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

The rapid and selective transport of Na⁺ 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⁺ and K⁺. Na⁺ conduction is shown to involve the loosely coupled “knock-on” movement of two solvated ions. Selectivity arises due to the inability of K⁺ 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⁺ channels, highlighting the importance of developing a separate mechanistic understanding of Na⁺ and Ca²⁺ channels

Insertion Mechanism and Stability of Boron Nitride Nanotubes in Lipid Bilayers

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

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?

<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?

<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.

<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

Comparison of shared and exclusive variants in serum and tumor tissue pairs compared to the COSMIC database of annotated somatic mutations.

<p>Comparison of shared and exclusive variants in serum and tumor tissue pairs compared to the COSMIC database of annotated somatic mutations.</p

Integrity of cfDNA and a corresponding sequencing library.

<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