Lymphoblastoid cell lines as a model to understand amyotrophic lateral sclerosis disease mechanisms

In the past, amyotrophic lateral sclerosis (ALS) has been considered a 'neurocentric' disease; however, new evidence suggests that it should instead be looked at from a 'multisystemic' or 'non-neurocentric' point of view. From 2006, we focused on the study of non-neural cells: ALS patients' peripheral blood mononuclear cells (PMBCs) and lymphoblastoid cell lines (LCLs). Here, we characterize LCLs of sporadic ALS (sALS) and patients carrying SOD1, TARDBP and FUS mutations to identify an ALS biologically relevant molecular signature, and determine whether and how mutations differentially affect ALS-linked pathways. Although LCLs are different from motor neurons (MNs), in LCLs we found some features typical of degenerating MNs in ALS, i.e. protein aggregation and mitochondrial dysfunction. Moreover, different gene mutations have different effects on ALS cellular mechanisms. TARDBP and FUS mutations imbalance mitochondrial dynamism toward increased fusion, whereas sALS and SOD1 mutations mainly affect fission. With regards to protein aggregation and/or mislocalization, TARDBP and SOD1 mutations show the presence of aggregates, whereas FUS mutation does not induce protein aggregation and/or mislocalization. Finally, all LCLs, independently from mutation, are not able to work in a condition of excessive energy request, suggesting that mitochondria from ALS patients are characterized by a significant metabolic defect. Taken together, these data indicate that LCLs could be a valid cellular model in ALS research in the identification and study of specific pathological pathways

Lymphoblastoid cell lines as a model to understand amyotrophic lateral sclerosis disease mechanisms

In the past, amyotrophic lateral sclerosis (ALS) has been considered a ‘neurocentric’ disease; however, new evidence suggests that it should instead be looked at from a ‘multisystemic’ or ‘non-neurocentric’ point of view. From 2006, we focused on the study of non-neural cells: ALS patients’ peripheral blood mononuclear cells (PMBCs) and lymphoblastoid cell lines (LCLs). Here, we characterize LCLs of sporadic ALS (sALS) and patients carrying SOD1, TARDBP and FUS mutations to identify an ALS biologically relevant molecular signature, and determine whether and how mutations differentially affect ALS-linked pathways. Although LCLs are different from motor neurons (MNs), in LCLs we found some features typical of degenerating MNs in ALS, i.e. protein aggregation and mitochondrial dysfunction. Moreover, different gene mutations have different effects on ALS cellular mechanisms. TARDBP and FUS mutations imbalance mitochondrial dynamism toward increased fusion, whereas sALS and SOD1 mutations mainly affect fission. With regards to protein aggregation and/or mislocalization, TARDBP and SOD1 mutations show the presence of aggregates, whereas FUS mutation does not induce protein aggregation and/or mislocalization. Finally, all LCLs, independently from mutation, are not able to work in a condition of excessive energy request, suggesting that mitochondria from ALS patients are characterized by a significant metabolic defect. Taken together, these data indicate that LCLs could be a valid cellular model in ALS research in the identification and study of specific pathological pathways

Ensinando matemática através de jogos, modelos geométricos e informática

One of the goals of the mathematics departments of Brazilian universities is to stimulate the interest of the students entering the logical reasoning. Another angle is to look for ways to encourage to students and teachers in an attempt to contribute to the improvement of the Brazilian situation that arises. As described in the National Curriculum Parameters (High School), Part III - Natural Sciences, Mathematics and its technologies, learn math in high school should be more than memorize results of science and the acquisition of mathematical knowledge must be linked to domain one know how to make mathematics and a knowledge mathematical thinking. So we want with this project stimulate a love for Mathematics, providing greater teacher / student interaction and promote a community approach / university, causing the student to have a new view of mathematics through games. Thus, in a playful way, I think this student the concepts learned in the classroom to question the logic used to do the thinking, making this student make connections between the various areas of mathematics.Um dos objetivos dos departamentos de Matemática das universidades brasileiras é estimular o interesse dos graduandos ingressantes pelo raciocínio lógico. Outro ângulo é buscar meios de incentivo para alunos e professores, na tentativa de colaborar para a melhoria do quadro brasileiro que se coloca. Conforme descrito nos Parâmetros Curriculares Nacionais (Ensino Médio), Parte III - Ciências da Natureza, Matemática e suas Tecnologias, aprender Matemática no Ensino Médio deve ser mais do que memorizar resultados dessa ciência e que a aquisição do conhecimento matemático deve estar vinculada ao domínio de um saber fazer Matemática e de um saber pensar matemático. Por isso queremos com este projeto estimular o gosto pela Matemática, propiciando uma interação maior entre professor/aluno e promover uma aproximação comunidade/universidade, fazendo com que o aluno tenha uma nova visão da Matemática através dos jogos. Assim, de forma lúdica, faremos este aluno pensar nos conceitos aprendidos na sala de aula, questionar a lógica usada para fazer o pensamento, fazendo com que este estudante crie conexões entre as várias áreas da matemática

Reclamo al CICR- commento all'art.9 TUB

Il reclamo al CICR resta apparentemente immutato come reclamo nazionale avverso i provvedimenti di vigilanza, mentre gli assetti dei poteri di vigilanza bancaria sono da tempo profondamente riconfigurati e incentrati sulla BCE. Nel nuovo sistema di vigilanza è previsto un diverso procediento di reclamo. Si affronta, quindi, principalmente il problema della convivenza dei due rimedi