Mutações inativadoras no gene MKRN3 são causa de puberdade precoce central familial

A maioria dos casos de puberdade precoce central (PPC) em meninas permanece idiopática. A hipótese de uma causa genética vem se fortalecendo após a descoberta de alguns genes associados a este fenótipo, sobretudo aqueles implicados com o sistema kisspeptina (KISS1 e KISS1R). Entretanto, apenas casos isolados de PPC foram relacionados à mutação na kisspeptina ou em seu receptor. Até recentemente, a maioria dos estudos genéticos em PPC buscava genes candidatos selecionados com base em modelos animais, análise genética de pacientes com hipogonadismo hipogonadotrófico, ou ainda, nos estudos de associação ampla do genoma. Neste trabalho, foi utilizado o sequenciamento exômico global, uma metodologia mais moderna de sequenciamento, para identificar variantes associadas ao fenótipo de PPC. Trinta e seis indivíduos com a forma de PPC familial (19 famílias) e 213 casos aparentemente esporádicos foram inicialmente selecionados. A forma familial foi definida pela presença de mais de um membro afetado na família. DNA genômico foi extraído dos leucócitos do sangue periférico de todos os pacientes. O estudo de sequenciamento exômico global realizado pela técnica ILLUMINA, em 40 membros de 15 famílias com PPC, identificou mutações inativadoras em um único gene, MKRN3, em cinco dessas famílias. Pesquisa de mutação no MKRN3 realizada por sequenciamento direto em duas famílias adicionais (quatro pacientes) identificou duas novas variantes nesse gene. O MKRN3 é um gene de um único éxon, localizado no cromossomo 15 em uma região crítica para a síndrome de Prader Willi. O gene MKRN3 sofre imprinting materno, sendo expresso apenas pelo alelo paterno. A descoberta de mutações em pacientes com PPC familial despertou o interesse para a pesquisa de mutações nesse gene em 213 pacientes com PPC aparentemente esporádica por meio de reação em cadeia de polimerase seguida de purificação enzimática e sequenciamento automático direto (Sanger). Três novas mutações e duas já anteriormente identificadas, incluindo quatro frameshifts e uma variante missense, foram encontradas, em heterozigose, em seis meninas não relacionadas. Todas as novas variantes identificadas estavam ausentes nos bancos de dados (1000 Genomes e Exome Variant Server). O estudo de segregação familial em três dessas meninas com PPC aparentemente esporádica e mutação no MKRN3 confirmou o padrão de herança autossômica dominante com penetrância completa e transmissão exclusiva pelo alelo paterno, demonstrando que esses casos eram, na verdade, também familiares. A maioria das mutações encontradas no MKRN3 era do tipo frameshift ou nonsense, levando a stop códons prematuros e proteínas truncadas e, portanto, confirmando a associação com o fenótipo. As duas mutações missenses (p.Arg365Ser e p.Phe417Ile) identificadas estavam localizadas em regiões de dedo ou anel de zinco, importantes para a função da proteína. Além disso, os estudos in silico dessas duas variantes demonstraram patogenicidade. Todos os pacientes com mutação no MKRN3 apresentavam características clínicas e hormonais típicas de ativação prematura do eixo reprodutivo. A mediana de idade de início da puberdade foi de 6 anos nas meninas (variando de 3 a 6,5) e 8 anos nos meninos (variando de 5,9 a 8,5). Tendo em vista o fenômeno de imprinting, análise de metilação foi também realizada em um subgrupo de 52 pacientes com PPC pela técnica de MS-MLPA, mas não foram encontradas alterações no padrão de metilação. Em conclusão, este trabalho identificou um novo gene associado ao fenótipo de PPC. Atualmente, mutações inativadoras no MKRN3 representam a causa genética mais comum de PPC familial (33%). O MKRN3 é o primeiro gene imprintado associado a distúrbios puberais em humanos. O mecanismo preciso de ação desse gene na regulação da secreção de GnRH necessita de estudos adicionais

O BANCO MUNDIAL E A EDUCAÇÃO NO BRASIL: ESTUDO REALIZADO A PARTIR DAS TESES DEFENDIDAS NA UNIVERSIDADE ESTADUAL DE CAMPINAS (UNICAMP), NO PERÍODO DE 1995 A 2007

Este estudo visa analisar as interferencias do Banco Mundial na Educacao Brasileira a partir do estudo de seis teses (aqui identificadas pelas iniciais A,B,C, D, E e F) de doutorado relativas ao tema, defendidas na Universidade Estadual de Campinas (Unicamp), sendo quatro delas (A, B, C, e D) voltadas a area de educacao e duas (E e F) a area de Ciencias Sociais e Economia. O estudo das teses parte dos objetivos de cada uma, que podem ser resumidos da seguinte forma: a Tese A - ¡ªA Mundializacao da Educacao: o Projeto Neoliberal de Sociedade e de Educacao no Brasil e na Venezuela. (MELO, 2003) -, sob a orientacao do Prof. Dr. Nilson Joseph Demange, teve como objetivo investigar o processo de mundializacao da educacao como elemento de uma nova fase de internacionalizacao e acumulacao capitalista, conduzida hegemonicamente pelos sujeitos politicos coletivos que assumem o projeto neoliberal de sociabilidade, especialmente o Fundo Monetario Internacional e o Banco Mundial, que buscam ser condutores das reformas estruturais para a America Latina e Caribe; a Tese B . ¡ªO Capital Financeiro e a Educacao no Brasil. (DEITOS, 2005) -, sob a orientacao da Profa. Dra. Maria Elizabete Sampaio Prado Xavier, teve como objetivo definir quais as consequencias da consolidacao do projeto, para a redefinicao das politicas educacionais na America Latina e Caribe; a Tese C . ¡ªGlobalizacao e Descentralizacao: o Processo de Desconstrucao do Sistema Educacional Brasileiro pela Via da Municipalizacao. (ROSAR, 1995) -, sob a orientacao do Prof. Dr. Demerval Saviani, teve como objetivo analisar as reformas educacionais empreendidas no Brasil, no periodo de 1995-2002, particularmente a politica educacional nacional para o ensino medio e profissional, com financiamento externo do Banco Internacional para Reforma e Desenvolvimento (BIRD); a Tese D . ¡ªAs Politicas Educacionais para o Desenvolvimento e o Trabalho Docente. (SOUZA, 1999) ., sob a orientacao da Profa. Dra. Liliana Rolisen Petrilli Segnini, trata da politica educacional para o ensino de 1¨¬ grau, tracada segundo a visao de seu autor no ambito de projetos federais, com o objetivo de induzir a municipalizacao do ensino, transferindo encargos para o municipio, sem a realizacao de investimentos financeiros satisfatorios nessa instancia; a Tese E . ¡ªEconomia, poder e influencias externa: O Grupo Banco Mundial e as Politicas de Ajustes Estruturais na America Latina, nas Decadas de Oitenta e Noventa. (COELHO, 2002) ., sob a orientacao do Prof. Dr. Sebastiao Carlos Velasco e Cruz, teve como objetivo analisar as relacoes entre o projeto educacional implementado pelo governo estadual, no periodo entre 1995 e 1998 e suas concepcoes de politicas educacionais; a Tese F - ¡ªA Questao Social e os Limites do Projeto Liberal no Brasil. (GIMENES, 2007) ., sob a orientacao do Prof. Dr. Carlos Alonso Barbosa de Oliveira, teve como objetivo analisar a relacao entre a economia, o poder politico e a influencia externa, focalizando o Grupo Banco Mundial e os programas de ajustamento estrutural na America Latina. Por fim este estudo mescla teses brasileiras advindas da area da Educacao e da Economia; foca o banco mundial e sua influencia no Brasil, oferecendo uma visao das conexoes logicas existentes entre elas. Como conclusao deste trabalho, apresentaremos as consideracoes finais de cada uma das teses, bem como as limitacoes e sugestoes para

Cenário da produção acadêmica em história da matemática no ensino de matemática: uma análise reflexiva das teses e dissertações (1990-2010)

This research aims to make a reflective analysis about the academic production originated in the stricto sensu post graduation programs in the country, produced in the period of 1990 to 2010, in the field of History of Mathematics, especifically on works about the History of Mathematics in Mathematics education and that present pedagogical proposals that make use of the History of Mathematics in order to teach Mathematics. Defending the thesis that the researches on mathematics education with goals turned to the use of didactic proposals related to the history of mathematic that take in consideration the coherency between epistemological aspects inherent to mathematics history and anthological elements materialized on the conceptions of mathematics and mathematics history and of apprenticeship (implicitly or explicitly exposed) may originate significant contribution to the field of history of mathematics on education. Among these, nine were Master’s Degree dissertations and five PHD’s theses. The reflective analysis was accomplished from two matrixes; one from theoretical nature and the other, ontologic nature, elaborated from the pretexts of Sanches Gamboa, about the epistemological analysis from academic production in the field of Mathematics Education and the following theoretical perspectives in the field of History of Mathematics Education, that are: linear evolutionary theory, structural construtivist operative, evolutionary discontinuous, historical and socialcultural investigation and the use of activities estimulating the usage of verbal and nonverbal expressions. These perspectives were based on the works of Miguel and Miorim, Mendes and Radford. As results, we have detected some established dissonances between the categories related to theoretical and ontologic levels and the pedagogical proposal presented in these researches. On the other hand, we have discovered works that are able to establish consonances between the theoretical and ontological elements and the presented pedagogical proposal. These works carry significative contributions to the field of History of Mathematics applied to Mathematics pedagogical practice, inclusively presenting significative theoretical elements to the production of knowledge recognized as scientific in the Mathematics field

Avaliação do ganho de peso de bebês prematuros em relação ao leite materno cru e leite pasteurizado

This study aims to evaluate the weight gain of premature newborns fed with breast milk from their mothers' from those that are fed with breast milk from the milk bank. The research is the quantitative, descriptive and observational kind. It was conducted in the Neonatal Intensive Care Unit and Housing from the Maternity Hospital Escola Januário Cicco (MEJC), that is a reference for high risk pregnancy and birth in Rio Grande do Norte. The premature newborns included were following these parameters: gestational age from 26 to 37 weeks, initially hospitalized at UTIN, with oral diet, by means by gavage, cup and/or suction. Studies with premature newborns with a zero diet longer than seven days or complications that interfered in the evaluation of weight gain were excluded from this study. The sample was selected for convenience and had data of all newborns hospitalized at UTIN from the May to June of 2014 time period, followed to their discharge, ended by August of 2014 and had the inclusion parameters of the study. From the period of the data collection, 60 premature newborns entered the maternity and 39 of those were the sample of research. The project was approved by the Research Ethics Committee from UFRN, under CAAE nº 0699.0.000.294-11. The data was analyzed by means of descriptive and deduced statistics. The results indicated that the involved in the study, were born from mother with average age of 25,36 years, with less than nine years education 21 (53,8%), had the family income less than a minimum wage 24 (61,5%). Among the newborn, the female gender predominated 20 (51,3%), had cesarean delivery 25 (64,1%), had moderate prematurity 29 (74,5%), more of 1.500g 22 (556,4%). The birth weight average was 1.608,49g. The total of diets were 9.994, and an average of 256 for each newborn, in a 32,12 days of hospitalization time period. Most of the diet supplies were from the breast milk bank (50,34%), however 56,4% of the newborns had most of the diet from their mothers' milked breast milk. It was detected that 38,5% of the newborns had, in some given moment, artificial milk. The daily weight gain average of all newborns was 2,59g, but 35% of them had an average above 10g per day. From the newborn's group (n=25) that had medium weight gain, only 9 of them (36,0%) received mainly their own mothers' milked breast milk. It's been conclusive that most of the premature newborns gained weight predominantly from diets from the breast milk of the Milk Bank, showing the need of a bigger incentive to exclusive breast feeding.

Avaliação da suplementação de vitamina E sobre a concentração de alfa-tocoferol no leite materno em mulheres com partos prematuros

The term vitamin E refers to a group of eight molecular compounds which differ in structure and bioavailability, and the RRR-alpha-tocopherol more biologically active form. The composition of vitamin E in breast milk undergoes variations during lactation, colostrum and milk richer in this micronutrient compared to transitional and mature milk. Newborns, especially premature infants are more susceptible to vitamin E deficiency and to prevent the damage caused by this deficiency has been proposed supplementation of neonates with this micronutrient, however, there is no consensus to carry out this intervention. Thus, maternal supplementation with RRRalpha-tocopherol in the postpartum period can be a good alternative to try to raise the alpha-tocopherol levels in breast milk and therefore provide the premature newborn adequate amounts of vitamin E. This study to evaluate the effect of supplementation with 400 UI acetate RRR-alpha-tocopherol in women with premature births, on the concentration of alpha-tocopherol in breast milk colostrum, transitional and mature. The study included 89 healthy adult women were enrolled in the control group (n = 51) and supplemented group (n = 38). Blood samples were collected and milk colostrum soon after birth (0h milk) twenty-four hours, new rate of colostrum milk was collected (24h milk). The transitional and mature milk were collected in seven days (7d milk) and thirty days (30d milk) after delivery, respectively. Supplementation in the supplemented group was held after the collection of blood and 0h milk. The alpha-tocopherol analyzes were performed by high-performance liquid chromatography. Serum levels of alpha-tocopherol less than 516 μg/dL were considered indicative of nutritional deficiency. The average concentration of alphatocopherol in the serum of the control group mothers was 1159.8 ± 292.4 μg/dL and the supplemented group was 1128.3 ± 407.2 μg/dL (p = 0.281). All women had nutritional status in vitamin E suitable. In both groups, it was observed that the concentration of vitamin E in colostrum milk was higher compared to transitional and mature milk. In the supplemented group, the concentration of alpha-tocopherol in the milk increased 60 % after supplementation, from 1339.3 ± 414.2 μg/dL (0h milk) to 2234.7 ± 997.3 μg/dL (24h milk). While the control group values in colostrum 0h and colostrum 24h were similar (p = 0.681). In the control group the follow-on milk alphatocopherol value was 875.3 ± 292.4 μg/dL and in the group supplemented 1352.8 ± 542.3 μg/dL, an increase of 35% in the supplemented group compared to control (p <0.001). In mature milk alpha-tocopherol concentrations between the control group (426.6 ± 187.5 μg/dL) and supplemented (416.4 ± 214.2 μg/dL) were similar (p = 0.853). Only 24h milk supplemented group answered the nutritional requirement of alpha-tocopherol (4 mg/day) of the newborn. These results show that the transport of this micronutrient for milk occurs in a controlled and limited way. Thus, the native vitamin E supplementation increases the concentration of alpha-tocopherol in colostrum and milk and transition does not influence the concentration in mature milk. Only the increase in colostrum milk was sufficient to meet the nutritional requirement of premature newborns.

Avaliação da concentração de vitamina A materna e de neonatos prematuros e a termo

Vitamin A is an essential nutrient for many physiological processes such as growth and development, so that their adequate nutritional state is essential during pregnancy and lactation. Lactating women and children in breastfeeding are considered risk groups for vitamin A deficiency and some factors may increase the risk of vitamin A deficiency, such as prematurity. The aim of this work was to evaluate the vitamin A concentration in preterm and term lactating women and newborns by determination of retinol in maternal serum, umbilical cord serum and breast milk collected until 72 hours postpartum. 182 mothers were recruited and divided into preterm group (GPT; n = 118) and term group (GT, n = 64). In preterm group were also analyzed transition milk (7th-15th day; n = 68) and mature milk (30th-55th day; n = 46) samples. Retinol was analyzed by high-performance liquid chromatography (HPLC). Maternal retinol concentration in serum was 48.6 ± 12.3 µg/dL in GPT and 42.8 ± 16.3 µg/dL in the GT (p <0.01). Cord serum retinol was 20.4 ± 7.4 µg/dL in GPT and 23.2 ± 7.6 µg/dL in GT (p> 0.05). Among newborns, 43% of premature and 36% of term had low levels of serum retinol in umbilical cord (<20 µg/dL). In colostrum, the retinol in preterm and term groups had an average of 100.8 ± 49.0 µg/dL and 127.5 ± 65.1 µg/dL, respectively (p <0.05). The retinol average in preterm milk increased to 112.5 ± 49.7 µg/dL in transition phase and decreased to 57.2 ± 23.4 µg/dL in mature milk, differing significantly in all stages (p <0.05). When comparing with the recommendation of vitamin A intake (400 µg/day) GT colostrum reached the recommendation for infants, but in GPT the recommendation was not achieved at any stage. Mothers of premature infants had higher serum retinol than mothers at term; however, this was not reflected in serum retinol of umbilical cord, since premature had lower concentration of retinol. Such condition can be explained due to lower maternal physiological hemodilution and placental transfer of retinol to the fetus during preterm gestation. Comparison of retinol in colostrum showed lower concentrations in GPT; however the transition phase there was a significant increase of retinol content released by the mammary gland of preterm mothers. This situation highlights a specific physiological adaptation of prematurity, likely to more contribute to formation of hepatic reserves of retinol in premature infants.

Resumo de dissertações e teses: a estrutura composicional à luz da Análise Textual dos Discursos

This doctoral dissertationproposes the description, interpretation and analysis of the compositional structure of thesis and dissertation abstracts, with regard to the linguistic mechanisms that evidence text zones of different typological sequences, such as those of the text plan. Along these lines, the research problem was developed from the notion of compositional structure (sequences and text plans), as one of the levels or plans of text analysis, according to the theoretical framework proposed by Jean-Michel Adam (2011a). The main objective of this study was to recognize how the compositional structure, of thesis and dissertation abstracts, is achieved, with respect to text units and the global organization of this text category. The hypothesis posed in this research posits that specific informational text composition categories of abstracts are necessary to process the representation of the original text and the way in which it makes its meaning. Subsequently, this study is based on the theoretical and methodological framework of Text Linguistics (TL) and, above all, Textual Discourse Analysis (TDA), as we endeavor to understand the organizational structure of abstracts from both a linguistic and textual perspective. This structure involves the text plan of abstracts, with respect to their communicative purpose, i.e, the sharing of scientific information in its standard textual form. Thus, the development of this study, from a theoretical and methodological perspective, is based on the theoretical and descriptive premises from TDA (ADAM, 2011a, 2012; PASSEGGI et al., 2010), and also from TL (BEAUGRANDE; DRESSLER, (2012 [1981]); COSERIU; LAMAS (2010); MARCUSCHI, 2009 [1983]; FÁVERO; KOCH, 1994;KOCH, 2006; BENTES, 2004; BENTES; LEITE, 2010), within the field of text studies. The methodology of this study relies on empirical, documental research, which is qualitative, and adopts a descriptive and interpretive approach. From the empirical perspective, our objective is to understand the problems pertaining to the textual composition of abstracts, aiming to elucidate them in light of the theoretical and methodological framework previously mentioned. The corpus of the analysis is comprised of seven abstracts designated for systematic data collection. These texts, written between 2004 and 2011,were selected from Master’s theses and Doctoral dissertations in their electronic version, from the graduate program at the Federal University of Rio Grande do Norte. A thorough review of the literature reveals a clear fluctuation in the terminology of the concept, ‘abstract’. The results of the analysis revealed that the abstracts, which comprise the corpus of analysis in this study, in general, present typological heterogeneity, while the text plan remains fixed. Finally, the new knowledge gained in this research contributes both to the understanding of the compositional structure of abstracts as well as their production.

A PESQUISA ACADÊMICA SOBRE COMUNICAÇÃO POPULAR, ALTERNATIVA E COMUNITÁRIA NO BRASIL: análise de dissertações e teses produzidas em Programas de Pós-Graduação em Comunicação entre 1972 - 2012

Mapeamento das dissertações e teses referentes à subárea da comunicação popular, alternativa e comunitária (CPAC) desenvolvidas nos Programas de Pós-Graduação em Comunicação stricto sensu no Brasil, de 1972 a 2012. Dentre os objetivos estão localizar as pesquisas; os autores; sua distribuição no tempo e espaço; identificar as instituições e orientadores que impulsionam a subárea; definir as abordagens teórico-metodológicas; e apontar autores/conceitos referência. Por meio de pesquisa exploratória e aplicação de quatro filtros, chegou-se a uma amostra final de 102 pesquisas, 87 dissertações e 15 teses, submetidas à análise quantitativa, por meio de Análise de Conteúdo a partir de partes pré-definidas (Resumo, Palavras chave, Introdução, Sumário, Considerações Finais e capítulo metodológico, quando presente), e a uma análise qualitativa do conteúdo completo das 15 teses. O método que orienta esta pesquisa é o histórico dialético, na perspectiva da busca de uma análise de conjunto e atenta às contradições e mudanças que o objeto está implicado; e a pesquisa bibliográfica que a fundamenta se ancora em autores como Jorge González, Cicilia Peruzzo, Regina Festa, Pedro Gilberto Gomes, Gilberto Giménez e Augusto Triviños e foi realizada com o apoio do software NVivo. Resultados quantitativos indicam: a) predominância de pesquisas sobre comunicação comunitária (68%) b) predominância de estudos empíricos (79%); c) a variedade de denominações atribuídas às experiências pelos pesquisadores; d) a constante luta das classes populares por democratização da comunicação e por direitos sociais ao longo dos anos; e) a influência e importância dos intelectuais orgânicos nas experiências estudadas, f) problemas metodológicos; g) UMESP, USP e UFRJ como instituições protagonistas, e, h) Cicilia Peruzzo e Raquel Paiva como as que mais orientam teses e dissertações sobre a temática. Quanto à análise qualitativa verificaram-se alguns critérios que permeiam a CPAC: 1) a definição de classes subalternas; 2) a importância da participação ativa das comunidades nos processos de comunicação; e 3) formas, conteúdos e objetivos que se complementam e dão identidade às experiências

Avaliação do banco de dissertações e teses da associação brasileira de antropologia: uma análise cienciométrica

VITULLO, Nadia Aurora Vanti. Avaliação do banco de dissertações e teses da Associação Brasileira de Antropologia: uma análise cienciométrica. 2001. 143 f. Dissertaçao (Mestrado) - Curso de Mestrado em Biblioteconomia e Ciência da Informação, Pontifícia Universidade Católica de Campinas, Campinas, 2001.

Biblioteca digital de teses e dissertaçoes: uma referência fundamental

OLIVEIRA, Raimundo Muniz de. Biblioteca digital de teses e dissertaçoes: uma referencia fundamental. In: CINFORM ENCONTRO NACIONAL DE ENSINO E PESQUISA DA INFORMAÇAO,HUMANISMO E DESENVOLVIMENTO CIENTIFICO E TECNOLOGICO,7.,2007,Salvador. Anais...Salvador:UFBA, 2007.Disponivel em:www.cinform.ufba.br>. Acesso em: 27 set. 2007. Acesso em: 27 set. 2010.