1,372 research outputs found

    Molecular Dynamics Simulation Studies of Cardiolipin Bilayers

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    The Morphologically Divided Redshift Distribution of Faint Galaxies

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    We have constructed a morphologically divided redshift distribution of faint field galaxies using a statistically unbiased sample of 196 galaxies brighter than I = 21.5 for which detailed morphological information (from the Hubble Space Telescope) as well as ground-based spectroscopic redshifts are available. Galaxies are classified into 3 rough morphological types according to their visual appearance (E/S0s, Spirals, Sdm/dE/Irr/Pec's), and redshift distributions are constructed for each type. The most striking feature is the abundance of low to moderate redshift Sdm/dE/Irr/Pec's at I < 19.5. This confirms that the faint end slope of the luminosity function (LF) is steep (alpha < -1.4) for these objects. We also find that Sdm/dE/Irr/Pec's are fairly abundant at moderate redshifts, and this can be explained by strong luminosity evolution. However, the normalization factor (or the number density) of the LF of Sdm/dE/Irr/Pec's is not much higher than that of the local LF of Sdm/dE/Irr/Pec's. Furthermore, as we go to fainter magnitudes, the abundance of moderate to high redshift Irr/Pec's increases considerably. This cannot be explained by strong luminosity evolution of the dwarf galaxy populations alone: these Irr/Pec's are probably the progenitors of present day ellipticals and spiral galaxies which are undergoing rapid star formation or merging with their neighbors. On the other hand, the redshift distributions of E/S0s and spirals are fairly consistent those expected from passive luminosity evolution, and are only in slight disagreement with the non-evolving model.Comment: 11 pages, 4 figures (published in ApJ

    Topical rosiglitazone is an effective anti-scarring agent in the cornea

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    Corneal scarring remains a major cause of blindness world-wide, with limited treatment options, all of which have side-effects. Here, we tested the hypothesis that topical application of Rosiglitazone, a Thiazolidinedione and ligand of peroxisome proliferator activated receptor gamma (PPARγ), can effectively block scar formation in a cat model of corneal damage. Adult cats underwent bilateral epithelial debridement followed by excimer laser ablation of the central corneal stroma to a depth of ~160 µm as a means of experimentally inducing a reproducible wound. Eyes were then left untreated, or received 50 µl of either 10 µM Rosiglitazone in DMSO/Celluvisc, DMSO/Celluvisc vehicle or Celluvisc vehicle twice daily for 2 weeks. Cellular aspects of corneal wound healing were evaluated with in vivo confocal imaging and post-mortem immunohistochemistry for alpha smooth muscle actin (αSMA). Impacts of the wound and treatments on optical quality were assessed using wavefront sensing and optical coherence tomography at 2, 4, 8 and 12 weeks post-operatively. In parallel, cat corneal fibroblasts were cultured to assess the effects of Rosiglitazone on TGFβ-induced αSMA expression. Topical application of Rosiglitazone to cat eyes after injury decreased αSMA expression and haze, as well as the induction of lower-order and residual, higher-order wavefront aberrations compared to vehicle-treated eyes. Rosiglitazone also inhibited TGFβ-induced αSMA expression in cultured corneal fibroblasts. In conclusion, Rosiglitazone effectively controlled corneal fibrosis in vivo and in vitro, while restoring corneal thickness and optics. Its topical application may represent an effective, new avenue for the prevention of corneal scarring with distinct advantages for pathologically thin corneas

    Brownian Dynamics Simulations of Ion Transport through the VDAC

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    This is the publisher's version. Copyright 2011 by Elsevier.It is important to gain a physical understanding of ion transport through the voltage-dependent anion channel (VDAC) because this channel provides primary permeation pathways for metabolites and electrolytes between the cytosol and mitochondria. We performed grand canonical Monte Carlo/Brownian dynamics (GCMC/BD) simulations to explore the ion transport properties of human VDAC isoform 1 (hVDAC1; PDB:2K4T) embedded in an implicit membrane. When the MD-derived, space-dependent diffusion constant was used in the GCMC/BD simulations, the current-voltage characteristics and ion number profiles inside the pore showed excellent agreement with those calculated from all-atom molecular-dynamics (MD) simulations, thereby validating the GCMC/BD approach. Of the 20 NMR models of hVDAC1 currently available, the third one (NMR03) best reproduces both experimental single-channel conductance and ion selectivity (i.e., the reversal potential). In addition, detailed analyses of the ion trajectories, one-dimensional multi-ion potential of mean force, and protein charge distribution reveal that electrostatic interactions play an important role in the channel structure and ion transport relationship. Finally, the GCMC/BD simulations of various mutants based on NMR03 show good agreement with experimental ion selectivity. The difference in ion selectivity between the wild-type and the mutants is the result of altered potential of mean force profiles that are dominated by the electrostatic interactions

    Molecular Dynamics Studies of Ion Permeation in VDAC

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    This is the publisher's version. Copyright 2011 by Elsevier.The voltage-dependent anion channel (VDAC) in the outer membrane of mitochondria serves an essential role in the transport of metabolites and electrolytes between the cell matrix and mitochondria. To examine its structure, dynamics, and the mechanisms underlying its electrophysiological properties, we performed a total of 1.77 μs molecular dynamics simulations of human VDAC isoform 1 in DOPE/DOPC mixed bilayers in 1 M KCl solution with transmembrane potentials of 0, ±25, ±50, ±75, and ±100 mV. The calculated conductance and ion selectivity are in good agreement with the experimental measurements. In addition, ion density distributions inside the channel reveal possible pathways for different ion species. Based on these observations, a mechanism underlying the anion selectivity is proposed; both ion species are transported across the channel, but the rate for K+ is smaller than that for Cl− because of the attractive interactions between K+ and residues on the channel wall. This difference leads to the anion selectivity of VDAC

    Assessing smectic liquid-crystal continuum models for elastic bilayer deformations

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    For four decades, since W. Helfrich’s pioneering study of smectic A liquid crystals in 1973, continuum elastic models (CEMs) have been employed as tools to understand the energetics of protein-induced lipid bilayer deformations. Among the assumptions underlying this use is that all relevant protein–lipid interactions can be included in the continuum representation of the protein–bilayer interactions through the physical parameters determined for protein-free bilayers and the choice of boundary conditions at the protein/bilayer interface. To better understand this assumption, we review the general structure of CEMs, examine how different choices of boundary conditions and physical moduli profiles alter the predicted bilayer thickness profiles around gramicidin A (gA) and mitochondrial voltage-dependent anion channels (VDAC), respectively, and compare these profiles with those obtained from all-atom molecular dynamics simulations. We find that the profiles differ qualitatively in the first lipid shell around the channels, indicating that the CEMs do not capture accurately the consequences of the protein-induced local changes in lipid bilayer dynamics. Therefore, one needs to be careful when interpreting the results of CEM-based analyses of lipid bilayer-membrane protein interactions

    Luminosity Functions of Elliptical Galaxies at z < 1.2

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    The luminosity functions of E/S0 galaxies are constructed in 3 different redshift bins (0.2 < z < 0.55, 0.55 < z < 0.8, 0.8 < z < 1.2), using the data from the Hubble Space Telescope Medium Deep Survey (HST MDS) and other HST surveys. These independent luminosity functions show the brightening in the luminosity of E/S0s by about 0.5~1.0 magnitude at z~1, and no sign of significant number evolution. This is the first direct measurement of the luminosity evolution of E/S0 galaxies, and our results support the hypothesis of a high redshift of formation (z > 1) for elliptical galaxies, together with weak evolution of the major merger rate at z < 1.Comment: To be published in ApJ Letters, 4 pages, AAS Latex, 4 figures, and 2 table
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