Biologically inspired oxidation catalysis

The development of processes for selective hydrocarbon oxidation is a goal that has long been pursued. An additional challenge is to make such processes environmentally friendly, for example by using non-toxic reagents and energy-efficient catalytic methods. Excellent examples are naturally occurring iron- or copper-containing metalloenzymes, and extensive studies have revealed the key chemical principles that underlie their efficacy as catalysts for aerobic oxidations. Important inroads have been made in applying this knowledge to the development of synthetic catalysts that model enzyme function. Such biologically inspired hydrocarbon oxidation catalysts hold great promise for wide-ranging synthetic applications.     

Sleep in Drosophila is regulated by adult mushroom bodies

Sleep is one of the few major whole-organ phenomena for which no function and no underlying mechanism have been conclusively demonstrated. Sleep could result from global changes in the brain during wakefulness or it could be regulated by specific loci that recruit the rest of the brain into the electrical and metabolic states characteristic of sleep. Here we address this issue by exploiting the genetic tractability of the fruitfly, Drosophila melanogaster, which exhibits the hallmarks of vertebrate sleep. We show that large changes in sleep are achieved by spatial and temporal enhancement of cyclic-AMP-dependent protein kinase (PKA) activity specifically in the adult mushroom bodies of Drosophila. Other manipulations of the mushroom bodies, such as electrical silencing, increasing excitation or ablation, also alter sleep. These results link sleep regulation to an anatomical locus known to be involved in learning and memory.     

BRAF mutation predicts sensitivity to MEK inhibition

The kinase pathway comprising RAS, RAF, mitogen-activated protein kinase kinase (MEK) and extracellular signal regulated kinase (ERK) is activated in most human tumours, often through gain-of-function mutations of RAS and RAF family members. Using small-molecule inhibitors of MEK and an integrated genetic and pharmacologic analysis, we find that mutation of BRAF is associated with enhanced and selective sensitivity to MEK inhibition when compared to either 'wild-type' cells or cells harbouring a RAS mutation. This MEK dependency was observed in BRAF mutant cells regardless of tissue lineage, and correlated with both downregulation of cyclin D1 protein expression and the induction of G1 arrest. Pharmacological MEK inhibition completely abrogated tumour growth in BRAF mutant xenografts, whereas RAS mutant tumours were only partially inhibited. These data suggest an exquisite dependency on MEK activity in BRAF mutant tumours, and offer a rational therapeutic strategy for this genetically defined tumour subtype.     

A late Miocene dust shower from the break-up of an asteroid in the main belt

Throughout the history of the Solar System, Earth has been bombarded by interplanetary dust particles (IDPs), which are asteroid and comet fragments of diameter approximately 1-1,000 microm. The IDP flux is believed to be in quasi-steady state: particles created by episodic main belt collisions or cometary fragmentation replace those removed by comminution, dynamical ejection, and planetary or solar impact. Because IDPs are rich in 3He, seafloor sediment 3He concentrations provide a unique means of probing the major events that have affected the IDP flux and its source bodies over geological timescales. Here we report that collisional disruption of the >150-km-diameter asteroid that created the Veritas family 8.3 +/- 0.5 Myr ago also produced a transient increase in the flux of interplanetary dust-derived 3He. The increase began at 8.2 +/- 0.1 Myr ago, reached a maximum of approximately 4 times pre-event levels, and dissipated over approximately 1.5 Myr. The terrestrial IDP accretion rate was overwhelmingly dominated by Veritas family fragments during the late Miocene. No other event of this magnitude over the past approximately 10(8) yr has been deduced from main belt asteroid orbits. One remarkably similar event is present in the 3He record 35 Myr ago, but its origin by comet shower or asteroid collision remains uncertain.     

MARSIS radar sounder evidence of buried basins in the northern lowlands of Mars

A hemispheric dichotomy on Mars is marked by the sharp contrast between the sparsely cratered northern lowland plains and the heavily cratered southern highlands. Mechanisms proposed to remove ancient crust or form younger lowland crust include one or more giant impacts, subcrustal transport by mantle convection, the generation of thinner crust by plate tectonics, and mantle overturn following solidification of an early magma ocean. The age of the northern lowland crust is a significant constraint on these models. The Mars Advanced Radar for Subsurface and Ionospheric Sounding (MARSIS) instrument on the European Space Agency's Mars Express spacecraft is providing new constraints on the martian subsurface. Here we show evidence of buried impact basins ranging in diameter from about 130 km to 470 km found over approximately 14 per cent of the northern lowlands. The number of detected buried basins >200 km in diameter indicates that the lowland crust is ancient, dating back to the Early Noachian epoch. This crater density is a lower limit because of the likelihood that not all buried basins in the area surveyed by MARSIS have been detected. An Early Noachian age for the lowland crust has been previously suggested on the basis of a large number of quasi-circular topographic depressions interpreted to be evidence of buried basins. Only a few of these depressions in the area surveyed by MARSIS, however, correlate with the detected subsurface echoes. On the basis of the MARSIS data, we conclude that the northern lowland crust is at least as old as the oldest exposed highland crust. This suggests that the crustal dichotomy formed early in the geologic evolution of Mars.     

Links between annual, Milankovitch and continuum temperature variability

Climate variability exists at all timescales-and climatic processes are intimately coupled, so that understanding variability at any one timescale requires some understanding of the whole. Records of the Earth's surface temperature illustrate this interdependence, having a continuum of variability following a power-law scaling. But although specific modes of interannual variability are relatively well understood, the general controls on continuum variability are uncertain and usually described as purely stochastic processes. Here we show that power-law relationships of surface temperature variability scale with annual and Milankovitch-period (23,000- and 41,000-year) cycles. The annual cycle corresponds to scaling at monthly to decadal periods, while millennial and longer periods are tied to the Milankovitch cycles. Thus the annual, Milankovitch and continuum temperature variability together represent the response to deterministic insolation forcing. The identification of a deterministic control on the continuum provides insight into the mechanisms governing interannual and longer-period climate variability.     

Navigation: bat orientation using Earth's magnetic field

Bats famously orientate at night by echolocation, but this works over only a short range, and little is known about how they navigate over longer distances. Here we show that the homing behaviour of Eptesicus fuscus, known as the big brown bat, can be altered by artificially shifting the Earth's magnetic field, indicating that these bats rely on a magnetic compass to return to their home roost. This finding adds to the impressive array of sensory abilities possessed by this animal for navigation in the dark.     

Introns and the origin of nucleus-cytosol compartmentalization

The origin of the eukaryotic nucleus marked a seminal evolutionary transition. We propose that the nuclear envelope's incipient function was to allow mRNA splicing, which is slow, to go to completion so that translation, which is fast, would occur only on mRNA with intact reading frames. The rapid, fortuitous spread of introns following the origin of mitochondria is adduced as the selective pressure that forged nucleus-cytosol compartmentalization.     

Mapping and sequencing of structural variation from eight human genomes

Genetic variation among individual humans occurs on many different scales, ranging from gross alterations in the human karyotype to single nucleotide changes. Here we explore variation on an intermediate scale--particularly insertions, deletions and inversions affecting from a few thousand to a few million base pairs. We employed a clone-based method to interrogate this intermediate structural variation in eight individuals of diverse geographic ancestry. Our analysis provides a comprehensive overview of the normal pattern of structural variation present in these genomes, refining the location of 1,695 structural variants. We find that 50% were seen in more than one individual and that nearly half lay outside regions of the genome previously described as structurally variant. We discover 525 new insertion sequences that are not present in the human reference genome and show that many of these are variable in copy number between individuals. Complete sequencing of 261 structural variants reveals considerable locus complexity and provides insights into the different mutational processes that have shaped the human genome. These data provide the first high-resolution sequence map of human structural variation--a standard for genotyping platforms and a prelude to future individual genome sequencing projects.