8-Hydroxyquinolylnitrones as multifunctional ligands for the therapy of neurodegenerative diseases

We describe the development of quinolylnitrones (QNs) as multifunctional ligands inhibiting cholinesterases (ChEs: acetylcholinesterase and butyrylcholinesterase-hBChE) and monoamine oxidases (hMAO-A/B) for the therapy of neurodegenerative diseases. We identified QN 19, a simple, low molecular weight nitrone, that is readily synthesized from commercially available 8-hydroxyquinoline-2-carbaldehyde. Quinolylnitrone 19 has no typical pharmacophoric element to suggest ChE or MAO inhibition, yet unexpectedly showed potent inhibition of hBChE (IC50 = 1.06 ± 0.31 nmol/L) and hMAO-B (IC50 = 4.46 ± 0.18 μmol/L). The crystal structures of 19 with hBChE and hMAO-B provided the structural basis for potent binding, which was further studied by enzyme kinetics. Compound 19 acted as a free radical scavenger and biometal chelator, crossed the blood-brain barrier, was not cytotoxic, and showed neuroprotective properties in a 6-hydroxydopamine cell model of Parkinson's disease. In addition, in vivo studies showed the anti-amnesic effect of 19 in the scopolamine-induced mouse model of AD without adverse effects on motoric function and coordination. Importantly, chronic treatment of double transgenic APPswe-PS1δE9 mice with 19 reduced amyloid plaque load in the hippocampus and cortex of female mice, underscoring the disease-modifying effect of QN 19.

Revisão sistemática de pesquisas sobre eficácia coletiva docente / Systematic review on researches about collective teacher efficacy

A eficácia coletiva docente é a percepção compartilhada pelos professores sobre a capacidade do corpo docente de organizar e executar ações necessárias a um efeito positivo no desempenho acadêmico dos alunos. Este artigo tem o objetivo de construir um panorama das pesquisas sobre eficácia coletiva de professores, analisando seus principais resultados. Para tanto, foram realizadas buscas de artigos publicados entre 2000 e 201 3, na base de dados Portal de Periódicos Capes. Os resultados indicam que a eficácia coletiva de professores está diretamente relacionada ao desempenho acadêmico dos alunos.Notou-se ainda que outras variáveis podem influenciar as crenças coletivas, tais como a autoeficácia e a situação socioeconômica da escola