Left-right asymmetric expression of dpp in the mantle of gastropods correlates with asymmetric shell coiling

This is the final version of the article. Available from BMC via the DOI in this record.BACKGROUND: Various shapes of gastropod shells have evolved ever since the Cambrian. Although theoretical analyses of morphogenesis exist, the molecular basis of shell development remains unclear. We compared expression patterns of the decapentaplegic (dpp) gene in the shell gland and mantle tissues at various developmental stages between coiled-shell and non-coiled-shell gastropods. RESULTS: We analyzed the expression patterns of dpp for the two limpets Patella vulgata and Nipponacmea fuscoviridis, and for the dextral wild-type and sinistral mutant lineage of the pond snail Lymnaea stagnalis. The limpets had symmetric expression patterns of dpp throughout ontogeny, whereas in the pond snail, the results indicated asymmetric and mirror image patterns between the dextral and sinistral lineages. CONCLUSION: We hypothesize that Dpp induces mantle expansion, and the presence of a left/right asymmetric gradient of the Dpp protein causes the formation of a coiled shell. Our results provide a molecular explanation for shell, coiling including new insights into expression patterns in post-embryonic development, which should aid in understanding how various shell shapes are formed and have evolved in the gastropods.This study was supported by the JSPS Grants-in-Aid for Scientific Research 15104009

Epoprostenol sodium for treatment of pulmonary arterial hypertension

Yukihiro Saito,1 Kazufumi Nakamura,1 Satoshi Akagi,1 Toshihiro Sarashina,1 Kentaro Ejiri,1 Aya Miura,1 Aiko Ogawa,2 Hiromi Matsubara,2 Hiroshi Ito1 1Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; 2Division of Cardiology, National Hospital Organization Okayama Medical Center, Okayama, Japan Abstract: The release of endogenous prostacyclin (PGI2) is depressed in patients with pulmonary arterial hypertension (PAH). PGI2 replacement therapy by epoprostenol infusion is one of the best treatments available for PAH. Here, we provide an overview of the current clinical data for epoprostenol. Epoprostenol treatment improves symptoms, exercise capacity, and hemodynamics, and is the only treatment that has been shown to reduce mortality in patients with idiopathic PAH (IPAH) in randomized clinical trials. We have reported that high-dose epoprostenol therapy (>40 ng/kg/min) also results in marked hemodynamic improvement in some patients with IPAH. High-dose epoprostenol has a pro-apoptotic effect on PAH-PASMCs via the IP receptor and upregulation of Fas ligand (FasL) in vitro. However, long-term intravenous administration of epoprostenol is sometimes associated with catheter-related infections and leads to considerable inconvenience for the patient. In the future, the development of new routes of administration or the development of powerful PGI2 analogs, IP-receptor agonists, and gene and cell-based therapy enhancing PGI2 production with new routes of administration is required. Keywords: pulmonary arterial hypertension, prostacyclin, apoptosi