Membrane interactions and the effect of metal ions of the amyloidogenic fragment Aβ(25–35) in comparison to Aβ(1–42)

AbstractAβ(1−42) peptide, found as aggregated species in Alzheimer's disease brain, is linked to the onset of Alzheimer's disease. Many reports have linked metals to inducing Aβ aggregation and amyloid plaque formation. Aβ(25–35), a fragment from the C-terminal end of Aβ(1−42), lacks the metal coordinating sites found in the full-length peptide and is neurotoxic to cortical cortex cell cultures. We report solid-state NMR studies of Aβ(25–35) in model lipid membrane systems of anionic phospholipids and cholesterol, and compare structural changes to those of Aβ(1–42). When added after vesicle formation, Aβ(25–35) was found to interact with the lipid headgroups and slightly perturb the lipid acyl-chain region; when Aβ(25–35) was included during vesicle formation, it inserted deeper into the bilayer. While Aβ(25–35) retained the same β-sheet structure irrespective of the mode of addition, the longer Aβ(1–42) appeared to have an increase in β-sheet structure at the C-terminus when added to phospholipid liposomes after vesicle formation. Since the Aβ(25–35) fragment is also neurotoxic, the full-length peptide may have more than one pathway for toxicity

Synthesis of stoichiometrically controlled reactive aluminosilicate and calcium-aluminosilicate powders

Aluminosilicate and calcium-aluminosilicate powders are synthesised via an organic steric entrapment route under conditions permitting strict stoichiometric control, utilising polyvinyl alcohol and polyethylene glycol as polymeric carriers. Polyethylene glycol is superior to polyvinyl alcohol for synthesis of calcium-aluminosilicate powders via this method, producing a more controllable product which generated less fine ash during calcination. This paper presents detailed description of synthesis and characterisation of the powders produced through this approach, including new insight into the nanostructures within the calcined powders. Aluminium environments are a mixture of 4-, 5- and 6-coordinated, while silicon is tetrahedral and shows a broad range of connectivity states. The powders are X-ray amorphous, display a high degree of homogeneity, and thus offer potential for utilisation as precursors for synthesis of hydrous aluminosilicates in the quaternary CaO-Na2O-Al2O3-SiO2 system

Geopolymers based on spent catalyst residue from a fluid catalytic cracking (FCC) process

This paper assesses the use of alkali activation technology in the valorization of a spent fluid catalytic cracking (FCC) catalyst, which is a residue derived from the oil-cracking process, to produce geopolymer binders. In particular, the effects of activation conditions on the structural characteristics of the spent catalyst- based geopolymers are determined. The zeolitic phases present in the spent catalyst are the main phases participating in the geopolymerization reaction, which is driven by the conversion of the zeolitic material to a highly Al-substituted aluminosilicate binder gel. Higher alkali content and SiO2/Na2O ratio lead to a denser structure with a higher degree of geopolymer gel formation and increased degree of crosslinking, as identified through 29Si MAS NMR. These results highlight the feasibility of using spent FCC catalyst as a precursor for geopolymer production.This study was sponsored by research scholarship BES-2008-002440 and EEBB-2011-43847 from the Ministerio de Ciencia y Tecnologia of Spain, the European regional development fund (FEDER), and the Universitat Politecnica de Valencia (Spain). The participation of SAB and JLP was funded by the Australian Research Council through the Discovery Projects program, and also including partial funding through the Particulate Fluids Processing Centre, a Special Research Centre of the ARC. The authors wish to acknowledge the Advanced Microscopy Facility at The University of Melbourne for assistance with the electron microscopy experiments conducted in this study.Rodriguez Martinez, ED.; Bernal, SA.; Provis, JL.; Gehman, JD.; Monzó Balbuena, JM.; Paya Bernabeu, JJ.; Borrachero Rosado, MV. (2013). Geopolymers based on spent catalyst residue from a fluid catalytic cracking (FCC) process. Fuel. 109:493-502. https://doi.org/10.1016/j.fuel.2013.02.053S49350210

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Generalised Anxiety Disorder – A Twin Study of Genetic Architecture, Genome-Wide Association and Differential Gene Expression

Generalised Anxiety Disorder (GAD) is a common anxiety-related diagnosis, affecting approximately 5% of the adult population. One characteristic of GAD is a high degree of anxiety sensitivity (AS), a personality trait which describes the fear of arousal-related sensations. Here we present a genome-wide association study of AS using a cohort of 730 MZ and DZ female twins. The GWAS showed a significant association for a variant within the RBFOX1 gene. A heritability analysis of the same cohort also confirmed a significant genetic component with h2 of 0.42. Additionally, a subset of the cohort (25 MZ twins discordant for AS) was studied for evidence of differential expression using RNA-seq data. Significant differential expression of two exons with the ITM2B gene within the discordant MZ subset was observed, a finding that was replicated in an independent cohort. While previous research has shown that anxiety has a high comorbidity with a variety of psychiatric and neurodegenerative disorders, our analysis suggests a novel etiology specific to AS

Disentanglement of Heterogeneous Dynamics in Mixed Lipid Systems

ABSTRACT Static phosphorous NMR has been a powerful technique for the study of model supramolecular phospholipid structures. Application to natural lipid bilayers with complex compositions, however, has been severely limited by the difficulty in deconvoluting overlapping broad lineshapes. We demonstrate a solution to this problem, using a global fit to a few slow magic-angle spinning spectra, in combination with an adaptation of Boltzmann statistics maximum entropy. The method provides a modelfree means to characterize a heterogeneous mix of lipid dynamics via a distribution of 31 P chemical shift anisotropies. It is used here to identify clear changes in membrane dynamics of a phosphatidylethanolamine and phosphatidylglycerol mixture, mimicking an Escherichia coli membrane upon addition of just 2% of the antimicrobial peptide maculatin 1.1. This illustration opens the prospect for investigation of arbitrarily complex natural lipid systems, important in many areas of biophysical chemistry and biomedicine. Received for publication 17 January 2011 and in final form 2 March 2011. *Correspondence: [email protected] With an escalation of interest in the role of lipids in natural membranes, there has been a resurgence in use of phosphorus NMR for the characterization of phospholipid systems. Disruption of bilayer order and dynamics by physiologically active molecules such as antimicrobial peptides are of particular recent interest, as these represent a potential new class of antibiotics (1). Membrane lipid compositions are highly variable in polar headgroups, backbones, and acyl chainsin contrast to the very simple lipid systems typically used to mimic them. This simplicity is motivated in part by the difficulty of interpreting spectra with overlapping 31 P static lineshapes arising from many local motional differences. More complex lipid systems that better mimic natural membranes can usually only be analyzed in terms of overall width, and other differences are discussed only qualitatively. In this Letter we demonstrate a means to characterize a heterogeneous distribution of chemical shift parameters in 31 P NMR spectra of mixed lipid vesicles. The approach uses just a few simple one-dimensional magic-angle spinning spectra (MAS) at slow spin rates, which can be collected with sufficient signal/noise in less time than a static spectrum. MAS also mitigates the complexities of lifetime broadening and magnetic field-induced lipid alignment (2) that plague interpretation of static spectra. The method also obviates the difficult choice of any specific number of components to deconvolute a static spectrum, by employing a Boltzmann-type maximum entropy strategy that gives a pseudo-continuous distribution of chemical shift anisotropy (d) and asymmetry (h) parameters. The analysis is performed with the use of Lagrange multipliers, introduced in an analogous fashion to the usual derivation of the Boltzmann distribution, as demonstrated previously for the analysis of rotational-echo double-resonance data (3). Spinning of the semisolid lipid vesicle sample around the magic-angle of wherep ðd;hÞ is a linearized representation of the two-dimensional distribution over chemical shift parameters (d,h); I ðN;n r Þ is the series of experimental sideband intensities N over one or more spinning speeds (n r ), each normalized to unity over N; and I z is the matrix of precalculated intensities (5), for distribution parameters (d,h) i and data parameters (N,n r ) j , where the probability P(b) f sin (b) as usual (4,5), and F 0 gives the unweighted and unnormalized contribution to sideband N j at MAS rate n rj by a crystallite with chemicalshift parameters d and h, and at an orientation (a, b, g) with respect to B 0 , Editor: Klaus Gawrisch