Cytoplasmic functions of the tumour suppressor p53

Nature 458, 1127 (2009). doi:10.1038/nature07986

Authors: Douglas R. Green & Guido Kroemer

The principal tumour-suppressor protein, p53, accumulates in cells in response to DNA damage, oncogene activation and other stresses. It acts as a nuclear transcription factor that transactivates genes involved in apoptosis, cell cycle regulation and numerous other processes. An emerging area of research unravels additional activities of p53 in the cytoplasm, where it triggers apoptosis and inhibits autophagy. These previously unknown functions contribute to the mission of p53 as a tumour suppressor.

Discrete sources as the origin of the Galactic X-ray ridge emission

Nature 458, 1142 (2009). doi:10.1038/nature07946

Authors: M. Revnivtsev, S. Sazonov, E. Churazov, W. Forman, A. Vikhlinin & R. Sunyaev

An unresolved X-ray glow (at energies above a few kiloelectronvolts) was discovered about 25 years ago and found to be coincident with the Galactic disk—the Galactic ridge X-ray emission. This emission has a spectrum characteristic of a ∼108 K optically thin thermal plasma, with a prominent iron emission line at 6.7 keV. The gravitational well of the Galactic disk, however, is far too shallow to confine such a hot interstellar medium; instead, it would flow away at a velocity of a few thousand kilometres per second, exceeding the speed of sound in the gas. To replenish the energy losses requires a source of 1043 erg s-1, exceeding by orders of magnitude all plausible energy sources in the Milky Way. An alternative is that the hot plasma is bound to a multitude of faint sources, which is supported by the recently observed similarities in the X-ray and near-infrared surface brightness distributions (the latter traces the Galactic stellar distribution). Here we report that at energies of ∼6–7 keV, more than 80 per cent of the seemingly diffuse X-ray emission is resolved into discrete sources, probably accreting white dwarfs and coronally active stars.

Serial time-encoded amplified imaging for real-time observation of fast dynamic phenomena

Nature 458, 1145 (2009). doi:10.1038/nature07980

Authors: K. Goda, K. K. Tsia & B. Jalali

Ultrafast real-time optical imaging is an indispensable tool for studying dynamical events such as shock waves, chemical dynamics in living cells, neural activity, laser surgery and microfluidics. However, conventional CCDs (charge-coupled devices) and their complementary metal–oxide–semiconductor (CMOS) counterparts are incapable of capturing fast dynamical processes with high sensitivity and resolution. This is due in part to a technological limitation—it takes time to read out the data from sensor arrays. Also, there is the fundamental compromise between sensitivity and frame rate; at high frame rates, fewer photons are collected during each frame—a problem that affects nearly all optical imaging systems. Here we report an imaging method that overcomes these limitations and offers frame rates that are at least 1,000 times faster than those of conventional CCDs. Our technique maps a two-dimensional (2D) image into a serial time-domain data stream and simultaneously amplifies the image in the optical domain. We capture an entire 2D image using a single-pixel photodetector and achieve a net image amplification of 25 dB (a factor of 316). This overcomes the compromise between sensitivity and frame rate without resorting to cooling and high-intensity illumination. As a proof of concept, we perform continuous real-time imaging at a frame speed of 163 ns (a frame rate of 6.1 MHz) and a shutter speed of 440 ps. We also demonstrate real-time imaging of microfluidic flow and phase-explosion effects that occur during laser ablation.

The Kondo effect in ferromagnetic atomic contacts

Nature 458, 1150 (2009). doi:10.1038/nature07878

Authors: M. Reyes Calvo, Joaquín Fernández-Rossier, Juan José Palacios, David Jacob, Douglas Natelson & Carlos Untiedt

Iron, cobalt and nickel are archetypal ferromagnetic metals. In bulk, electronic conduction in these materials takes place mainly through the s and p electrons, whereas the magnetic moments are mostly in the narrow d-electron bands, where they tend to align. This general picture may change at the nanoscale because electrons at the surfaces of materials experience interactions that differ from those in the bulk. Here we show direct evidence for such changes: electronic transport in atomic-scale contacts of pure ferromagnets (iron, cobalt and nickel), despite their strong bulk ferromagnetism, unexpectedly reveal Kondo physics, that is, the screening of local magnetic moments by the conduction electrons below a characteristic temperature. The Kondo effect creates a sharp resonance at the Fermi energy, affecting the electrical properties of the system; this appears as a Fano–Kondo resonance in the conductance characteristics as observed in other artificial nanostructures. The study of hundreds of contacts shows material-dependent log-normal distributions of the resonance width that arise naturally from Kondo theory. These resonances broaden and disappear with increasing temperature, also as in standard Kondo systems. Our observations, supported by calculations, imply that coordination changes can significantly modify magnetism at the nanoscale. Therefore, in addition to standard micromagnetic physics, strong electronic correlations along with atomic-scale geometry need to be considered when investigating the magnetic properties of magnetic nanostructures.

The ITQ-37 mesoporous chiral zeolite

Nature 458, 1154 (2009). doi:10.1038/nature07957

Authors: Junliang Sun, Charlotte Bonneau, Ángel Cantín, Avelino Corma, María J. Díaz-Cabañas, Manuel Moliner, Daliang Zhang, Mingrun Li & Xiaodong Zou

The synthesis of crystalline molecular sieves with pore dimensions that fill the gap between microporous and mesoporous materials is a matter of fundamental and industrial interest. The preparation of zeolitic materials with extralarge pores and chiral frameworks would permit many new applications. Two important steps in this direction include the synthesis of ITQ-33, a stable zeolite with 18 × 10 × 10 ring windows, and the synthesis of SU-32, which has an intrinsically chiral zeolite structure and where each crystal exhibits only one handedness. Here we present a germanosilicate zeolite (ITQ-37) with extralarge 30-ring windows. Its structure was determined by combining selected area electron diffraction (SAED) and powder X-ray diffraction (PXRD) in a charge-flipping algorithm. The framework follows the SrSi2 (srs) minimal net and forms two unique cavities, each of which is connected to three other cavities to form a gyroidal channel system. These cavities comprise the enantiomorphous srs net of the framework. ITQ-37 is the first chiral zeolite with one single gyroidal channel. It has the lowest framework density (10.3 T atoms per 1,000 Å3) of all existing 4-coordinated crystalline oxide frameworks, and the pore volume of the corresponding silica polymorph would be 0.38 cm3 g-1.

Greenhouse-gas emission targets for limiting global warming to 2 °C

Nature 458, 1158 (2009). doi:10.1038/nature08017

Authors: Malte Meinshausen, Nicolai Meinshausen, William Hare, Sarah C. B. Raper, Katja Frieler, Reto Knutti, David J. Frame & Myles R. Allen

More than 100 countries have adopted a global warming limit of 2 °C or below (relative to pre-industrial levels) as a guiding principle for mitigation efforts to reduce climate change risks, impacts and damages. However, the greenhouse gas (GHG) emissions corresponding to a specified maximum warming are poorly known owing to uncertainties in the carbon cycle and the climate response. Here we provide a comprehensive probabilistic analysis aimed at quantifying GHG emission budgets for the 2000–50 period that would limit warming throughout the twenty-first century to below 2 °C, based on a combination of published distributions of climate system properties and observational constraints. We show that, for the chosen class of emission scenarios, both cumulative emissions up to 2050 and emission levels in 2050 are robust indicators of the probability that twenty-first century warming will not exceed 2 °C relative to pre-industrial temperatures. Limiting cumulative CO2 emissions over 2000–50 to 1,000 Gt CO2 yields a 25% probability of warming exceeding 2 °C—and a limit of 1,440 Gt CO2 yields a 50% probability—given a representative estimate of the distribution of climate system properties. As known 2000–06 CO2 emissions were ∼234 Gt CO2, less than half the proven economically recoverable oil, gas and coal reserves can still be emitted up to 2050 to achieve such a goal. Recent G8 Communiqués envisage halved global GHG emissions by 2050, for which we estimate a 12–45% probability of exceeding 2 °C—assuming 1990 as emission base year and a range of published climate sensitivity distributions. Emissions levels in 2020 are a less robust indicator, but for the scenarios considered, the probability of exceeding 2 °C rises to 53–87% if global GHG emissions are still more than 25% above 2000 levels in 2020.

Warming caused by cumulative carbon emissions towards the trillionth tonne

Nature 458, 1163 (2009). doi:10.1038/nature08019

Authors: Myles R. Allen, David J. Frame, Chris Huntingford, Chris D. Jones, Jason A. Lowe, Malte Meinshausen & Nicolai Meinshausen

Global efforts to mitigate climate change are guided by projections of future temperatures. But the eventual equilibrium global mean temperature associated with a given stabilization level of atmospheric greenhouse gas concentrations remains uncertain, complicating the setting of stabilization targets to avoid potentially dangerous levels of global warming. Similar problems apply to the carbon cycle: observations currently provide only a weak constraint on the response to future emissions. Here we use ensemble simulations of simple climate-carbon-cycle models constrained by observations and projections from more comprehensive models to simulate the temperature response to a broad range of carbon dioxide emission pathways. We find that the peak warming caused by a given cumulative carbon dioxide emission is better constrained than the warming response to a stabilization scenario. Furthermore, the relationship between cumulative emissions and peak warming is remarkably insensitive to the emission pathway (timing of emissions or peak emission rate). Hence policy targets based on limiting cumulative emissions of carbon dioxide are likely to be more robust to scientific uncertainty than emission-rate or concentration targets. Total anthropogenic emissions of one trillion tonnes of carbon (3.67 trillion tonnes of CO2), about half of which has already been emitted since industrialization began, results in a most likely peak carbon-dioxide-induced warming of 2 °C above pre-industrial temperatures, with a 5–95% confidence interval of 1.3–3.9 °C.

Orally delivered siRNA targeting macrophage Map4k4 suppresses systemic inflammation

Nature 458, 1180 (2009). doi:10.1038/nature07774

Authors: Myriam Aouadi, Gregory J. Tesz, Sarah M. Nicoloro, Mengxi Wang, My Chouinard, Ernesto Soto, Gary R. Ostroff & Michael P. Czech

Gene silencing by double-stranded RNA, denoted RNA interference, represents a new paradigm for rational drug design. However, the transformative therapeutic potential of short interfering RNA (siRNA) has been stymied by a key obstacle—safe delivery to specified target cells in vivo. Macrophages are particularly attractive targets for RNA interference therapy because they promote pathogenic inflammatory responses in diseases such as rheumatoid arthritis, atherosclerosis, inflammatory bowel disease and diabetes. Here we report the engineering of β1,3-d-glucan-encapsulated siRNA particles (GeRPs) as efficient oral delivery vehicles that potently silence genes in mouse macrophages in vitro and in vivo. Oral gavage of mice with GeRPs containing as little as 20 μg kg-1 siRNA directed against tumour necrosis factor α (Tnf-α) depleted its messenger RNA in macrophages recovered from the peritoneum, spleen, liver and lung, and lowered serum Tnf-α levels. Screening with GeRPs for inflammation genes revealed that the mitogen-activated protein kinase kinase kinase kinase 4 (Map4k4) is a previously unknown mediator of cytokine expression. Importantly, silencing Map4k4 in macrophages in vivo protected mice from lipopolysaccharide-induced lethality by inhibiting Tnf-α and interleukin-1β production. This technology defines a new strategy for oral delivery of siRNA to attenuate inflammatory responses in human disease.

Mantle skewness and ridge segmentation

Nature 458, E11 (2009). doi:10.1038/nature07887

Authors: Satish C. Singh & Ken C. Macdonald

Arising from: D. R. Toomey, D. Jousselin, R. A. Dunn, W. S. D. Wilcock & R. S. Detrick Nature446, 409–414 (2007); Toomey et al. replyMantle upwelling is generally assumed to be symmetric. Toomey et al. observe low seismic-wave velocity in off-axis mantle, and suggest that mantle upwelling is skewed, which has important implications for asthenospheric flow, ridge segmentation, crustal accretion, and volcanic, tectonic and hydrothermal vent activities along the ridge axis. However, we point out here that the mantle low-velocity zone (MLVZ) presented by Toomey et al. is not constrained by their data. We conclude that inferences pertaining to ridge segmentation and mantle flow are not reliable.

Toomey et al. reply

Nature 458, E12 (2009). doi:10.1038/nature07888

Authors: Douglas R. Toomey, David Jousselin, Robert A. Dunn, William S. D. Wilcock & R. S. Detrick

Replying to: S. S. Singh & K. C. Macdonald Nature458, 10.1038/nature07887 (2009)We think that the Singh and Macdonald description of the experimental uncertainties in our data is a misrepresentation of what we have done, and that they are incorrect in stating that our results on the structure of the uppermost mantle in the subaxial region beneath the East Pacific Rise are unconstrained by data.

Solar wind as the origin of rapid reddening of asteroid surfaces

Nature 458, 993 (2009). doi:10.1038/nature07956

Authors: P. Vernazza, R. P. Binzel, A. Rossi, M. Fulchignoni & M. Birlan

A comparison of the laboratory reflectance spectra of meteorites with observations of asteroids revealed that the latter are much ‘redder’, with the spectral difference explained by ‘space weathering’, though the actual processes and timescales involved have remained controversial. A recent study of young asteroid families concluded that they suffered only minimal space weathering. Here we report additional observations of those families, revealing that space weathering must be a very rapid process—the final colour of a silicate-rich asteroid is acquired shortly after its ‘birth’ (within 106 years of undergoing a catastrophic collision). This rapid timescale favours solar wind implantation as the main mechanism of space weathering, as laboratory experiments have shown that it is the most rapid of several competing processes. We further demonstrate the necessity to take account of composition when evaluating weathering effectiveness, as both laboratory and asteroid data show an apparent dependence of weathering on olivine abundance. The rapid colour change that we find implies that colour trends seen among asteroids are most probably due to compositional or surface-particle-size properties, rather than to different relative ages. Apparently fresh surfaces most frequently seen among small near-Earth asteroids may be the result of tidal shaking that rejuvenates their surfaces during planetary encounters.

Optimized dynamical decoupling in a model quantum memory

Nature 458, 996 (2009). doi:10.1038/nature07951

Authors: Michael J. Biercuk, Hermann Uys, Aaron P. VanDevender, Nobuyasu Shiga, Wayne M. Itano & John J. Bollinger

Any quantum system, such as those used in quantum information or magnetic resonance, is subject to random phase errors that can dramatically affect the fidelity of a desired quantum operation or measurement. In the context of quantum information, quantum error correction techniques have been developed to correct these errors, but resource requirements are extraordinary. The realization of a physically tractable quantum information system will therefore be facilitated if qubit (quantum bit) error rates are far below the so-called fault-tolerance error threshold, predicted to be of the order of 10-3–10-6. The need to realize such low error rates motivates a search for alternative strategies to suppress dephasing in quantum systems. Here we experimentally demonstrate massive suppression of qubit error rates by the application of optimized dynamical decoupling pulse sequences, using a model quantum system capable of simulating a variety of qubit technologies. We demonstrate an analytically derived pulse sequence, UDD, and find novel sequences through active, real-time experimental feedback. The latter sequences are tailored to maximize error suppression without the need for a priori knowledge of the ambient noise environment, and are capable of suppressing errors by orders of magnitude compared to other existing sequences (including the benchmark multi-pulse spin echo). Our work includes the extension of a treatment to predict qubit decoherence under realistic conditions, yielding strong agreement between experimental data and theory for arbitrary pulse sequences incorporating nonidealized control pulses. These results demonstrate the robustness of qubit memory error suppression through dynamical decoupling techniques across a variety of qubit technologies.

Universal transduction scheme for nanomechanical systems based on dielectric forces

Nature 458, 1001 (2009). doi:10.1038/nature07932

Authors: Quirin P. Unterreithmeier, Eva M. Weig & Jörg P. Kotthaus

Any polarizable body placed in an inhomogeneous electric field experiences a dielectric force. This phenomenon is well known from the macroscopic world: a water jet is deflected when approached by a charged object. This fundamental mechanism is exploited in a variety of contexts—for example, trapping microscopic particles in an optical tweezer, where the trapping force is controlled via the intensity of a laser beam, or dielectrophoresis, where electric fields are used to manipulate particles in liquids. Here we extend the underlying concept to the rapidly evolving field of nanoelectromechanical systems (NEMS). A broad range of possible applications are anticipated for these systems, but drive and detection schemes for nanomechanical motion still need to be optimized. Our approach is based on the application of dielectric gradient forces for the controlled and local transduction of NEMS. Using a set of on-chip electrodes to create an electric field gradient, we polarize a dielectric resonator and subject it to an attractive force that can be modulated at high frequencies. This universal actuation scheme is efficient, broadband and scalable. It also separates the driving scheme from the driven mechanical element, allowing for arbitrary polarizable materials and thus potentially ultralow dissipation NEMS. In addition, it enables simple voltage tuning of the mechanical resonance over a wide frequency range, because the dielectric force depends strongly on the resonator–electrode separation. We use the modulation of the resonance frequency to demonstrate parametric actuation. Moreover, we reverse the actuation principle to realize dielectric detection, thus allowing universal transduction of NEMS. We expect this combination to be useful both in the study of fundamental principles and in applications such as signal processing and sensing.

Observation of ultralong-range Rydberg molecules

Nature 458, 1005 (2009). doi:10.1038/nature07945

Authors: Vera Bendkowsky, Björn Butscher, Johannes Nipper, James P. Shaffer, Robert Löw & Tilman Pfau

Rydberg atoms have an electron in a state with a very high principal quantum number, and as a result can exhibit unusually long-range interactions. One example is the bonding of two such atoms by multipole forces to form Rydberg–Rydberg molecules with very large internuclear distances. Notably, bonding interactions can also arise from the low-energy scattering of a Rydberg electron with negative scattering length from a ground-state atom. In this case, the scattering-induced attractive interaction binds the ground-state atom to the Rydberg atom at a well-localized position within the Rydberg electron wavefunction and thereby yields giant molecules that can have internuclear separations of several thousand Bohr radii. Here we report the spectroscopic characterization of such exotic molecular states formed by rubidium Rydberg atoms that are in the spherically symmetric s state and have principal quantum numbers, n, between 34 and 40. We find that the spectra of the vibrational ground state and of the first excited state of the Rydberg molecule, the rubidium dimer Rb(5s)–Rb(ns), agree well with simple model predictions. The data allow us to extract the s-wave scattering length for scattering between the Rydberg electron and the ground-state atom, Rb(5s), in the low-energy regime (kinetic energy, <100 meV), and to determine the lifetimes and the polarizabilities of the Rydberg molecules. Given our successful characterization of s-wave bound Rydberg states, we anticipate that p-wave bound states, trimer states and bound states involving a Rydberg electron with large angular momentum—so-called trilobite molecules—will also be realized and directly probed in the near future.

The carbon balance of terrestrial ecosystems in China

Nature 458, 1009 (2009). doi:10.1038/nature07944

Authors: Shilong Piao, Jingyun Fang, Philippe Ciais, Philippe Peylin, Yao Huang, Stephen Sitch & Tao Wang

Global terrestrial ecosystems absorbed carbon at a rate of 1–4 Pg yr-1 during the 1980s and 1990s, offsetting 10–60 per cent of the fossil-fuel emissions. The regional patterns and causes of terrestrial carbon sources and sinks, however, remain uncertain. With increasing scientific and political interest in regional aspects of the global carbon cycle, there is a strong impetus to better understand the carbon balance of China. This is not only because China is the world’s most populous country and the largest emitter of fossil-fuel CO2 into the atmosphere, but also because it has experienced regionally distinct land-use histories and climate trends, which together control the carbon budget of its ecosystems. Here we analyse the current terrestrial carbon balance of China and its driving mechanisms during the 1980s and 1990s using three different methods: biomass and soil carbon inventories extrapolated by satellite greenness measurements, ecosystem models and atmospheric inversions. The three methods produce similar estimates of a net carbon sink in the range of 0.19–0.26 Pg carbon (PgC) per year, which is smaller than that in the conterminous United States but comparable to that in geographic Europe. We find that northeast China is a net source of CO2 to the atmosphere owing to overharvesting and degradation of forests. By contrast, southern China accounts for more than 65 per cent of the carbon sink, which can be attributed to regional climate change, large-scale plantation programmes active since the 1980s and shrub recovery. Shrub recovery is identified as the most uncertain factor contributing to the carbon sink. Our data and model results together indicate that China’s terrestrial ecosystems absorbed 28–37 per cent of its cumulated fossil carbon emissions during the 1980s and 1990s.

Impact of changes in diffuse radiation on the global land carbon sink

Nature 458, 1014 (2009). doi:10.1038/nature07949

Authors: Lina M. Mercado, Nicolas Bellouin, Stephen Sitch, Olivier Boucher, Chris Huntingford, Martin Wild & Peter M. Cox

Plant photosynthesis tends to increase with irradiance. However, recent theoretical and observational studies have demonstrated that photosynthesis is also more efficient under diffuse light conditions. Changes in cloud cover or atmospheric aerosol loadings, arising from either volcanic or anthropogenic emissions, alter both the total photosynthetically active radiation reaching the surface and the fraction of this radiation that is diffuse, with uncertain overall effects on global plant productivity and the land carbon sink. Here we estimate the impact of variations in diffuse fraction on the land carbon sink using a global model modified to account for the effects of variations in both direct and diffuse radiation on canopy photosynthesis. We estimate that variations in diffuse fraction, associated largely with the ‘global dimming’ period, enhanced the land carbon sink by approximately one-quarter between 1960 and 1999. However, under a climate mitigation scenario for the twenty-first century in which sulphate aerosols decline before atmospheric CO2 is stabilized, this ‘diffuse-radiation’ fertilization effect declines rapidly to near zero by the end of the twenty-first century.

The architecture of mutualistic networks minimizes competition and increases biodiversity

Nature 458, 1018 (2009). doi:10.1038/nature07950

Authors: Ugo Bastolla, Miguel A. Fortuna, Alberto Pascual-García, Antonio Ferrera, Bartolo Luque & Jordi Bascompte

The main theories of biodiversity either neglect species interactions or assume that species interact randomly with each other. However, recent empirical work has revealed that ecological networks are highly structured, and the lack of a theory that takes into account the structure of interactions precludes further assessment of the implications of such network patterns for biodiversity. Here we use a combination of analytical and empirical approaches to quantify the influence of network architecture on the number of coexisting species. As a case study we consider mutualistic networks between plants and their animal pollinators or seed dispersers. These networks have been found to be highly nested, with the more specialist species interacting only with proper subsets of the species that interact with the more generalist. We show that nestedness reduces effective interspecific competition and enhances the number of coexisting species. Furthermore, we show that a nested network will naturally emerge if new species are more likely to enter the community where they have minimal competitive load. Nested networks seem to occur in many biological and social contexts, suggesting that our results are relevant in a wide range of fields.

A semi-aquatic Arctic mammalian carnivore from the Miocene epoch and origin of Pinnipedia

Nature 458, 1021 (2009). doi:10.1038/nature07985

Authors: Natalia Rybczynski, Mary R. Dawson & Richard H. Tedford

Modern pinnipeds (seals, sea lions and the walrus) are semi-aquatic, generally marine carnivores the limbs of which have been modified into flippers. Recent phylogenetic studies using morphological and molecular evidence support pinniped monophyly, and suggest a sister relationship with ursoids (for example bears) or musteloids (the clade that includes skunks, badgers, weasels and otters). Although the position of pinnipeds within modern carnivores appears moderately well resolved, fossil evidence of the morphological steps leading from a terrestrial ancestor to the modern marine forms has been weak or contentious. The earliest well-represented fossil pinniped is Enaliarctos, a marine form with flippers, which had appeared on the northwestern shores of North America by the early Miocene epoch. Here we report the discovery of a nearly complete skeleton of a new semi-aquatic carnivore from an early Miocene lake deposit in Nunavut, Canada, that represents a morphological link in early pinniped evolution. The new taxon retains a long tail and the proportions of its fore- and hindlimbs are more similar to those of modern terrestrial carnivores than to modern pinnipeds. Morphological traits indicative of semi-aquatic adaptation include a forelimb with a prominent deltopectoral ridge on the humerus, a posterodorsally expanded scapula, a pelvis with relatively short ilium, a shortened femur and flattened phalanges, suggestive of webbing. The new fossil shows evidence of pinniped affinities and similarities to the early Oligocene Amphicticeps from Asia and the late Oligocene and Miocene Potamotherium from Europe. The discovery suggests that the evolution of pinnipeds included a freshwater transitional phase, and may support the hypothesis that the Arctic was an early centre of pinniped evolution.

Discovery of insect and human dengue virus host factors

Nature 458, 1047 (2009). doi:10.1038/nature07967

Authors: October M. Sessions, Nicholas J. Barrows, Jayme A. Souza-Neto, Timothy J. Robinson, Christine L. Hershey, Mary A. Rodgers, Jose L. Ramirez, George Dimopoulos, Priscilla L. Yang, James L. Pearson & Mariano A. Garcia-Blanco

Dengue fever is the most frequent arthropod-borne viral disease of humans, with almost half of the world’s population at risk of infection. The high prevalence, lack of an effective vaccine, and absence of specific treatment conspire to make dengue fever a global public health threat. Given their compact genomes, dengue viruses (DENV-1–4) and other flaviviruses probably require an extensive number of host factors; however, only a limited number of human, and an even smaller number of insect host factors, have been identified. Here we identify insect host factors required for DENV-2 propagation, by carrying out a genome-wide RNA interference screen in Drosophila melanogaster cells using a well-established 22,632 double-stranded RNA library. This screen identified 116 candidate dengue virus host factors (DVHFs). Although some were previously associated with flaviviruses (for example, V-ATPases and α-glucosidases), most of the DVHFs were newly implicated in dengue virus propagation. The dipteran DVHFs had 82 readily recognizable human homologues and, using a targeted short-interfering-RNA screen, we showed that 42 of these are human DVHFs. This indicates notable conservation of required factors between dipteran and human hosts. This work suggests new approaches to control infection in the insect vector and the mammalian host.

Making the paper: Luke Harmon

Nature 458, 1075 (2009). doi:10.1038/72421075a

Evolution can put the squeeze back on the ecosystem.