In Vitro and In Vivo Antagonism of a G Protein-Coupled Receptor (S1P3) with a Novel Blocking Monoclonal Antibody

Background: S1P 3 is a lipid-activated G protein-couple receptor (GPCR) that has been implicated in the pathological processes of a number of diseases, including sepsis and cancer. Currently, there are no available high-affinity, subtypeselective drug compounds that can block activation of S1P3. We have developed a monoclonal antibody (7H9) that specifically recognizes S1P3 and acts as a functional antagonist. Methodology/Principal Findings: Specific binding of 7H9 was demonstrated by immunocytochemistry using cells that over-express individual members of the S1P receptor family. We show, in vitro, that 7H9 can inhibit the activation of S1P3mediated cellular processes, including arrestin translocation, receptor internalization, adenylate cyclase inhibiton, and calcium mobilization. We also demonstrate that 7H9 blocks activation of S1P3 in vivo, 1) by preventing lethality due to systemic inflammation, and 2) by altering the progression of breast tumor xenografts. Conclusions/Significance: We have developed the first-reported monoclonal antibody that selectively recognizes a lipidactivated GPCR and blocks functional activity. In addition to serving as a lead drug compound for the treatment of sepsi

A new genus and species of Apseudomorpha (Crustacea: Tanaidacea) from the Mar del Plata submarine Canyon, South West Atlantic, and replacement of the preoccupied name Hoplomachus Guţu 2002

A new apseudomorph tanaidacean, Deidamiapseudes poseidon n. gen., n. sp., is fully described and illustrated based on many specimens collected in the Mar del Plata Submarine Canyon, South West Atlantic, at 1144 m depth. The new genus Deidamiapseudes is closely related to the genus Hoplomachus Guţu, 2002, from which it can be distinguished by the lack of ommatidia, and by having antennule accessory flagellum of three articles, antenna with small scale, and pleopods with a few setae. In addition, Deidamiapseudes poseidon n. gen., n. sp. was found in deep-sea waters, whereas Hoplomachus is a shallow water genus. The uncertain family position of these two genera is discussed. The name Hoplomachus Guţu, 2002, preoccupied by Hoplomachus Fieber, 1858, is replaced with the name Hoplopolemius.Fil: Sganga, Daniela Eliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Biodiversidad y Biología Experimental y Aplicada. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biodiversidad y Biología Experimental y Aplicada; ArgentinaFil: Roccatagliata, Daniel Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Biodiversidad y Biología Experimental y Aplicada. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biodiversidad y Biología Experimental y Aplicada; Argentin