Somatostatin, an In Vivo Binder to Aβ Oligomers, Binds to βPFOAβ(1-42) Tetramer

Somatostatin (SST14) is strongly related to Alzheimer’s disease (AD), as its levels decline during aging, it regulates the proteolytic degradation of the amyloid beta peptide (Aβ), and it binds to Aβ oligomers in vivo. Recently, the 3D structure of a membrane-associated β-sheet pore forming tetramer (βPFOAβ(1-42) tetramer) has been reported. Here we show that SST14 binds selectively to the βPFOAβ(1-42) tetramer without binding to monomeric Aβ(1-42). Specific NMR chemical shift perturbations, observed during titration of SST14, define a binding site in the βPFOAβ(1-42) tetramer and are in agreement with a 2:1 stoichiometry determined by both native MS and ITC. These results enabled us to perform driven docking and model the binding mode for the interaction. The present study provides additional evidence on the relation between SST14 and the amyloid cascade, as well as positions the βPFOAβ(1-42) tetramer as a relevant aggregation form of Aβ and as a potential target for AD.

Abundance and Spatial Distribution of Aerobic Anoxygenic Phototrophic Bacteria in Tama River, Japan

Aerobic anoxygenic phototrophic bacteria (AAnPB) are widely distributed and regarded as key players driving the carbon cycle in surface water of global oceans, coastal and estuary areas and in other freshwater environments (e.g., ponds and lakes). However, the abundance and spatial distribution of AAnPB in rivers is much less well-known. Here we investigated the variation of the absolute cell abundances of the total bacteria, AAnPB and cyanobacteria, at four different sites in Tama River, Japan, and the spatial distribution (i.e., free-living or particle-attached existence form) of AAnPB at two out of the four sites using infra-red epifluorescence microscopy. Free-living cell abundances for the total bacteria, AAnPB and cyanobacteria were 1.6–3 × 105, 1.5–4.4 × 104 and <3.2 × 104 cells mL−1, respectively. The free-living AAnPB accounted for 6.1%–19.6% of the total bacterial abundance in the river. The peaks of the AAnPB and cyanobacteria abundances were found at the same site, suggesting that the AAnPB could potentially coexist with cyanobacteria. Meanwhile, the particle-attached AAnPB were observed at the two sites of the river, accounting for 52.2% of the total bacteria abundance in the particle. Our results showed the existence and aggregation form of AAnPB in the riverine environment.

Effect of aggregation form on bioavailability of zeaxanthin in humans: a randomised cross-over study

Carotenoid bioavailability from plant and animal food is highly variable depending on numerous factors such as the physical deposition form of carotenoids. As the carotenoid zeaxanthin is believed to play an important role in eye and brain health, we sought to compare the human bioavailability of an H-aggregated with that of a J-aggregated deposition form of zeaxanthin encapsulated into identical formulation matrices. A randomised two-way cross-over study with sixteen participants was designed to compare the post-prandial bioavailability of an H-aggregated zeaxanthin and a J-aggregated zeaxanthin dipalmitate formulation, both delivering 10 mg of free zeaxanthin. Carotenoid levels in TAG-rich lipoprotein fractions were analysed over 9·5 h after test meal consumption. Bioavailability from the J-aggregated formulation (AUC=55·9 nmol h/l) was 23 % higher than from the H-aggregated one (AUC=45·5 nmol h/l), although being only marginally significant (P=0·064). Furthermore, the same formulations were subjected to an internationally recognisedin vitrodigestion protocol to reveal potential strengths and weaknesses of simulated digestions. In agreement with our human study, liberation of zeaxanthin from the J-aggregated formulation into the simulated duodenal fluids was superior to that from the H-aggregated form. However, micellization rate (bioaccessibility) of the J-aggregated zeaxanthin dipalmitate was lower than that of the H-aggregated zeaxanthin, being contradictory to ourin vivoresults. An insufficient ester cleavage during simulated digestion was suggested to be the root cause for these observations. In brief, combining ourin vitroandin vivoobservations, the effect of the different aggregation forms on human bioavailability was lower than expected.