Characterization of MTAP gene expression in breast cancer patients and cell lines

MTAP is a ubiquitously expressed gene important for adenine and methionine salvage. The gene is located at 9p21, a chromosome region often deleted in breast carcinomas, similar to CDKN2A, a recognized tumor suppressor gene. Several research groups have shown that MTAP acts as a tumor suppressor, and some therapeutic approaches were proposed based on a tumors\ub4 MTAP status. We analyzed MTAP and CDKN2A gene (RT-qPCR) and protein (western-blotting) expression in seven breast cancer cell lines and evaluated their promoter methylation patterns to better characterize the contribution of these genes to breast cancer. Cytotoxicity assays with inhibitors of de novo adenine synthesis (5-FU, AZA and MTX) after MTAP gene knockdown showed an increased sensitivity, mainly to 5-FU. MTAP expression was also evaluated in two groups of samples from breast cancer patients, fresh tumors and paired normal breast tissue, and from formalin-fixed paraffin embedded (FFPE) core breast cancer samples diagnosed as Luminal-A tumors and triple negative breast tumors (TNBC). The difference of MTAP expression between fresh tumors and normal tissues was not statistically significant. However, MTAP expression was significantly higher in Luminal-A breast tumors than in TNBC, suggesting the lack of expression in more aggressive breast tumors and the possibility of using the new approaches based on MTAP status in TNB

The Role of bZIP Transcription Factors in Green Plant Evolution: Adaptive Features Emerging from Four Founder Genes

BACKGROUND: Transcription factors of the basic leucine zipper (bZIP) family control important processes in all eukaryotes. In plants, bZIPs are regulators of many central developmental and physiological processes including photomorphogenesis, leaf and seed formation, energy homeostasis, and abiotic and biotic stress responses. Here we performed a comprehensive phylogenetic analysis of bZIP genes from algae, mosses, ferns, gymnosperms and angiosperms. METHODOLOGY/PRINCIPAL FINDINGS: We identified 13 groups of bZIP homologues in angiosperms, three more than known before, that represent 34 Possible Groups of Orthologues (PoGOs). The 34 PoGOs may correspond to the complete set of ancestral angiosperm bZIP genes that participated in the diversification of flowering plants. Homologous genes dedicated to seed-related processes and ABA-mediated stress responses originated in the common ancestor of seed plants, and three groups of homologues emerged in the angiosperm lineage, of which one group plays a role in optimizing the use of energy. CONCLUSIONS/SIGNIFICANCE: Our data suggest that the ancestor of green plants possessed four bZIP genes functionally involved in oxidative stress and unfolded protein responses that are bZIP-mediated processes in all eukaryotes, but also in light-dependent regulations. The four founder genes amplified and diverged significantly, generating traits that benefited the colonization of new environments

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age-and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men &lt;= 50y, men &gt; 50y, women &lt;= 50y, women &gt; 50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR&lt; 5%) age-specific effects, of which 11 had larger effects in younger (&lt; 50y) than in older adults (&gt;= 50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.</p

Entre ganhos e perdas simbólicas: a (des) mobilização das enfermeiras que atuaram na Segunda Guerra Mundial Entre lucros y perjuicios simbólicos: la (des) movilización de las enfermeras que actuaron en la Segunda Guerra Mundial Between profits and symbolic losses: the (de) mobilization of the nurses who had acted in the World War II

Estudo histórico-social. Objetivos: descrever as circunstâncias que ensejaram a mobilização e a desmobilização do primeiro grupamento feminino de enfermagem do Exército que atuou no Serviço de Saúde da Força Expedicionária Brasileira durante a Segunda Guerra Mundial e analisar os efeitos simbólicos advindos da atuação deste grupamento. As fontes primárias constituíram-se de depoimentos orais, documentos escritos e/ou oficiais, jornais da época e biografias. As secundárias foram compostas do acervo bibliográfico existente sobre a referida temática. Os achados foram iluminados pelos conceitos de habitus e campo do sociólogo Pierre Bourdieu, que evidenciaram ganhos e perdas simbólicas processadas por ocasião da mobilização e da desmobilização destas voluntárias para a guerra. Conclui-se que das lutas simbólicas travadas, as enfermeiras acabaram sofrendo os reflexos da dominação masculina orquestrada no contexto político-social do Brasil à época, o que trouxe como conseqüência a (re) atualização de seu habitus.<br>Estudio histórico-social. Objetivos: describir las circunstancias que ocasionaron la movilización y la desmovilización del primer grupo femenino de enfermería del Ejército que participó del Servicio de Salud de la Fuerza de Expedición Brasileña mientras la Segunda Guerra Mundial ocurría y analizar los efectos simbólicos del funcionamiento de este grupo. Las fuentes primarias fueron declaraciones orales, documentos escritos, biografías y periódicos de la época. Las secundarias fueron compuestas del acervo bibliográfico que existe sobre la referida temática. Todo lo que fue descubierto fue iluminado por los conceptos de "habitus" y campo del sociólogo Pierre Bordieu, que evidenciaron lucros y perjuicios simbólicos por ocasión de la movilización y de la desmovilización de estas voluntarias para la Guerra. Se ha concluido que de las luchas simbólicas trabadas, las enfermeras acabaron sUfriendo los reflejos de la dominación masculina en el contexto político-social de Brasil a la época, lo que trajo como consecuencia la (re) actualización de sus "habitus".<br>Descriptive and social study. Objectives: to describe the circumstances that had tried the mobilization and the demobilization of the first feminine grouping of nursing of the Army that acted in the Service of Health of the Force Brazilian Member of an expedition during World War II and to analyze the happened symbolic effect of the performance of this grouping. The primary sources had consisted of verbal depositions, written and/or official documents, periodicals of the time and biographies. The secondary ones had been composed of the existing bibliographical quantity on the thematic related one. The findings had been illuminated by the concepts of "habitus" and field of the sociologist Pierre Bourdieu, whom profits and processed symbolic losses for occasion of the mobilization and the demobilization of these volunteers for the war had evidenced. It was concluded that to stop symbolic fights, the nurses had finished suffering the consequences from the masculine domination orchestrated in the Brazil's political and social context at the time, what brought as consequence the update of its "habitus"

A visibilidade da atuação de uma enfermeira do Exército Brasileiro a um ferido na 2ª Guerra Mundial Análisis Fotográfico de la asistencia prestada por una enfermera del Ejército Brasileño a un herido en la 2ª Guerra Mundial The visibility of the care given by a Brazilian Army nurse to a wounded soldier during World War II

Estudo histórico-sociológico com o objetivo de analisar e descrever a visibilidade da atuação de uma enfermeira do Exército inserida na Força Expedicionária Brasileira (FEB) durante a 2º Guerra Mundial. Fonte primária: uma fotografia da época, articulada aos depoimentos orais de dezenove agentes. Essa modalidade de obtenção de dados possibilitou criar um método de pesquisa que denominamos Analítico Fotográfico Oral. Escolhemos a foto no acervo iconográfico do Exército localizado no Comando Militar do Leste, no Rio de Janeiro. Fontes secundárias: acervo literário sobre o contexto histórico social da época. Utilizamos os conceitos de habitus, poder e capital cultural de Pierre Bourdieu. Os resultados evidenciaram que para enfrentar o desafio, as voluntárias precisaram adquirir novos habitus mediante treinamento obrigatório, orientado pelos militares para cuidar dos feridos de guerra.<br>Este estudio histórico-sociológico tiene como objetivo analizar y describir la visibilidad de la actuación de una enfermera del Ejército insertada en la Fuerza Expedicionaria Brasileña (FEB) por ocasión de la 2ª guerra mundial. Fuente primaria: una fotografía de la época articulada a los testimonios orales de diecinueve agentes. Esta modalidad de obtención de datos posibilitó crear un método de investigación que lo denominamos de Analítico Fotográfico Oral. Escogimos la foto en el acervo iconográfico del Ejército en el Comando Militar del Este en Río de Janeiro. Fuentes secundarias: el acervo literario del contexto histórico social de la época. Utilizamos los conceptos de habitus, poder y capital cultural de Pierre Bourdieu. Los resultados evidenciaron que para enfrentar el desafío, las enfermeras necesitaron adquirir nuevos habitus mediante el entrenamiento obligatorio, orientado por los militares para cuidar a los heridos de guerra.<br>A historical-sociological study aimed at analyzing and describing the visibility of the performance of a Brazilian Army nurse engaged in the Força Expedicionária Brasileira - FEB (Brazilian Expeditionary Force) during the Second World War. Primary source: a photograph taken at the time, along with the oral testimony of nineteen agents. This mode of gathering data resulted in the creation of a new method of research, which we named Oral-Photographic Analysis. The photo was picked in the Brazilian Army's iconographic collection, located at the Comando Militar do Leste (Eastern Military Command), in Rio de Janeiro. Secondary sources: literature on the socio-historical context of the period. We used Pierre Bourdieu's concepts of habitus, power and cultural capital. The results showed that, in order to face such challenge and care for the wounded, the volunteer nurses had to acquire new habitus through mandatory training given by the military