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.     

林木生物质热裂解液化制备胶黏剂技术经济分析

 将热裂解液化得到的生物油作为清洁化工原料用于制备酚醛树脂胶黏剂是林木生物质高效利用的重要方式。本文介绍了林木生物质热裂解液化制取生物油及生物油制备胶黏剂的技术概况,对比分析了生物油的利用方式,以河北地区年4000t处理量规模为例,对林木生物质热裂解液化生产线设备组成及投资规模、生物油生产成本和生物油替代苯酚制备酚醛树脂胶黏剂的经济效益等进行了探讨。分析表明,河北地区年4000t处理量的林木生物质热裂解液化项目投资约为250万元,生物油的实际生产成本约为1200元/t,将生物油全部用于制备酚醛树脂胶黏剂的直接经济效益至少可达330万元/a。林木生物质热裂解液化制备胶黏剂项目技术经济效益显著,具有良好的发展和应用前景。     

Expression of active human factor VIII from recombinant DNA clones

DNA clones encoding the complete 2,351 amino acid sequence for human factor VIII have been isolated and used to produce biologically active factor VIII in cultured mammalian cells. The recombinant protein corrects the clotting time of plasma from haemophiliacs and has many of the biochemical and immunological characteristics of serum-derived factor VIII.