The S4 segment of voltage-sensing domains (VSDs) directly responds to voltage changes by reorienting within the electric field as a permion. A narrow hydrophobic "gasket" or charge transfer center at the core of most VSDs focuses the electric field into a narrow region and catalyzes the sequential and reversible translocation of S4 positive gating charge residues across the electric field while preventing the permeation of physiological ions. Mutating specific S4 gating charges can cause ionic leak currents through the VSDs. These gating pores or omega currents play important pathophysiological roles in many diseases of excitability. Here, we show that mutating D129, a key countercharge residue in the Ciona intestinalis voltage-sensing phosphatase (Ci-VSP), leads to the generation of unique anionic omega currents. Neutralizing D129 causes a dramatic positive shift of activation, facilitates the formation of a continuous water path through the VSD, and creates a positive electrostatic potential landscape inside the VSD that contributes to its unique anionic selectivity. Increasing the population or dwell time of the conducting state by a high external pH or an engineered Cd2+ bridge markedly increases the current magnitude. Our findings uncover a new role of countercharge residues in the impermeable VSD of Ci-VSP and offer insights into mechanisms of the conduction of anionic omega currents linked to countercharge residue mutations.
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http://dx.doi.org/10.1085/jgp.202213311 | DOI Listing |
JHEP Rep
February 2025
Division of Hematology/Oncology, Department of Medicine, Tisch Cancer Institute, Mount Sinai Hospital, New York, NY, USA.
Background & Aims: Atezolizumab/bevacizumab (A/B) is now a standard first-line treatment for advanced hepatocellular carcinoma (HCC), but the optimal second-line regimen is not known. We evaluated real-world treatment patterns and outcomes to investigate factors associated with post-progression survival (PPS).
Methods: In this multicenter, international, retrospective study, we examined clinical characteristics and outcomes of patients with advanced HCC who progressed on first-line A/B.
RSC Adv
January 2025
Department of Physics, BITS Pilani-Pilani Campus RJ-333031 India
The study reports solid-state ceramic supercapacitors (SSCs) assembled using a novel composite electrolyte based on Li ion conducting perovskite-type LLTO (LiLaTiO) and an ionic liquid (EMIM BF). Small amounts of various ionic liquids (ILs) were added to LLTO to enhance the ionic conductivity and improve electrode compatibility. The optimal composition with approximately ∼6 wt% EMIM BF in LLTO exhibited a high ionic conductivity of around ∼10 Ω cm at room temperature, nearly three orders of magnitude higher than that of the pristine LLTO.
View Article and Find Full Text PDFActa Biomater
January 2025
Department of Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ, USA. Electronic address:
In injured and diseased tissues, changes in molecular and cellular compositions, as well as tissue architecture, lead to alterations in both physiological and physical characteristics. Notably, the electrical properties of tissues, which can be characterized as bioelectrical impedance (bioimpedance), are closely linked to the health and pathological conditions of the tissues. This highlights the significant role of quantitatively characterizing these electrical properties in improving the accuracy and speed of diagnosis and prognosis.
View Article and Find Full Text PDFACS Appl Mater Interfaces
January 2025
Department of Physics, School of Electrical and Electronics Engineering, SASTRA Deemed to be University, Thanjavur 613 401, Tamil Nadu, India.
This study presents the fabrication of highly conducting Au fabric electrodes using a layer-by-layer (LBL) approach and its application toward energy storage. Through the ligand-exchange mechanism, the alternating layers of tris(2-aminoethyl)amine (TREN) and gold nanoparticles (Au NPs) encapsulated with tetraoctylammonium bromide (TOABr) ligands (Au-TOABr) were deposited onto the fabric to achieve a highly conducting Au fabric (0.12 Ω/□) at room temperature in just two LBL cycles.
View Article and Find Full Text PDFACS Omega
January 2025
Institute for Micro Integration (IFM), University of Stuttgart, Allmandring 9B, 70569 Stuttgart, Germany.
The current demand for highly sensitive, optical sensors in biodiagnostics has prompted the development of ultrathin metal coatings on a range of substrates. Given the potential attenuation of the signal from a plasmonic sensor for the detection of fluorescent molecules when an adhesion layer between the substrate and coating is employed, this study examines the impact of various factors on the adhesion strength between gold coatings and substrates comprising glass and cyclo-olefin-polymer (COP). The objective is to identify potential configurations for high adhesion strength, thereby eliminating the need for an adhesion layer in the fabrication of optical sensors with gold coatings for diagnostic applications or to utilize a minimal adhesion layer thickness.
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