Molecular Requirements for Ethanol Differential Allosteric Modulation of Ligand-Gated Ion Channels Based on Selective G Beta Gamma Modulation

It is now believed that the allosteric modulation produced by ethanol in glycine receptors (GlyRs) depends on alcohol binding to discrete sites within the protein structure. Thus, the differential ethanol sensitivity of diverse GlyR isoforms and mutants was explained by the presence of specific residues in putative alcohol pockets. Here, we demonstrate that ethanol sensitivity in two LGIC members, the GlyR adult alpha1 and embryonic alpha2 subunits, can be modified through selective mutations that rescued or impaired Gbetagamma modulation. Even though that both isoforms were able to physically interact with Gbetagamma, only the alpha1 GlyR was functionally modulated by Gbetagamma and pharmacological ethanol concentrations. Remarkably, the simultaneous switching of two transmembrane and a single extracellular residue in alpha2 GlyRs was enough to generate GlyRs modulated by Gbetagamma and low ethanol concentrations. Interestingly, while we found that these TM residues were different to those in the alcohol binding site, the extracellular residue was recently implicated in conformational changes important to generate a pre-open activated state that precedes ion channel gating. Thus, these results support the idea that the differential ethanol sensitivity of these two GlyR isoforms rests on conformational changes in transmembrane and extracellular residues within the ion channel structure rather than in differences in alcohol binding pockets. Our results describe the molecular basis for the differential ethanol sensitivity of two LGIC members based on selective Gbetagamma modulation and provide a new mechanistic framework for allosteric modulations of abuse drugs

Cage-size control of guest vibration and thermal conductivity in Sr8Ga16Si30-xGex

We present a systematic study of thermal conductivity, specific heat, electrical resistivity, thermopower and x-ray diffraction measurements performed on single-crystalline samples of the pseudoquaternary type-I clathrate system Sr8Ga16Si30-xGex, in the full range of 0 < x < 30. All the samples show metallic behavior with n-type majority carriers. However, the thermal conductivity and specific heat strongly depend on x. Upon increasing x from 0 to 30, the lattice parameter increases by 3%, from 10.446 to 10.726 A, and the localized vibrational energies of the Sr guest ions in the tetrakaidekahedron (dodecahedron) cages decrease from 59 (120) K to 35 (90) K. Furthermore, the lattice thermal conductivity at low temperatures is largely suppressed. In fact, a crystalline peak found at 15 K for x = 0 gradually decreases and disappears for x > 20, evolving into the anomalous glass-like behavior observed for x = 30. It is found that the increase of the free space for the Sr guest motion directly correlates with a continuous transition from on-center harmonic vibration to off-center anharmonic vibration, with consequent increase in the coupling strength between the guest's low-energy modes and the cage's acoustic phonon modes.Comment: 7 pages, 7 figures, submitted to PR

Structure and Subhalo Population of Halos in a Self-Interacting Dark Matter Cosmology

We study the structure of Milky Way (MW)- and cluster-sized halos in a Lambda Cold Dark Matter (CDM) cosmology with self-interacting (SI) dark particles. The cross section per unit of particle mass has the form sigma = sig_0(1/v_100)^alpha, where sig_0 is a constant in units of cm^2/gr and v_100 is the relative velocity in units of 100 km/s. Different values for sigma with alpha= 0 or 1 were used. For small values of sigma = const. (sig_0<0.5), the core density of the halos at z=0 is typically higher at a given mass for lower values of sig_0 or, at a given sig_0, for lower masses. For values of sig_0 as high as 3.0, the halos may undergo the gravothermal catastrophe before z=0. When alpha = 1, the core density of cluster- and MW-sized halos is similar. Using sigma = 0.5-1.0x(1/v_100), our predictions agree with the central densities and the core scaling laws of halos both inferred from the observations of dwarf and LSB galaxies and clusters of galaxies. The cumulative Vmax-functions of subhalos in MW-sized halos with (sig_0,alpha) = (0.1,0.0), (0.5,0.0) and (0.5,1.0) agree roughly with observations (luminous satellites) for Vmax > 30 km/s, while at Vmax = 20 km/s the functions are a factor 5-8 higher, similar to the CDM predictions. The halos with SI have slightly more specific angular momentum at a given mass shell and are rounder than their CDM counterparts. We conclude that the introduction of SI particles with sigma \propto 1/v_100 may remedy the cuspy core problem of the CDM cosmogony, while the subhalo population number remains similar to that of the CDM halos.Comment: To appear in ApJ, December 20, 2002. We added plots showing the evolution of the heat capacity profile for halos in the core expansion and gravothermal catastrophe phases. Minor changes in the text were introduce

Stability of nonuniform rotor blades in hover using a mixed formulation

A mixed formulation for calculating static equilibrium and stability eigenvalues of nonuniform rotor blades in hover is presented. The static equilibrium equations are nonlinear and are solved by an accurate and efficient collocation method. The linearized perturbation equations are solved by a one step, second order integration scheme. The numerical results correlate very well with published results from a nearly identical stability analysis based on a displacement formulation. Slight differences in the results are traced to terms in the equations that relate moments to derivatives of rotations. With the present ordering scheme, in which terms of the order of squares of rotations are neglected with respect to unity, it is not possible to achieve completely equivalent models based on mixed and displacement formulations. The one step methods reveal that a second order Taylor expansion is necessary to achieve good convergence for nonuniform rotating blades. Numerical results for a hypothetical nonuniform blade, including the nonlinear static equilibrium solution, were obtained with no more effort or computer time than that required for a uniform blade

Coalescent-based species delimitation in the sand lizards of the Liolaemus wiegmannii complex (Squamata: Liolaemidae)

Coalescent-based algorithms coupled with the access to genome-wide data have become powerful tools forassessing questions on recent or rapid diversification, as well as delineating species boundaries in the absence of reciprocal monophyly. In southern South America, the diversification of Liolaemus lizards during the Pleistocene is well documented and has been attributed to the climatic changes that characterized this recent period of time. Past climatic changes had harsh effects at extreme latitudes, including Patagonia, but habitat changes at intermediate latitudes of South America have also been recorded, including expansion of sand fields over northern Patagonia and Pampas). In this work, we apply a coalescent-based approach to study the diversification of the Liolaemus wiegmannii species complex, a morphologically conservative clade that inhabits sandy soils across northwest and south-central Argentina, and the south shores of Uruguay. Using four standard sequence markers (mitochondrial DNA and three nuclear loci) along with ddRADseq data we inferred species limits and a time calibrated species tree for the L. wiegmannii complex in order to evaluate the influence of Quaternary sand expansion/retraction cycles on diversification. We also evaluated the evolutionary independence of the recently described L. gardeli and inferred its phylogenetic position relative to L. wiegmannii. We find strong evidence for six allopatric candidate species within L. wiegmannii, which diversified during the Pleistocene. The Great Patagonian Glaciation (∼1 million years before present) likely split the species complex into two main groups: one composed of lineages associated with sub-Andean sedimentary formations, and the other mostly related to sand fields in the Pampas and northern Patagonia. We hypothesize that early speciation within L. wiegmannii was influenced by the expansion of sand dunes throughout central Argentina and Pampas. Finally, L. gardeli is supported as a distinct lineage nested within the L. wiegmannii complex.Fil: Villamil, Joaquín. Universidad de la República. Facultad de Ciencias; UruguayFil: Avila, Luciano Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico para el Estudio de los Ecosistemas Continentales; ArgentinaFil: Morando, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico para el Estudio de los Ecosistemas Continentales; ArgentinaFil: Sites, Jack W.. University Brigham Young; Estados UnidosFil: Leaché, Adam D.. University of Washington; Estados UnidosFil: Maneyro, Raúl. Universidad de la República. Facultad de Ciencias; UruguayFil: Camargo Bentaberry, Arley. Universidad de la República; Urugua

Turbulent dissipation in the ISM: the coexistence of forced and decaying regimes and implications for galaxy formation and evolution

We discuss the dissipation of turbulent kinetic energy Ek in the global ISM by means of 2-D, MHD, non-isothermal simulations in the presence of model radiative heating and cooling. We argue that dissipation in 2D is representative of that in three dimensions as long as it is dominated by shocks rather than by a turbulent cascade. Energy is injected at a few isolated sites in space, over relatively small scales, and over short time periods. This leads to the coexistence of forced and decaying regimes in the same flow. We find that the ISM-like flow dissipates its turbulent energy rapidly. In simulations with forcing, the input parameters are the radius l_f of the forcing region, the total kinetic energy e_k each source deposits into the flow, and the rate of formation of those regions, sfr_OB. The global dissipation time t_d depends mainly on l_f. In terms of measurable properties of the ISM, t_d >= Sigma_g u_rms^2/(e_k sfr_OB), where Sigma_g is the average gas surface density and u_rms is the rms velocity dispersion. For the solar neighborhood, t_d >= 1.5x10^7 yr. The global dissipation time is consistently smaller than the crossing time of the largest energy-containing scales. In decaying simulations, Ek decreases with time as t^-n, where n~0.8-0.9. This suggests a decay with distance d as Ek\propto d^{-2n/(2-n)} in the mixed forced+decaying case. If applicable to the vertical direction, our results support models of galaxy evolution in which stellar energy injection provides significant support for the gas disk thickness, but not models of galaxy formation in which this energy injection is supposed to reheat an intra-halo medium at distances of up to 10-20 times the optical galaxy size, as the dissipation occurs on distances comparable to the disk height.Comment: 23 pages, including figures. To appear in ApJ. Abstract abridge