A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis

The incidence of tuberculosis has been increasing substantially on a worldwide basis over the past decade, but no tuberculosis-specific drugs have been discovered in 40 years. We identified a diarylquinoline, R207910, that potently inhibits both drug-sensitive and drug-resistant Mycobacterium tuberculosis in vitro (minimum inhibitory concentration 0.06 mug/ml). In mice, R207910 exceeded the bactericidal activities of isoniazid and rifampin by at least 1 log unit. Substitution of drugs included in the World Health Organization's first-line tuberculosis treatment regimen (rifampin, isoniazid, and pyrazinamide) with R207910 accelerated bactericidal activity, leading to complete culture conversion after 2 months of treatment in some combinations. A single dose of R207910 inhibited mycobacterial growth for 1 week. Plasma levels associated with efficacy in mice were well tolerated in healthy human volunteers. Mutants selected in vitro suggest that the drug targets the proton pump of adenosine triphosphate (ATP) synthase.     

Fluctuations of landings and environmental conditions in the north-western Mediterranean Sea

Most of the monthly catches and CPUE of 13 studied commercial species in the coastal waters of the north-western Mediterranean were significantly positively correlated with run-off of local rivers (Rhône and Muga) and the wind mixing index during the spawning season, with time lags of less than a year (transfer function analyses). Rhône and Ebre interannual fluctuations in run-off were synchronous and were related to the North Atlantic Oscillation (NAO), river run-offs being negatively correlated to high NAO episodes. The fluctuations of river discharges and the wind mixing index were cyclic but not related. The results showed that enhanced hydroclimatic conditions in the NW Mediterranean were favourable for the productivity of the fish and invertebrate stocks, and suggest the presence of linkage between recruitment of Mediterranean species and local (river discharges, wind conditions) and global (NAO) environmental conditions.