Templating S100A9 amyloids on Aβ fibrillar surfaces revealed by charge detection mass spectrometry,microscopy, kinetic and microfluidic analyses

The mechanism of amyloid co-aggregation and its nucleation process are not fully understood in spite of extensive studies. Deciphering the interactions between proinflammatory S100A9 protein and Aβ₄₂ peptide in Alzheimer''s disease is fundamental since inflammation plays a central role in the disease onset. Here we use innovative charge detection mass spectrometry (CDMS) together with biophysical techniques to provide mechanistic insight into the co-aggregation process and differentiate amyloid complexes at a single particle level. Combination of mass and charge distributions of amyloids together with reconstruction of the differences between them and detailed microscopy reveals that co-aggregation involves templating of S100A9 fibrils on the surface of Aβ₄₂ amyloids. Kinetic analysis further corroborates that the surfaces available for the Aβ₄₂ secondary nucleation are diminished due to the coating by S100A9 amyloids, while the binding of S100A9 to Aβ₄₂ fibrils is validated by a microfluidic assay. We demonstrate that synergy between CDMS, microscopy, kinetic and microfluidic analyses opens new directions in interdisciplinary research.

Templating mechanism of S100A9 amyloids on Aβ fibrillar surfaces during amyloid co-aggregation process was revealed by synergy of biophysical methods including charge detection mass spectrometry, microscopy, kinetic and microfluidic analyses.     

Low-energy inelastic neutrino reactions on 4He

The inelastic scattering of neutrino off 4He is calculated microscopically at energies typical for core-collapse supernova environment. The calculation is carried out with the Argonne V18 nucleon-nucleon potential and the Urbana IX three-nucleon force. Full final state interaction is included via the Lorentz integral transform method. The contribution of axial meson exchange currents to the cross sections is taken into account from effective field theory of nucleons and pions to order O(Q3).     

Carpenter,tractors and microbes for the development of logical–mathematical thinking – the way 10th graders and pre-service teachers solve thinking challenges

The objective of this case study was to investigate the ability of 10th graders and pre-service teachers to solve logical–mathematical thinking challenges. The challenges do not require mathematical knowledge beyond that of primary school but rather an informed use of the problem representation. The percentage of correct answers given by the 10th graders was higher than that of the pre-service teachers. Unlike the 10th graders, some of whom used various strategies for representing the problem, most of the pre-service teachers’ answers were based on a technical algorithm, without using control processes. The obvious conclusion drawn from the findings supports and recommends expanding and enhancing the development of logical–mathematical thinking, both in specific lessons and as an integral part of other lessons in pre-service frameworks.     

Co-Assembly between Fmoc Diphenylalanine and Diphenylalanine within a 3D Fibrous Viscous Network Confers Atypical Curvature and Branching

Supramolecular polymer co-assembly is a useful approach to modulate peptide nanostructures. However, the co-assembly scenario where one of the peptide building blocks simultaneously forms a hydrogel is yet to be studied. Herein, we investigate the co-assembly formation of diphenylalanine (FF), and Fmoc-diphenylalanine (FmocFF) within the 3D network of FmocFF hydrogel. The overlapping peptide sequence between the two building blocks leads to their co-assembly within the gel state modulating the nature of the FF crystals. We observe the formation of branched microcrystalline aggregates with an atypical curvature, in contrast to the FF assemblies obtained from aqueous solution. Optical microscopy reveal the sigmoidal kinetic growth profile of these aggregates. Microfluidics and ToF-SIMS experiments exhibit the presence of co-assembled structures of FF and FmocFF in the crystalline aggregates. Molecular dynamics simulation was used to decipher the mechanism of co-assembly formation.     

Cognitive‐Performance Recovery of Alzheimer's Disease Model Mice by Modulation of Early Soluble Amyloidal Assemblies

A rationally designed oligomerization inhibitor interacts with early intermediate assemblies of amyloid‐β polypeptide (Aβ) through the aromatic elements and inhibits their assembly into the toxic oligomers that cause Alzheimer's disease by a unique C^α‐methylation β‐breakage strategy. The electrostatic potential of the low‐energy conformation of the dipeptide inhibitor bound to Aβ is shown.

     

Thermal and chemical stability of diphenylalanine peptide nanotubes: implications for nanotechnological applications

The diphenylalanine peptide, the core recognition motif of the beta-amyloid polypeptide, efficiently self-assembles into discrete, well-ordered nanotubes. Here, we describe the notable thermal and chemical stability of these tubular structures both in aqueous solution and under dry conditions. Scanning and transmission electron microscopy (SEM and TEM) as well as atomic force microscopy (AFM) revealed the stability of the nanotubes in aqueous solution at temperatures above the boiling point of water upon autoclave treatment. The nanotubes preserved their secondary structure at temperatures up to 90 degrees C, as shown by circular dichroism (CD) spectra. Cold field emission gun (CFEG) high-resolution scanning electron microscope (HRSEM) and thermogravimetric analysis (TGA) of the peptide nanotubes after dry heat revealed durability at higher temperature. It was shown that the thermal stability of diphenylalanine peptide nanotubes is significantly higher than that of a nonassembling dipeptide, dialanine. In addition to thermal stability, the peptide nanotubes were chemically stable in organic solvents such as ethanol, methanol, 2-propanol, acetone, and acetonitrile, as shown by SEM analysis. Moreover, the acetone environment enabled AFM imaging of the nanotubes in solution. The significant thermal and chemical stability of the peptide nanotubes demonstrated here points toward their possible use in conventional microelectronic and microelectromechanics processes and fabrication into functional nanotechnological devices.