Ohel Avraham : reshimat ha-sefarim asher asaf ṿe-ḳibets ... Avraham Mertsbakher

hotseʾtiha la-or Refaʾel Neṭaʿ Rabinoṿiṭts

Aprender a incluir em contexto de sala de aula do 1º ano de escolaridade

O presente trabalho teve por objectivo investigar e construir um Plano de Intervenção baseado numa sala de 1º ano de escolaridade na cidade de Portalegre com vista à inclusão, na turma, de um aluno em situação de Necessidade Educativa Especial. Este plano integra uma componente teórica – prática uma vez que foi feita uma análise teórica prévia que tinha como objectivo conhecer e caracterizar cientificamente toda a situação – problema e, consequentemente foram aplicadas técnicas de análise e recolha de dados: pesquisa documental, entrevista, sociometria e observação naturalista com base na literatura de referência para a aplicação dessas técnicas. Posteriormente foi feita a análise de toda a situação e foram identificadas quais as áreas de intervenção que seriam pertinentes para a problemática em estudo com o intuito de ser elaborado um Plano de Intervenção, realizado durante quatro meses em contexto de sala de aula e com o objectivo de proporcionar alguma mudança face à situação – problema encontrada. Este projecto de investigação – acção teve como objectivo responder à questão de partida: Como promover as aprendizagens numa ambiência inclusiva numa turma de 1º ano de escolaridade? O Plano de Intervenção foi estruturado em quinze sessões de aproximadamente 90 minutos cada, onde foram desenvolvidas actividades com a turma que promovessem, o mais possível, a progressão académica e a participação do aluno em situação de NEE. Para a avaliação do Plano de Intervenção recorreu-se às técnicas de recolha e análise de dados: entrevista e sociometria, assim como às reflexões semanais elaboradas após cada intervenção. O Plano de Intervenção interferiu positivamente na inclusão do aluno em situação de NEE na sua turma. Palavras

Complex rearrangements in patients with duplications of MECP2 can occur by fork stalling and template switching

Duplication at the Xq28 band including the MECP2 gene is one of the most common genomic rearrangements identified in neurodevelopmentally delayed males. Such duplications are non-recurrent and can be generated by a non-homologous end joining (NHEJ) mechanism. We investigated the potential mechanisms for MECP2 duplication and examined whether genomic architectural features may play a role in their origin using a custom designed 4-Mb tiling-path oligonucleotide array CGH assay. Each of the 30 patients analyzed showed a unique duplication varying in size from similar to 250 kb to similar to 2.6 Mb. Interestingly, in 77% of these non-recurrent duplications, the distal breakpoints grouped within a 215 kb genomic interval, located 47 kb telomeric to the MECP2 gene. The genomic architecture of this region contains both direct and inverted low-copy repeat (LCR) sequences; this same region undergoes polymorphic structural variation in the general population. Array CGH revealed complex rearrangements in eight patients; in six patients the duplication contained an embedded triplicated segment, and in the other two, stretches of non-duplicated sequences occurred within the duplicated region. Breakpoint junction sequencing was achieved in four duplications and identified an inversion in one patient, demonstrating further complexity. We propose that the presence of LCRs in the vicinity of the MECP2 gene may generate an unstable DNA structure that can induce DNA strand lesions, such as a collapsed fork, and facilitate a Fork Stalling and Template Switching event producing the complex rearrangements involving MECP2.

Nonrecurrent MECP2 duplications mediated by genomic architecture-driven DNA breaks and break-induced replication repair

Recurrent submicroscopic genomic copy number changes are the result of nonallelic homologous recombination (NAHR). Nonrecurrent aberrations, however, can result from different nonexclusive recombination-repair mechanisms. We previously described small microduplications at Xq28 containing MECP2 in four male patients with a severe neurological phenotype. Here, we report on the fine-mapping and breakpoint analysis of 16 unique microduplications. The size of the overlapping copy number changes varies between 0.3 and 2.3 Mb, and FISH analysis on three patients demonstrated a tandem orientation. Although eight of the 32 breakpoint regions coincide with low-copy repeats, none of the duplications are the result of NAHR. Bioinformatics analysis of the breakpoint regions demonstrated a 2.5-fold higher frequency of Alu interspersed repeats as compared with control regions, as well as a very high GC content (53%). Unexpectedly, we obtained the junction in only one patient by long-range PCR, which revealed nonhomologous end joining as the mechanism. Breakpoint analysis in two other patients by inverse PCR and subsequent array comparative genomic hybridization analysis demonstrated the presence of a second duplicated region more telomeric at Xq28, of which one copy was inserted in between the duplicated MECP2 regions. These data suggest a two-step mechanism in which part of Xq28 is first inserted near the MECP2 locus, followed by breakage-induced replication with strand invasion of the normal sister chromatid. Our results indicate that the mechanism by which copy number changes occur in regions with a complex genomic architecture can yield complex rearrangements.

O potêncial de poço duplo e a molécula de amônia

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Cannabidiol protects oligodendrocyte progenitor cells from inflammation-induced apoptosis by attenuating endoplasmic reticulum stress

Cannabidiol (CBD) is the most abundant cannabinoid in Cannabis sativa that has no psychoactive properties. CBD has been approved to treat inflammation, pain and spasticity associated with multiple sclerosis (MS), of which demyelination and oligodendrocyte loss are hallmarks. Thus, we investigated the protective effects of CBD against the damage to oligodendrocyte progenitor cells (OPCs) mediated by the immune system. Doses of 1 mu M CBD protect OPCs from oxidative stress by decreasing the production of reactive oxygen species. CBD also protects OPCs from apoptosis induced by LPS/IFN gamma through the decrease of caspase 3 induction via mechanisms that do not involve CB1, CB2, TRPV1 or PPAR gamma receptors. Tunicamycin-induced OPC death was attenuated by CBD, suggesting a role of endoplasmic reticulum (ER) stress in the mode of action of CBD. This protection against ER stress-induced apoptosis was associated with reduced phosphorylation of eiF2 alpha, one of the initiators of the ER stress pathway. Indeed, CBD diminished the phosphorylation of PKR and eiF2 alpha induced by LPS/IFN gamma. The pro-survival effects of CBD in OPCs were accompanied by decreases in the expression of ER apoptotic effectors (CHOP, Bax and caspase 12), and increased expression of the anti-apoptotic Bcl-2. These findings suggest that attenuation of the ER stress pathway is involved in the 'oligoprotective' effects of CBD during inflammation. Cell Death and Disease (2012) 3, e331; doi:10.1038/cddis.2012.71; published online 28 June 2012

Ms. hebr. oct. 107,1 - Mishpaṭ shalom

Vorbesitzer: Abraham Merzbacher

Ms. hebr. oct. 1 - Otsrot Ḥayyim

Vorbesitzer: Abraham Merzbacher

Ms. hebr. oct. 100 - Minḥat Yehuda

Vorbesitzer: Abraham Merzbacher

Ms. hebr. qu. 13,10 - Responsen

Vorbesitzer: Abraham Merzbacher

Ms. hebr. oct. 3 - Perush sifre le-rabenu Hilel

Vorbesitzer: Abraham Merzbacher

Ms. hebr. oct. 134 - Sidur tefilot

Vorbesitzer: Eljāqīm Carmoly; Abraham Merzbacher

Ms. hebr. oct. 135 - Sheʾelot u-teshuvot

Vorbesitzer: Abraham Merzbacher

Ms. hebr. oct. 136 - Tosafot

Vorbesitzer: Mē'īr Wilmersdorfer; Abraham Merzbacher