Modelling how ribavirin improves interferon response rates in hepatitis C virus infection

Nearly 200 million individuals worldwide are currently infected with hepatitis C virus (HCV). Combination therapy with pegylated interferon and ribavirin, the latest treatment for HCV infection, elicits long-term responses in only about 50% of patients treated. No effective alternative treatments exist for non-responders. Consequently, significant efforts are continuing to maximize response to combination therapy. However, rational therapy optimization is precluded by the poor understanding of the mechanism(s) of ribavirin action against HCV. Ribavirin alone induces either a transient early decline or no decrease in HCV viral load, but in combination with interferon it significantly improves long-term response rates. Here we present a model of HCV dynamics in which, on the basis of growing evidence, we assume that ribavirin decreases HCV infectivity in an infected individual in a dose-dependent manner. The model quantitatively predicts long-term response rates to interferon monotherapy and combination therapy, fits observed patterns of HCV RNA decline in patients undergoing therapy, reconciles conflicting observations of the influence of ribavirin on HCV RNA decline, provides key insights into the mechanism of ribavirin action against HCV, and establishes a framework for rational therapy optimization.     

The genome of Cryptosporidium hominis

Cryptosporidium species cause acute gastroenteritis and diarrhoea worldwide. They are members of the Apicomplexa--protozoan pathogens that invade host cells by using a specialized apical complex and are usually transmitted by an invertebrate vector or intermediate host. In contrast to other Apicomplexans, Cryptosporidium is transmitted by ingestion of oocysts and completes its life cycle in a single host. No therapy is available, and control focuses on eliminating oocysts in water supplies. Two species, C. hominis and C. parvum, which differ in host range, genotype and pathogenicity, are most relevant to humans. C. hominis is restricted to humans, whereas C. parvum also infects other mammals. Here we describe the eight-chromosome approximately 9.2-million-base genome of C. hominis. The complement of C. hominis protein-coding genes shows a striking concordance with the requirements imposed by the environmental niches the parasite inhabits. Energy metabolism is largely from glycolysis. Both aerobic and anaerobic metabolisms are available, the former requiring an alternative electron transport system in a simplified mitochondrion. Biosynthesis capabilities are limited, explaining an extensive array of transporters. Evidence of an apicoplast is absent, but genes associated with apical complex organelles are present. C. hominis and C. parvum exhibit very similar gene complements, and phenotypic differences between these parasites must be due to subtle sequence divergence.     

Convergence across biomes to a common rain-use efficiency

Water availability limits plant growth and production in almost all terrestrial ecosystems. However, biomes differ substantially in sensitivity of aboveground net primary production (ANPP) to between-year variation in precipitation. Average rain-use efficiency (RUE; ANPP/precipitation) also varies between biomes, supposedly because of differences in vegetation structure and/or biogeochemical constraints. Here we show that RUE decreases across biomes as mean annual precipitation increases. However, during the driest years at each site, there is convergence to a common maximum RUE (RUE(max)) that is typical of arid ecosystems. RUE(max) was also identified by experimentally altering the degree of limitation by water and other resources. Thus, in years when water is most limiting, deserts, grasslands and forests all exhibit the same rate of biomass production per unit rainfall, despite differences in physiognomy and site-level RUE. Global climate models predict increased between-year variability in precipitation, more frequent extreme drought events, and changes in temperature. Forecasts of future ecosystem behaviour should take into account this convergent feature of terrestrial biomes.     

Chaos-based communications at high bit rates using commercial fibre-optic links

Chaotic signals have been proposed as broadband information carriers with the potential of providing a high level of robustness and privacy in data transmission. Laboratory demonstrations of chaos-based optical communications have already shown the potential of this technology, but a field experiment using commercial optical networks has not been undertaken so far. Here we demonstrate high-speed long-distance communication based on chaos synchronization over a commercial fibre-optic channel. An optical carrier wave generated by a chaotic laser is used to encode a message for transmission over 120 km of optical fibre in the metropolitan area network of Athens, Greece. The message is decoded using an appropriate second laser which, by synchronizing with the chaotic carrier, allows for the separation of the carrier and the message. Transmission rates in the gigabit per second range are achieved, with corresponding bit-error rates below 10(-7). The system uses matched pairs of semiconductor lasers as chaotic emitters and receivers, and off-the-shelf fibre-optic telecommunication components. Our results show that information can be transmitted at high bit rates using deterministic chaos in a manner that is robust to perturbations and channel disturbances unavoidable under real-world conditions.     

Planetary science: are there active glaciers on Mars?

Head et al. interpret spectacular images from the Mars Express high-resolution stereo camera as evidence of geologically recent rock glaciers in Tharsis and of a piedmont ('hourglass') glacier at the base of a 3-km-high massif east of Hellas. They attribute growth of the low-latitude glaciers to snowfall during periods of increased spin-axis obliquity. The age of the hourglass glacier, considered to be inactive and slowly shrinking beneath a debris cover in the absence of modern snowfall, is estimated to be more than 40 Myr. Although we agree that the maximum glacier extent was climatically controlled, we find evidence in the images to support local augmentation of accumulation from snowfall through a mechanism that does not require climate change on Mars.     

Photoperiodic induction of synchronous flowering near the Equator

In tropical rainforests, 30-65% of tree species grow at densities of less than one individual per hectare. At these low population densities, successful cross-pollination relies on synchronous flowering. In rainforests with low climatic seasonality, photoperiodic control is the only reliable mechanism for inducing synchronous flowering. This poses a problem because there is no variation in day length at the Equator. Here we propose a new mechanism of photoperiodic timekeeping based on the perception of variation in sunrise or sunset time, which explains and predicts the annually repeated, staggered, synchronous and bimodal flowering of many tree species in Amazonian rainforests near the Equator.     

Geophysical evidence from the MELT area for compositional controls on oceanic plates

Magnetotelluric and seismic data, collected during the MELT experiment at the southern East Pacific Rise, constrain the distribution of melt beneath this mid-ocean-ridge spreading centre and also the evolution of the oceanic lithosphere during its early cooling history. Here we focus on structures imaged at distances approximately 100 to 350 km east of the ridge crest, corresponding to seafloor ages of approximately 1.3 to 4.5 million years (Myr), where the seismic and electrical conductivity structure is nearly constant and independent of age. Beginning at a depth of about 60 km, we image a large increase in electrical conductivity and a change from isotropic to transversely anisotropic electrical structure, with higher conductivity in the direction of fast propagation for seismic waves. Conductive cooling models predict structure that increases in depth with age, extending to about 30 km at 4.5 Myr ago. We infer, however, that the structure of young oceanic plates is instead controlled by a decrease in water content above a depth of 60 km induced by the melting process beneath the spreading centre.