An NS3 protease inhibitor with antiviral effects in humans infected with hepatitis C virus

Hepatitis C virus (HCV) infection is a serious cause of chronic liver disease worldwide with more than 170 million infected individuals at risk of developing significant morbidity and mortality. Current interferon-based therapies are suboptimal especially in patients infected with HCV genotype 1, and they are poorly tolerated, highlighting the unmet medical need for new therapeutics. The HCV-encoded NS3 protease is essential for viral replication and has long been considered an attractive target for therapeutic intervention in HCV-infected patients. Here we identify a class of specific and potent NS3 protease inhibitors and report the evaluation of BILN 2061, a small molecule inhibitor biologically available through oral ingestion and the first of its class in human trials. Administration of BILN 2061 to patients infected with HCV genotype 1 for 2 days resulted in an impressive reduction of HCV RNA plasma levels, and established proof-of-concept in humans for an HCV NS3 protease inhibitor. Our results further illustrate the potential of the viral-enzyme-targeted drug discovery approach for the development of new HCV therapeutics.     

The evolutionary inheritance of elemental stoichiometry in marine phytoplankton

Phytoplankton is a nineteenth century ecological construct for a biologically diverse group of pelagic photoautotrophs that share common metabolic functions but not evolutionary histories. In contrast to terrestrial plants, a major schism occurred in the evolution of the eukaryotic phytoplankton that gave rise to two major plastid superfamilies. The green superfamily appropriated chlorophyll b, whereas the red superfamily uses chlorophyll c as an accessory photosynthetic pigment. Fossil evidence suggests that the green superfamily dominated Palaeozoic oceans. However, after the end-Permian extinction, members of the red superfamily rose to ecological prominence. The processes responsible for this shift are obscure. Here we present an analysis of major nutrients and trace elements in 15 species of marine phytoplankton from the two superfamilies. Our results indicate that there are systematic phylogenetic differences in the two plastid types where macronutrient (carbon:nitrogen:phosphorus) stoichiometries primarily reflect ancestral pre-symbiotic host cell phenotypes, but trace element composition reflects differences in the acquired plastids. The compositional differences between the two plastid superfamilies suggest that changes in ocean redox state strongly influenced the evolution and selection of eukaryotic phytoplankton since the Proterozoic era.     

Environmentally mediated synergy between perception and behaviour in mobile robots

The notion that behaviour influences perception seems self-evident, but the mechanism of their interaction is not known. Perception and behaviour are usually considered to be separate processes. In this view, perceptual learning constructs compact representations of sensory events, reflecting their statistical properties, independently of behavioural relevance. Behavioural learning, however, forms associations between perception and action, organized by reinforcement, without regard for the construction of perception. It is generally assumed that the interaction between these two processes is internal to the agent, and can be explained solely in terms of the neuronal substrate. Here we show, instead, that perception and behaviour can interact synergistically via the environment. Using simulated and real mobile robots, we demonstrate that perceptual learning directly supports behavioural learning and so promotes a progressive structuring of behaviour. This structuring leads to a systematic bias in input sampling, which directly affects the organization of the perceptual system. This external, environmentally mediated feedback matches the perceptual system to the emerging behavioural structure, so that the behaviour is stabilized.