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  • Uhlmann, Eric, L., et al. (författare)
  • Subjective Evidence Evaluation Survey For Multi-Analyst Studies
  • 2024
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Multi-analyst studies explore how well an empirical claim withstands plausible alternative analyses of the same data set by multiple, independent analysis teams. Conclusions from these studies typically rely on a single outcome metric (e.g., effect size) provided by each analysis team. Although informative about the range of plausible effects in a data set, a single effect size from each team does not provide a complete, nuanced understanding of how analysis choices are related to the outcome. We used the Delphi consensus technique with input from 37 experts to develop an 18-item Subjective Evidence Evaluation Survey (SEES) to evaluate how each analysis team views the methodological appropriateness of the research design and the strength of evidence for the hypothesis. We illustrate the usefulness of the SEES in providing richer evidence assessment with pilot data from a previous multi-analyst study.
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  • Bergh, Cathrine, et al. (författare)
  • Discovery of lipid binding sites in a ligand-gated ion channel by integrating simulations and cryo-EM
  • 2024
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Ligand-gated ion channels transduce electrochemical signals in neurons and other excitable cells. Aside from canonical ligands, phospholipids are thought to bind specifically to the transmembrane domain of several ion channels. However, structural details of such lipid contacts remain elusive, partly due to limited resolution of these regions in experimental structures. Here, we discovered multiple lipid interactions in the channel GLIC by integrating cryo-electron microscopy and large-scale molecular simulations. We identified 25 bound lipids in the GLIC closed state, a conformation where none, to our knowledge, were previously known.Three lipids were associated with each subunit in the inner leaflet, including a buried interaction disrupted in mutant simulations. In the outer leaflet, two intrasubunit sites were evident in both closed and open states, while a putative intersubunit site was preferred in open-state simulations. This work offers molecular details of GLIC-lipid contacts particularly in the ill-characterized closed state, testable hypotheses for state-dependent binding, and a multidisciplinary strategy for modeling protein-lipid interactions.
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