Inactivation and Secondary Structure in the D4/S4-5 Region of the SkM1 Sodium Channel

The D4/S4-5 interhelical region plays a role in sodium channel fast inactivation. Examination of S4-5 primary structure in all domains suggests a possible amphipathic helical conformation in which a conserved group of small hydrophobic residues occupies one contiguous surface with a more variable complement of nonpolar and polar residues on the opposite face. We evaluated this potential structure by replacing each residue in D4/S4-5 of the rat SkM1 skeletal muscle sodium channel with substitutions having different side chain properties. Of the 63 mutations analyzed, 44 produced functional channels. P1473 was intolerant of substitutions. Nonpolar substitutions in the conserved hydrophobic region were functionally similar to wild type, while charged mutations in this region before P1473 were nonfunctional. Charged mutations at F1466, M1469, M1470, and A1474, located on the opposite surface of the predicted helix, produced functional channels with pronounced slowing of inactivation, shifted voltage dependence of steady-state inactivation, and increased rate of recovery from inactivation. The substituted-cysteine-accessibility method was used to probe accessibility at each position. Residues L1465, F1466, A1467, M1469, M1470, L1472, A1474, and F1476C were easily accessible for modification by sulfhydryl reagents; L1464, L1468, S1471, and L1475 were not accessible within the time frame of our measurements. Molecular dynamics simulations of residues A1458 to N1477 were then used to explore energetically favorable local structures. Based on mutagenesis, substituted-cysteine-accessibility method, and modeling results, we suggest a secondary structure for the D4/S4-5 region in which the peptide chain is α-helical proximal to P1473, bends at this residue, and may continue beyond this point as a random coil. In this configuration, the entire resultant loop is amphipathic; four residues on one surface could form part of the binding site for the inactivation particle

Curing of epoxy resin DER-331by Hexakis (4-acetamidophenoxy) cyclotriphosphazene and properties of the prepared composition

The method of optical wedge revealed that the optimum temperature for compatibility of hexakis(4-acetamidophenoxy)cyclotriphosphazene (ACP) and DER-331 epoxy resin is in the range of 220–260◦C. The interdiffusion time of components at these temperatures is about 30 min. The TGA and differential scanning calorimetry (DSC) methods revealed the curing temperature of 280◦C for thiscomposition. IRspectroscopyconfirmedthatthereactionbetweentheresinandACPiscompleted within 10 mi

Nucleon-induced fission cross-sections of tantalum and separated tungsten isotopes and "compound nucleus" effect in intermediate energy region

Neutron- and proton-induced fission cross-sections of separated isotopes of tungsten (182W, 183W, 184W, and 186W) and 181Ta relative to 209Bi have been measured in the incident nucleon energy region 50 - 200 MeV using fission chambers based on thin-film breakdown counters (TFBC) using quasi-monoenergetic neutrons from the 7Li(p,n) reaction and at the proton beams of The Svedberg Laboratory (TSL), Uppsala University (Uppsala, Sweden). The results are compared with predictions by the CEM03.01 event generator, as well as with the recent data for nuclei in the lead-bismuth region. The effect of "compound nucleus" in the intermediate energy region is discussed, displaying in exponential dependence of nucleon-induced fission cross-sections on the parameter Z^2/A of the composite system (projectile+target nucleus), and in other characteristics of the fission process for which parameter Z^2/A plays a role similar to the one of the usual liquid-drop parameter Z^2/A of compound nuclei.Comment: 4 pages, 3 figures, 2 tables, only pdf file, to be published in Proc. Int. Conf. on Nucl. Data for Sci. and Technology (ND2007), Nice, France, April 22-27, 200

Влияние равномерности волокнистых материалов, получаемых методом электроформования, на их свойства

The influence of the structure and substrate type on the uniformity of fibrous materials obtained by electrospinning is studied. It is shown that the type of the substrate material makes considerable impact on the properties of fibrous materials.Изучено влияние структуры и типа подложки на равномерность волокнистых материалов, получаемых методом электроформования. Показано, что тип материала подложки оказывает значительное влияние на свойства волокнистых материалов

Evidence of neutral transcriptome evolution in plants

The transcriptome of an organism is its set of gene transcripts (mRNAs) at a defined spatial and temporal locus. Because gene expression is affected markedly by environmental and developmental perturbations, it is widely assumed that transcriptome divergence among taxa represents adaptive phenotypic selection. This assumption has been challenged by neutral theories which propose that stochastic processes drive transcriptome evolution. To test for evidence of neutral transcriptome evolution in plants, we quantified 18 494 gene transcripts in nonsenescent leaves of 14 taxa of Brassicaceae using robust cross-species transcriptomics which includes a two-step physical and in silicobased normalization procedure based on DNA similarity among taxa. Transcriptome divergence correlates positively with evolutionary distance between taxa and with variation in gene expression among samples. Results are similar for pseudogenes and chloroplast genes evolving at different rates. Remarkably, variation in transcript abundance among root-cell samples correlates positively with transcriptome divergence among root tissues and among taxa. Because neutral processes affect transcriptome evolution in plants, many differences in gene expression among or within taxa may be nonfunctional, reflecting ancestral plasticity and founder effects. Appropriate null models are required when comparing transcriptomes in space and time

MATHEMAТICAL SIMULAТION AND REALIZATION OF ЕСМ PROCESS OF DROP DIES

355-35

A Hydrophobic Gate in an Ion Channel: The Closed State of the Nicotinic Acetylcholine Receptor

The nicotinic acetylcholine receptor (nAChR) is the prototypic member of the `Cys-loop' superfamily of ligand-gated ion channels which mediate synaptic neurotransmission, and whose other members include receptors for glycine, gamma-aminobutyric acid, and serotonin. Cryo-electron microscopy has yielded a three dimensional structure of the nAChR in its closed state. However, the exact nature and location of the channel gate remains uncertain. Although the transmembrane pore is constricted close to its center, it is not completely occluded. Rather, the pore has a central hydrophobic zone of radius about 3 A. Model calculations suggest that such a constriction may form a hydrophobic gate, preventing movement of ions through a channel. We present a detailed and quantitative simulation study of the hydrophobic gating model of the nicotinic receptor, in order to fully evaluate this hypothesis. We demonstrate that the hydrophobic constriction of the nAChR pore indeed forms a closed gate. Potential of mean force (PMF) calculations reveal that the constriction presents a barrier of height ca. 10 kT to the permeation of sodium ions, placing an upper bound on the closed channel conductance of 0.3 pS. Thus, a 3 A radius hydrophobic pore can form a functional barrier to the permeation of a 1 A radius Na+ ion. Using a united atom force field for the protein instead of an all atom one retains the qualitative features but results in differing conductances, showing that the PMF is sensitive to the detailed molecular interactions.Comment: Accepted by Physical Biology; includes a supplement and a supplementary mpeg movie can be found at http://sbcb.bioch.ox.ac.uk/oliver/download/Movies/watergate.mp