The paralogues MAGOH and MAGOHB are oncogenic factors in high-grade gliomas and safeguard the splicing of cell division and cell cycle genes

The exon junction complex (EJC) plays key roles throughout the lifespan of RNA and is particularly relevant in the nervous system. We investigated the roles of two EJC members, the paralogs MAGOH and MAGOHB, with respect to brain tumour development. High MAGOH/MAGOHB expression was observed in 14 tumour types; glioblastoma (GBM) showed the greatest difference compared to normal tissue. Increased MAGOH/MAGOHB expression was associated with poor prognosis in glioma patients, while knockdown of MAGOH/MAGOHB affected different cancer phenotypes. Reduced MAGOH/MAGOHB expression in GBM cells caused alterations in the splicing profile, including re-splicing and skipping of multiple exons. The binding profiles of EJC proteins indicated that exons affected by MAGOH/MAGOHB knockdown accumulated fewer complexes on average, providing a possible explanation for their sensitivity to MAGOH/MAGOHB knockdown. Transcripts (genes) showing alterations in the splicing profile are mainly implicated in cell division, cell cycle, splicing, and translation. We propose that high MAGOH/MAGOHB levels are required to safeguard the splicing of genes in high demand in scenarios requiring increased cell proliferation (brain development and GBM growth), ensuring efficient cell division, cell cycle regulation, and gene expression (splicing and translation). Since differentiated neuronal cells do not require increased MAGOH/MAGOHB expression, targeting these paralogs is a potential option for treating GBM

Short-Term Withdrawal of Mitogens Prior to Plating Increases Neuronal Differentiation of Human Neural Precursor Cells

Background: Human neural precursor cells (hNPC) are candidates for neural transplantation in a wide range of neurological disorders. Recently, much work has been done to determine how the environment for NPC culture in vitro may alter their plasticity. Epidermal growth factor (EGF) and fibroblast growth factor-2 (FGF-2) are used to expand NPC; however, it is not clear if continuous exposure to mitogens may abrogate their subsequent differentiation. Here we evaluated if short-term removal of FGF-2 and EGF prior to plating may improve hNPC differentiation into neurons.Principal Findings: We demonstrate that culture of neurospheres in suspension for 2 weeks without EGF-FGF-2 significantly increases neuronal differentiation and neurite extension when compared to cells cultured using standard protocols. in this condition, neurons were preferentially located in the core of the neurospheres instead of the shell. Moreover, after plating, neurons presented radial rather than randomly oriented and longer processes than controls, comprised mostly by neurons with short processes. These changes were followed by alterations in the expression of genes related to cell survival.Conclusions: These results show that EGF and FGF-2 removal affects NPC fate and plasticity. Taking into account that a three dimensional structure is essential for NPC differentiation, here we evaluated, for the first time, the effects of growth factors removal in whole neurospheres rather than in plated cell culture.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Institutos do Milenio de Bioengenharia TecidualUniversidade Federal de São Paulo, Dept Physiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biophys, São Paulo, BrazilUniv Fed Rio de Janeiro, Inst Ciencias Biomed, BR-21941 Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Dept Physiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biophys, São Paulo, BrazilFAPESP: fellowCNPq: fellowWeb of Scienc

Investigação de um sistema de alimentação em recém-nascidos prematuros a partir de estimulação gustativa

Objetivo: investigar a existência do sistema de alimentação em recém-nascidos prematuros a partir da estimulação gustativa. Métodos: estudo experimental, analítico, duplo-cego. Participaram 90 recém-nascidos prematuros, de uma maternidade pública de Sergipe. O teste foi filmado, constituindo-se por três momentos de cinco minutos. O primeiro e último momento sem realizar estímulo, o segundo momento com estimulação gustativa, sendo que os recém-nascidos foram divididos em dois grupos (água ou sacarose). Foram estudados os comportamentos específicos sucção de mão direita e esquerda, protrusão de língua e movimentos de sucção nos estados comportamentais sono profundo, sono leve, sonolento, agitado/irritado e choro. Para caracterizar a população foram utilizadas média, desvio-padrão e prevalências. Foi utilizado o teste não paramétrico Mann-Whitney para comparação de médias. O teste de Spearman verificou correlação entre estados comportamentais e comportamentos específicos em cada momento do teste. O valor de p foi significante quando menor que 0,05. Resultados: independente do estímulo administrado, a correlação aumentou em todos os comportamentos específicos. Comparando os grupos separadamente, após a estimulação, observou-se aumento de correlação em sucção de mão direita e protrusão de língua para ambos os grupos. O mesmo aconteceu em sucção, com exceção do estado agitado/irritado. Após a estimulação, houve maior correlação para o comportamento de sucção de mão esquerda no grupo sacarose quando comparado ao grupo água. Os resultados evidenciam que estímulos gustativos podem contribuir na prontidão para alimentação nesta população. Conclusões: evidenciou-se nos recém-nascidos prematuros aumento de correlação para os comportamentos específicos relacionados ao sistema de alimentação, após estimulação oral, o que vislumbra a possibilidade da estimulação gustativa ser utilizada para ativação de um sistema de alimentação em recém-nascidos prematuros. _________________________________________________________________________________________ ABSTRACT: Purpose: to investigate the existence of the alimentation system in premature newborns in response to gustatory stimulation. Methods: experimental, analytical, double-blind study. 90 premature newborns of a public maternity in Sergipe took part in the test which was filmed and divided into three parts of five minutes. In the first and last, there was no stimulus; in the second, the gustatory stimulation was applied and the newborn children were divided into two groups (water or sucrose). We studied the specific behaviors suction right and left hands, tongue protrusion and suction movements in behavioral states deep sleep, light sleep, drowsy, restless / irritable and crying. In the statistical analysis of the population, average, standard deviation and prevalence studies were performed. We used the non-parametric Mann-Whitney test to compare averages. The Spearman test observed correlation between behavioral states at each time of the test. The p value was significant when less than 0.05. Results: independent of the given stimulus, the correlation increased in all specific behaviors. Comparing the groups separately, after stimulation, we observed an increase in correlation in right hand suction and tongue protrusion for both. The same happened in suction, except for the agitated/irritated state. After stimulation, there was a higher correlation to the behavior of left hand suction in the sucrose group when compared to water. The results show that gustatory stimuli may contribute to the readiness to feed this population. Conclusions: it was found in premature newborns an increased in correlation for the specific behaviors related to the alimentation system after oral stimulation, which envisions the possibility of gustatory stimulation be used for activating a alimentation system in premature newborns