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Li SQ, Han C, Liu, et al

In any case, the structure of the Co II -bound NiCo riboswitch reveals four Co II binding sites that likely nucleate formation of a four-way junction stabilized by a network of contacts that may explain how cooperative binding of Co II ions to adjacent sites might be achieved (Figure 22D)

Additionally, oxidative stress significantly impairs RFC function: Low glutathione: Reduces RFC function ~20-40% High nitric oxide: Reduces RFC function ~35% Hyperglycemia: Reduces RFC function ~20-35% Even if you're taking Leucovorin, oxidative stress can prevent it from reaching your brain

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