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Phosphate rebinding induces force reversal via slow backward cycling of cross-bridges.
Front Physiol
January 2025
Institute of Vegetative Physiology, University of Cologne, Köln, Germany.
Objective: Previous studies on muscle fibers, myofibrils, and myosin revealed that the release of inorganic phosphate (P) and the force-generating step(s) are reversible, with cross-bridges also cycling backward through these steps by reversing force-generating steps and rebinding P. The aim was to explore the significance of force redevelopment kinetics (rate constant ) in cardiac myofibrils for the coupling between the P binding induced force reversal and the rate-limiting transition for backward cycling of cross-bridges from force-generating to non-force-generating states.
Methods: and force generation of cardiac myofibrils from guinea pigs were investigated at 0.
Precise intracellular uptake and endosomal release of diverse functional mRNA payloads via glutathione-responsive nanogels.
Mater Today Bio
February 2025
Department of Chemistry, Molecular Sciences Research Hub, Imperial College London, W12 0BZ, London, UK.
We present a novel, highly customizable glutathione-responsive nanogel (NG) platform for efficient mRNA delivery with precise mRNA payload release control. Optimization of various cationic monomers, including newly synthesized cationic polyarginine, polyhistidine, and acrylated guanidine monomers, allowed fine-tuning of NG properties for mRNA binding. By incorporating a poly(ethylene) glycol-based disulphide crosslinker, we achieved glutathione-triggered mRNA release, enabling targeted intracellular delivery.
View Article and Find Full Text PDFQuantitative Analysis of Phosphorothioate Isomers in CRISPR sgRNA at Single-Residue Resolution Using Endonuclease Digestion Coupled with Liquid Chromatography Cyclic Ion Mobility Mass Spectrometry (LC/cIMS).
Anal Chem
January 2025
Analytical Chemistry Group, ‡VI-NEXT Group, Regeneron Pharmaceuticals, Inc., Tarrytown, New York 10591-6706, United States.
Phosphorothioate (PS) modifications in single-guided RNA (sgRNA) are crucial for genome editing applications using the CRISPR/Cas9 system. These modifications may enhance sgRNA stability, pharmacokinetics, and binding to targets, thereby facilitating the desired genetic alterations. Incorporating multiple PS groups at varying positions may introduce chiral centers into the sgRNA backbone, resulting in a complex mixture of constitutional- and stereoisomers that challenges current analytical capabilities for reliable identification and quantification.
View Article and Find Full Text PDFPET Imaging of a Transgenic Tau Rat Model SHR24 with [F]AV1451.
Mol Imaging Biol
January 2025
Molecular Imaging Chemistry Laboratory, Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Cambridge, CB2 0QQ, UK.
Purpose: Positron Emission Tomography (PET) scans with radioligands targeting tau neurofibrillary tangles (NFT) have accelerated our understanding of the role of misfolded tau in neurodegeneration. While intended for human research, applying these radioligands to small animals establishes a vital translational link. Transgenic animal models of dementia, such as the tau rat SHR24, play a crucial role in enhancing our understanding of these disorders.
View Article and Find Full Text PDFSalvicsite A-C: Three Seco-Norabietane Diterpenoids Including an Unusual Tetracyclic Skeleton from Diels f. Stib.
J Org Chem
January 2025
School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
Three seco-norabietane diterpenoids, salvicsites A-C (-), along with two known compounds, were isolated from the roots and rhizomes of Diels f. Stib. Salvicsite A () represents an unprecedented structural combination, featuring an eight-membered α-methyl-α,β-unsaturated lactone ring and a five-membered α,β-unsaturated lactone ring, based on a 6/6/5/8 ring system.
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