Thymic selection threshold defined by compartmentalization of Ras/MAPK signalling

A healthy individual can mount an immune response to exogenous pathogens while avoiding an autoimmune attack on normal tissues. The ability to distinguish between self and non-self is called 'immunological tolerance' and, for T lymphocytes, involves the generation of a diverse pool of functional T cells through positive selection and the removal of overtly self-reactive thymocytes by negative selection during T-cell ontogeny. To elucidate how thymocytes arrive at these cell fate decisions, here we have identified ligands that define an extremely narrow gap spanning the threshold that distinguishes positive from negative selection. We show that, at the selection threshold, a small increase in ligand affinity for the T-cell antigen receptor leads to a marked change in the activation and subcellular localization of Ras and mitogen-activated protein kinase (MAPK) signalling intermediates and the induction of negative selection. The ability to compartmentalize signalling molecules differentially in the cell endows the thymocyte with the ability to convert a small change in analogue input (affinity) into a digital output (positive versus negative selection) and provides the basis for establishing central tolerance.     

Species diversity enhances ecosystem functioning through interspecific facilitation.

Facilitation between species is thought to be a key mechanism by which biodiversity affects the rates of resource use that govern the efficiency and productivity of ecosystems; however, there is no direct empirical evidence to support this hypothesis. Here we show that increasing the species diversity of a functional group of aquatic organisms induces facilitative interactions, leading to non-additive changes in resource consumption. We increased the richness and evenness of suspension-feeding caddisfly larvae (Insecta, Trichoptera) in stream mesocosms and found that the increased topographical complexity of the benthic habitat alters patterns of near-bed flow such that the feeding success of individuals is enhanced. Species diversity reduces 'current shading' (that is, the deceleration of flow from upstream to downstream neighbours), allowing diverse assemblages to capture a greater fraction of suspended resources than is caught by any species monoculture. The fundamental nature of this form of hydrodynamic facilitation suggests that it is broadly applicable to freshwater and marine habitats; in addition, it has several analogues in terrestrial ecosystems where fluxes of energy and matter can be influenced by biophysical complexity. Thus, changes in species diversity may alter the probability of positive species interactions, resulting in disproportionately large changes in the functioning of ecosystems.     

A link between prompt optical and prompt gamma-ray emission in gamma-ray bursts

The prompt optical emission that arrives with the gamma-rays from a cosmic gamma-ray burst (GRB) is a signature of the engine powering the burst, the properties of the ultra-relativistic ejecta of the explosion, and the ejecta's interactions with the surroundings. Until now, only GRB 990123 had been detected at optical wavelengths during the burst phase. Its prompt optical emission was variable and uncorrelated with the prompt gamma-ray emission, suggesting that the optical emission was generated by a reverse shock arising from the ejecta's collision with surrounding material. Here we report prompt optical emission from GRB 041219a. It is variable and correlated with the prompt gamma-rays, indicating a common origin for the optical light and the gamma-rays. Within the context of the standard fireball model of GRBs, we attribute this new optical component to internal shocks driven into the burst ejecta by variations of the inner engine. The correlated optical emission is a direct probe of the jet isolated from the medium. The timing of the uncorrelated optical emission is strongly dependent on the nature of the medium.     

A giant gamma-ray flare from the magnetar SGR 1806-20

Two classes of rotating neutron stars-soft gamma-ray repeaters (SGRs) and anomalous X-ray pulsars-are magnetars, whose X-ray emission is powered by a very strong magnetic field (B approximately 10(15) G). SGRs occasionally become 'active', producing many short X-ray bursts. Extremely rarely, an SGR emits a giant flare with a total energy about a thousand times higher than in a typical burst. Here we report that SGR 1806-20 emitted a giant flare on 27 December 2004. The total (isotropic) flare energy is 2 x 10(46) erg, which is about a hundred times higher than the other two previously observed giant flares. The energy release probably occurred during a catastrophic reconfiguration of the neutron star's magnetic field. If the event had occurred at a larger distance, but within 40 megaparsecs, it would have resembled a short, hard gamma-ray burst, suggesting that flares from extragalactic SGRs may form a subclass of such bursts.     

Malaria risk: estimation of the malaria burden

Accurate estimates of the global burden of malaria are important for planning, monitoring and advocacy. Snow et al. attempt to address the shortcomings of previous estimates of the incidence of malaria caused by Plasmodium falciparum by combining current and historical data. However, we believe that the design of their model and its inputs have led to a significant overestimate of the malaria burden outside Africa--as in the example of the World Health Organization (WHO) western Pacific region (WPR), for which their model predicts 60 times the 2002 incidence reported by national malaria-control programmes.