24 research outputs found

    Mechanism of Ion Permeation and Selectivity in a Voltage Gated Sodium Channel

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    The rapid and selective transport of Na<sup>+</sup> through sodium channels is essential for initiating action potentials within excitable cells. However, an understanding of how these channels discriminate between different ion types and how ions permeate the pore has remained elusive. Using the recently published crystal structure of a prokaryotic sodium channel from <i>Arcobacter butzleri</i>, we are able to determine the steps involved in ion transport and to pinpoint the location and likely mechanism used to discriminate between Na<sup>+</sup> and K<sup>+</sup>. Na<sup>+</sup> conduction is shown to involve the loosely coupled “knock-on” movement of two solvated ions. Selectivity arises due to the inability of K<sup>+</sup> to fit between a plane of glutamate residues with the preferred solvation geometry that involves water molecules bridging between the ion and carboxylate groups. These mechanisms are different to those described for K<sup>+</sup> channels, highlighting the importance of developing a separate mechanistic understanding of Na<sup>+</sup> and Ca<sup>2+</sup> channels

    Insertion Mechanism and Stability of Boron Nitride Nanotubes in Lipid Bilayers

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    We provide insight into the interaction of boron nitride nanotubes (BNNTs) with cell membranes to better understand their improved biocompatibility compared to carbon nanotubes (CNTs). Contrary to CNTs, no computational studies exist investigating the insertion mechanism and stability of BNNTs in membranes. Our molecular dynamics simulations demonstrate that BNNTs are spontaneously attracted to lipid bilayers and are stable once inserted. They insert via a lipid-mediated, passive insertion mechanism. BNNTs demonstrate similar characteristics to more biocompatible functionalized CNTs

    Additional file 1: of Psychoactive pharmaceuticals at environmental concentrations induce in vitro gene expression associated with neurological disorders

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    R-programming code for RNA-Seq analysis and multi-dimensional scaling (MDS) function. The file contains R-code for analysis of RNA-Seq data for mixture and valproate treatments. This file also includes the code for plotMDS function for using multi-dimensional scaling. (DOCX 61 kb

    Appendix C -Supplemental material for A comparison of the minimum data sets for primary shoulder arthroplasty between national shoulder arthroplasty registries. Is international harmonization feasible?

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    <p>Supplemental material, Appendix C for A comparison of the minimum data sets for primary shoulder arthroplasty between national shoulder arthroplasty registries. Is international harmonization feasible? in Shoulder & Elbow</p

    Appendix B -Supplemental material for A comparison of the minimum data sets for primary shoulder arthroplasty between national shoulder arthroplasty registries. Is international harmonization feasible?

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    <p>Supplemental material, Appendix B for A comparison of the minimum data sets for primary shoulder arthroplasty between national shoulder arthroplasty registries. Is international harmonization feasible? in Shoulder & Elbow</p

    Sanger sequencing results from patient 4.

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    <p>Confirmation of the presence of the <i>MTOR</i> mutation c.4228C>A (p.P1410T) at a lower allele frequency in cfDNA and its absence in the corresponding primary tumor tissue.</p

    Additional file 1: Figure S1. of Determination of the Cell Permissiveness Spectrum, Mode of RNA Replication, and RNA-Protein Interaction of Zika Virus

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    Immunofluorescent assay and RISH to show ZIKV viral RNA replication and protein production in Vero cells. Vero cells were infected with MR766 (A1-D1, A3-D3) or PRVABC59 (PR) (A2-D2, A4-D4) at an MOI of 0.5 for 24 h. After fixation with 1% formaldehyde, the cells were permeabilized and immunostained for viral protein in red (B1-B4). After refixation with 4% formaldehyde, the cells were hybridized with single strand DNA probe (labeled with biotin) made from ZIKV genomic DNA. The RNA was stained in green (A1-A4). The cell nuclei were shown in blue using DAPI staining (C1-C4). The merged image was shown in D1-D4. In the panels 1 and 2, the pictures were taken using a 40× lens. In the panels 3 and 4, the pictures were taken using an 100× lens. Scale bar: 10 μm. (PSD 5413 kb

    Integrity of cfDNA and a corresponding sequencing library.

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    <p>(A) Integrity and size distribution of cfDNA fragments from patient 1 showing a nucleosomal laddering of cfDNA with fragment sizes of 166, 360, and 515 bp; (B) Corresponding sequencing library from patient 1, prepared from 10ng cfDNA.</p
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