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It's the gap between aligning a peptide protocol with the biology it was designed to exploit versus forcing it to work against circadian receptor rhythms that have been conserved across 200 million years of mammalian evolution

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Mol Microbiol 105:413425 Schnupf P, Hofmann J, Norseen J, Glomski IJ, Schwartzstein H, Decatur AL (2006) Regulated translation of Listeriolysin O controls virulence of Listeria monocytogenes

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