State and Perspectives of Submerged Sites in Japan

The Japanese people have long been interested in ancient relics found in the sea, lakes, and rivers. Documents from the eighteenth and nineteenth centuries recorded the discoveries of lithic tools from Lake Biwa and from the Seto Inland Sea (Ishihara, Considering Methods for the Protection of Archaeological Sites, pp. 5–6, 2000; Shiga Prefectural Association for Cultural Heritage, World of Underwater Archaeology at Lake Biwa, 13, 2010). Awareness of submerged prehistoric relics led to the discoveries of numerous important underwater sites. This, for example, includes the early discovery of a Paleolithic site in the bed of Lake Nojiri in Nagano Prefecture (Nakamura and Nojiri-ko Excavation Research Group, The Quaternary Research 28(4): pp. 257–268, 1989). A few submerged prehistoric sites, most of them dating to the Jomon Period (16,000–3,300 years ago), have been identified through rescue excavations. These sites, however, have not been studied within a thematic framework, particularly as submerged sites. The following illustrates the state of submerged prehistoric site research in Japan, beginning with a history of research on submerged sites. Following this is a brief overview of Japanese environmental history and use of marine resources, as well as a discussion of underwater site formation processes. Finally, the importance of submerged sites pertaining to Japanese archaeology is addressed

Lethal mutagenesis of hepatitis C virus induced by favipiravir

Lethal mutagenesis is an antiviral approach that consists in extinguishing a virus by an excess of mutations acquired during replication in the presence of a mutagen. Here we show that favipiravir (T-705) is a potent mutagenic agent for hepatitis C virus (HCV) during its replication in human hepatoma cells. T-705 leads to an excess of G!A and C!U transitions in the mutant spectrum of preextinction HCV populations. Infectivity decreased significantly in the presence of concentrations of T-705 which are 2- to 8-fold lower than its cytotoxic concentration 50 (CC50). Passaging the virus five times in the presence of 400 μM T-705 resulted in virus extinction. Since T-705 has undergone advanced clinical trials for approval for human use, the results open a new approach based on lethal mutagenesis to treat hepatitis C virus infections. If proven effective for HCV in vivo, this new anti-HCV agent may be useful in patient groups that fail current therapeutic regimens.BFU-2011-23604, SAF2014-52400-R, S2013/ABI-2906 (PLATESA from Comunidad de Madrid/FEDER) and Fundación R. Areces. The work in Barcelona was funded by Instituto de Salud Carlos III, grants PI13-00456 and PI15-00829, cofinanced by the European Regional Development Fund (ERDF).Peer Reviewe