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

Facile whole mitochondrial genome resequencing from nipple aspirate fluid using MitoChip v2.0

<p>Abstract</p> <p>Background</p> <p>Mutations in the mitochondrial genome (mtgenome) have been associated with many disorders, including breast cancer. Nipple aspirate fluid (NAF) from symptomatic women could potentially serve as a minimally invasive sample for breast cancer screening by detecting somatic mutations in this biofluid. This study is aimed at 1) demonstrating the feasibility of NAF recovery from symptomatic women, 2) examining the feasibility of sequencing the entire mitochondrial genome from NAF samples, 3) cross validation of the Human mitochondrial resequencing array 2.0 (MCv2), and 4) assessing the somatic mtDNA mutation rate in benign breast diseases as a potential tool for monitoring early somatic mutations associated with breast cancer.</p> <p>Methods</p> <p>NAF and blood were obtained from women with symptomatic benign breast conditions, and we successfully assessed the mutation load in the entire mitochondrial genome of 19 of these women. DNA extracts from NAF were sequenced using the mitochondrial resequencing array MCv2 and by capillary electrophoresis (CE) methods as a quality comparison. Sequencing was performed independently at two institutions and the results compared. The germline mtDNA sequence determined using DNA isolated from the patient's blood (control) was compared to the mutations present in cellular mtDNA recovered from patient's NAF.</p> <p>Results</p> <p>From the cohort of 28 women recruited for this study, NAF was successfully recovered from 23 participants (82%). Twenty two (96%) of the women produced fluids from both breasts. Twenty NAF samples and corresponding blood were chosen for this study. Except for one NAF sample, the whole mtgenome was successfully amplified using a single primer pair, or three pairs of overlapping primers. Comparison of MCv2 data from the two institutions demonstrates 99.200% concordance. Moreover, MCv2 data was 99.999% identical to CE sequencing, indicating that MCv2 is a reliable method to rapidly sequence the entire mtgenome. Four NAF samples contained somatic mutations.</p> <p>Conclusion</p> <p>We have demonstrated that NAF is a suitable material for mtDNA sequence analysis using the rapid and reliable MCv2. Somatic mtDNA mutations present in NAF of women with benign breast diseases could potentially be used as risk factors for progression to breast cancer, but this will require a much larger study with clinical follow up.</p

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