Systematic review of risk factors for eating psychopathology in athletes: A critique of an etiological model

Objective: The theoretical model by Petrie and Greenleaf (2007, 2012) is an admirable attempt to collate the causal factors of disordered eating in athletes. The aims of this systematic review are (a) to provide an overview of the findings from the relevant literature, (b) to assess whether the model is supported by the existing research, (c) to evaluate the different designs, methods, and measures used to test the mediators in the model, and (d) to highlight areas for improvements and future research. Method: A systematic review of four major online databases identified 37 relevant papers on risk factors of disordered eating in athletes, which were reviewed and critically compared with the theoretical model. Results: There is a lack of longitudinal research with the relevant mediators in athlete populations, which makes it difficult to determine whether the potential mediators described by Petrie and Greenleaf are causal risk factors rather than simply correlates of disordered eating for athletes. Findings for all the potential mediators are inconsistent, and the range of measures used makes it problematic to draw conclusions. Conclusions: Future research needs to use gold standard measures and longitudinal designs in order to fully test and possibly update the model

The diversity and utility of amyloid fibrils formed by short amyloidogenic peptides

Amyloidogenic peptides are well known for their involvement in diseases such as type 2 diabetes and Alzheimer's disease. However, more recently, amyloid fibrils have been shown to provide scaffolding and protection as functional materials in a range of organisms from bacteria to humans. These roles highlight the incredible tensile strength of the cross-β amyloid architecture. Many amino acid sequences are able to self-assemble to form amyloid with a cross-β core. Here we describe our recent advances in understanding how sequence contributes to amyloidogenicity and structure. For example, we describe penta- and hexapeptides that assemble to form different morphologies; a 12mer peptide that forms fibrous crystals; and an eight-residue peptide originating from α-synuclein that has the ability to form nanotubes. This work provides a wide range of peptides that may be exploited as fibrous bionanomaterials. These fibrils provide a scaffold upon which functional groups may be added, or templated assembly may be performed

Gaia on-board metrology: basic angle and best focus

The Gaia payload ensures maximum passive stability using a single material, SiC, for most of its elements. Dedicated metrology instruments are, however, required to carry out two functions: monitoring the basic angle and refocusing the telescope. Two interferometers fed by the same laser are used to measure the basic angle changes at the level of $\mu$as (prad, micropixel), which is the highest level ever achieved in space. Two Shack-Hartmann wavefront sensors, combined with an ad-hoc analysis of the scientific data are used to define and reach the overall best-focus. In this contribution, the systems, data analysis, procedures and performance achieved during commissioning are presentedComment: 18 pages, 14 figures. To appear in SPIE proceedings 9143-30. Space Telescopes and Instrumentation 2014: Optical, Infrared, and Millimeter Wav

Protofilaments, filaments, ribbons, and fibrils from peptidomimetic self-assembly: Implications for amyloid fibril formation and materials science

Deciphering the mechanism(s) of beta-sheet mediated self-assembly is essential for understanding amyloid fibril formation and for the fabrication of polypeptide materials. Herein, we report a simple peptidomimetic that self-assembles into polymorphic beta-sheet quaternary structures including protofilaments, filaments, fibrils, and ribbons that are reminiscent of the highly ordered structures displayed by the amyloidogenic peptides A beta, calcitonin, and amylin. The distribution of quaternary structures can be controlled by and in some cases specified by manipulating the pH, buffer composition, and the ionic strength. The ability to control beta-sheet-mediated assembly takes advantage of quaternary structure dependent pK(a) perturbations. Biophysical methods including analytical ultracentrifugation studies as well as far-UV circular dichroism and FT-IR spectroscopy demonstrate that linked secondary and quaternary structural changes mediate peptidomimetic self-assembly. Electron and atomic force microscopy reveal that peptidomimetic assembly involves numerous quaternary structural intermediates that appear to self-assemble in a convergent fashion affording quaternary structures of increasing complexity. The ability to control the assembly pathway(s) and the final quaternary structure(s) afforded should prove to be particularly useful in deciphering the quaternary structural requirements for amyloid fibril formation and for the construction of noncovalent macromolecular structure

A central role for dityrosine crosslinking of Amyloid-β in Alzheimer’s disease

Background Alzheimer’s disease (AD) is characterized by the deposition of insoluble amyloid plaques in the neuropil composed of highly stable, self-assembled Amyloid-beta (Aβ) fibrils. Copper has been implicated to play a role in Alzheimer’s disease. Dimers of Aβ have been isolated from AD brain and have been shown to be neurotoxic. Results We have investigated the formation of dityrosine cross-links in Aβ42 formed by covalent ortho-ortho coupling of two tyrosine residues under conditions of oxidative stress with elevated copper and shown that dityrosine can be formed in vitro in Aβ oligomers and fibrils and that these links further stabilize the fibrils. Dityrosine crosslinking was present in internalized Aβ in cell cultures treated with oligomeric Aβ42 using a specific antibody for dityrosine by immunogold labeling transmission electron microscopy. Results also revealed the prevalence of dityrosine crosslinks in amyloid plaques in brain tissue and in cerebrospinal fluid from AD patients. Conclusions Aβ dimers may be stabilized by dityrosine crosslinking. These results indicate that dityrosine cross-links may play an important role in the pathogenesis of Alzheimer’s disease and can be generated by reactive oxygen species catalyzed by Cu2+ ions. The observation of increased Aβ and dityrosine in CSF from AD patients suggests that this could be used as a potential biomarker of oxidative stress in AD

The effect of self-sorting and co-assembly on the mechanical properties of low molecular weight hydrogels

Self-sorting in low molecular weight hydrogels can be achieved using a pH triggered approach. We show here that this method can be used to prepare gels with different types of mechanical properties. Cooperative, disruptive or orthogonal assembled systems can be produced. Gels with interesting behaviour can be also prepared, for example self-sorted gels where delayed switch-on of gelation occurs. By careful choice of gelator, co-assembled structures can also be generated, which leads to synergistic strengthening of the mechanical properties

The architecture of amyloid-like peptide fibrils revealed by X-ray scattering, diffraction and electron microscopy

Structural analysis of protein fibrillation is inherently challenging. Given the crucial role of fibrils in amyloid diseases, method advancement is urgently needed. A hybrid modelling approach is presented enabling detailed analysis of a highly ordered and hierarchically organized fibril of the GNNQQNY peptide fragment of a yeast prion protein. Data from small-angle X-ray solution scattering, fibre diffraction and electron microscopy are combined with existing high-resolution X-ray crystallographic structures to investigate the fibrillation process and the hierarchical fibril structure of the peptide fragment. The elongation of these fibrils proceeds without the accumulation of any detectable amount of intermediate oligomeric species, as is otherwise reported for, for example, glucagon, insulin and [alpha]-synuclein. Ribbons constituted of linearly arranged protofilaments are formed. An additional hierarchical layer is generated via the pairing of ribbons during fibril maturation. Based on the complementary data, a quasi-atomic resolution model of the protofilament peptide arrangement is suggested. The peptide structure appears in a [beta]-sheet arrangement reminiscent of the [beta]-zipper structures evident from high-resolution crystal structures, with specific differences in the relative peptide orientation. The complexity of protein fibrillation and structure emphasizes the need to use multiple complementary methods

Discrete molecular dynamics simulations of peptide aggregation

We study the aggregation of peptides using the discrete molecular dynamics simulations. At temperatures above the alpha-helix melting temperature of a single peptide, the model peptides aggregate into a multi-layer parallel beta-sheet structure. This structure has an inter-strand distance of 0.48 nm and an inter-sheet distance of 1.0 nm, which agree with experimental observations. In this model, the hydrogen bond interactions give rise to the inter-strand spacing in beta-sheets, while the Go interactions among side chains make beta-strands parallel to each other and allow beta-sheets to pack into layers. The aggregates also contain free edges which may allow for further aggregation of model peptides to form elongated fibrils.Comment: 15 pages, 8 figure

A randomised placebo-controlled Phase III multicentre trial: low-dose intravenous immunoglobulin treatment for long-standing complex regional pain syndrome (LIPS trial)

BACKGROUND: Complex regional pain syndrome (CRPS) is a rare, severe post-traumatic pain condition affecting distal limbs. Patients who do not spontaneously improve in 12 months are classed as having ‘long-standing CRPS’ and often cannot be effectively treated, leading to a poor prognosis. CRPS is associated with functional autoantibodies. Two small trials, including a randomised controlled trial, have suggested that low-dose intravenous immunoglobulin (IVIg) may be an effective treatment for some patients. OBJECTIVE: We hypothesised that low-dose IVIg is effective for reducing pain in long-standing CRPS. METHODS: A randomised, double blinded placebo-controlled multicentre trial in seven UK pain management centres. Patients were eligible if they had moderate or severe long-standing CRPS that they had experienced for up to 5 years. Participants were randomly allocated to receive 0.5 g/kg IVIg, the active intervention, or visually indistinguishable 0.1% albumin in saline placebo. Randomisation was initiated by study sites via an independent online randomisation system and was 1 : 1 with varying block sizes, stratified by study centre. Participants, investigators and assessors were blinded to group assignment. The study drug/placebo was infused intravenously at the study centres on day 1 and day 23 after randomisation. The primary outcome was the 24-hour average pain intensity between day 6 and day 42, on an 11-point (0–10) numeric rating scale, compared between the groups. Outcomes were analysed using a mixed-effects regression model that used 37 measurements of pain intensity (the primary outcome) per participant. All patients who received an infusion and provided any outcome were included in the intention-to-treat analysis. RESULTS: A total of 111 patients were recruited and assigned between 27 August 2013 and 28 October 2015. Three patients were excluded because they had been inappropriately randomised, five patients were withdrawn from the primary analysis because they provided no outcomes and 103 patients were analysed for the primary outcome. The average pain score in the IVIg group was 0.27 units (95% confidence interval –0.24 to 0.80 units) higher than in the placebo group. Therefore, there is no significant evidence of a treatment effect at the 5% level and there was no significant difference between groups. Six serious adverse events but no suspected unexpected serious adverse reactions were reported during the blinded and open-label phase. CONCLUSION AND FUTURE WORK: Low-dose immunoglobulin was not effective in relieving pain in patients with moderate to severe CRPS of 1–5 years’ duration. Better drug treatments for long-standing CRPS are urgently required. TRIAL REGISTRATION: Current Controlled Trials ISRCTN42179756. FUNDING: This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research partnership. Additional funding was obtained by the Pain Relief Foundation. Biotest UK Ltd provided the active study medication at no cost

«Малобюджетний» маркетинг

В умовах сьогоднішньої економічної кризи, яка зачепила всі вітчизняні підприємства, та постійного зниження української національної валюти актуальними стають питання пошуку способів економії коштів. Вирішенням таких проблем може стати «мало бюджетний» маркетинг, який допоможе розвиватися підприємству з використанням мінімальної кількості ресурсів. «Малобюджетний» маркетинг – це маркетингові інструменти залучення й утримання клієнтів, які припускають мінімальні витрати, а іноді можна взагалі обійтися без бюджету