Expanded Conformations of Monomeric Tau Initiate Its Amyloidogenesis**

Understanding early amyloidogenesis is key to rationally develop therapeutic strategies. Tau protein forms well-characterized pathological deposits but its aggregation mechanism is still poorly understood. Using single-molecule force spectroscopy based on a mechanical protection strategy, we studied the conformational landscape of the monomeric tau repeat domain (tau-RD_244-368). We found two sets of conformational states, whose frequency is influenced by mutations and the chemical context. While pathological mutations Δ280K and P301L and a pro-amyloidogenic milieu favored expanded conformations and destabilized local structures, an anti-amyloidogenic environment promoted a compact ensemble, including a conformer whose topology might mask two amyloidogenic segments. Our results reveal that to initiate aggregation, monomeric tau-RD_244-368 decreases its polymorphism adopting expanded conformations. This could account for the distinct structures found in vitro and across tauopathies.     

Efficient synthesis of B-alkylated oxazaborolidines derived from ephedrine and norephedrine

[reaction: see text] Representative B-butyl- and B-methyl-1,3,2-oxazaborolidines derived from ephedrine and norephedrine were prepared in good yield and excellent purity by one-pot treatment of B-H oxazaborolidines with the corresponding organolithium reagent and subsequent hydrolysis of the cyclic borohydride intermediate with anhydrous ammonium chloride.     

Squeezed states and uncertainty relations since 1991

A brief review of the history of ten workshops/conferences on “Squeezed States and Uncertainty Relations” and main achievements in the related fields of quantum physics for the period from 1991 to 2007 are presented.     

Highly selective and sensitive chromo-fluorogenic detection of the Tetryl explosive using functional silica nanoparticles

Silica nanoparticles containing polyamines and thiol groups have been used as probes for the selective detection of Tetryl.     

Naproxen: Hydroxypropyl-β-Cyclodextrin:Polyvinylpyrrolidone Ternary Complex Formation

The aim of the present study was to investigate the effect of the presence of thewater-soluble polymer polyvinylpyrrolidone (PVP) MW = 24000 g/mol, on thecomplexation of the phototoxic anti-inflammatory drug naproxen, in its sodiumsalt form, with hydroxypropil-β-cyclodextrin (HP-β-CD). The datashown that the polymer interacts with the free naproxen and with thenaproxen:HP-β-CD inclusion complex. The presence of different proportions of PVP, in the 0–1%(w/w) rangesystematically increased the K_app of the naproxen:HP-β-CD inclusioncomplex formation. The cause of this increase is that the polymer interactswith the HP-β-CD with a binding constant of K₂ = 29000 ± 53 M^-1; and with the naproxen:HP-β-CD inclusion complex, to givea ternary complex naproxen:HP-β-CD:PVP. The binding constant of thisprocess was K₃ = 5350 ± 1 M^-1. NMR data revealed that in the ternary system, PVP is outside of the cyclodextrin, and therefore must be wholly or partially recovering the naproxen:HP-β-CD inclusion complex.     

Linear and non-linear nature of the flow of polypropylene filled with ferrite particles: from low to concentrated composites

The flow behavior of a filled suspension consisting of ferrite particles suspended in a polypropylene matrix with and without the addition of a commercial dispersant (Solplus DP310) was studied. The composites were filled with 10, 20, 30, and 40 vol.%. Both capillary and parallel disk rotational flows were employed. On the one hand, dynamic results confirm general trends found for highly concentrated systems. The higher is the filler level, the lower is the linear viscoelastic domain. When adding the dispersant agent, it was shown a larger linear viscoelastic domain, lower moduli values and thus, lower viscosity. Also, the critical strain, G′ and G′′ showed a power law dependency on the volume fraction. On the other hand, the capillary results showed no dependency of the flow properties on the die. Thus, no slip of the suspension at the wall was observed. Actually, this experimental finding elucidated that the significant decrease on viscosity produced by the addition of the dispersant agent at 40 vol.% is principally due to lubricant effects and not at all to slip contributions. The results also reveal three distinct flow regimes. Low, moderate, and high shear rates lead to different microstructure under flow.