An orally available compound prevents deficits in memory caused by the Alzheimer amyloid-B oligomers.

Despite progress in defining a pathogenic role for amyloid beta protein (Abeta) in Alzheimer's disease, orally bioavailable compounds that prevent its effects on hippocampal synaptic plasticity and cognitive function have not yet emerged. A particularly attractive therapeutic strategy is to selectively neutralize small, soluble Abeta oligomers that have recently been shown to mediate synaptic dysfunction. METHODS: Using electrophysiological, biochemical, and behavioral assays, we studied how scyllo-inositol (AZD-103; molecular weight, 180) neutralizes the acutely toxic effects of Abeta on synaptic function and memory recall. RESULTS: Scyllo-inositol, but not its stereoisomer, chiro-inositol, dose-dependently rescued long-term potentiation in mouse hippocampus from the inhibitory effects of soluble oligomers of cell-derived human Abeta. Cerebroventricular injection into rats of the soluble Abeta oligomers interfered with learned performance on a complex lever-pressing task, but administration of scyllo-inositol via the drinking water fully prevented oligomer-induced errors. INTERPRETATION: A small, orally available natural product penetrates into the brain in vivo to rescue the memory impairment produced by soluble Abeta oligomers through a mechanism that restores hippocampal synaptic plasticity.

Base free dynamic kinetic resolution of secondary alcohols using ‘piano stool’ complexes of N-heterocyclic carbenes

Piano stool complexes of rhodium and iridium activated by fluorinated and non-fluorinated N-heterocyclic carbene (NHC) ligands were shown to be catalysts for racemization in the one-pot chemoenzymic dynamic kinetic resolution (DKR) of secondary alcohols. Excellent conversions and good enantioselectivities were observed for alkyl aryl and dialkyl secondary alcohols.

Generalized compound transport of charged particles in turbulent magnetized plasmas

The transport of charged particles in partially turbulent magnetic systems is investigated from first principles. A generalized compound transport model is proposed, providing an explicit relation between the mean-square deviation of the particle parallel and perpendicular to a magnetic mean field, and the mean-square deviation which characterizes the stochastic field-line topology. The model is applied in various cases of study, and the relation to previous models is discussed.