Adsorption-Induced Deformation in Nanopores: Unexpected Results Obtained by Molecular Simulations

International audienceThe adsorption of a fluid in a nanoporous material induces deformations of the solid. The saturating regime, where the solid is filled with liquid, generally exhibits a linear relationship between the liquid pressure and the solid strain. This provides an experimental way to measure the elastic moduli of the solid walls. For large pores, the strain is determined by the pressure of the liquid saturating the pores and the mechanical properties of the porous solid. What happens at the nanometric scale, where liquid/matrix interfacial effects dominate? We have performed molecular simulations of a simple Lennard-Jones fluid confined between deformable nanoplatelets. The simulations provide the deformation of the nanopore as a function of the liquid pressure, in a way similar to what is done experimentally. The results show unexpected interface effects, which could be relevant to experimental data analysis

Possible Effects of Noncommutative Geometry on Weak CP Violation and Unitarity Triangles

Possible effects of noncommutative geometry on weak CP violation and unitarity triangles are discussed by taking account of a simple version of the momentum-dependent quark mixing matrix in the noncommutative standard model. In particular, we calculate nine rephasing invariants of CP violation and illustrate the noncommutative CP-violating effect in a couple of charged D-meson decays. We also show how inner angles of the deformed unitarity triangles are related to CP-violating asymmetries in some typical B_d and B_s transitions into CP eigenstates. B-meson factories are expected to help probe or constrain noncommutative geometry at low energies in the near future.Comment: RexTev 16 pages. Modifications made. References added. Accepted for publication in Phys. Rev.

Signal Transduction Pathways in the Pentameric Ligand-Gated Ion Channels

The mechanisms of allosteric action within pentameric ligand-gated ion channels (pLGICs) remain to be determined. Using crystallography, site-directed mutagenesis, and two-electrode voltage clamp measurements, we identified two functionally relevant sites in the extracellular (EC) domain of the bacterial pLGIC from Gloeobacter violaceus (GLIC). One site is at the C-loop region, where the NQN mutation (D91N, E177Q, and D178N) eliminated inter-subunit salt bridges in the open-channel GLIC structure and thereby shifted the channel activation to a higher agonist concentration. The other site is below the C-loop, where binding of the anesthetic ketamine inhibited GLIC currents in a concentration dependent manner. To understand how a perturbation signal in the EC domain, either resulting from the NQN mutation or ketamine binding, is transduced to the channel gate, we have used the Perturbation-based Markovian Transmission (PMT) model to determine dynamic responses of the GLIC channel and signaling pathways upon initial perturbations in the EC domain of GLIC. Despite the existence of many possible routes for the initial perturbation signal to reach the channel gate, the PMT model in combination with Yen's algorithm revealed that perturbation signals with the highest probability flow travel either via the β1-β2 loop or through pre-TM1. The β1-β2 loop occurs in either intra- or inter-subunit pathways, while pre-TM1 occurs exclusively in inter-subunit pathways. Residues involved in both types of pathways are well supported by previous experimental data on nAChR. The direct coupling between pre-TM1 and TM2 of the adjacent subunit adds new insight into the allosteric signaling mechanism in pLGICs. © 2013 Mowrey et al

GPML: an XML-based standard for the interchange of genetic programming trees

We propose a Genetic Programming Markup Language (GPML), an XML based standard for the interchange of genetic programming trees, and outline the benefits such a format would bring in allowing the deployment of trained genetic programming (GP) models in applications as well as the subsidiary benefit of allowing GP researchers to directly share trained trees. We present a formal definition of this standard and describe details of an implementation. In addition, we present a case study where GPML is used to implement a model predictive controller for the control of a building heating plant

Evidence of a landlocked reproducing population of the marine pejerrey Odontesthes argentinensis (Actinopterygii; Atherinopsidae)

In South America, the order Atheriniformes includes the monophyletic genus Odontesthes with 20 species that inhabit freshwater, estuarine and coastal environments. Pejerrey Odontesthes argentinensis is widely distributed in coastal and estuarine areas of the Atlantic Ocean and is known to foray into estuaries of river systems, particularly in conditions of elevated salinity. However, to our knowledge, a landlocked self‐sustaining population has never been recorded. In this study, we examined the pejerrey population of Salada de Pedro Luro Lake (south‐east of Buenos Aires Province, Argentina) to clarify its taxonomic identity. An integrative taxonomic analysis based on traditional meristic, landmark‐based morphometrics and genetic techniques suggests that the Salada de Pedro Luro pejerrey population represents a novel case of physiological and morphological adaptation of a marine pejerrey species to a landlocked environment and emphasises the environmental plasticity of this group of fishesFil: Colautti, Dario César. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Limnología "Dr. Raúl A. Ringuelet". Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Limnología; ArgentinaFil: Miranda, Leandro Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: González Castro, M.. Universidad Nacional de Mar del Plata; ArgentinaFil: Villanova, Vanina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Strüssmann, Carlos A.. Tokyo University Of Marine Science And Technology; JapónFil: Mancini, Miguel Alberto. Universidad Nacional de Río Cuarto; ArgentinaFil: Maiztegui, Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Limnología "Dr. Raúl A. Ringuelet". Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Instituto de Limnología; ArgentinaFil: Berasain, Gustavo. Provincia de Buenos Aires. Ministerio de Asuntos Agrarios; ArgentinaFil: Hattori, Ricardo Shohei. Tokyo University of Marine Science and Technology; JapónFil: Grosman, Manuel Fabián. Universidad Nacional del Centro de la Provincia de Buenos Aires; ArgentinaFil: Sanzano, Pablo Miguel. Universidad Nacional del Centro de la Provincia de Buenos Aires; ArgentinaFil: Lozano, I.. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Llamazares Vegh, Sabina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Salinas, V.. Universidad Nacional de Río Cuarto; ArgentinaFil: Del Ponti, O.. Universidad Nacional de La Pampa; ArgentinaFil: Fresno, P.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Minotti, Priscilla Gail. Universidad Nacional de San Martín; ArgentinaFil: Yamamoto, Y.. Tokyo University Of Marine Science And Technology; JapónFil: Baigún, C.. Universidad Nacional de San Martín; Argentin

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

Gating at the Mouth of the Acetylcholine Receptor Channel: Energetic Consequences of Mutations in the αM2-Cap

Gating of nicotinic acetylcholine receptors from a C(losed) to an O(pen) conformation is the initial event in the postsynaptic signaling cascade at the vertebrate nerve-muscle junction. Studies of receptor structure and function show that many residues in this large, five-subunit membrane protein contribute to the energy difference between C and O. Of special interest are amino acids located at the two transmitter binding sites and in the narrow region of the channel, where C↔O gating motions generate a low↔high change in the affinity for agonists and in the ionic conductance, respectively. We have measured the energy changes and relative timing of gating movements for residues that lie between these two locations, in the C-terminus of the pore-lining M2 helix of the α subunit (‘αM2-cap’). This region contains a binding site for non-competitive inhibitors and a charged ring that influences the conductance of the open pore. αM2-cap mutations have large effects on gating but much smaller effects on agonist binding, channel conductance, channel block and desensitization. Three αM2-cap residues (αI260, αP265 and αS268) appear to move at the outset of channel-opening, about at the same time as those at the transmitter binding site. The results suggest that the αM2-cap changes its secondary structure to link gating motions in the extracellular domain with those in the channel that regulate ionic conductance

Twenty Thousand-Year-Old Huts at a Hunter-Gatherer Settlement in Eastern Jordan

Ten thousand years before Neolithic farmers settled in permanent villages, hunter-gatherer groups of the Epipalaeolithic period (c. 22–11,600 cal BP) inhabited much of southwest Asia. The latest Epipalaeolithic phase (Natufian) is well-known for the appearance of stone-built houses, complex site organization, a sedentary lifestyle and social complexity—precursors for a Neolithic way of life. In contrast, pre-Natufian sites are much less well known and generally considered as campsites for small groups of seasonally-mobile hunter-gatherers. Work at the Early and Middle Epipalaeolithic aggregation site of Kharaneh IV in eastern Jordan highlights that some of these earlier sites were large aggregation base camps not unlike those of the Natufian and contributes to ongoing debates on their duration of occupation. Here we discuss the excavation of two 20,000-year-old hut structures at Kharaneh IV that pre-date the renowned stone houses of the Natufian. Exceptionally dense and extensive occupational deposits exhibit repeated habitation over prolonged periods, and contain structural remains associated with exotic and potentially symbolic caches of objects (shell, red ochre, and burnt horn cores) that indicate substantial settlement of the site pre-dating the Natufian and outside of the Natufian homeland as currently understood

Structure of the pentameric ligand-gated ion channel ELIC cocrystallized with its competitive antagonist acetylcholine

ELIC, the pentameric ligand-gated ion channel from Erwinia chrysanthemi, is a prototype for Cys-loop receptors. Here we show that acetylcholine is a competitive antagonist for ELIC. We determine the acetylcholine–ELIC cocrystal structure to a 2.9-Å resolution and find that acetylcholine binding to an aromatic cage at the subunit interface induces a significant contraction of loop C and other structural rearrangements in the extracellular domain. The side chain of the pore-lining residue F247 reorients and the pore size consequently enlarges, but the channel remains closed. We attribute the inability of acetylcholine to activate ELIC primarily to weak cation-π and electrostatic interactions in the pocket, because an acetylcholine derivative with a simple quaternary-to-tertiary ammonium substitution activates the channel. This study presents a compelling case for understanding the structural underpinning of the functional relationship between agonism and competitive antagonism in the Cys-loop receptors, providing a new framework for developing novel therapeutic drugs