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This left the question of whether the substrate for conversion to PrP Sc is is newly synthesized PrP just headed out to the plasma membrane for its first time ever (and getting intercepted by PrP Sc in the Golgi, perhaps), or PrP C that has already reached the cell surface and then been re-internalized

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The reasons are far-reaching and include stress, physical issues, anxiety, and even too much coffee - sometimes, there is no simple explanation