Propensity to Form Amyloid Fibrils Is Encoded as Excitations in the Free Energy Landscape of Monomeric Proteins

Protein aggregation, linked to many of diseases, is initiated when monomers access rogue conformations that are poised to form amyloid fibrils. We show, using simulations of src SH3 domain, that mechanical force enhances the population of the aggregation-prone (N*) states, which are rarely populated under force free native conditions but are encoded in the spectrum of native fluctuations. The folding phase diagrams of SH3 as a function of denaturant concentration (C]), mechanical force (f), and temperature exhibit an apparent two-state behavior, without revealing the presence of the elusive N* states. Interestingly, the phase boundaries separating the folded and unfolded states at all C] and f fall on a master curve, which can be quantitatively described using an analogy to superconductors in a magnetic field. The free energy profiles as a function of the molecular extension (R), which are accessible in pulling experiments, (R), reveal the presence of a native-like N* with a disordered solvent-exposed amino-terminal beta-strand. The structure of the N* state is identical with that found in Fyn SH3 by NMR dispersion experiments. We show that the timescale for fibril formation can be estimated from the population of the N* state, determined by the free energy gap separating the native structure and the N* state, a finding that can be used to assess fibril forming tendencies of proteins. The structures of the N* state are used to show that oligomer formation and likely route to fibrils occur by a domain-swap mechanism in SH3 domain. (C) 2014 Elsevier Ltd. All rights reserved.

Multidimensional free energy surface of unfolding of HP-36: Microscopic origin of ruggedness

The protein folding funnel paradigm suggests that folding and unfolding proceed as directed diffusion in a multidimensional free energy surface where a multitude of pathways can be traversed during the protein's sojourn from initial to final state. However, finding even a single pathway, with the detail chronicling of intermediates, is an arduous task. In this work we explore the free energy surface of unfolding pathway through umbrella sampling, for a small globular a-helical protein chicken-villin headpiece (HP-36) when the melting of secondary structures is induced by adding DMSO in aqueous solution. We find that the unfolding proceeds through the initial separation or melting of aggregated hydrophobic core that comprises of three phenylalanine residues (Phe7, Phe11, and Phe18). This separation is accompanied by simultaneous melting of the second helix. Unfolding is found to be a multistage process involving crossing of three consecutive minima and two barriers at the initial stage. At a molecular level, Phe18 is observed to reorient itself towards other hydrophobic grooves to stabilize the intermediate states. We identify the configuration of the intermediates and correlate the intermediates with those obtained in our previous works. We also give an estimate of the barriers for different transition states and observe the softening of the barriers with increasing DMSO concentration. We show that higher concentration of DMSO tunes the unfolding pathway by destabilizing the third minimum and stabilizing the second one, indicating the development of a solvent modified, less rugged pathway. The prime outcome of this work is the demonstration that mixed solvents can profoundly transform the nature of the energy landscape and induce unfolding via a modified route. A successful application of Kramer's rate equation correlating the free energy simulation results shows faster rate of unfolding with increasing DMSO concentration. This work perhaps presents the first systematic theoretical study of the effect of a chemical denaturant on the microscopic free energy surface and rates of unfolding of HP-36. (C) 2014 AIP Publishing LLC.

Impact of Stone-Wales and lattice vacancy defects on the electro-thermal transport of the free standing structure of metallic ZGNR

We report the effect of topological as well as lattice vacancy defects on the electro-thermal transport properties of the metallic zigzag graphene nano ribbons at their ballistic limit. We employ the density function theory-Non equilibrium green's function combination to calculate the transmission details. We then present an elaborated study considering the variation in the electrical current and the heat current transport with the change in temperature as well as the voltage gradient across the nano ribbons. The comparative analysis shows, that in the case of topological defects, such as the Stone-Wales defect, the electrical current transport is minimum. Besides, for the voltage gradient of 0.5 Volt and the temperature gradient of 300 K, the heat current transport reduces by similar to 62 % and similar to 50% for the cases of Stones-Wales defect and lattice vacancy defect respectively, compared to that of the perfect one.

Efficient coupled polynomial interpolation scheme for out-of-plane free vibration analysis of curved beams

The performance of two curved beam finite element models based on coupled polynomial displacement fields is investigated for out-of-plane vibration of arches. These two-noded beam models employ curvilinear strain definitions and have three degrees of freedom per node namely, out-of-plane translation (v), out-of-plane bending rotation (theta(z)) and torsion rotation (theta(s)). The coupled polynomial interpolation fields are derived independently for Timoshenko and Euler-Bernoulli beam elements using the force-moment equilibrium equations. Numerical performance of these elements for constrained and unconstrained arches is compared with the conventional curved beam models which are based on independent polynomial fields. The formulation is shown to be free from any spurious constraints in the limit of `flexureless torsion' and `torsionless flexure' and hence devoid of flexure and torsion locking. The resulting stiffness and consistent mass matrices generated from the coupled displacement models show excellent convergence of natural frequencies in locking regimes. The accuracy of the shear flexibility added to the elements is also demonstrated. The coupled polynomial models are shown to perform consistently over a wide range of flexure-to-shear (EI/GA) and flexure-to-torsion (EI/GJ) stiffness ratios and are inherently devoid of flexure, torsion and shear locking phenomena. (C) 2015 Elsevier B.V. All rights reserved.

Template-free electrochemical nanofabrication of polyaniline nanobrush and hybrid polyaniline with carbon nanohorns for supercapacitors.

Polyaniline (PANI) nanobrushes were synthesized by template-free electrochemical galvanostatic methods. When the same method was applied to the carbon nanohorn (CNH) solution containing aniline monomers, a hybrid nanostructure containing PANI and CNHs was enabled after electropolymerization. This is the first report on the template-free method to make PANI nanobrushes and homogeneous hybrid soft matter (PANI) with carbon nanoparticles. Raman spectroscopy was used to analyze the interaction between CNH and PANI. Electrochemical nanofabrication offers simplicity and good control when used to make electronic devices. Both of these materials were applied in supercapacitors and an improvement capacitive current by using the hybrid material was observed.

Influence Of Free Surface Curvature Of A Liquid Layer On The Critical Marangoni Convection

The Pearson instability was suggested to discuss the onset of Marangoni convection in a liquid layer of large Prandtl number under an applied temperature difference perpendicular to the free surface in the microgravity environment. In this case, the temperature distribution on the curved free surface is nonuniform, and the thermocapillary convection is induced and coupled with the Marangoni convection. In the present paper the effect of volume ratio of the liquid layer on the critical Marangoni convection and the corresponding spatial variation of the convection structure in zero-gravity condition were numerically investigated by two-dimensional model. (C) 2008 Elsevier Ltd. All rights reserved.

Experimental-study of free-surface oscillations of a liquid bridge by optical diagnostics

A non-contact optical method, consisting of a projecting grating technique for the relative measurement of a surface, and a technique of absolute measurement at a fixed point on the surface, are applied to measure the free surface vibration in a liquid bridge of half floating zone with small typical scale of a few of mm for emphasizing the thermocapillary effect in comparison with the effect of buoyancy. The radii variations in both longitudinal and azimuthal directions are obtained, and, then, the feature of surface wave could be analyzed in detail. The results show that there are values of principal oscillatory frequencies at different positions of free surface. The amplitudes of surface waves in longitudinal and azimuthal directions are several mum and several tenths of mum in order of magnitude. The phase of two-dimensional surface waves is different at different height for fixed cross section or at different azimuthal angle for fixed height. The wave features are discussed for the cases of typical parameter ranges.

Free surface oscillation of thermocapillary convection in liquid bridge of half-floating-zone

Free surface deformations of thermocapillary convection in a small liquid bridge of half floating-zone are studied in the present paper. The relative displacement and phase difference of free surface oscillation are experimentally studied, and the features of free surface oscillation for various applied temperature differences are obtained. It is discovered that there is a sort of surface waves having the character of small perturbation, and having a wave mode of unusually large amplitude in one corner region of the liquid bridge.

Geometric documentation and reconstruction of the church of the Monastery of San Prudencio (La Rioja, Spain)

[EN] Data contained in this record come from the following accademic activity (from which it is possible to locate additional records related with the Monastery):

Manual Control of Phragmites australis on Pondshores of Cape Cod National Seashore, Masachusetts, USA

The non-native, invasive genotype of the common reed ( Phragmites australis (Cav.) Trin. ex Steudel) has become a problem of significant proportions throughout wetlands of North America (Saltonstall 2001). Although attempts to suppress or eradicate Phragmites have utilized a wide variety of techniques, herbicides have generally been most effective (Marks et al. 1994). In the spring, mid-summer, and late summer of 2003, we attempted to opportunistically control Phragmites in five freshwater ponds within Cape Cod National Seashore (CCNS) by repeatedly severing stems underwater, at ground level.(PDF has 4 pages.)