Filters

2020 - 20222

More filters

2021 - 20232
Reset filters

Settings

Author: Dahl, Andreas × End date: 2024 × Start date: 2020 ×

Search Results

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    Targeting cardiomyocyte ADAM10 ectodomain shedding promotes survival early after myocardial infarction
    ([London] : Nature Publishing Group UK, 2022) Klapproth, Erik; Witt, Anke; Klose, Pauline; Wiedemann, Johanna; Vavilthota, Nikitha; Künzel, Stephan R.; Kämmerer, Susanne; Günscht, Mario; Sprott, David; Lesche, Mathias; Rost, Fabian; Dahl, Andreas; Rauch, Erik; Kattner, Lars; Weber, Silvio; Mirtschink, Peter; Kopaliani, Irakli; Guan, Kaomei; Lorenz, Kristina; Saftig, Paul; Wagner, Michael; El-Armouche, Ali
    After myocardial infarction the innate immune response is pivotal in clearing of tissue debris as well as scar formation, but exaggerated cytokine and chemokine secretion with subsequent leukocyte infiltration also leads to further tissue damage. Here, we address the value of targeting a previously unknown a disintegrin and metalloprotease 10 (ADAM10)/CX3CL1 axis in the regulation of neutrophil recruitment early after MI. We show that myocardial ADAM10 is distinctly upregulated in myocardial biopsies from patients with ischemia-driven cardiomyopathy. Intriguingly, upon MI in mice, pharmacological ADAM10 inhibition as well as genetic cardiomycyte-specific ADAM10 deletion improves survival with markedly enhanced heart function and reduced scar size. Mechanistically, abolished ADAM10-mediated CX3CL1 ectodomain shedding leads to diminished IL-1β-dependent inflammation, reduced neutrophil bone marrow egress as well as myocardial tissue infiltration. Thus, our data shows a conceptual insight into how acute MI induces chemotactic signaling via ectodomain shedding in cardiomyocytes.
  • Thumbnail Image
    Item
    A smart polymer for sequence-selective binding, pulldown, and release of DNA targets
    (London : Springer Nature, 2020) Krieg, Elisha; Gupta, Krishna; Dahl, Andreas; Lesche, Mathias; Boye, Susanne; Lederer, Albena; Shih, William M.
    Selective isolation of DNA is crucial for applications in biology, bionanotechnology, clinical diagnostics and forensics. We herein report a smart methanol-responsive polymer (MeRPy) that can be programmed to bind and separate single- as well as double-stranded DNA targets. Captured targets are quickly isolated and released back into solution by denaturation (sequence-agnostic) or toehold-mediated strand displacement (sequence-selective). The latter mode allows 99.8% efficient removal of unwanted sequences and 79% recovery of highly pure target sequences. We applied MeRPy for the depletion of insulin, glucagon, and transthyretin cDNA from clinical next-generation sequencing (NGS) libraries. This step improved the data quality for low-abundance transcripts in expression profiles of pancreatic tissues. Its low cost, scalability, high stability and ease of use make MeRPy suitable for diverse applications in research and clinical laboratories, including enhancement of NGS libraries, extraction of DNA from biological samples, preparative-scale DNA isolations, and sorting of DNA-labeled non-nucleic acid targets. © 2020, The Author(s).