3 of ID. The interaction was confirmed in vitro assays and by in vivo coimmunoprecipitations. The significance of eIF3L for replication of YFV was investigated using overexpression of eIF3L in BHK21-RepYF17D LucNeoIres cells. eIF3L was purified using a combination of affinity and subsequent size exclusion chromatography for subsequent structural characterization. Results. In this work we describe and characterize the interaction of NS5 with the translation factor eIF3L. The interaction between NS5 and eIF3L was confirmed by in vitro binding and in vivo coimmunoprecipitation assays. This interaction occurs in a region (Interaction Domain of RNApol domain) that is conserved in several... (Complete abstract click electronic access below)

Orientador: Maurício Lacerda Nogueira / Banca: Fátima Pereira de Souza / Banca: Cleslei Fernando Zanelli / Banca: Eurico de Arruda Neto / Banca: Luciana Barros de Arruda / Resumo: O vírus da Febre Amarela (YFV) pertence ao gênero Flavivirus e causa uma importante doença. Nos últimos anos, uma alarmante ressurgência da circulação viral e expansão do vírus em áreas endêmicas têm sido detectadas na África e América do Sul. NS5 é uma proteína viral não estrutural com duas atividades essenciais para a replicação viral, uma de metiltransferase e outra de RNA Polimerase dependente de RNA (RdRp). Para o melhor entendimento dos mecanismos de replicação viral, interações entre NS5 e proteínas celulares têm sido amplamente estudadas. Assim, os objetivos desse estudo foram caracterizar a interação da proteína NS5 e eIF3L, avaliar a função de eIF3L na replicação do vírus da febre amarela, e caracterizar estruturalmente a proteína eIF3L. Métodos. Para identificar a interação de NS5 YFV com eIF3L, foi realizado ensaios em sistema duplo-híbrido usando RdRp NS5 YFV contra eIF3L. Para o mapeamento da interação, foram construídos mutantes deletantes de RNApol e analisados em sistema duplo-híbrido. A região de interação de RNApol foi segmentada em três fragmentos e analisada na presença de eIF3L. Para mapear os resíduos de NS5 críticos para a interação, foi realizada mutagênese sítio-dirigida no segmento 3 de ID. A interação foi analisada em ensaios in vitro e em cultura de células de mamíferos. A significância de eIF3L para a replicação do YFV foi investigada usando superexpressão de eIF3L em células BHK21-RepYF17D LucNeoIres. A proteína eIF3L foi purificada usando uma combinação de cromatografia de afinidade e de exclusão molecular para subsequente caracterização estrutural. Resultados. Nesse estudo, foi caracterizada a interação de NS5 com o fator eucariótico de início de tradução... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Yellow fever virus (YFV) belongs to the Flavivirus genus and causes an important disease. An alarming resurgence of viral circulation and expansion of the YFV endemic zones have been detected in Africa and South America in recent years. NS5 is a viral protein that contains the methyltransferase and RNA-dependent RNA polymerase domains, which are essential during viral replication. Interactions among NS5 and cellular proteins have been studied for the understanding of viral replication. The aim of this study was to characterize the interaction of NS5 protein with EIF3L and evaluate the role of EIF3L in yellow fever replication. Methods. To identify the interaction of YFV NS5 with cellular proteins, we performed a two-hybrid screen using YFV NS5 RdRp domain as bait and a human cDNA library. For mapping the interaction, RNApol deletions mutants were performed and analyses in two-hybrid system. The RNApol region of interaction was segmented in three fragments and analyses into yeast containing eIF3L. To map residues of NS5 that are critical for its interaction, we performed a site-direct mutagenesis in segment 3 of ID. The interaction was confirmed in vitro assays and by in vivo coimmunoprecipitations. The significance of eIF3L for replication of YFV was investigated using overexpression of eIF3L in BHK21-RepYF17D LucNeoIres cells. eIF3L was purified using a combination of affinity and subsequent size exclusion chromatography for subsequent structural characterization. Results. In this work we describe and characterize the interaction of NS5 with the translation factor eIF3L. The interaction between NS5 and eIF3L was confirmed by in vitro binding and in vivo coimmunoprecipitation assays. This interaction occurs in a region (Interaction Domain of RNApol domain) that is conserved in several... (Complete abstract click electronic access below) / Doutor

This thesis examines two crises that occurred in Philadelphia in the middle of the 1790s: the arrival of refugees from the revolution in the French West Indian colony of Saint-Domingue and the outbreak of yellow fever the followed their arrival. These crises are studied together in order to understand the challenges that they posed to the post-Revolutionary culture of sensibility and to the sympathetic construction of social order that drew upon this culture. Philadelphians’ post-Revolutionary sentimental project – the reorganization of society along lines of fellow-feeling, benevolence, and emotional parity – was strained by the arrival of refugees from Saint-Domingue and by the outbreak of epidemic disease. Both of these events were opportunities to actuate sympathetic ideologies, and in both cases, action fell short of rhetoric. This thesis examines why this was the case. Central to Philadelphians’ ambivalence in creating sympathetic social bonds was the presence of people of color – American and foreign – in the city. When asked to extend fellow-feeling to black Philadelphians and black Saint-Domingan refugees, white Philadelphians equivocated. The reorganization of society in the post-Revolutionary period had presumed emotional equality among Americans, but the issue of race repeatedly demonstrated weaknesses in the application of this ideology. The crises examined within this work demonstrate the enduring appeal of sensibility in 1790s Philadelphia. They also demonstrate its weaknesses. As more and more groups use the language of sympathy and benevolence to voice their demands, sensibility faltered. This thesis builds upon a growing scholarship that examines the effect of the Haitian Revolution on the United States to argue that the arrival of refugees from that revolution to Philadelphia highlighted fundamental ambivalences and fault lines in the United States’ post-Revolutionary sentimental project.

Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3460. Adviser: Carl S. Hacker. Includes bibliographical references.

O risco de transmissão placentária para o feto, associados à susceptibilidade de neuroinvasão pelo vírus 17D levaram à recomendação de que a vacina contra febre amarela (FA) não fosse administrada durante a gravidez. Pretendeu-se avaliar o efeito desta no desempenho gestacional de camundongos prenhes. Os resultados mostraram decréscimo na viabilidade fetal causado pela vacinação. Reatividade ao antígeno da FA foi observada nos tecidos hepáticos maternos e de fetos vivos. Na placenta, o antígeno viral não foi observado na barreira materno-fetal. Nos fetos natimortos e em reabsorção, esta passagem pareceu mais acentuada; reatividade foi observada em diversos órgãos. O antígeno viral foi detectado em todas as regiões placentárias. A detecção de RNA viral nas amostras indica que há atividade viral nos tecidos fetais. Nossos achados indicam que há fases gestacionais mais susceptíveis à infecção viral vacinal e que podem determinar perdas fetais. A presença do antígeno e de atividade viral no fígado fetal sugere que o vírus vacinal é transmitido da mãe para o feto. / The risk of placental transmission to the fetus, associated with susceptibility to neuroinvasion of the 17D virus led to the recommendation that the vaccine against yellow fever (YF) was not administered during pregnancy. Intended to evaluate the effect of the vaccine in gestational performance of pregnant mice. The results showed a decrease in fetal viability caused by vaccination. Antigen reactivity of YF was observed in maternal and live fetuses liver tissue. In the placenta, the viral antigen was not observed in maternal-fetal barrier. In the stillborn fetuses and resorption, this passage seemed more pronounced; reactivity was observed in several organs. The viral antigen was detected in all placental regions. The detection of viral RNA in the samples indicates that there is viral activity in fetal tissues. Our findings indicate that there are stages of pregnancy more susceptible to viral vaccine infection that could determine fetal loss. The presence of the antigen and viral activity in fetal liver suggests that the vaccine virus is transmitted from mother to fetus.

Thesis--Université de Paris Sud, Centre d'Orsay, 1977. / Summary in French and English. Includes bibliographical references (p. 225-228).

Orientador: Cristina de Campos / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Geociências / Made available in DSpace on 2018-08-22T20:46:44Z (GMT). No. of bitstreams: 1 HernandezTasco_Aleidys_M.pdf: 2499047 bytes, checksum: 236f6901a7068d237ee969ad03880acc (MD5) Previous issue date: 2013 / Resumo: Em 1927 a luta contra a febre amarela parecia finalizada no continente americano. A Fundação Rockefeller, instituição filantrópica estadunidense que tinha como principal objetivo o combate da febre amarela na primeira metade do século XX, assegurava que a doença estava quase erradicada. No entanto, a ocorrência das epidemias de febre amarela no Rio de Janeiro em 1928 (Brasil) e em Socorro em 1929 (Colômbia), colocou em dúvida as medidas profiláticas recomendadas e aplicadas tanto pelos órgãos nacionais de Saúde Pública como os da Fundação Rockefeller que participou da luta contra essa doença em ambos os países. Ao mesmo tempo em que ocorriam as epidemias, uma controvérsia instalou-se em torno à descoberta de Stokes, Bauer e Hudson na África, em 1927, que demonstrou que a febre amarela era facilmente inoculável no Macacus Rhesus. Tal descoberta acabou por rejeitar a concepção etiológica estabelecida em 1919 por Noguchi. A nova descoberta dos pesquisadores, as epidemias e a rejeição da teoria de Noguchi geraram uma enorme desconfiança na época, dando a sensação de que nada era seguro em assuntos relacionados à febre amarela, despertando uma crise nos estudos da doença. Esta pesquisa assume a responsabilidade de fazer um estudo comparativo a partir da ciência, da política e da técnica que ambos os países usaram no combate à doença, com intuito de conhecer as experiências desenvolvidas com o fenômeno da febre amarela. Assim, a dissertação tem dois objetivos principais. Primeiro, analisar o processo histórico da febre amarela, a fim de entender a crise que predominou nos estudos da doença entre os anos de 1927 e 1930. Para isso iremos analisar os múltiplos atores locais, nacionais e internacionais no domínio teórico e técnico da doença, durante a epidemia de febre amarela no Rio de Janeiro, em 1928-29, e em Socorro, em 1929. O segundo objetivo é analisar as manifestações científicas contra o avanço da febre amarela no Brasil e na Colômbia, a partir das duas últimas grandes epidemias registradas no Rio de Janeiro (1928-1929) e em Socorro (1929), através das tensões entre o ideal de uma ciência médica universal, representada pela Fundação Rockefeller e pelas Conferências Pan-Americanas, e as práticas de saúde pública, representadas por médicos e pesquisadores, elaboradas localmente para minimizar o alcance da febre amarela no período de 1930 a 1948 / Abstract: In 1927 the fight against yellow fever seemed to have concluded in American continent. In the first half of the twentieth century, a philanthropic American organization had as primary goal the fight against that outbreak (The Rockefeller Foundation) and, they ensured that epidemic was almost completely eradicated in that time. Nonetheless, two yellow fever outbreaks recorded in Rio de Janeiro in 1928 (Brazil) and Socorro in 1929 (Colombia) put in doubt the prophylactic measures recommended and implemented by the National Agencies of Public Health and the Rockefeller Foundation. This later institution took part in the fight against the disease in both countries. A controversy was established, while those epidemics took place in both countries, due to the discovery made by Stokes, Bauer e Hudson in Africa in 1927, which demonstrated Macacus Rhesus could be easily inoculated with the virus of yellow fever. That discovery eventually rejected the etiological agent theory established by Noguchi in 1919. In this fashion, with the new discovery, the epidemics and the rejecting of Noguchi's theory, a huge distrust grew up in those days, giving the impression that nothing was safe in issues related to yellow fever, and generating a crisis in studies of disease. Therefore, a comparative study from science, policy and technical that both Colombia and Brazil used in fighting against disease is carried out in this research in order to know the experiences developed with the yellow fever. In this manner, this dissertation has two mains objectives. First, the historical process of yellow fever will be analyzed by this research to understand the crisis that prevailed in studies of that disease between 1927 and 1930. For this reason, the multiple local actors, national and international in theoretical and technical field of the disease were analyzed during yellow fever outbreak in 1928-29 in Rio de Janeiro and in 1929 in Socorro. Second, several scientific manifestations against the progress of yellow fever in Brazil and Colombia were also studied from the last two major epidemics recorded in Rio de Janeiro (1928-1929) and Socorro (1929). Thus, controversies between an ideal of universal medical science represented by Rockefeller Foundation and Pan-American Conference, and the local public health practices developed to minimize the propagation of yellow fever in the period between 1930 and 1948 / Mestrado / Politica Cientifica e Tecnologica / Mestra em Política Científica e Tecnológica

O risco de transmissão placentária para o feto, associados à susceptibilidade de neuroinvasão pelo vírus 17D levaram à recomendação de que a vacina contra febre amarela (FA) não fosse administrada durante a gravidez. Pretendeu-se avaliar o efeito desta no desempenho gestacional de camundongos prenhes. Os resultados mostraram decréscimo na viabilidade fetal causado pela vacinação. Reatividade ao antígeno da FA foi observada nos tecidos hepáticos maternos e de fetos vivos. Na placenta, o antígeno viral não foi observado na barreira materno-fetal. Nos fetos natimortos e em reabsorção, esta passagem pareceu mais acentuada; reatividade foi observada em diversos órgãos. O antígeno viral foi detectado em todas as regiões placentárias. A detecção de RNA viral nas amostras indica que há atividade viral nos tecidos fetais. Nossos achados indicam que há fases gestacionais mais susceptíveis à infecção viral vacinal e que podem determinar perdas fetais. A presença do antígeno e de atividade viral no fígado fetal sugere que o vírus vacinal é transmitido da mãe para o feto. / The risk of placental transmission to the fetus, associated with susceptibility to neuroinvasion of the 17D virus led to the recommendation that the vaccine against yellow fever (YF) was not administered during pregnancy. Intended to evaluate the effect of the vaccine in gestational performance of pregnant mice. The results showed a decrease in fetal viability caused by vaccination. Antigen reactivity of YF was observed in maternal and live fetuses liver tissue. In the placenta, the viral antigen was not observed in maternal-fetal barrier. In the stillborn fetuses and resorption, this passage seemed more pronounced; reactivity was observed in several organs. The viral antigen was detected in all placental regions. The detection of viral RNA in the samples indicates that there is viral activity in fetal tissues. Our findings indicate that there are stages of pregnancy more susceptible to viral vaccine infection that could determine fetal loss. The presence of the antigen and viral activity in fetal liver suggests that the vaccine virus is transmitted from mother to fetus.

Before the consolidation of the germ theory of human diseases at the end of the nineteenth century, medical explanations about disease causation were dominated by the environmental notions of medical geography. This dissertation explores how nineteenth-century Colombian physicians transformed the medical geographical approach using the early concepts and technologies of the emerging Pasteurian germ theory. I follow this transformation in the cases of periodic fevers (yellow fever and malaria), continuous fevers (typhoid fever and typhus) and leprosy. The analysis reveals that by mid century physicians had incorporated neo-Hippocratic versions of disease causation and French medical geographical ideas in order to make sense of disease of the warm, temperate and cold lands. Their conceptual network revolved around the specific, predisposing and occasional causes in which climate and geography played a determinant role. Evidence indicates that this was the case of periodic fevers of the warm lands (yellow fever and malaria). I argue that the “parasitic” hypothesis of yellow fever was accepted during the controversy around the prophylactic inoculations inspired by Pasteurism that were applied in Colombia in 1887. However, doctors struggled to reconcile the medical geographical and the bacteriological perspective of both yellow fever and malaria. Continuous fevers, on the other hand, were also framed within the medical geography scheme of disease causation. I show how during the debates about typhoid fever and typhus happening in the Colombian highlands during the 70s, 80s and 90s, doctors used medical geographical notions and developed anti-pasteurian arguments, while the international scientific community had identified the specific bacilli for typhoid fever. Finally, I argue that the strong interest of Colombian doctors on leprosy –also understood in neo-Hippocratic terms- that foster the search for local treatments based on Pasteurism (antiseptics in the 1880s and serotherapy in the 1890s) also prompted the extension of the bacteriological model and techniques to other diseases in those decades.

Albert Baldwin Wood and his screw pumps modernized New Orleans by bringing flood-free streets and cleaner water to the city while providing the potential for growth by pumping swamp lands dry. While Wood was never part of the local Progressive movement, his work with the pumps fit with Progressive initiatives for modernization. At first, the screw pumps removed rain water from the streets. Then New Orleans expanded the drainage to include sewerage removal and water purification. The pumps successfully drained thousands of acres of land once considered uninhabitable swamp land. This additional land extended New Orleans city limits but also aided in the acceleration of residential segregation. Cities from around the world used the designs for the screw pump and consulted Wood for advice on drainage systems.