Intestinal Epithelial Cell-Specific Deletion of PLD2 Alleviates DSS-Induced Colitis by Regulating Occludin

Ulcerative colitis is a multi-factorial disease involving a dysregulated immune response. Disruptions to the intestinal epithelial barrier and translocation of bacteria, resulting in inflammation, are common in colitis. The mechanisms underlying epithelial barrier dysfunction or regulation of tight junction proteins during disease progression of colitis have not been clearly elucidated. Increase in phospholipase D (PLD) activity is associated with disease severity in colitis animal models. However, the role of PLD2 in the maintenance of intestinal barrier integrity remains elusive. We have generated intestinal specific Pld2 knockout mice (Pld2 IEC-KO) to investigate the mechanism of intestinal epithelial PLD2 in colitis. We show that the knockout of Pld2 confers protection against dextran sodium sulphate (DSS)-induced colitis in mice. Treatment with DSS induced the expression of PLD2 and downregulated occludin in colon epithelial cells. PLD2 was shown to mediate phosphorylation of occludin and induce its proteasomal degradation in a c-Src kinase-dependent pathway. Additionally, we have shown that treatment with an inhibitor of PLD2 can rescue mice from DSS-induced colitis. To our knowledge, this is the first report showing that PLD2 is pivotal in the regulation of the integrity of epithelial tight junctions and occludin turn over, thereby implicating it in the pathogenesis of colitis

The argonaut shell: gas-mediated buoyancy control in a pelagic octopus

Argonauts (Cephalopoda: Argonautidae) are a group of rarely encountered open-ocean pelagic octopuses with benthic ancestry. Female argonauts inhabit a brittle ‘paper nautilus’ shell, the role of which has puzzled naturalists for millennia. The primary role attributed to the shell has been as a receptacle for egg deposition and brooding. Our observations of wild argonauts have revealed that the thin calcareous shell also functions as a hydrostatic structure, employed by the female argonaut to precisely control buoyancy at varying depths. Female argonauts use the shell to ‘gulp’ a measured volume of air at the sea surface, seal off the captured gas using flanged arms and forcefully dive to a depth where the compressed gas buoyancy counteracts body weight. This process allows the female argonaut to attain neutral buoyancy at depth and potentially adjust buoyancy to counter the increased (and significant) weight of eggs during reproductive periods. Evolution of this air-capture strategy enables this negatively buoyant octopus to survive free of the sea floor. This major shift in life mode from benthic to pelagic shows strong evolutionary parallels with the origins of all cephalopods, which attained gas-mediated buoyancy via the closed-chambered shells of the true nautiluses and their relatives