Lessons from management of syphilis in Nunavut, Canada, 2012-2020.

Background: Nunavut, part of Inuit Nunangat, is a geographically vast territory in northern Canada, with a population of over 38,000 people. Most (85%) of the population identify as Inuit. Nunavut has experienced a significant rise in heterosexual infectious syphilis cases since 2012.

Molecular Characterization and Antimicrobial Resistance in Neisseria gonorrhoeae, Nunavut Region of Inuit Nunangat, Canada, 2018-2019.

We assessed antimicrobial resistance (AMR) in Neisseria gonorrhoeae in Nunavut, Canada, using remnant gonorrhea nucleic acid amplification test-positive urine specimens. This study confirms the feasibility of conducting N. gonorrhoeae AMR surveillance and highlights the diversity of gonococcal sequence types and geographic variation of AMR patterns in the territory.

Hydrophobic gasket mutation produces gating pore currents in closed human voltage-gated proton channels.

The hydrophobic gasket (HG), a ring of hydrophobic amino acids in the voltage-sensing domain of most voltage-gated ion channels, forms a constriction between internal and external aqueous vestibules. Cationic Arg or Lys side chains lining the S4 helix move through this "gating pore" when the channel opens. S4 movement may occur during gating of the human voltage-gated proton channel, hH1, but proton current flows through the same pore in open channels.

Orkambi® and amplifier co-therapy improves function from a rare mutation in gene-edited cells and patient tissue.

The combination therapy of lumacaftor and ivacaftor (Orkambi) is approved for patients bearing the major cystic fibrosis (CF) mutation: It has been predicted that Orkambi could treat patients with rarer mutations of similar "theratype"; however, a standardized approach confirming efficacy in these cohorts has not been reported. Here, we demonstrate that patients bearing the rare mutation: c.3700 A>G, causing protein misprocessing and altered channel function-similar to ΔF508-CFTR, are unlikely to yield a robust Orkambi response.

Peregrination of the selectivity filter delineates the pore of the human voltage-gated proton channel hHV1.

Extraordinary selectivity is crucial to all proton-conducting molecules, including the human voltage-gated proton channel (hHV1), because the proton concentration is >10(6) times lower than that of other cations. Here we use "selectivity filter scanning" to elucidate the molecular requirements for proton-specific conduction in hHV1. Asp(112), in the middle of the S1 transmembrane helix, is an essential part of the selectivity filter in wild-type (WT) channels.

Construction and validation of a homology model of the human voltage-gated proton channel hHV1.

The topological similarity of voltage-gated proton channels (H(V)1s) to the voltage-sensing domain (VSD) of other voltage-gated ion channels raises the central question of whether H(V)1s have a similar structure. We present the construction and validation of a homology model of the human H(V)1 (hH(V)1). Multiple structural alignment was used to construct structural models of the open (proton-conducting) state of hH(V)1 by exploiting the homology of hH(V)1 with VSDs of K(+) and Na(+) channels of known three-dimensional structure.