Stability of a Recently Found Triple-β-Stranded Aβ1–42 Fibril Motif

Amyloid-β peptides form polymorphous amyloid fibrils are correlated with the pathogenesis of Alzheimer’s disease. Recently, a new ssNMR high-resolution structure has been reported for wild-type Aβ1–42 fibrils that is characterized by a strand-turn-strand-turn-strand motif instead of the U-shape form seen in previously known wild-type Aβ-fibril structures. Analyzing molecular dynamics simulations we comment on the relative weight of the new fibril structure and present evidence that its stability depends on hydrophobic contacts involving the C-terminal residues I41 and A42, but not on the salt bridge K28–A42. We further argue that Aβ1–42 peptides with this structure may assemble in fibrils with a 2-fold packing symmetry and discuss two possible arrangements

Cluster Size and Quinary Structure Determine the Rheological Effects of Antibody Self-Association at High Concentrations

The question of how nonspecific reversible intermolecular protein interactions affect solution rheology at high concentrations is fundamentally rooted in the translation of nanometer-scale interactions into macroscopic properties. Well-defined solutions of purified monoclonal antibodies (mAbs) provide a useful system with which to investigate the manifold intricacies of weak protein interactions at high concentrations. Recently, characterization of self-associating IgG1 antibody (mAb2) solutions has established the direct role of protein clusters on concentrated mAb rheology. Expanding on our earlier work with three additional mAbs (mAb1, mAb3, and mAb4), the observed concentration-dependent static light scattering and rheological data present a substantially more complex relationship between protein interactions and solution viscosity at high concentrations. The four mAb systems exhibited divergent correlations between cluster formation (size) and concentrated solution viscosities dependent on mAb primary sequence and solution conditions. To address this challenge, well-established features of colloidal cluster phenomena could be applied as a framework for interpreting our observations. The initial stages of mAb cluster formation were investigated with small-angle X-ray scattering (SAXS) and ensemble-optimized fit methods, to uncover shifts in the dimer structure populations which are produced by changes in mAb interaction modes and association valence under the different solution conditions. Analysis of mAb average cluster number and effective hydrodynamic radii at high concentrations revealed cluster architectures can have a wide range of fractal dimensions. Collectively, the static light scattering, SAXS, and rheological characterization demonstrate that nonspecific and anisotropic attractive intermolecular interactions produce antibody clusters with different quinary structures to regulate the rheological properties of concentrated mAb solutions

Two round 4-pixel Feistel structure of [33].

<p>Two round 4-pixel Feistel structure of [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0165937#pone.0165937.ref033" target="_blank">33</a>].</p

Vertical correlation of two adjacent pixel of all-zero’s cipher.

<p>Vertical correlation of two adjacent pixel of all-zero’s cipher.</p

Modified 4-pixel Feistel structure.

<p>Modified 4-pixel Feistel structure.</p

Results of Lena, all-zero image, white, flower and mountain.

<p>(a) Plain image Lena; (b) Encrypted image of Lena; (c) Recovered image of Lena; (d) all-zero image; (e)Encrypted image of all-zero image; (f)Recovered image of all-zero image; (g) Plain image white; (h) Encrypted image of white; (i) Recovered image of white; (j) Plain image flower; (k) Encrypted image of flower; (l) Recovered image of flower; (m) Plain image mountain; (n) Encrypted image of mountain; (o) Recovered image of mountain.</p

Horizontal correlation of two adjacent pixel of Lena’s cipher.

<p>Horizontal correlation of two adjacent pixel of Lena’s cipher.</p

Randomness test results.

<p>Randomness test results.</p

First iteration of dependent encryption using original 4-pixel Feistel structure.

<p>First iteration of dependent encryption using original 4-pixel Feistel structure.</p

NPCR and UACI of Lena.

<p>NPCR and UACI of Lena.</p