Membrane inserted APP fragments containing the βA4 sequence of Alzheimer's disease do not aggregate

AbstractPreviously we have shown that the COOH-terminal fragment (A4CT) of the Alzheimer amyloid protein precursor (APP), which at the NH2-terminus carries the sequence of the amyloid βA4 protein, forms highly insoluble aggregates [EMBO J. (1988) 7, 949–957]. Here we report that aggregation is prevented if A4CT is expressed in vitro with a signal sequence at the NH2-terminus (SPA4CT) under conditions which allow membrane insertion. Aggregates from SPA4CT are obtained after removal of membranes by chloroform/methanol extraction or heating

Cognitive impairment and decline in cognitively normal older adults with high amyloid-β: A meta-analysis

AbstractIntroductionThis meta-analysis aimed to characterize the nature and magnitude of amyloid (Aβ)-related cognitive impairment and decline in cognitively normal (CN) older individuals.MethodMEDLINE Ovid was searched from 2012 to June 2016 for studies reporting relationships between cerebrospinal fluid or positron emission tomography (PET) Aβ levels and cognitive impairment (cross-sectional) and decline (longitudinal) in CN older adults. Neuropsychological data were classified into domains of episodic memory, executive function, working memory, processing speed, visuospatial function, semantic memory, and global cognition. Type of Aβ measure, how Aβ burden was analyzed, inclusion of control variables, and clinical criteria used to exclude participants, were considered as moderators. Random-effects models were used for analyses with effect sizes expressed as Cohen's d.ResultsA total of 38 studies met inclusion criteria contributing 30 cross-sectional (N = 5005) and 14 longitudinal (N = 2584) samples. Aβ-related cognitive impairment was observed for global cognition (d = 0.32), visuospatial function (d = 0.25), processing speed (d = 0.18), episodic memory, and executive function (both d's = 0.15), with decline observed for global cognition (d = 0.30), semantic memory (d = 0.28), visuospatial function (d = 0.25), and episodic memory (d = 0.24). Aβ-related impairment was moderated by age, amyloid measure, type of analysis, and inclusion of control variables and decline moderated by amyloid measure, type of analysis, inclusion of control variables, and exclusion criteria used.DiscussionCN older adults with high Aβ show a small general cognitive impairment and small to moderate decline in episodic memory, visuospatial function, semantic memory, and global cognition

Simulation of Neptunium Extraction in an Advanced PUREX Process — Model Improvement

Routing neptunium to a single product in spent nuclear fuel reprocessing is a significant challenge. In this work, we have further improved the simulation of neptunium extraction in an advanced PUREX flowsheet by applying a revised model of the Np(V)-Np(VI) redox reaction kinetics, a new nitric acid radiolysis model and by evaluating various models for the nitrous acid distribution coefficient. The Np disproportionation reaction is shown to have a negligible effect. The models are validated against published ‘cold test’ experimental results; the ‘hot test’ simulation suggests high neptunium radiolysis could help to achieve high recoveries using this flowsheet

The proposed Caroline ESA M3 mission to a Main Belt Comet

We describe Caroline, a mission proposal submitted to the European Space Agency in 2010 in response to the Cosmic Visions M3 call for medium-sized missions. Caroline would have travelled to a Main Belt Comet (MBC), characterizing the object during a flyby, and capturing dust from its tenuous coma for return to Earth. MBCs are suspected to be transition objects straddling the traditional boundary between volatile–poor rocky asteroids and volatile–rich comets. The weak cometary activity exhibited by these objects indicates the presence of water ice, and may represent the primary type of object that delivered water to the early Earth. The Caroline mission would have employed aerogel as a medium for the capture of dust grains, as successfully used by the NASA Stardust mission to Comet 81P/Wild 2. We describe the proposed mission design, primary elements of the spacecraft, and provide an overview of the science instruments and their measurement goals. Caroline was ultimately not selected by the European Space Agency during the M3 call; we briefly reflect on the pros and cons of the mission as proposed, and how current and future mission MBC mission proposals such as Castalia could best be approached