H-1, C-13, and N-15 NMR Backbone Assignments and Secondary Structure of Human Interferon-Gamma

Debido a sus múltiples beneficios se ha recomendado la conversión de bosques puros de coníferas en bosques mixtos en zonas potencialmente sensibles a cambios climáticos y medioambientales. En este trabajo se analiza la influencia de la intensidad de clara a medio plazo (8-9 años tras la clara) y el tipo de dosel sobre el crecimiento secundario de pino silvestre y el ciclo de nutrientes (cambios químicos en suelo, retranslocación, y trascolación). El estudio forma parte de una investigación a largo plazo sobre el funcionamiento del bosque y la sostenibilidad de las claras forestales desde una perspectiva ecológica. El área de estudio está localizada en Aspurz, Navarra, en los Pirineos occidentales

Self-assembly of beta-amyloid 42 is retarded by small molecular ligands at the stage of structural intermediates

Assemblyof the amyloid-beta peptide (Abeta) into fibrils and its deposition in distinct brain areas is considered responsible for the pathogenesis of Alzheimer's disease (AD). Thus, inhibition of fibril assembly is a potential strategy for therapeutic intervention. Electron cryomicroscopy was used to monitor the initial, native assembly structure of Abeta42. In addition to the known fibrillar intermediates, a nonfibrillar, polymeric sheet-like structure was identified. A temporary sequence of supramolecular structures was revealed with (i) polymeric Abeta42 sheets during the onset of assembly, inversely related to the appearance of (ii) fibril intermediates, which again are time-dependently replaced by (iii) mature fibrils. A cell-based primary screening assay was used to identify compounds that decrease Abeta42-induced toxicity. Hit compounds were further assayed for binding to Abeta42, radical scavenger activity, and their influence on the assembly structure of Abeta42. One compound, Ro 90-7501, was found to efficiently retard mature fibril formation, while extended polymeric Abeta42 sheets and fibrillar intermediates are accumulated. Ro 90-7501 may serve as a prototypic inhibitor for Abeta42 fibril formation and as a tool for studying the molecular mechanism of fibril assembly