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A Ligand-specific Blockade of the Integrin Mac-1 Selectively Targets Pathologic Inflammation While Maintaining Protective Host-defense
Abstract: Integrin-based therapeutics have garnered considerable interest in the medical treatment of inflammation. Integrins mediate the fast recruitment of monocytes and neutrophils to the site of inflammation, but are also required for host defense, limiting their therapeutic use. Here, we report a novel monoclonal antibody, anti-M7, that specifically blocks the interaction of the integrin Mac-1 with its pro-inflammatory ligand CD40L, while not interfering with alternative ligands. Anti-M7 selectively reduces leukocyte recruitment in vitro and in vivo. In contrast, conventional anti-Mac-1 therapy is not specific and blocks a broad repertoire of integrin functionality, inhibits phagocytosis, promotes apoptosis, and fuels a cytokine storm in vivo. Whereas conventional anti-integrin therapy potentiates bacterial sepsis, bacteremia, and mortality, a ligand-specific intervention with anti-M7 is protective. These findings deepen our understanding of ligand-specific integrin functions and open a path for a new field of ligand-targeted anti-integrin therapy to prevent inflammatory conditions
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Kürschners Deutscher Gelehrten-Kalender 2003
First published in 1925, "Kurschners Deutscher Gelehrten-Kalender is the most eminent directory of German-speaking academics living today. Includes biographical and bibliographical information on approximately 71,800 academics.
Sociolinguistics / Soziolinguistik. Volume 2
Since the publication of the first edition of the handbook Sociolinguistics/Soziolinguistik , the then young discipline has changed and developed considerably. The field has left behind its status as an interdiscipline between sociology and linguistics and is now a worldwide established field. Sociolinguistics continues to contribute to solving practical problems in areas such as language planning and standardization, language policy, as well as in language didactics and speech therapy. Moreover, new topics and areas of application have arisen from the autonomy of the discipline - these have been systematically and extensively included in the second edition of the handbook. The new overall c...
The Lost Planets
A fascinating account of the pioneering astronomer who claimed (erroneously) to have discovered a planet outside the solar system. There are innumerable planets revolving around innumerable stars across our galaxy. Between 2009 and 2018, NASA's Kepler space telescope discovered thousands of them. But exoplanets—planets outside the solar system—appeared in science fiction before they appeared in telescopes. Astronomers in the early decades of the twentieth century spent entire careers searching for planets in other stellar systems. In The Lost Planets, John Wenz offers an account of the pioneering astronomer Peter van de Kamp, who was one of the first to claim discovery of exoplanets. Van...
