Conformational indeterminism in protein misfolding: chiral amplification on amyloidogenic pathway of insulin

Unlike folding, protein aggregation is a multipathway, kinetically controlled process yielding different conformations of fibrils. The dynamics and determinism/indeterminism boundaries of misfolded conformations remain obscure. Here we show that, upon vortexing, insulin forms two distinct types of fibrils with opposite local chiral preferences, which manifest in the opposite twists of bound dye, thioflavin T. Occurrence of either type of fibrils in a test tube is only stochastically determined. By acting through an autocatalytic, "chiral amplification"-like mechanism, a random conformational fluctuation triggers conversion of the macroscopic amount of insulin into aggregates with uniformly biased chiral moieties, which bind and twist likewise the achiral dye. Although a convection-driven chiral amplification in achiral systems, which results in randomly distributed excesses of optically active forms, is known, observation of such a phenomenon in misfolded protein built of l-amino acids is unprecedented. The two optical variants of insulin fibrils show distinct morphologies and can propagate their chiral biases upon seeding to nonagitated insulin solutions. Our findings point to a new aspect of topological complexity of protein fibrils: a chiral feature of hierarchically assembled polypeptides, which is partly emancipated from the innate left-handedness of amino acids. Because altering chirality of a molecule changes dramatically its biological activity, the finding may have important ramifications in the context of the structural basis of "amyloid strains".     

Analytical Representation of Solutions to Lattice‐Hole Theory

The Simha and Somcynsky (S‐S) lattice‐hole theory has been shown to represent accurately the pressure‐volume‐temperature (PVT) surface of chain molecular melts and their mixtures. Proceeding beyond its original intent, it has led to correlations with other properties and extension into the steady state and relaxing glass. The equilibrium results appear as the solutions of two coupled equations, involving the variables of state and the hole fraction, h = h (V, T) – a kind of free volume quantity. These are to be solved numerically. Notwithstanding the theory's quantitative success, its implicit form has on some occasions been a practical limitation. We remedy this situation by fitting the scaled and thus general solutions of the coupled equations to accurate algebraic equations, V = V (T, P) and h = hV, T). In this manner, explicit analytical expressions for configurational thermodynamic functions and their derivatives are now available. The new expressions for V and h are simple to employ; the convergence of the non‐linear least‐squares fit is obtained in seconds. The numerical values of the scaling parameters so derived are nearly identical to those computed from the original coupled equations. Having h and V from the original theory, the cohesive energy density [CED = δ²V, T)] was also considered. The results are again well represented by a simple algebraic expression. An expression for the reduced solubility parameter δ = δ (T, P) is also given. The usefulness of these solutions is further illustrated by an application to the PVT surfaces of polystyrene and polyphenylene ether blends.     

Interfacial tension in polymer blends

Theoretical models of the interfacial tension coefficient in polymer blends, v₁₂, were evaluated. A new working relation was derived that makes it possible to compute v₁₂ from the chemical structure of two polymers. The calculations involve determination of the dispersive, polar and hydrogen-bonding parts of the solubility parameter from the tabulated group and bond contributions. The computed values of v₁₂ for 46 blends were found to follow the experimental ones with a reasonable scatter of ± 36%. Next, the experimental methods of v₁₂-measurements were critically examined. Although many have been developed for low viscosity Newtonian fluids, most are irrelevant to industrial polymeric systems. For the present studies two were selected. Values of v₁₂ were measured using the so-called “capillary breakup method,” and a newly developed method based on the retraction rate of deformed drop.     

Enhancement of the SPR Effect in an Optical Fiber Device Utilizing a Thin Ag Layer and a 3092A Liquid Crystal Mixture

This paper is a continuation of previous work and shows the enhancement of the surface plasmon resonance effect in a tapered optical fiber device. The study investigated liquid crystal cells containing a tapered optical fiber covered with a silver nanolayer, surrounded by a low refractive index liquid crystal in terms of the properties of light propagation in the taper structure. Silver films with a thickness of d = 10 nm were deposited on the tapered waist area. Measurements were performed at room temperature; liquid crystal steering voltage U from 0 to 200 V, with and without any amplitude modulation with a frequency of f = 5 Hz, and the wavelength λ ranged from 550 to 1200 nm. A significant influence of the initial arrangement of liquid crystals molecules on light propagation was observed. Three types of liquid crystal cells—orthogonal, parallel, and twist—were considered. During the measurements, resonant peaks were obtained—the position of which can also be controlled by the type of liquid crystal cells and the steering voltage. Based on the obtained results, the best parameters, such as highest peak’s width reduction, and the highest SNR value were received for twisted cells. In addition, the present work was compared with the previous work and showed the possibility of improving properties of the manufactured probes, and consequently, the surface plasmon resonance effect. In the presented paper, the novelty is mainly focused on the used materials as well as suitable changes in applied technological parameters. In contrast to gold, silver is characterized by different optic and dielectric properties, e.g., refractive index, extension coefficient, and permittivity, which results in changes in the light propagation and the SPR wavelengths.     

An Existence Theorem for Wave‐Type Hyperbolic Hemivariational Inequalities

In this paper we prove the existence of solutions for a hyperbolic hemivariationalinequality of the form u″ + Bu + ∂j (u) ∋ f where B is a linear elliptic operator and ∂j is the Clarke subdifferential of a locally Lipschitz function j. Our result is based on the parabolic regularization method.     

Preliminary studies on the surface layer of starch

Characterization of the surface layer of starch powder, originated from potato or maize, was carried out applying various experimental techniques: Fourier-transformed infrared internal reflection spectroscopy (FTIR-IRS), inverse gas chromatography (IGC) and scanning electron microscopy (SEM). The main kinds of starch were studied as potential fillers for rubber and results discussed in terms of factors requiring modification to improve starch miscibility and activity towards rubber. Starch of high amylopectine content shows surface enrichment with amylose what makes crystallinity of the surface layer higher than in bulk of the material. Particles of the both kinds of starch have very smooth surface (morphological index, I_m = 0.995), highly resistant to its geometrical development. Dispersive component of the surface energy of starch was found to be similar to that of low energy polymers (γ_s^d = 32.5 mJ/m² at 23°C) and its surface to be of electron-donor character.     

The power of adaptive algorithms for functions with singularities

This is an overview of recent results on complexity and optimality of adaptive algorithms for integrating and approximating scalar piecewise r-smooth functions with unknown singular points. We provide adaptive algorithms that use at most n function samples and have the worst case errors proportional to n^−r for functions with at most one unknown singularity. This is a tremendous improvement over nonadaptive algorithms whose worst case errors are at best proportional to n⁻¹ for integration and n^−1/p for the L^p approximation problem. For functions with multiple singular points the adaptive algorithms cease to dominate the nonadaptive ones in the worst case setting. Fortunately, they regain their superiority in the asymptotic setting. Indeed, they yield convergence of order n^−r for piecewise r-smooth functions with an arbitrary (unknown but finite) number of singularities. None of these results hold for the L^∞ approximation. However, they hold for the Skorohodmetric, which we argue to be more appropriate than L^∞ for dealing with discontinuous functions. Numerical test results and possible extensions are also discussed.     

Steric control of bacteriochlorophyll ligation

The axial coordination of central Mg(2+) ion in chlorophylls is of great structural and functional importance for virtually all photosynthetic chlorophyll proteins; however, little thermodynamic data are available on the ligand binding to these pigments. In the present study, spectral deconvolution of the bacteriochlorophyll Q(X) band serves to determine the ligand binding equilibria and relationships between thermodynamic parameters of ligand binding, ligand properties, and steric interactions occurring within the pigment. On the basis of the temperature effects on coordination, DeltaH degrees, DeltaS degrees, and DeltaG degrees of binding various types of ligands (acetone, dimethylformamide, imidazole, and pyridine) to diastereoisomeric bacteriochlorophylls were derived from respective van't Hoff's plots. At ambient temperatures, only ligation by imidazole and pyridine occurs spontaneously while DeltaG degrees becomes positive for ligation by acetone and dimethylformamide, due to a relatively large entropic effect, which is dominating when the energetic effects of ligation are small. It reflects, in quantitative terms, the control of the equatorial coordination of the Mg(2+) ion via the axial coordination: a "hard" free Mg(2+) ion is made into a softer center through the coordination of tetrapyrrole. Pigment structural features have comparable effects on the energetic and entropic contributions to the difference of ligation free energy between the diastereoisomers of bacteriochlorophyll. DeltaS degrees and DeltaH degrees values are consistently lower for the S epimer, most likely due to the steric crowding between bulky substituents. The two epimers show a 5 J.mol(-1).K(-1) difference in DeltaS degrees values, regardless of the ligand type, while the difference in DeltaH degrees amounts to 1.7 kJ.mol(-1), depending on the ligand. Such steric control of ligation would relate to the partial diastereoselectivity of chlorophyll self-assembly and, in particular, the very high diastereoselectivity of the ligation of chlorophylls in photosynthetic proteins.     

An apparent critical point in binary mixtures: experimental and simulation study

We report the experimental and simulation studies for the system of nitrobenzene-cyclododecane, showing an apparent critical point, which lies in their metastable, experimentally inaccessible state, below their melting point, affecting physical and chemical properties of this system in the stable liquid phase. The nonlinear dielectric effect (NDE) was measured in the mixture of nitrobenzene with cyclododecane. The mixture has been found to show an apparent critical point which lies below the melting point, manifested as anomalous NDE behavior in the vicinity of the critical concentrations in the stable liquid phase. The melting temperature of this system was estimated using the differential scanning calorimetry method. For such a system, we also performed Monte Carlo (MC) simulations that aimed to analyze the kinds of phase transitions observed and the conditions of their occurrence in Lennard-Jones mixture. The enthalpy, configurational energy, and radial distribution function have been estimated by the MC simulation method in the N-P-T system. Immiscibility conditions according to the approach by Schoen and Hoheisel [Mol. Phys. 57, 65 (1986)] are also discussed.