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The BRCA1 protein, one of the major players responsible for DNA damage response has recently been linked to Alzheimer's disease (AD). Using primary fibroblasts and neurons reprogrammed from induced pluripotent stem cells (iPSC) derived from familial AD (FAD) patients, we studied the role of the BRCA1 protein underlying molecular neurodegeneration. By whole-transcriptome approach, we have found wide range of disturbances in cell cycle and DNA damage response in FAD fibroblasts. This was manifested by significantly increased content of BRCA1 phosphorylated on Ser1524 and abnormal ubiquitination and subcellular distribution of presenilin 1 (PS1). Accordingly, the iPSC-derived FAD neurons showed increased content of BRCA1(Ser1524) colocalized with degraded PS1, accompanied by an enhanced immunostaining pattern of amyloid-beta. Finally, overactivation of BRCA1 was followed by an increased content of Cdc25C phosphorylated on Ser216, likely triggering cell cycle re-entry in FAD neurons. This study suggests that overactivated BRCA1 could both influence PS1 turnover leading to amyloid-beta pathology and promote cell cycle re-entry-driven cell death of postmitotic neurons in AD.

CTL07-II is a healthy feeder-free and characterized human induced pluripotent stem (iPS) cell line. Cultured under xeno-free and defined conditions. The line is generated from healthy human fibroblasts with non-integrating Sendai virus vectors encoding the four Yamanaka factors, OCT4, SOX2, KLF4 and cMYC. The generated iPS cells are free from reprogramming vectors and their purity, karyotypic stability and pluripotent capacity is confirmed.

Currently, the debate about the teaching of foreign languages in Brazil runs two different paths: one methodological, guided by the applied linguistics; and one political, guided by what Haugen (1999) refers to as “applied sociolinguistics” or, more appropriately, Language Education Policy, as per Petitjean (2006). This paper proposes a brief discussion on political linguistic matters, such as the Brazilian Educational Legislation (LDB, 9394/96, law #11.161), recommendations (PCN), linguistic representations, and multilingualism (BEACCO; BYRAN, 2003). These matters underlie many of the problems in the country's foreign language teaching, even though they are purely conceived in a methodological framework, as exposed by Celani (1997), Campani (2006) and Leffa (1999). The arguments presented lead to a complementary analysis of the foreign language teaching problems and to a language perception, grounded on the foreign languages' social role., Atualmente, o debate em torno do ensino de línguas estrangeiras no Brasil encontra-se dividido em duas correntes: uma de caráter metodológico, conduzida preferencialmente pela Linguística Aplicada, e outra de caráter político, orientada pelo que Haugen (1999) denominou de Sociolinguística Aplicada ou, mais apropriadamente, pela Política Linguística Educativa conforme Petitjean (2006). Este ensaio propõe uma breve reflexão acerca de questões de ordem político-linguísticas, tais como ordenamento jurídico (LDB 9394/96, Lei 11.161/2005), recomendações (PCNs), representações linguísticas e multilinguismo (BEACCO; BYRAN, 2003). Tais questões subjazem muitos dos problemas do ensino de língua estrangeira no país, embora sejam concebidos puramente como de âmbito metodológico, como indicam Celani (1997), Campani (2006) e Leffa (1999). Os argumentos apresentados apontam para uma análise complementar dos problemas no ensino de LE e para uma percepção das línguas, na escola, calcada no papel social das LE., Actualmente, el debate sobre la enseñanza de lenguas extranjeras en Brasil se encuentra dividido entre dos corrientes, una de carácter metodológica conducida preferencialmente por la Lingüística Aplicada y otra de carácter político, orientada por lo que Haugen (1999) ha denominado como Sociolingüística Aplicada o más apropiadamente, de Política Lingüística Educativa conforme Petitjean (2006). Este ensayo trae una breve reflexión sobre cuestiones político-lingüísticas, tales como de orden jurídico (LDB, 9394/96, Ley 11.161), recomendaciones (PCNs), representaciones lingüísticas y multilingüismo (BEACCO; BYRAN, 2003), que someten muchos de los problemas en la enseñanza de lenguas extranjeras (LE) en el país, muchos de los cuales fueron concebidos puramente como ámbito metodológico como indica Celani (1997), Campani (2006) y Leffa (1999). Los argumentos apuntan hacia un análisis complementario de los problemas de enseñanza de LE y una percepción de las lenguas en la escuela, calcado en la función social de las LE.