Three series of 22-residue peptides derived from the transmembrane M2 segment of the glycine receptor a1-subunit (M2GlyR) have been designed, synthesized, and tested to determine the plasticity of a channel-forming sequence and to define whether channel pores with enhanced conductive properties could be created. Sixteen sequences were examined for aqueous solubility, solution-association tendency, secondary structure, and half-maximal concentration for supramolecular assembly, channel activity, and ion transport properties across epithelial monolayers. All peptides interact strongly with membranes: associating with, inserting across, and assembling to form homooligomeric bundles when in micromolar concentrations. Single and double amino acid replacements involving arginine and/or aromatic amino acids within the final five C-terminal residues of the peptide cause dramatic effects on the concentration dependence, yielding a range of K 1/2 values from 36 6 5 to 390 6 220 mM for transport activity. New water/lipid interfacial boundaries were established for the transmembrane segment using charged or aromatic amino acids, thus limiting the peptides' ability to move perpendicularly to the plane of the bilayer. Formation of discrete water/lipid interfacial boundaries appears to be necessary for efficient supramolecular assembly and high anion transport activity. A peptide sequence is identified that may show efficacy in channel replacement therapy for channelopathies such as cystic fibrosis.
We did not find a statistical correlation to surgical failure after a laparoscopic uterosacral ligament suspension with LA muscle defects on preoperative magnetic resonance images within this specific patient population.
This video demonstrates a novel box-stitch technique of laparoscopic post-hysterectomy uterosacral ligament suspension as a native tissue option for minimally invasive reconstructive surgery. The procedure is a reasonable option to address apical prolapse in patients who do not desire or who are unable to have synthetic or biologic mesh placed for restorative reconstructive prolapse surgery.
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