Simple, Reliable Protocol for High-Yield Solubilization of Seedless Amyloid-β Monomer.

Self-assembly of the amyloid-β (Aβ) peptide to form toxic oligomers and fibrils is a key causal event in the onset of Alzheimer's disease, and Aβ is the focus of intense research in neuroscience, biophysics, and structural biology aimed at therapeutic development. Due to its rapid self-assembly and extreme sensitivity to aggregation conditions, preparation of seedless, reproducible Aβ solutions is highly challenging, and there are serious ongoing issues with consistency in the literature. In this paper, we use a liquid-phase separation technique, asymmetric flow field-flow fractionation with multiangle light scattering (AF4-MALS), to develop and validate a simple, effective, economical method for re-solubilization and quality control of purified, lyophilized Aβ samples.

General Principles Underpinning Amyloid Structure.

Amyloid fibrils are a pathologically and functionally relevant state of protein folding, which is generally accessible to polypeptide chains and differs fundamentally from the globular state in terms of molecular symmetry, long-range conformational order, and supramolecular scale. Although amyloid structures are challenging to study, recent developments in techniques such as cryo-EM, solid-state NMR, and AFM have led to an explosion of information about the molecular and supramolecular organization of these assemblies. With these rapid advances, it is now possible to assess the prevalence and significance of proposed general structural features in the context of a diverse body of high-resolution models, and develop a unified view of the principles that control amyloid formation and give rise to their unique properties.

Biological and methodological complexities of beta-amyloid peptide: Implications for Alzheimer's disease research.

Although controversial, the amyloid cascade hypothesis remains central to the Alzheimer's disease (AD) field and posits amyloid-beta (Aβ) as the central factor initiating disease onset. In recent years, there has been an increase in emphasis on studying the role of low molecular weight aggregates, such as oligomers, which are suggested to be more neurotoxic than fibrillary Aβ. Other Aβ isoforms, such as truncated Aβ, have also been implicated in disease.

A two-step biopolymer nucleation model shows a nonequilibrium critical point.

Biopolymer self-assembly pathways are complicated by the ability of their monomeric subunits to adopt different conformational states. This means nucleation often involves a two-step mechanism where the monomers first condense to form a metastable intermediate, which then converts to a stable polymer by conformational rearrangement of constituent monomers. Nucleation intermediates play a causative role in amyloid diseases such as Alzheimer's and Parkinson's.

Public health practitioners' perspectives of migrant health in an English region.

Objectives: Migration is a complex and contested topic of public debate. Professionals working in public health must negotiate this politicised complexity, yet few studies examine the perspectives and practices of public health professionals in relation to migrant health. This study seeks to redress this by exploring how migrant health is conceptualised and addressed by public health professionals after a key transitional point in the reorganisation of public health in England and the public vote for the UK to leave the EU.