Structural mechanism of WASP activation by the enterohaemorrhagic E. coli effector EspF(U)

During infection, enterohaemorrhagic Escherichia coli (EHEC) takes over the actin cytoskeleton of eukaryotic cells by injecting the EspF(U) protein into the host cytoplasm. EspF(U) controls actin by activating members of the Wiskott-Aldrich syndrome protein (WASP) family. Here we show that EspF(U) binds to the autoinhibitory GTPase binding domain (GBD) in WASP proteins and displaces it from the activity-bearing VCA domain (for verprolin homology, central hydrophobic and acidic regions). This interaction potently activates WASP and neural (N)-WASP in vitro and induces localized actin assembly in cells. In the solution structure of the GBD-EspF(U) complex, EspF(U) forms an amphipathic helix that binds the GBD, mimicking interactions of the VCA domain in autoinhibited WASP. Thus, EspF(U) activates WASP by competing directly for the VCA binding site on the GBD. This mechanism is distinct from that used by the eukaryotic activators Cdc42 and SH2 domains, which globally destabilize the GBD fold to release the VCA. Such diversity of mechanism in WASP proteins is distinct from other multimodular systems, and may result from the intrinsically unstructured nature of the isolated GBD and VCA elements. The structural incompatibility of the GBD complexes with EspF(U) and Cdc42/SH2, plus high-affinity EspF(U) binding, enable EHEC to hijack the eukaryotic cytoskeletal machinery effectively.     

The diploid genome sequence of an Asian individual

Here we present the first diploid genome sequence of an Asian individual. The genome was sequenced to 36-fold average coverage using massively parallel sequencing technology. We aligned the short reads onto the NCBI human reference genome to 99.97% coverage, and guided by the reference genome, we used uniquely mapped reads to assemble a high-quality consensus sequence for 92% of the Asian individual's genome. We identified approximately 3 million single-nucleotide polymorphisms (SNPs) inside this region, of which 13.6% were not in the dbSNP database. Genotyping analysis showed that SNP identification had high accuracy and consistency, indicating the high sequence quality of this assembly. We also carried out heterozygote phasing and haplotype prediction against HapMap CHB and JPT haplotypes (Chinese and Japanese, respectively), sequence comparison with the two available individual genomes (J. D. Watson and J. C. Venter), and structural variation identification. These variations were considered for their potential biological impact. Our sequence data and analyses demonstrate the potential usefulness of next-generation sequencing technologies for personal genomics.     

Cool heliosheath plasma and deceleration of the upstream solar wind at the termination shock

The solar wind blows outward from the Sun and forms a bubble of solar material in the interstellar medium. The termination shock occurs where the solar wind changes from being supersonic (with respect to the surrounding interstellar medium) to being subsonic. The shock was crossed by Voyager 1 at a heliocentric radius of 94 au (1 au is the Earth-Sun distance) in December 2004 (refs 1-3). The Voyager 2 plasma experiment observed a decrease in solar wind speed commencing on about 9 June 2007, which culminated in several crossings of the termination shock between 30 August and 1 September 2007 (refs 4-7). Since then, Voyager 2 has remained in the heliosheath, the region of shocked solar wind. Here we report observations of plasma at and near the termination shock and in the heliosheath. The heliosphere is asymmetric, pushed inward in the Voyager 2 direction relative to the Voyager 1 direction. The termination shock is a weak, quasi-perpendicular shock that heats the thermal plasma very little. An unexpected finding is that the flow is still supersonic with respect to the thermal ions downstream of the termination shock. Most of the solar wind energy is transferred to the pickup ions or other energetic particles both upstream of and at the termination shock.     

Non-random segregation of sister chromosomes in Escherichia coli

It has long been known that the 5' to 3' polarity of DNA synthesis results in both a leading and lagging strand at all replication forks. Until now, however, there has been no evidence that leading or lagging strands are spatially organized in any way within a cell. Here we show that chromosome segregation in Escherichia coli is not random but is driven in a manner that results in the leading and lagging strands being addressed to particular cellular destinations. These destinations are consistent with the known patterns of chromosome segregation. Our work demonstrates a new level of organization relating to the replication and segregation of the E. coli chromosome.     

Extensive halogen-mediated ozone destruction over the tropical Atlantic Ocean

Increasing tropospheric ozone levels over the past 150 years have led to a significant climate perturbation; the prediction of future trends in tropospheric ozone will require a full understanding of both its precursor emissions and its destruction processes. A large proportion of tropospheric ozone loss occurs in the tropical marine boundary layer and is thought to be driven primarily by high ozone photolysis rates in the presence of high concentrations of water vapour. A further reduction in the tropospheric ozone burden through bromine and iodine emitted from open-ocean marine sources has been postulated by numerical models, but thus far has not been verified by observations. Here we report eight months of spectroscopic measurements at the Cape Verde Observatory indicative of the ubiquitous daytime presence of bromine monoxide and iodine monoxide in the tropical marine boundary layer. A year-round data set of co-located in situ surface trace gas measurements made in conjunction with low-level aircraft observations shows that the mean daily observed ozone loss is approximately 50 per cent greater than that simulated by a global chemistry model using a classical photochemistry scheme that excludes halogen chemistry. We perform box model calculations that indicate that the observed halogen concentrations induce the extra ozone loss required for the models to match observations. Our results show that halogen chemistry has a significant and extensive influence on photochemical ozone loss in the tropical Atlantic Ocean boundary layer. The omission of halogen sources and their chemistry in atmospheric models may lead to significant errors in calculations of global ozone budgets, tropospheric oxidizing capacity and methane oxidation rates, both historically and in the future.     

The coevolution of choosiness and cooperation

Explaining the rise and maintenance of cooperation is central to our understanding of biological systems and human societies. When an individual's cooperativeness is used by other individuals as a choice criterion, there can be competition to be more generous than others, a situation called competitive altruism. The evolution of cooperation between non-relatives can then be driven by a positive feedback between increasing levels of cooperativeness and choosiness. Here we use evolutionary simulations to show that, in a situation where individuals have the opportunity to engage in repeated pairwise interactions, the equilibrium degree of cooperativeness depends critically on the amount of behavioural variation that is being maintained in the population by processes such as mutation. Because our model does not invoke complex mechanisms such as negotiation behaviour, it can be applied to a wide range of species. The results suggest an important role of lifespan in the evolution of cooperation.     

Calendars with Olympiad display and eclipse prediction on the Antikythera Mechanism

Previous research on the Antikythera Mechanism established a highly complex ancient Greek geared mechanism with front and back output dials. The upper back dial is a 19-year calendar, based on the Metonic cycle, arranged as a five-turn spiral. The lower back dial is a Saros eclipse-prediction dial, arranged as a four-turn spiral of 223 lunar months, with glyphs indicating eclipse predictions. Here we add surprising findings concerning these back dials. Though no month names on the Metonic calendar were previously known, we have now identified all 12 months, which are unexpectedly of Corinthian origin. The Corinthian colonies of northwestern Greece or Syracuse in Sicily are leading contenders-the latter suggesting a heritage going back to Archimedes. Calendars with excluded days to regulate month lengths, described in a first century bc source, have hitherto been dismissed as implausible. We demonstrate their existence in the Antikythera calendar, and in the process establish why the Metonic dial has five turns. The upper subsidiary dial is not a 76-year Callippic dial as previously thought, but follows the four-year cycle of the Olympiad and its associated Panhellenic Games. Newly identified index letters in each glyph on the Saros dial show that a previous reconstruction needs modification. We explore models for generating the unusual glyph distribution, and show how the eclipse times appear to be contradictory. We explain the four turns of the Saros dial in terms of the full moon cycle and the Exeligmos dial as indicating a necessary correction to the predicted eclipse times. The new results on the Metonic calendar, Olympiad dial and eclipse prediction link the cycles of human institutions with the celestial cycles embedded in the Mechanism's gearwork.     

Lethargus is a Caenorhabditis elegans sleep-like state

There are fundamental similarities between sleep in mammals and quiescence in the arthropod Drosophila melanogaster, suggesting that sleep-like states are evolutionarily ancient. The nematode Caenorhabditis elegans also has a quiescent behavioural state during a period called lethargus, which occurs before each of the four moults. Like sleep, lethargus maintains a constant temporal relationship with the expression of the C. elegans Period homologue LIN-42 (ref. 5). Here we show that quiescence associated with lethargus has the additional sleep-like properties of reversibility, reduced responsiveness and homeostasis. We identify the cGMP-dependent protein kinase (PKG) gene egl-4 as a regulator of sleep-like behaviour, and show that egl-4 functions in sensory neurons to promote the C. elegans sleep-like state. Conserved effects on sleep-like behaviour of homologous genes in C. elegans and Drosophila suggest a common genetic regulation of sleep-like states in arthropods and nematodes. Our results indicate that C. elegans is a suitable model system for the study of sleep regulation. The association of this C. elegans sleep-like state with developmental changes that occur with larval moults suggests that sleep may have evolved to allow for developmental changes.