Co-Localization of the Oncogenic Transcription Factor MYCN and the DNA Methyl Binding Protein MeCP2 at Genomic Sites in Neuroblastoma

MYCN is a transcription factor that is expressed during the development of the neural crest and its dysregulation plays a major role in the pathogenesis of pediatric cancers such as neuroblastoma, medulloblastoma and rhabdomyosarcoma. MeCP2 is a CpG methyl binding protein which has been associated with a number of cancers and developmental disorders, particularly Rett syndrome.Using an integrative global genomics approach involving chromatin immunoprecipitation applied to microarrays, we have determined that MYCN and MeCP2 co-localize to gene promoter regions, as well as inter/intragenic sites, within the neuroblastoma genome (MYCN amplified Kelly cells) at high frequency (70.2% of MYCN sites were also positive for MeCP2). Intriguingly, the frequency of co-localization was significantly less at promoter regions exhibiting substantial hypermethylation (8.7%), as determined by methylated DNA immunoprecipitation (MeDIP) applied to the same microarrays. Co-immunoprecipitation of MYCN using an anti-MeCP2 antibody indicated that a MYCN/MeCP2 interaction occurs at protein level. mRNA expression profiling revealed that the median expression of genes with promoters bound by MYCN was significantly higher than for genes bound by MeCP2, and that genes bound by both proteins had intermediate expression. Pathway analysis was carried out for genes bound by MYCN, MeCP2 or MYCN/MeCP2, revealing higher order functions.Our results indicate that MYCN and MeCP2 protein interact and co-localize to similar genomic sites at very high frequency, and that the patterns of binding of these proteins can be associated with significant differences in transcriptional activity. Although it is not yet known if this interaction contributes to neuroblastoma disease pathogenesis, it is intriguing that the interaction occurs at the promoter regions of several genes important for the development of neuroblastoma, including ALK, AURKA and BDNF

Determinação da carga de treino nos exercícios supino e rosca bíceps em mulheres jovens Defining the training load in bench press and biceps curl exercises in young women

O objetivo deste estudo foi avaliar a força máxima dinâmica (1RM) nos exercícios supino e rosca scott, e relacioná-la com a massa corporal total (MCT) e com a massa corporal magra (MCM), bem como avaliar o número máximo de repetições em diferentes percentuais de 1RM. Onze mulheres (24 ± 1,4 anos) foram submetidas à avaliação da composição corporal, testes de 1RM e testes de repetições máximas em 50, 60, 70 e 80% de 1RM. No tratamento dos dados, foram utilizados a regressão linear múltipla, a ANOVA para medidas repetidas e o teste t pareado. A MCM é a variável que melhor explica a variância de 1RM, podendo ser utilizada para a determinação de um coeficiente para a estimativa da carga de treino. Houve diferenças significativas entre os números de repetições em todos os percentuais e em ambos os exercícios [(supino (p=0,000) e rosca scott (p=0,000)], sendo esses números progressivamente menores com o incremento da carga.<br>The purpose of this study was to assess maximum strength (1RM) in the bench press and biceps curl exercises, and relate it to total body mass (BM) and fat-free mass (FFM), as well as to assess the maximum repetition number at different percentages of 1-RM. Eleven women (age: 24 ± 1.4 years) were submitted to body composition assessment, 1-RM tests, and maximum repetition tests at 50, 60, 70 and 80% of 1-RM. For data treatment, multiple linear regression, repeated measures ANOVA and paired t-test were used. FFM explains better than BM the 1-RM variance and can be used to determine a coefficient to estimate the training load. Significant differences were found in the maximum repetition numbers in all percentages and both exercises (bench press (p=0,000) and biceps curl (p=0,000). These results revealed a gradual decrease in the number of repetitions as the load increased

Modelo de predição de uma repetição máxima (1RM) baseado nas características antropométricas de homens e mulheres Modelo de predicción de una repetición máxima (1RM) basado en las características antropométricas de hombres y mujeres Prediction model of a maximal repetition (1RM) based on male and female anthropometrical characteristics

O objetivo do presente estudo foi desenvolver uma equação para predição da carga de uma repetição máxima (1RM) em homens e mulheres, usando exclusivamente as características antropométricas. Participaram deste estudo 44 jovens de baixo risco, com experiência em treinamento de força, sendo 22 do sexo masculino (23 &plusmn; 4 anos, 76,6 &plusmn; 12,7kg, 173,9 &plusmn; 5,5cm, 11 &plusmn; 4,5% de gordura) e 22 do feminino (22 &plusmn; 4 anos, 54 &plusmn; 6,0kg, 161 &plusmn; 5,8cm, 18 &plusmn; 2,2% de gordura). Inicialmente, eles passaram por uma avaliação antropométrica seguida de um teste de 1RM de familiarização no exercício de desenvolvimento, que foi repetido após 48h. A repetibilidade do teste de 1RM foi testada pelo Wilcoxon matched paired test. Finalmente, a carga de 1RM foi modelada em função das variáveis antropométricas por regressão linear múltipla (forward stepwise) usando como critério de corte das variáveis independentes deltar² < 0,01. A confiabilidade dos modelos foi expressa pela análise de Bland e Altman. Adotou-se em todos os testes alfa = 0,05. Não se registraram diferenças entre teste e reteste, resultando em 44,6 &plusmn; 13,2kg e 12,2 &plusmn; 3,2kg nos indivíduos do sexo masculino (SM) e feminino (SF), respectivamente. Além das variáveis antropométricas, incluiu-se aos modelos o tempo de experiência em treinamento de força. No SM, o modelo resultou em 84% da variância explicada, com erro padrão equivalente a 12%. Por outro lado, no SF, a capacidade preditiva do modelo obtido foi mais fraca, resultando em 56% da variância explicada e erro padrão equivalente a 20%. Em conclusão, os modelos obtidos mostraram adequada confiabilidade, de forma que podem ser utilizados como ferramentas para predição da carga de 1RM.<br>El objetivo del presente estudio ha sido desarrollar una ecuación para predecir la carga de una repetición máxima (1RM) en hombres y mujeres, usando exclusivamente las características antropométricas. Participaron de este estudio 44 jóvenes de bajo riesgo, con experiencia en entrenamiento de fuerza, 22 del sexo masculino (23 &plusmn; 4 años, 76,6 &plusmn; 12,7 kg, 173,9 &plusmn; 5,5 cm, 11 &plusmn; 4,5% de grasa) y 22 del sexo femenino (22 &plusmn; 4 años, 54 &plusmn; 6,0 kg, 161 &plusmn; 5,8 cm, 18 &plusmn; 2,2% de grasa). Al inicio, estos pasaron por una evaluación antropométrica seguida de un test de 1RM de familiarización en el ejercicio en desarrollo, que fue repetido después de 48 h. La repetibilidad del test de 1RM fue probada por Wilcoxon matched paired test. Finalmente la carga de 1RM fue modelada en función de las variables antropométricas por regresión lineal múltiple (forward stepwise) usando como criterio de aglomeración de las variables independientes deltar² < 0,01. La confiabilidad de los modelos se expresó por el análisis de Bland y Altman. En todos los tests se adoptó alfa = 0,05. No se registraron diferencias entre el test y el retest, resultando en 44,6 &plusmn; 13,2 kg y 12,2 &plusmn; 3,2kg en los individuos del sexo masculino (SM) y femenino (SF), respectivamente. Fuera de las variables antropométricas, se incluyó a los modelos el tiempo de experiencia en la actividad de fuerza. En el SM, el modelo resultó en 84% de la varianza explicada, con un error padrón equivalente a 12%. Por otro lado, en el SF, la capacidad predictiva del modelo obtenido no fue tan eficaz, resultando en 56% de la varianza explicada y un error padrón equivalente a 20%. En conclusión, los modelos obtenidos mostraron adecuada confiabilidad, de forma que pueden ser utilizados como herramientas para predecir la carga de 1RM.<br>The goal of the present study was to develop an equation for predicting the workload of one maximal repetition (1RM) in women and men, based exclusively on anthropometrical characteristics. Forty-four low-risk and experienced in strength training young subjects, being 22 male (23 &plusmn; 4 years, 76.6 &plusmn; 12.7 kg, 173.9 &plusmn; 5.5 cm, 11 &plusmn; 4.5 % of body fat) and 22 female (22 &plusmn; 4 years, 54 &plusmn; 6.0 kg, 161 &plusmn; 5.8 cm, 18 &plusmn; 2.2 % of body fat) volunteered for this study. All subjects were submitted to an anthropometrical evaluation followed by a 1RM familiarization test (shoulder press), which was repeated after 48h. The repeatability was tested using Wilcoxon Matched paired test. Finally, the 1RM workload was modeled in relation to the anthropometrical variables through multiple linear regression (forward stepwise) using as cutoff criteria for the independent variables deltar² < 0.01. The models reliability was expressed by the Bland and Altman analysis. All tests assumed alpha = 0.05. No significant differences were recorded between the two tests, resulting 44.6 &plusmn; 13.2 kg and 12.2 &plusmn; 3.2kg, for male (MS) and female (FS) subjects respectively. The time of practice in strength training was also included in the models. The model resulted in 84% of explained variance and a standard error of 12% for the MS. On the other hand, for the FS the predictive capacity was weaker than for = the MS, resulting in 56% of the explained variance and a standard error of 20%. In conclusion, the obtained models showed acceptable reliability so that they can be currently used as a tool for predicting the 1RM workload