Point Mutations of Nicotinic Receptor α1 Subunit Reveal New Molecular Features of G153S Slow-Channel Myasthenia

Slow-channel congenital myasthenic syndromes (SCCMSs) are rare genetic diseases caused by mutations in muscle nicotinic acetylcholine receptor (nAChR) subunits. Most of the known SCCMS-associated mutations localize at the transmembrane region near the ion pore. Only two SCCMS point mutations are at the extracellular domains near the acetylcholine binding site, α1(G153S) being one of them. In this work, a combination of molecular dynamics, targeted mutagenesis, fluorescent Ca²⁺ imaging and patch-clamp electrophysiology has been applied to G153S mutant muscle nAChR to investigate the role of hydrogen bonds formed by Ser 153 with C-loop residues near the acetylcholine-binding site. Introduction of L199T mutation to the C-loop in the vicinity of Ser 153 changed hydrogen bonds distribution, decreased acetylcholine potency (EC₅₀ 2607 vs. 146 nM) of the double mutant and decay kinetics of acetylcholine-evoked cytoplasmic Ca²⁺ rise (τ 14.2 ± 0.3 vs. 34.0 ± 0.4 s). These results shed light on molecular mechanisms of nAChR activation-desensitization and on the involvement of such mechanisms in channelopathy genesis.     

Vanadium valency charge state in solid solutions ScNb2−2xTa2xVO9

Phase equilibria in the Sc₂O₃-V₂O₅-Nb₂O₅-Ta₂O₅ system and properties of ScNb_2−2xTa_2xVO₉ phases were studied by X-ray phase analysis, optical and radio spectroscopy. A continuous series of solid solutions was shown to exist at 0≤x≤1. V(IV) centers with different crystallographic surrounding were detected for all the considered compositions. A correlation between the number of V(IV) ions and the width of the forbidden gap in the solid solutions was found.     

Degradative chain transfer in vinyl acetate polymerizations using toluene as solvent

In this work, we propose that retardation in vinyl acetate polymerization rate in the presence of toluene is due to degradative chain transfer. The transfer constant to toluene (C_trs) determined using the Mayo method is equal to 3.8 × 10^?3, which is remarkably similar to the value calculated from the rate data, assuming degradative chain transfer (2.7 × 10^?3). Simulations, including chain‐length‐dependent termination, were carried out to compare our degradative chain transfer model with experimental results. The conversion–time profiles showed excellent agreement between experiment and simulation. Good agreement was found for the M_n data as a function of conversion. The experimental and simulation data strongly support the postulate that degradative chain transfer is the dominant kinetic mechanism. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 3620–3625, 2007     

Three-dimensional flow of supersonic jets past bodies

Translated from Aktual'nye Voprosy Prikladnoi Matematiki, pp. 228–235, 1989.     

Global solvability of the Cauchy-Dirichlet problem for nondiagonal parabolic systems with variational structure in the case of two spatial variables

The Cauchy-Dirichlet problem for quasilinear parabolic systems of second-order equations is considered in the case of two spatial variables. Under the condition that the corresponding elliptic operator has variational structure, the global in time solvability is established. The solution is smooth almost everywhere and the number of singular points is finite. Sufficient conditions that guarantee the absence of singular points are given. Bibliography: 23 titles. Translated fromProblemy Matematicheskogo Analiza No. 16, 1997, pp. 3–40.     

Regularity results for quasilinear elliptic systems with nonlinear boundary conditions

It is proved that a solution of the boundary-value problem for a second-order quasilinear system with controlled order of nonlinearity is partially smooth all the way to the boundary of a domain. The boundary condition is imposed by means of a second-order nonlinear operator which can be regarded as a generalization of the “directional derivative” to the case of quasilinear systems. Bibliography: 6 titles. Translated fromProblemy Matematicheskogo Analiza, No. 14, 1995, pp. 23–50.     

Can the pi-facial selectivity of solvation be predicted by atomistic simulation?

This work is concerned with the rationalization and prediction of solvent and temperature effects in nucleophilic addition to alpha-chiral carbonyl compounds leading to facial diastereoselectivity. We study, using molecular dynamics simulations, the facial solvation of (R)-2-phenyl-propionaldehyde in n-pentane and n-octane at a number of temperatures and compare it with experimental selectivity data for the nBuLi addition leading to syn- and anti-(2R)-2-phenyl-3-heptanol, which give nonlinear Eyring plots with the presence of inversion temperatures. We have found from simulations that the facial solvation changes with temperature and alkane. Moreover, by introducing a suitable molecular chirality index we have been able to predict break temperatures (T(CI)) for the two solvents within less than 20 degrees of the inversion temperatures experimentally observed in the diastereoselective nBuLi addition. We believe this could lead to a viable approach for predicting inversion temperatures and other subtle solvent effects in a number of stereoselective reactions.