Perturbation theory for non-spherical fluids based on discretization of the interactions

7 páginas, 5 figuras; PACS: 65.20.De, 61.20.JaAn extension of the discrete perturbation theory [A. L. Benavides and A. Gil-Villegas, Mol. Phys. 97(12), 1225 (1999)10.1080/00268979909482924] accounting for non-spherical interactions is presented. An analytical expression for the Helmholtz free energy for an equivalent discrete potential is given as a function of density, temperature, and intermolecular parameters with implicit shape dependence. The presented procedure is suitable for the description of the thermodynamics of general intermolecular potential models of arbitrary shape. The overlap and dispersion forces are represented by a discrete potential formed by a sequence of square-well and square-shoulders potentials of shape-dependent widths. By varying the intermolecular parameters through their geometrical dependence, some illustrative cases of square-well spherocylinders and Kihara fluids are considered, and their vapor-liquid phase diagrams are tested against available simulation data. It is found that this theoretical approach is able to reproduce qualitatively and quantitatively well the Monte Carlo data for the selected potentials, except near the critical region.A.L.B. acknowledges funding received by Grant No. 152684 CONACYT (México). F.G. acknowledges funding through Project No. P07-FQM-02600 (Junta de Andalucía-FEDER) for his postdoctoral fellowship.Peer reviewe

Fluorescence correlation spectroscopy reveals a cooperative unfolding of monomeric amyloid-β 42 with a low Gibbs free energy

The amyloid-beta peptide (Aβ) plays a major role in the progression of Alzheimer’s disease. Due to its high toxicity, the 42 amino acid long isoform Aβ42 has become of considerable interest. The Aβ42 monomer is prone to aggregation down to the nanomolar range which makes conventional structural methods such as NMR or X-ray crystallography infeasible. Conformational information, however, will be helpful to understand the different aggregation pathways reported in the literature and will allow to identify potential conditions that favour aggregation-incompetent conformations. In this study, we applied fluorescence correlation spectroscopy (FCS) to investigate the unfolding of Alexa Fluor 488 labelled monomeric Aβ42 using guanidine hydrochloride as a denaturant. We show that our Aβ42 pre-treatment and the low-nanomolar concentrations, typically used for FCS measurements, strongly favour the presence of monomers. Our results reveal that there is an unfolding/folding behaviour of monomeric Aβ42. The existence of a cooperative unfolding curve suggests the presence of structural elements with a Gibbs free energy of unfolding of about 2.8 kcal/mol

Dynamics of dilute colloidal suspensions in modulated potentials

The dynamics of dilute suspensions of charged polystyrene spheres have been studied in a sinusoidal potential. We investigated experimentally and theoretically the effect of the wavelength and amplitude of this potential as well as the particle size on the mean square displacement, the distribution of displacements and the non-Gaussian parameter. These properties scale with the radius of the particles and the magnitude of the wavevector of the potential as expected from a dimensional analysis. In contrast, they show a non-trivial dependence on the amplitude of the potential, which determines the barrier height encountered in long-distance motions and also the intermediate-time dynamics in the potential well. The periodic potential leads to particle dynamics which resemble the self dynamics of various systems approaching their glass transition. In particular, we found that the time-dependent mean square displacements determined in our system are surprisingly close to the ones in a quasi twodimensional colloidal supercooled liquid. In this case, the role of the colloid volume fraction is played by the amplitude of the potential. The similarity of the mean square displacements is particularly striking since an individual colloidal particle in a periodic potential represents a considerably simpler situation than a highly concentrated multi-particle system

Desmoglein 4 Mutations Underlie Localized Autosomal Recessive Hypotrichosis in Humans, Mice, and Rats

3 páginas.A newly defined form of inherited hair loss, named localized autosomal recessive hypotrichosis (LAH, OMIM 607903), was recently described in the literature and shown to be linked to chromosome 18. A large, intragenic deletion in the desmoglein 4 gene (DSG4) as the underlying mutation in several unrelated families of Pakistani origin. LAH is an autosomal recessive form of hypotrichosis affecting the scalp, trunk, and extremities, and largely sparing the facial, pubic, and axillary hair. Typical hairs are fragile and break easily, leaving short sparse scalp hairs with a characteristic appearance. Using comparative genomics, we also demonstrated that human LAH is allelic with the lanceolate hair (lah) mouse, as well as the lanceolate hair (lah) rat phenotype. Together, these models provide new information about the role of desmosomal cadherins in disease, and serve as in vivo models for functional and mechanistic studies into the role of desmoglein 4 in the skin and hair follicle.This study was supported in part by grants USPHS NIH R01-AR44924 (A. M. C.).Peer reviewe