Hsp90 stress potentiates rapid cellular adaptation through induction of aneuploidy

Aneuploidy--the state of having uneven numbers of chromosomes--is a hallmark of cancer and a feature identified in yeast from diverse habitats. Recent studies have shown that aneuploidy is a form of large-effect mutation that is able to confer adaptive phenotypes under diverse stress conditions. Here we investigate whether pleiotropic stress could induce aneuploidy in budding yeast (Saccharomyces cerevisae). We show that whereas diverse stress conditions can induce an increase in chromosome instability, proteotoxic stress, caused by transient Hsp90 (also known as Hsp82 or Hsc82) inhibition or heat shock, markedly increased chromosome instability to produce a cell population with high karyotype diversity. The induced chromosome instability is linked to an evolutionarily conserved role for the Hsp90 chaperone complex in kinetochore assembly. Continued growth in the presence of an Hsp90 inhibitor resulted in the emergence of drug-resistant colonies with chromosome XV gain. This drug-resistance phenotype is a quantitative trait involving copy number increases of at least two genes located on chromosome XV. Short-term exposure to Hsp90 stress potentiated fast adaptation to unrelated cytotoxic compounds by means of different aneuploid chromosome stoichiometries. These findings demonstrate that aneuploidy is a form of stress-inducible mutation in eukaryotes, capable of fuelling rapid phenotypic evolution and drug resistance, and reveal a new role for Hsp90 in regulating the emergence of adaptive traits under stress.     

An abundance of small exoplanets around stars with a wide range of metallicities

The abundance of heavy elements (metallicity) in the photospheres of stars similar to the Sun provides a 'fossil' record of the chemical composition of the initial protoplanetary disk. Metal-rich stars are much more likely to harbour gas giant planets, supporting the model that planets form by accumulation of dust and ice particles. Recent ground-based surveys suggest that this correlation is weakened for Neptunian-sized planets. However, how the relationship between size and metallicity extends into the regime of terrestrial-sized exoplanets is unknown. Here we report spectroscopic metallicities of the host stars of 226 small exoplanet candidates discovered by NASA's Kepler mission, including objects that are comparable in size to the terrestrial planets in the Solar System. We find that planets with radii less than four Earth radii form around host stars with a wide range of metallicities (but on average a metallicity close to that of the Sun), whereas large planets preferentially form around stars with higher metallicities. This observation suggests that terrestrial planets may be widespread in the disk of the Galaxy, with no special requirement of enhanced metallicity for their formation.     

A Cenozoic record of the equatorial Pacific carbonate compensation depth

Atmospheric carbon dioxide concentrations and climate are regulated on geological timescales by the balance between carbon input from volcanic and metamorphic outgassing and its removal by weathering feedbacks; these feedbacks involve the erosion of silicate rocks and organic-carbon-bearing rocks. The integrated effect of these processes is reflected in the calcium carbonate compensation depth, which is the oceanic depth at which calcium carbonate is dissolved. Here we present a carbonate accumulation record that covers the past 53 million years from a depth transect in the equatorial Pacific Ocean. The carbonate compensation depth tracks long-term ocean cooling, deepening from 3.0-3.5?kilometres during the early Cenozoic (approximately 55?million years ago) to 4.6 kilometres at present, consistent with an overall Cenozoic increase in weathering. We find large superimposed fluctuations in carbonate compensation depth during the middle and late Eocene. Using Earth system models, we identify changes in weathering and the mode of organic-carbon delivery as two key processes to explain these large-scale Eocene fluctuations of the carbonate compensation depth.     

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.     

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.     

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.     

Stream denitrification across biomes and its response to anthropogenic nitrate loading

Anthropogenic addition of bioavailable nitrogen to the biosphere is increasing and terrestrial ecosystems are becoming increasingly nitrogen-saturated, causing more bioavailable nitrogen to enter groundwater and surface waters. Large-scale nitrogen budgets show that an average of about 20-25 per cent of the nitrogen added to the biosphere is exported from rivers to the ocean or inland basins, indicating that substantial sinks for nitrogen must exist in the landscape. Streams and rivers may themselves be important sinks for bioavailable nitrogen owing to their hydrological connections with terrestrial systems, high rates of biological activity, and streambed sediment environments that favour microbial denitrification. Here we present data from nitrogen stable isotope tracer experiments across 72 streams and 8 regions representing several biomes. We show that total biotic uptake and denitrification of nitrate increase with stream nitrate concentration, but that the efficiency of biotic uptake and denitrification declines as concentration increases, reducing the proportion of in-stream nitrate that is removed from transport. Our data suggest that the total uptake of nitrate is related to ecosystem photosynthesis and that denitrification is related to ecosystem respiration. In addition, we use a stream network model to demonstrate that excess nitrate in streams elicits a disproportionate increase in the fraction of nitrate that is exported to receiving waters and reduces the relative role of small versus large streams as nitrate sinks.