MicroRNAs (miRNAs) are small non-coding RNAs with a length of 18 to 25 nucleotides playing a pivotal role in post-transcriptional regulation of gene expression. There are miRNAs whose expression is limited to a certain tissue type and diseases which are characterized by a unique miRNA expression profile. I assumed spontaneous preterm birth (PTB) and preterm prelabor rupture of membranes (PPROM) would be characterized by a unique miRNA expression profile. I observed the gene expression of 15 placental specific miRNAs (miR-512-5p, miR-515-5p, miR-516b-5p, miR-517-5p, miR-518b, miR-518f-5p, miR-519a-5p, miR-519d-3p, miR-519e- 5p, miR-520a-5p, miR-520h, miR-524-5p, miR-525-5p, miR-526a and miR-526b-5p) in placental tissue of pacients with PTB, PPROM and women with term in labor pregnancies (FG). PTB group consisted of 24 pacients, PPROM group of 75 pacients and FG group of 20 pacients. Quantitative real-time PCR was used to quantify gene expression. In the group of PTB pregnancies I identified 3 significantly upregulated miRNAs (miR-516b-5p, miR-519d-3p and miR-524-5p) and 4 miRNAs (miR-518b, miR-519a-5p, miR-520h and miR-526a) with a trend to upregulation compared to controls (FG). In the group of PPROM pregnancies I identified 3 miRNAs (miR-519d-3p, miR-520h and miR-256b-5p) with a trend to...

Made available in DSpace on 2016-04-27T19:30:46Z (GMT). No. of bitstreams: 1 Maria Nicolau.pdf: 3580336 bytes, checksum: 53f653658e8e5bfac29360c77d813c19 (MD5) Previous issue date: 2013-05-24 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / The present research analyses the emerging leadership in the municipal district of São João da Boa Vista (SP) allied to Brazilian Labor Party (PTB) during the years of 1950. This person leader is called Miguel Jorge Nicolau descendent from an Arabic-Lebanese immigrant family and belonging to the rural quotidian of this town. He initiated his trajectory through the quotidian of the factory FIATECE, whose workers were especially women in their majority. Despite of the Arabic-Lebanese community other than seen as a group who had with them a certain restriction common to those typical inhabitants, and also for the unusual particularities from his private life, those which were very unconventional, though all this, Miguel Jorge Nicolau became a public man. He was elected for the city hall as a mayor and became later a regional representative in the Legislative House as a deputy for the PTB. Since then, he was seen with distrust by the political police, as a dangerous communist infiltrated in PTB or as a risk to the national security, and, based on these information, the agents of the dictatorship, in 1964, he had his political rights annulled. The documentation used for this research has the amount of interviews, newspaper articles, Annals from the Legislative House. We shall give attention to the last two sources as the outstanding discourses and speeches in the Chamber of Deputies / A presente pesquisa analisa a emergência de um líder petebista no Município de São João da Boa Vista (SP), durante os anos de 1950. De nome Miguel Jorge Nicolau, oriundo de uma família de imigrantes árabe-libanesa, iniciou sua trajetória na vida pública a partir de seu quotidiano em uma fábrica têxtil da cidade (Fiatece), cujos trabalhadores eram fundamentalmente mulheres. Apesar da comunidade árabe-libanesa ser vista com certas reservas por parte daquela população interiorana, a que se acresciam particularidades pouco convencionais de sua vida pessoal, Miguel Jorge Nicolau tornou-se um homem público. Elegeu-se para a prefeitura da cidade e tornou-se o representante regional do PTB na Assembleia Legislativa, na qualidade de Deputado Estadual. Desde 1953 foi vigiado pela polícia política, como um perigoso comunista infiltrado no PTB ou um risco à segurança nacional, e, em 1964, teve seus direitos políticos cassados. A documentação utilizada para esta pesquisa constituiu-se de entrevistas, notícias de jornais, Anais da Assembleia Legislativa. Destacamos destes dois últimos acervos, seus artigos e discursos

Preterm birth (PTB) is defined as birth before 37 weeks gestational age. PTB is a common outcome and one that may be increasing in prevalence with serious individual and public health implications both immediately and long term. While PTB is a pregnancy specific outcome it is more appropriately viewed as the culmination of risk factors present both before pregnancy and possibly in past generations. This thesis attempts to review the implications, risk factors and current prevention strategies directed at PTB while placing it in an intergenerational and life cycle context. Three novel investigations are presented and their consequences are discussed. These investigations cover the lifespan and relate to identifying PTB and treating its immediate health outcomes. The first examines mitochondrial genetics and it's relation to PTB. There is a strong a priori hypothesis that mitochondrial genetics, being maternally inherited, may contribute to an individual's risk for PTB. However, in two genome wide association studies, no evidence is found for any mitochondrial polymorphisms being related to PTB. The second investigation reports an attempt to identify women at risk for PTB within a given pregnancy. Using routinely collected maternal information and serum screening data a potentially useful screening method is derived. While the algorithm does not have ideal performance characteristics it compares favorably to other population wide screening techniques and could be improved through future validation and data collection. The third and final investigation attempts to address quality of care for infants born preterm. In a network of neonatal intensive care units, wide variations in mortality outcomes are observed. Intensity of medical intervention appears to be an important predictor of mortality for the lowest gestational age infants. However, this intensity of intervention does not fully explain the observed differences in mortality outcomes. Finally, these study are discussed in context with one another and a new framework for considering PTB is presented that may help to guide future investigation into predicting, preventing and caring for those at risk for or experiencing a PTB.

PTB (HnRNP I) is a multifunctional RNA binding protein which participates in a variety of RNA metabolic processes put together called as post transcriptional gene regulation. It interacts with shuttling hnRNPs L, K and E2 of the spliceosomal machinery and also with other RNA binding proteins like PSF, Raver1 and Raver2, which assists PTB in splicing. Based on the complexity of these processes and multifunctional nature of PTB, we hypothesized that; it might interact with various additional proteins not identified till date. Keeping this objective in mind, we set out to screen the custom made 18 day old mouse testes cDNA library in pGAD10 vector available in the laboratory, to hunt for novel interacting partners of PTB using the Clontech’s Matchmaker Gal4 yeast two hybrid system III. PTB1, the prototype of PTB was chosen and the above mentioned cDNA library was screened for novel PTB interacting partners. Twenty five large scale library transformations (spanning 8*106 independent clones) were performed and 99 putatives were obtained. By re-transformation of these library plasmids with bait construct to check for the interaction phenotype and eliminating bait independent activation of reporter genes and elimination of known false positives, only 5 clones were consistent with the interaction phenotype. All these library plasmids were sequenced with vector specific primers, ORF was identified and BLAST analysis for the identification of insert was done. Two of these clones encoded the partial CDS of mouse Protein Inhibitor of Activated STAT3-PIAS3. One of these encoded the partial CDS of mouse TOLL Interacting Protein-TOLLIP. The other two encoded the partial CDS of mouse importin-α and mouse hnRNP K, both of which were already known interacting partners of PTB. GST pull down assay and mammalian matchmaker co-immunoprecipitation was used for confirming the in vitro one to one physical interaction between PTB and these newly identified protein partners. Indirect Immunofloresence was used for demonstrating the co-localization of PTB and PIAS3 in Gc1Spg mouse spermatogonial cell line. The fact that PIAS3 an E3 SUMO ligase was picked up as an interacting partner of PTB was interesting and we hypothesized that PTB might be a sumoylation substrate. Towards this, we first resorted to the prediction of sumoylation consensus motif by using SUMOPLOT. PTB indeed was found to have sumoylation consensus sites. Subsequently, in vivo sumoylation of PTB was demonstrated, where in over expression of donor protein [SUMO-1] and acceptor protein [PTB] in RAG-1 mouse kidney cell line had resulted in the identification of an approximately 67 kDa slow moving SUMO modified myc tagged PTB band apart from the bulk of unmodified 57 kDa myc-PTB. This confirmed the fact that PTB is SUMO modified only at a single consensus target site in vivo and attempts are made to map this site of modification. SUMOylation regulates diverse biological processes in vivo ranging from nucleo- cytoplasmic shuttling, alteration of protein-protein interaction, DNA protein interaction etc. PTB shuttles rapidly between the nucleus and cytoplasm in a transcription sensitive manner and the translocation of PTB to the cytoplasm, happens under the conditions of cell stress, viral infections, apoptosis and exposure of cells to genotoxic agents like doxorubicin. Phosphorylation of PTB at Ser-16 residue has been shown to modulate the nucleo-cytoplasmic shuttling of PTB, albeit shuttling can also occur irrespective of this modification. Interaction of PTB with an E3 SUMO ligase-PIAS3 and the fact that it is SUMOylated in vivo, we hypothesize that K-47 residue present in the NLS/NES might be the most probable site of this SUMO modification and SUMOylation of PTB by PIAS3 might regulate the nucleo-cytoplasmic shuttling of PTB.

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Arquitetado para ser um partido para os trabalhadores, o Partido Trabalhista Brasileiro (PTB) foi um partido bastante heterogêneo, acolhendo nas suas hostes lideranças sindicais, profissionais liberais, políticos profissionais, empresários, latifundiários, comunistas e líderes progressistas. Em virtude disso, o antigo PTB tornou-se um partido complexo, com diversas subunidades (ou frações) partidárias: os “pragmáticos-getulistas”, os “doutrinários-trabalhistas”, os “pragmáticos-reformistas” e os “reformistas radicais”. Constituindo-se, ao mesmo tempo, em um partido de fisiológicos e reformistas, de progressistas e conservadores, de sindicalistas e plutocratas (empresários e latifundiários), o antigo PTB foi um partido paradoxal, que contava com um poderoso arsenal de elementos simbólicos e mobilizadores – o carisma de Getúlio Vargas e a doutrina trabalhista, nacionalista e reformista – que contribuíram para o seu significativo crescimento eleitoral durante o período democrático de 1945-1964. Soma-se a isso o fato de que sobre o PTB sempre pairou certa mística, tanto que das três grandes siglas extintas com o Ato Institucional nº 2, em 1965, o PTB foi a única resgatada durante os anos finais da ditadura. Dessa forma, a presente tese pretende analisar a história e a atuação do antigo Partido Trabalhista Brasileiro do Paraná, focalizando-o em duas perspectivas: internamente e externamente. No que tange à análise interna, a presente pesquisa visa a responder a seguinte questão: qual era o caráter do PTB do Paraná? Foi um partido fisiológico ou reformista? Foi um partido progressista ou conservador? Quem eram os membros que integraram a elite partidária? Quais eram as alas que existiram dentro do partido e como se processou as disputas internas pelo poder nas hostes petebistas? Nesse sentido, deve-se salientar que o foco de análise será o Diretório Estadual do Partido Trabalhista Brasileiro do Paraná, sediado em Curitiba, e, mais especificamente, a sua elite partidária, isto é, os dirigentes e as pessoas influentes dentro da agremiação. Externamente, o objetivo é verificar a atuação e a importância do PTB na política paranaense entre os anos de 1945 a 1965. E mais, também se pretende investigar quais são os fatores que explicam o crescimento eleitoral do partido no Paraná no período em foco. / Architected to be a party for the workers, the Brazilian Labor Party (PTB in Portuguese) was a very heterogeneous party, welcoming in their hosts union leaders, liberal professionals, professional politicians, businessmen, landowners, communist and progressive liberal leaders. As a result, former PTB has become a complex party, with several parties’ subunits (or fractions): the "pragmatic-getulistas", the "doctrinal-labor", the ‘pragmatic-reformist” and the “radical reformers”. Constituting at the same time, into a physiological and reformist party, of progressives and conservatives, of trade unionists and plutocrats (businessmen and landowners), former PTB was a paradoxical party, which had a powerful arsenal of symbolic elements and mobilizes - the charisma of Vargas and labor, nationalist and reformist doctrine - which contributed to its significant electoral growth during the democratic period of 1945-1964. Summing to this the fact that the PTB always hovered over certain mystique, so that the three large extinct acronyms with the Institutional Act No. 2 in 1965, the PTB was the only rescued during the final years of the dictatorship Thus, this thesis aims to analyze the history and activities of former Brazilian Labor Party of Paraná, focusing on the two perspectives: internal and external. Regarding internal analysis, this research aims to answer the following question: what was the character of the PTB of Paraná? Was it a physiological or a reformist party? Was it a progressive or a conservative party? Who were the members who joined the party elite? What were the wings that existed within the party and how were processed the internal power struggles in PTB hosts? In this sense, it should be noted that the focus of analysis will be the Diretório Estadual do Partido Trabalhista Brasileiro do Paraná (State Board of Brazilian Labor Party of Paraná), based in Curitiba, and more specifically, its party elite, which means, the leaders and influential people within the guild. Externally, the objective is to verify the performance and the importance of PTB in Paraná state politics between the years of 1945-1965. And more, it is also intended to investigate what are the factors that explain the electoral growth of the party in Paraná in the period in focus.

Arquitetado para ser um partido para os trabalhadores, o Partido Trabalhista Brasileiro (PTB) foi um partido bastante heterogêneo, acolhendo nas suas hostes lideranças sindicais, profissionais liberais, políticos profissionais, empresários, latifundiários, comunistas e líderes progressistas. Em virtude disso, o antigo PTB tornou-se um partido complexo, com diversas subunidades (ou frações) partidárias: os “pragmáticos-getulistas”, os “doutrinários-trabalhistas”, os “pragmáticos-reformistas” e os “reformistas radicais”. Constituindo-se, ao mesmo tempo, em um partido de fisiológicos e reformistas, de progressistas e conservadores, de sindicalistas e plutocratas (empresários e latifundiários), o antigo PTB foi um partido paradoxal, que contava com um poderoso arsenal de elementos simbólicos e mobilizadores – o carisma de Getúlio Vargas e a doutrina trabalhista, nacionalista e reformista – que contribuíram para o seu significativo crescimento eleitoral durante o período democrático de 1945-1964. Soma-se a isso o fato de que sobre o PTB sempre pairou certa mística, tanto que das três grandes siglas extintas com o Ato Institucional nº 2, em 1965, o PTB foi a única resgatada durante os anos finais da ditadura. Dessa forma, a presente tese pretende analisar a história e a atuação do antigo Partido Trabalhista Brasileiro do Paraná, focalizando-o em duas perspectivas: internamente e externamente. No que tange à análise interna, a presente pesquisa visa a responder a seguinte questão: qual era o caráter do PTB do Paraná? Foi um partido fisiológico ou reformista? Foi um partido progressista ou conservador? Quem eram os membros que integraram a elite partidária? Quais eram as alas que existiram dentro do partido e como se processou as disputas internas pelo poder nas hostes petebistas? Nesse sentido, deve-se salientar que o foco de análise será o Diretório Estadual do Partido Trabalhista Brasileiro do Paraná, sediado em Curitiba, e, mais especificamente, a sua elite partidária, isto é, os dirigentes e as pessoas influentes dentro da agremiação. Externamente, o objetivo é verificar a atuação e a importância do PTB na política paranaense entre os anos de 1945 a 1965. E mais, também se pretende investigar quais são os fatores que explicam o crescimento eleitoral do partido no Paraná no período em foco. / Architected to be a party for the workers, the Brazilian Labor Party (PTB in Portuguese) was a very heterogeneous party, welcoming in their hosts union leaders, liberal professionals, professional politicians, businessmen, landowners, communist and progressive liberal leaders. As a result, former PTB has become a complex party, with several parties’ subunits (or fractions): the "pragmatic-getulistas", the "doctrinal-labor", the ‘pragmatic-reformist” and the “radical reformers”. Constituting at the same time, into a physiological and reformist party, of progressives and conservatives, of trade unionists and plutocrats (businessmen and landowners), former PTB was a paradoxical party, which had a powerful arsenal of symbolic elements and mobilizes - the charisma of Vargas and labor, nationalist and reformist doctrine - which contributed to its significant electoral growth during the democratic period of 1945-1964. Summing to this the fact that the PTB always hovered over certain mystique, so that the three large extinct acronyms with the Institutional Act No. 2 in 1965, the PTB was the only rescued during the final years of the dictatorship Thus, this thesis aims to analyze the history and activities of former Brazilian Labor Party of Paraná, focusing on the two perspectives: internal and external. Regarding internal analysis, this research aims to answer the following question: what was the character of the PTB of Paraná? Was it a physiological or a reformist party? Was it a progressive or a conservative party? Who were the members who joined the party elite? What were the wings that existed within the party and how were processed the internal power struggles in PTB hosts? In this sense, it should be noted that the focus of analysis will be the Diretório Estadual do Partido Trabalhista Brasileiro do Paraná (State Board of Brazilian Labor Party of Paraná), based in Curitiba, and more specifically, its party elite, which means, the leaders and influential people within the guild. Externally, the objective is to verify the performance and the importance of PTB in Paraná state politics between the years of 1945-1965. And more, it is also intended to investigate what are the factors that explain the electoral growth of the party in Paraná in the period in focus.

Arquitetado para ser um partido para os trabalhadores, o Partido Trabalhista Brasileiro (PTB) foi um partido bastante heterogêneo, acolhendo nas suas hostes lideranças sindicais, profissionais liberais, políticos profissionais, empresários, latifundiários, comunistas e líderes progressistas. Em virtude disso, o antigo PTB tornou-se um partido complexo, com diversas subunidades (ou frações) partidárias: os “pragmáticos-getulistas”, os “doutrinários-trabalhistas”, os “pragmáticos-reformistas” e os “reformistas radicais”. Constituindo-se, ao mesmo tempo, em um partido de fisiológicos e reformistas, de progressistas e conservadores, de sindicalistas e plutocratas (empresários e latifundiários), o antigo PTB foi um partido paradoxal, que contava com um poderoso arsenal de elementos simbólicos e mobilizadores – o carisma de Getúlio Vargas e a doutrina trabalhista, nacionalista e reformista – que contribuíram para o seu significativo crescimento eleitoral durante o período democrático de 1945-1964. Soma-se a isso o fato de que sobre o PTB sempre pairou certa mística, tanto que das três grandes siglas extintas com o Ato Institucional nº 2, em 1965, o PTB foi a única resgatada durante os anos finais da ditadura. Dessa forma, a presente tese pretende analisar a história e a atuação do antigo Partido Trabalhista Brasileiro do Paraná, focalizando-o em duas perspectivas: internamente e externamente. No que tange à análise interna, a presente pesquisa visa a responder a seguinte questão: qual era o caráter do PTB do Paraná? Foi um partido fisiológico ou reformista? Foi um partido progressista ou conservador? Quem eram os membros que integraram a elite partidária? Quais eram as alas que existiram dentro do partido e como se processou as disputas internas pelo poder nas hostes petebistas? Nesse sentido, deve-se salientar que o foco de análise será o Diretório Estadual do Partido Trabalhista Brasileiro do Paraná, sediado em Curitiba, e, mais especificamente, a sua elite partidária, isto é, os dirigentes e as pessoas influentes dentro da agremiação. Externamente, o objetivo é verificar a atuação e a importância do PTB na política paranaense entre os anos de 1945 a 1965. E mais, também se pretende investigar quais são os fatores que explicam o crescimento eleitoral do partido no Paraná no período em foco. / Architected to be a party for the workers, the Brazilian Labor Party (PTB in Portuguese) was a very heterogeneous party, welcoming in their hosts union leaders, liberal professionals, professional politicians, businessmen, landowners, communist and progressive liberal leaders. As a result, former PTB has become a complex party, with several parties’ subunits (or fractions): the "pragmatic-getulistas", the "doctrinal-labor", the ‘pragmatic-reformist” and the “radical reformers”. Constituting at the same time, into a physiological and reformist party, of progressives and conservatives, of trade unionists and plutocrats (businessmen and landowners), former PTB was a paradoxical party, which had a powerful arsenal of symbolic elements and mobilizes - the charisma of Vargas and labor, nationalist and reformist doctrine - which contributed to its significant electoral growth during the democratic period of 1945-1964. Summing to this the fact that the PTB always hovered over certain mystique, so that the three large extinct acronyms with the Institutional Act No. 2 in 1965, the PTB was the only rescued during the final years of the dictatorship Thus, this thesis aims to analyze the history and activities of former Brazilian Labor Party of Paraná, focusing on the two perspectives: internal and external. Regarding internal analysis, this research aims to answer the following question: what was the character of the PTB of Paraná? Was it a physiological or a reformist party? Was it a progressive or a conservative party? Who were the members who joined the party elite? What were the wings that existed within the party and how were processed the internal power struggles in PTB hosts? In this sense, it should be noted that the focus of analysis will be the Diretório Estadual do Partido Trabalhista Brasileiro do Paraná (State Board of Brazilian Labor Party of Paraná), based in Curitiba, and more specifically, its party elite, which means, the leaders and influential people within the guild. Externally, the objective is to verify the performance and the importance of PTB in Paraná state politics between the years of 1945-1965. And more, it is also intended to investigate what are the factors that explain the electoral growth of the party in Paraná in the period in focus.

Background: The prevalence of opioid use disorder has increased across the United States, but the rural population of Appalachia has been disproportionately impacted. Concurrently, the slow, but steady progress in the legalization of marijuana may be affecting perception of marijuana use in pregnancy. However, marijuana use in pregnancy has been associated with adverse perinatal outcomes. Concomitant use of opioids and marijuana in pregnancy has not been evaluated. Objective: The primary aim of the study was to evaluate the association between confirmed marijuana use in late pregnancy and preterm birth in opioid-exposed pregnancies. Methodology: A retrospective chart review was conducted that included all births from July 2011 to June 2016 from 6 delivery hospitals in South-Central Appalachia. Out of 18,732 births, 2368 singleton pregnancies indicated opioid use and met remaining inclusion criteria, with 108 of these mothers testing positive for marijuana at delivery. Independent sample t-test and Chi-Square analyses compared marijuana and non-marijuana exposed groups on maternal and neonatal outcomes. Regression analyses controlled for confounding variables in predicting neonatal abstinence syndrome (NAS), NICU admission, preterm birth, small for gestational age, and low birth weight outcomes as shown in Table 1. Results: Neonates born to marijuana-positive women in opioid-exposed pregnancy were more likely to be born preterm, small for gestational age, have low birth weight, and be admitted to NICU. After statistically controlling for parity, marital status, tobacco and benzodiazepine use, preterm birth and low birth weight remained statistically significant with aOR of 2.35 (1.30–4.24) and 2.01 (1.18–3.44), respectively. Conclusions: Maternal use of marijuana in any opioid-exposed pregnancy may increase risk of preterm birth and low-birth weight infants. Prospective studies need to examine the dose and timing of marijuana and opioid use in pregnancy to better delineate perinatal effects. Nonetheless, pregnant women using opioids, including recommended medication assisted treatment for opioid use disorder, should be educated about the risks of concurrent marijuana use during pregnancy and may need to be counseled to abstain from marijuana use during pregnancy for an optimal outcome.

Preterm birth (PTB) results in over 15 million early births annually and is the leading cause of neonatal deaths. There are no clinical methods currently available to evaluate risk of PTB at early stages in pregnancy; thus, a rapid diagnostic to analyze PTB risk would be beneficial. Microfluidic immunoaffinity extraction is a promising platform for preparing complex samples, such as maternal serum with PTB risk biomarkers. 3D printed microfluidic devices have advantages over conventional microfluidic systems including simple fabrication and potential for iterative optimization to improve designs. In this work, I developed immunoaffinity monoliths in 3D printed microfluidic devices modified with antibodies to enrich PTB biomarkers from human blood serum. I retained and eluted a peptide PTB biomarker in both buffer and blood serum using an immunoaffinity column. An additional three PTB biomarkers were also successfully extracted either from buffer or blood serum on single-antibody columns. Both polyclonal and monoclonal antibodies to PTB biomarkers were characterized by dot blots, biolayer interferometry, and surface plasmon resonance to determine their specificity and dissociation constants. I created multiplexed immunoaffinity columns to simultaneously enrich three PTB biomarkers from depleted human blood serum in a single extraction. This is the first demonstration of multiplexed immunoaffinity columns for PTB biomarkers in a 3D printed microfluidic device. My work is a key step towards the future development of 3D printed microfluidic devices for rapid PTB testing.