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Pro-inflammatory cytokine production in response to the bacterial cell wall component lipopolysaccharide (LPS) or the gram-negative bacterial component endotoxin (lipid A) is inhibited by clotting Factor VII (FVII) and coagulation Factor X (FX). Here we show that these inhibitors act at the level of lipopolysaccharide receptor (LPSR) dimerization. The FVII and FX inhibitors prevented Nod1/2-mediated stimulation of a NF-κB-dependent reporter construct in cells, and they inhibited NF-κB activation by LPS. Moreover, the formation of LPSR/Nod1/2 complexes in cell lysates was prevented by FXa and FVIIa. FXa, like the FVIIa-FX complex, inhibited Nod1/2-dependent NF-κB activation and formation of LPSR/Nod1/2 complexes. Co-immunoprecipitation experiments also showed that clotting factors inhibited Nod1-induced LPSR/Nod1 interaction in vivo. These results demonstrate a role for FVII/FX-mediated inhibition of Nod1 signaling by preventing complex formation between Nod1 and LPSR.
United States Coast Guard Commissioner Robert Papp (Photo: Marine Safety/U.S. Coast Guard)
The Coast Guard Commissioner has announced that it will disband the marine safety component of the International Ice Patrol, an organization that tracks shipping activity in icebound Arctic waters, and shift the Coast Guard’s icebreaking mission to the U.S. Coast Guard Cutter Polar Star.
The current effort – which has been underway since 1989 – is the 11th iteration of the icebreaking operation, which began under the name Icebreaker Unit 75 and was tasked with patrolling the Arctic Ocean in search of vessels operating in “the ice-free waters between the north and the south coast of Greenland.”
The search and rescue element of the mission was relocated