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There can be a second shell and a third, which form because of the preferential orientation of the waters of the previous shell, though the effect wears off after a few shells

Mellen, H

Clin Exp Immunol 134:127137 Michielan A, DInc R (2015) Intestinal Permeability in Inflammatory Bowel Disease: Pathogenesis, Clinical Evaluation, and Therapy of Leaky Gut

However, prolonged activation of UPR leads to activation of JNK, glycogen synthase kinase 3 (GSK3), and transcription factor CCAAT/enhancer-binding homologous protein (CHOP), all of which upregulate pro-death proteins such as p53 up-regulation of apoptosis regulators (PUMA) and extrinsic pathways including tumor necrosis factor (TNF)-associated apoptosis-inducing ligands (TRAIL) to induce cell death through transcriptional upregulation of TRAIL receptor 2 (TRAIL-R2) expression