Nature 456, E1 (2008). doi:10.1038/nature07402

Authors: A. Lecavelier des Etangs, A. Vidal-Madjar & J.-M. Désert

Arising from: M. Holmström et al.Nature451, 970–972 (2008); Holmström et al.replyUsing numerical simulation, Holmström et al. proposed a plausible alternative explanation of the observed Lyman-α absorption that was seen during the transit of HD 209458b (ref. 2). They conclude that radiation pressure alone cannot explain the observations and that a peculiar stellar wind is needed. Here we show that radiation pressure alone can in fact produce the observed high-velocity hydrogen atoms. We also emphasize that even if the stellar wind is responsible for the observed hydrogen, to have a sufficient number of atoms for charge exchange with stellar wind, the energetic neutral atom (ENA) model also needs a significant escape from the planet atmosphere of similar amplitude as quoted in ref. 2.

Nature 456, E1 (2008). doi:10.1038/nature07403

Authors: M. Holmström, A. Ekenbäck, F. Selsis, T. Penz, H. Lammer & P. Wurz

Replying to: A. Lecavelier des Etangs, A. Vidal-Madjar & J.-M. Désert Nature456, 10.1038/nature07402 (2008)Lecavelier des Etangs et al. object to the conclusion by Holmström et al. that radiation pressure alone cannot explain the Lyman-α absorption observed during transits of HD 209458b. We agree that hydrogen atoms can be accelerated to large velocities by radiation pressure. However, with our model we cannot reproduce the observed spectrum, as shown in the Supplementary Information and Fig. 3 of ref. 2.

Nature 456, xiii (2008). doi:10.1038/7219xiiia

An innovative cooling device chills a brain circuit and slows birdsong.

Nature 456, xiii (2008). doi:10.1038/7219xiiib

First authorClimate is never static, but it does veer between relatively steady states and periods of drastic fluctuation. During the past 3 million years, climate has become increasingly variable. About 1 million years ago, the magnitude of glacial–interglacial oscillations increased significantly, with two of

Nature 456, xiii (2008). doi:10.1038/7219xiiic

In its November editorial, Nature Reviews Microbiology (6, 794; 2008) reports that the archive of the International Journal of Systematic and Evolutionary Microbiology (IJSEM) has been made available free online: a boon for scientists, historians and the public. As

Nature 456, 141 (2008). doi:10.1038/456141a

The response to the financial crisis needs to go beyond the immediate pressures. Policy-makers must seize this moment to solidify the science and innovation required for sustained economic growth.

Nature 456, 142 (2008). doi:10.1038/456142a

Italy's universities should be free to hire who they want — and should be accountable for the result.

Nature 456, 142 (2008). doi:10.1038/456142b

A company's lawsuit against researchers should not be allowed to intimidate others.

Nature 456, 144 (2008). doi:10.1038/456144a

Proc. Natl Acad. Sci. USA doi:10.1073/pnas.0806166105 (2008)Mice stored at −20 °C for 16 years have been cloned, purportedly raising the possibility that extinct animals could be 'resurrected' from frozen tissue samples.Researchers had previously cloned mice from frozen cells

Nature 456, 144 (2008). doi:10.1038/456144b

Astrophys. J.687, 1004–1018 (2008) 10.1086/591658Star formation in galaxies is a tug-of-war between opposing forces. Clouds of gas collapse, feeding fledgling stars. These can, in turn, prevent new stars from forming by blowing away the nurturing gas with

Nature 456, 144 (2008). doi:10.1038/456144c

Water Resour. Res. doi:10.1029/2007WR006514 (2008)Monsoons are driven in large part by contrasts between land and sea temperatures, which are key to their prediction. However, other factors are also at play, such as soil moisture; higher moisture makes the transfer

Nature 456, 144 (2008). doi:10.1038/456144d

Naturwissenschaften doi:10.1007/s00114-008-0465-x (2008)Honeybees that find nectar tell the rest of the hive about it by dancing. But bumblebees instruct nestmates through smell, find Mathieu Molet and his colleagues at Queen Mary, University of London.They exposed bumblebees (Bombus

Nature 456, 144 (2008). doi:10.1038/456144e

Cell135, 437–448 (2008) 10.1016/j.cell.2008.08.041An existing cancer drug may be effective against a specific type of nerve tumour because of its ability to block a particular metabolic pathway.Wade Clapp at the Indiana University School of Medicine in

Nature 456, 145 (2008). doi:10.1038/456145a

Nature Chem. Biol. doi:10.1038/nchembio.124 (2008)In some invertebrates, such as horseshoe crabs, the presence of bacteria can directly trigger blood clotting, which stops infection from spreading. But the initiation of vertebrate blood clotting was thought to require a more complex

Nature 456, 145 (2008). doi:10.1038/456145b

Nature Phys. doi:10.1038/nphys1112 (2008) Quantum information is usually sent by light that is 'entangled'. This means that properties of photons sent between the two parties are quantum mechanically linked, and that the information changes when it is 'read', thus providing

Nature 456, 145 (2008). doi:10.1038/456145c

Science322, 957–960 (2008) 10.1126/science.1162011Certain stem cells may link ageing and obesity, according to Gary Ruvkun and his colleagues at the Massachusetts General Hospital in Boston. When they halted the development of germline stem cells — those that

Nature 456, 145 (2008). doi:10.1038/456145d

Geochem. Geophys. Geosys. doi:10.1029/2008GC002113 (2008) Monowai Cone (pictured below) is an undersea volcano north of New Zealand. It is probably the world's most active, making it a good model system for studying how submarine eruptions cause landslides, and how both

Nature 456, 145 (2008). doi:10.1038/456145e

Author: Douglas Natelson

A physicist foresees a new era in electronics.A material's electronic properties depend largely on its density of mobile charge carriers (electrons and holes). The most common way of tuning that density is 'doping'. This involves carefully adding atoms or molecules that donate or take

Nature 456, 166 (2008). doi:10.1038/456166a

Author: Rete Nazionale Ricercatori Precari

SirYour News story 'New law threatens Italian research jobs' (Nature455, 840–841; 2008) and Editorial 'Cut-throat savings' (Nature455, 835–836; 10.1038/455835b2008) both describe the dire situation for research scientists in Italy. But that's only

Nature 456, 166 (2008). doi:10.1038/456166b

Author: Ferdinando Boero

SirThe Italian government's proposed diversion of funds from scientific research to help boost the economy — discussed in your Editorial 'Cut-throat savings' (Nature455, 835–836; 10.1038/455835b2008) — is lamentable. According to various independent surveys based on ISI

Nature 456, 166 (2008). doi:10.1038/456166c

Author: Irene M. Pepperberg

SirI take exception to Clive Wynne's Review of my book Alex & Me: How a Scientist and a Parrot Discovered a Hidden World of Animal Intelligence — and Formed a Deep Bond in the Process (Nature455, 864–865;

Nature 456, 168 (2008). doi:10.1038/456168a

Authors: Andrew Lawrence, Luke Clark, Jamie Nicole Labuzetta, Barbara Sahakian & Shai Vyakarnum

'Hot' decision-making, involving the evaluation of reward and punishment, is essential to the entrepreneurial process and may be possible to teach, argue Barbara Sahakian and her coauthors.

Nature 456, 170 (2008). doi:10.1038/456170a

Author: Michael Bond

Two books exploring the relationship between Buddhism and science reveal surprising synergies — and hint that insights into the brain may come from studying the religion's practices, finds Michael Bond.

Nature 456, 171 (2008). doi:10.1038/456171a

Author: Warren Mansell

The field of behavioural science, combining psychology, sociology and neuroscience, has diversified over the past century such that there is a desperate need for an integrative theory. William T. Powers, medical physicist and engineer, proposes that 'control' is the unifying process. Living Control Systems III

Nature 456, 172 (2008). doi:10.1038/456172a

Author: Josie Glausiusz

A thin red line snakes along a wall, rising from below knee level to a height of three metres. The long glowing tube plots global carbon dioxide concentrations from the year 1600 — when the world's population was less than 600 million, goods were transported

Nature 456, 173 (2008). doi:10.1038/456173a

Author: J. Doyne Farmer

Released in the middle of the greatest financial crisis in the United States for 70 years, the timing of this book could hardly be better. Physicists on Wall Street and Other Essays on Science and Society presents a diverse collection of writings by essayist

Nature 456, 174 (2008). doi:10.1038/456174a

Authors: Martin Kemp & Nathan Flis

A detailed sketch by architect Christopher Wren reveals his surprising contribution to neuroscience, explain Martin Kemp and Nathan Flis.

Nature 456, 175 (2008). doi:10.1038/456175a

Author: Ian Deary

We must discover why cognitive differences are related to morbidity and mortality, argues Ian Deary, in order to help tackle health inequalities.

Nature 456, 177 (2008). doi:10.1038/456177a

Authors: Stefan Thor

In tadpoles, the number of neurons expressing the neurotransmitter dopamine increases on exposure to light. Such plasticity might allow animals to match their brains' response to environmental stimuli.

Nature 456, 178 (2008). doi:10.1038/456178a

Authors: Jeffrey S. Erickson & Frances S. Ligler

Fed up with sitting in the doctor's surgery among all those sneezy patients, waiting for the results of a health check? With the latest technology, you could one day perform bioassays on your home compact-disc player.

Nature 456, 179 (2008). doi:10.1038/456179a

Authors: Ronald P. Kiene

Sequence data on a second species of diatom provide abundant insights into the evolution and metabolic capabilities of this group, as well as into mechanisms of gene acquisition and diversification.

Nature 456, 182 (2008). doi:10.1038/456182a

Authors: Keiichi Edamatsu

For now, quantum information processing systems remain a dream. Step by step, however, progress towards that goal is being made, with one promising route involving a novel means of manipulating electron spin.

Nature 456, 183 (2008). doi:10.1038/456183a

Authors: J. R. Bankston & R. S. Kass

Decoding the workings of voltage-gated sodium channels is crucial because their mutation leads to severe disease and their activity is modulated by toxins and drugs. An innovative approach now allows such investigations.

Nature 456, 185 (2008). doi:10.1038/456185a

Authors: Alexis T. Bell

Solid catalysts speed up many industrial chemical reactions and steer them towards making desired products. A microscopy technique could reveal the changes in composition that catalysts undergo as they perform.

Nature 456, 186 (2008). doi:10.1038/456186a

Authors: Jan C. M. van Hest

A jack of all trades is a master of none, as the saying goes. But a protein has been discovered that shuns specialism, and that multitasks to give flexibility to its biosynthetic repertoire.

Nature 456, 187 (2008). doi:10.1038/456187a

Authors: Chris M. Glaze & Todd Troyer

Cooling a specific cluster of neurons in songbirds' brains slows song tempo without changing other acoustic features. This clever technique could be used for understanding neural control of other complex behaviours.

Nature 456, 189 (2008). doi:10.1038/nature07448

Authors: Michael A. Long & Michale S. Fee

Many complex behaviours, like speech or music, have a hierarchical organization with structure on many timescales, but it is not known how the brain controls the timing of behavioural sequences, or whether different circuits control different timescales of the behaviour. Here we address these issues

Nature 456, 195 (2008). doi:10.1038/nature07569

Authors: Davide Dulcis & Nicholas C. Spitzer

Specification of the appropriate neurotransmitter is a crucial step in neuronal differentiation because it enables signalling among populations of neurons. Experimental manipulations demonstrate that both autonomous and activity-dependent genetic programs contribute to this process during development, but whether natural environmental stimuli specify transmitter expression in

Nature 456, 202 (2008). doi:10.1038/nature07473

Authors: Frank Bosmans, Marie-France Martin-Eauclaire & Kenton J. Swartz

Voltage-activated sodium (Nav) channels are crucial for the generation and propagation of nerve impulses, and as such are widely targeted by toxins and drugs. The four voltage sensors in Nav channels have distinct amino acid sequences, raising fundamental questions about their

Nature 456, 209 (2008). doi:10.1038/nature07315

Authors: Yanli Wang, Gang Sheng, Stefan Juranek, Thomas Tuschl & Dinshaw J. Patel

The slicer activity of the RNA-induced silencing complex is associated with argonaute, the RNase H-like PIWI domain of which catalyses guide-strand-mediated sequence-specific cleavage of target messenger RNA. Here we report on the crystal structure of Thermus thermophilus argonaute bound to a 5′-phosphorylated 21-base DNA guide

Nature 456, 214 (2008). doi:10.1038/nature07440

Authors: Tom Stallard, Steve Miller, Makenzie Lystrup, Nicholas Achilleos, Emma J. Bunce, Christopher S. Arridge, Michele K. Dougherty, Stan W. H. Cowley, Sarah V. Badman, Dean L. Talboys, Robert H. Brown, Kevin H. Baines, Bonnie J. Buratti, Roger N. Clark, Christophe Sotin, Phil D. Nicholson & Pierre Drossart

The majority of planetary aurorae are produced by electrical currents flowing between the ionosphere and the magnetosphere which accelerate energetic charged particles that hit the upper atmosphere. At Saturn, these processes collisionally excite hydrogen, causing ultraviolet emission, and ionize the hydrogen, leading to H3+ infrared emission. Although the morphology of these aurorae is affected by changes in the solar wind, the source of the currents which produce them is a matter of debate. Recent models predict only weak emission away from the main auroral oval. Here we report images that show emission both poleward and equatorward of the main oval (separated by a region of low emission). The extensive polar emission is highly variable with time, and disappears when the main oval has a spiral morphology; this suggests that although the polar emission may be associated with minor increases in the dynamic pressure from the solar wind, it is not directly linked to strong magnetospheric compressions. This aurora appears to be unique to Saturn and cannot be explained using our current understanding of Saturn’s magnetosphere. The equatorward arc of emission exists only on the nightside of the planet, and arises from internal magnetospheric processes that are currently unknown.

Nature 456, 218 (2008). doi:10.1038/nature07530

Authors: David Press, Thaddeus D. Ladd, Bingyang Zhang & Yoshihisa Yamamoto

A basic requirement for quantum information processing systems is the ability to completely control the state of a single qubit. For qubits based on electron spin, a universal single-qubit gate is realized by a rotation of the spin by any angle about an arbitrary axis. Driven, coherent Rabi oscillations between two spin states can be used to demonstrate control of the rotation angle. Ramsey interference, produced by two coherent spin rotations separated by a variable time delay, demonstrates control over the axis of rotation. Full quantum control of an electron spin in a quantum dot has previously been demonstrated using resonant radio-frequency pulses that require many spin precession periods. However, optical manipulation of the spin allows quantum control on a picosecond or femtosecond timescale, permitting an arbitrary rotation to be completed within one spin precession period. Recent work in optical single-spin control has demonstrated the initialization of a spin state in a quantum dot, as well as the ultrafast manipulation of coherence in a largely unpolarized single-spin state. Here we demonstrate complete coherent control over an initialized electron spin state in a quantum dot using picosecond optical pulses. First we vary the intensity of a single optical pulse to observe over six Rabi oscillations between the two spin states; then we apply two sequential pulses to observe high-contrast Ramsey interference. Such a two-pulse sequence realizes an arbitrary single-qubit gate completed on a picosecond timescale. Along with the spin initialization and final projective measurement of the spin state, these results demonstrate a complete set of all-optical single-qubit operations.

Nature 456, 222 (2008). doi:10.1038/nature07516

Authors: Emiel de Smit, Ingmar Swart, J. Fredrik Creemer, Gerard H. Hoveling, Mary K. Gilles, Tolek Tyliszczak, Patricia J. Kooyman, Henny W. Zandbergen, Cynthia Morin, Bert M. Weckhuysen & Frank M. F. de Groot

The modern chemical industry uses heterogeneous catalysts in almost every production process. They commonly consist of nanometre-size active components (typically metals or metal oxides) dispersed on a high-surface-area solid support, with performance depending on the catalysts’ nanometre-size features and on interactions involving the active components, the support and the reactant and product molecules. To gain insight into the mechanisms of heterogeneous catalysts, which could guide the design of improved or novel catalysts, it is thus necessary to have a detailed characterization of the physicochemical composition of heterogeneous catalysts in their working state at the nanometre scale. Scanning probe microscopy methods have been used to study inorganic catalyst phases at subnanometre resolution, but detailed chemical information of the materials in their working state is often difficult to obtain. By contrast, optical microspectroscopic approaches offer much flexibility for in situ chemical characterization; however, this comes at the expense of limited spatial resolution. A recent development promising high spatial resolution and chemical characterization capabilities is scanning transmission X-ray microscopy, which has been used in a proof-of-principle study to characterize a solid catalyst. Here we show that when adapting a nanoreactor specially designed for high-resolution electron microscopy, scanning transmission X-ray microscopy can be used at atmospheric pressure and up to 350 °C to monitor in situ phase changes in a complex iron-based Fisher–Tropsch catalyst and the nature and location of carbon species produced. We expect that our system, which is capable of operating up to 500 °C, will open new opportunities for nanometre-resolution imaging of a range of important chemical processes taking place on solids in gaseous or liquid environments.

Nature 456, 226 (2008). doi:10.1038/nature07365

Authors: Thomas J. Crowley & William T. Hyde

Climate in the early Pleistocene varied with a period of 41 kyr and was related to variations in Earth's obliquity. About 900 kyr ago, variability increased and oscillated primarily at a period of ∼100 kyr, suggesting that the link was then with the eccentricity of Earth's orbit. This transition has often been attributed to a nonlinear response to small changes in external boundary conditions. Here we propose that increasing variablility within the past million years may indicate that the climate system was approaching a second climate bifurcation point, after which it would transition again to a new stable state characterized by permanent mid-latitude Northern Hemisphere glaciation. From this perspective the past million years can be viewed as a transient interval in the evolution of Earth's climate. We support our hypothesis using a coupled energy-balance/ice-sheet model, which furthermore predicts that the future transition would involve a large expansion of the Eurasian ice sheet. The process responsible for the abrupt change seems to be the albedo discontinuity at the snow–ice edge. The best-fit model run, which explains almost 60% of the variance in global ice volume during the past 400 kyr, predicts a rapid transition in the geologically near future to the proposed glacial state. Should it be attained, this state would be more ‘symmetric’ than the present climate, with comparable areas of ice/sea-ice cover in each hemisphere, and would represent the culmination of 50 million years of evolution from bipolar nonglacial climates to bipolar glacial climates.

Nature 456, 231 (2008). doi:10.1038/nature07412

Authors: Alexander F. Goncharov, Benjamin D. Haugen, Viktor V. Struzhkin, Pierre Beck & Steven D. Jacobsen

Iron in crustal and mantle minerals adopts several possible oxidation states: this has implications for biogeochemical processes, oxygenation of the atmosphere and the oxidation state of the mantle. In the deep Earth, iron in silicate perovskite, (Mg0.9Fe0.1)SiO3, and ferropericlase, (Mg0.85Fe0.15)O, influences the thermal conductivity of the lower mantle and therefore heat flux from the core. Little is known, however, about the effect of iron oxidation states on transport properties. Here we show that the radiative component of thermal conductivity in the dominant silicate perovskite material of Earth’s lower mantle is controlled by the amount of ferric iron, Fe3+. We obtained the optical absorption spectra of silicate perovskite and ferropericlase at pressures up to 133 GPa, corresponding to pressures at the core–mantle boundary. Absorption spectra of ferropericlase up to 800 K and 60 GPa exhibit minimal temperature dependence. The results on silicate perovskite show that optical absorption in the visible and near-infrared spectral range is dominated by O–Fe3+ charge transfer and Fe3+–Fe2+ intervalence transitions, whereas a contribution from the Fe2+ crystal-field transitions is substantially smaller. The estimated pressure-dependent radiative conductivity, krad, from these data is 2–5 times lower than previously inferred from model extrapolations, with implications for the evolution of the mantle, such as generation and stability of thermo-chemical plumes in the lower mantle.

Nature 456, 235 (2008). doi:10.1038/nature07248

Authors: Peter Chesson & Jessica J. Kuang

Competition and predation are the most heavily investigated species interactions in ecology, dominating studies of species diversity maintenance. However, these two interactions are most commonly viewed highly asymmetrically. Competition for resources is seen as the primary interaction limiting diversity, with predation modifying what competition does, although theoretical models have long supported diverse views. Here we show, using a comprehensive three-trophic-level model, that competition and predation should be viewed symmetrically: these two interactions are equally able to either limit or promote diversity. Diversity maintenance requires within-species density feedback loops to be stronger than between-species feedback loops. We quantify the contributions of predation and competition to these loops in a simple, interpretable form, showing their equivalent potential to strengthen or weaken diversity maintenance. Moreover, we show that competition and predation can undermine each other, with the tendency of the stronger interaction to promote or limit diversity prevailing. The past failure to appreciate the symmetrical effects and interactions of competition and predation has unduly restricted diversity maintenance studies. A multitrophic perspective should be adopted to examine a greater variety of possible effects of predation than generally considered in the past. Conservation and management strategies need to be much more concerned with the implications of changes in the strengths of trophic interactions.

Nature 456, 239 (2008). doi:10.1038/nature07410

Authors: Chris Bowler, Andrew E. Allen, Jonathan H. Badger, Jane Grimwood, Kamel Jabbari, Alan Kuo, Uma Maheswari, Cindy Martens, Florian Maumus, Robert P. Otillar, Edda Rayko, Asaf Salamov, Klaas Vandepoele, Bank Beszteri, Ansgar Gruber, Marc Heijde, Michael Katinka, Thomas Mock, Klaus Valentin, Fréderic Verret, John A. Berges, Colin Brownlee, Jean-Paul Cadoret, Anthony Chiovitti, Chang Jae Choi, Sacha Coesel, Alessandra De Martino, J. Chris Detter, Colleen Durkin, Angela Falciatore, Jérome Fournet, Miyoshi Haruta, Marie J. J. Huysman, Bethany D. Jenkins, Katerina Jiroutova, Richard E. Jorgensen, Yolaine Joubert, Aaron Kaplan, Nils Kröger, Peter G. Kroth, Julie La Roche, Erica Lindquist, Markus Lommer, Véronique Martin–Jézéquel, Pascal J. Lopez, Susan Lucas, Manuela Mangogna, Karen McGinnis, Linda K. Medlin, Anton Montsant, Marie-Pierre Oudot–Le Secq, Carolyn Napoli, Miroslav Obornik, Micaela Schnitzler Parker, Jean-Louis Petit, Betina M. Porcel, Nicole Poulsen, Matthew Robison, Leszek Rychlewski, Tatiana A. Rynearson, Jeremy Schmutz, Harris Shapiro, Magali Siaut, Michele Stanley, Michael R. Sussman, Alison R. Taylor, Assaf Vardi, Peter von Dassow, Wim Vyverman, Anusuya Willis, Lucjan S. Wyrwicz, Daniel S. Rokhsar, Jean Weissenbach, E. Virginia Armbrust, Beverley R. Green, Yves Van de Peer & Igor V. Grigoriev

Diatoms are photosynthetic secondary endosymbionts found throughout marine and freshwater environments, and are believed to be responsible for around one-fifth of the primary productivity on Earth. The genome sequence of the marine centric diatom Thalassiosira pseudonana was recently reported, revealing a wealth of information about diatom biology. Here we report the complete genome sequence of the pennate diatom Phaeodactylum tricornutum and compare it with that of T. pseudonana to clarify evolutionary origins, functional significance and ubiquity of these features throughout diatoms. In spite of the fact that the pennate and centric lineages have only been diverging for 90 million years, their genome structures are dramatically different and a substantial fraction of genes (∼40%) are not shared by these representatives of the two lineages. Analysis of molecular divergence compared with yeasts and metazoans reveals rapid rates of gene diversification in diatoms. Contributing factors include selective gene family expansions, differential losses and gains of genes and introns, and differential mobilization of transposable elements. Most significantly, we document the presence of hundreds of genes from bacteria. More than 300 of these gene transfers are found in both diatoms, attesting to their ancient origins, and many are likely to provide novel possibilities for metabolite management and for perception of environmental signals. These findings go a long way towards explaining the incredible diversity and success of the diatoms in contemporary oceans.

Nature 456, 245 (2008). doi:10.1038/nature07538

Authors: Timothy E. J. Behrens, Laurence T. Hunt, Mark W. Woolrich & Matthew F. S. Rushworth

Our decisions are guided by information learnt from our environment. This information may come via personal experiences of reward, but also from the behaviour of social partners. Social learning is widely held to be distinct from other forms of learning in its mechanism and neural implementation; it is often assumed to compete with simpler mechanisms, such as reward-based associative learning, to drive behaviour. Recently, neural signals have been observed during social exchange reminiscent of signals seen in studies of associative learning. Here we demonstrate that social information may be acquired using the same associative processes assumed to underlie reward-based learning. We find that key computational variables for learning in the social and reward domains are processed in a similar fashion, but in parallel neural processing streams. Two neighbouring divisions of the anterior cingulate cortex were central to learning about social and reward-based information, and for determining the extent to which each source of information guides behaviour. When making a decision, however, the information learnt using these parallel streams was combined within ventromedial prefrontal cortex. These findings suggest that human social valuation can be realized by means of the same associative processes previously established for learning other, simpler, features of the environment.

Nature 456, 250 (2008). doi:10.1038/nature07406

Authors: François Majo, Ariane Rochat, Michael Nicolas, Georges Abou Jaoudé & Yann Barrandon

The integrity of the cornea, the most anterior part of the eye, is indispensable for vision. Forty-five million individuals worldwide are bilaterally blind and another 135 million have severely impaired vision in both eyes because of loss of corneal transparency; treatments range from local medications to corneal transplants, and more recently to stem cell therapy. The corneal epithelium is a squamous epithelium that is constantly renewing, with a vertical turnover of 7 to 14 days in many mammals. Identification of slow cycling cells (label-retaining cells) in the limbus of the mouse has led to the notion that the limbus is the niche for the stem cells responsible for the long-term renewal of the cornea; hence, the corneal epithelium is supposedly renewed by cells generated at and migrating from the limbus, in marked opposition to other squamous epithelia in which each resident stem cell has in charge a limited area of epithelium. Here we show that the corneal epithelium of the mouse can be serially transplanted, is self-maintained and contains oligopotent stem cells with the capacity to generate goblet cells if provided with a conjunctival environment. Furthermore, the entire ocular surface of the pig, including the cornea, contains oligopotent stem cells (holoclones) with the capacity to generate individual colonies of corneal and conjunctival cells. Therefore, the limbus is not the only niche for corneal stem cells and corneal renewal is not different from other squamous epithelia. We propose a model that unifies our observations with the literature and explains why the limbal region is enriched in stem cells.

Nature 456, 255 (2008). doi:10.1038/nature07380

Authors: Elisabeth Verpy, Dominique Weil, Michel Leibovici, Richard J. Goodyear, Ghislaine Hamard, Carine Houdon, Gaelle M. Lefèvre, Jean-Pierre Hardelin, Guy P. Richardson, Paul Avan & Christine Petit

Although the cochlea is an amplifier and a remarkably sensitive and finely tuned detector of sounds, it also produces conspicuous mechanical and electrical waveform distortions. These distortions reflect nonlinear mechanical interactions within the cochlea. By allowing one tone to suppress another (masking effect), they contribute to speech intelligibility. Tones can also combine to produce sounds with frequencies not present in the acoustic stimulus. These sounds compose the otoacoustic emissions that are extensively used to screen hearing in newborns. Because both cochlear amplification and distortion originate from the outer hair cells-one of the two types of sensory receptor cells-it has been speculated that they stem from a common mechanism. Here we show that the nonlinearity underlying cochlear waveform distortions relies on the presence of stereocilin, a protein defective in a recessive form of human deafness. Stereocilin was detected in association with horizontal top connectors, lateral links that join adjacent stereocilia within the outer hair cell's hair bundle. These links were absent in stereocilin-null mutant mice, which became progressively deaf. At the onset of hearing, however, their cochlear sensitivity and frequency tuning were almost normal, although masking was much reduced and both acoustic and electrical waveform distortions were completely lacking. From this unique functional situation, we conclude that the main source of cochlear waveform distortions is a deflection-dependent hair bundle stiffness resulting from constraints imposed by the horizontal top connectors, and not from the intrinsic nonlinear behaviour of the mechanoelectrical transducer channel.

Nature 456, 259 (2008). doi:10.1038/nature07416

Authors: Ken Cadwell, John Y. Liu, Sarah L. Brown, Hiroyuki Miyoshi, Joy Loh, Jochen K. Lennerz, Chieko Kishi, Wumesh Kc, Javier A. Carrero, Steven Hunt, Christian D. Stone, Elizabeth M. Brunt, Ramnik J. Xavier, Barry P. Sleckman, Ellen Li, Noboru Mizushima, Thaddeus S. Stappenbeck & Herbert W. Virgin IV

Susceptibility to Crohn’s disease, a complex inflammatory disease involving the small intestine, is controlled by over 30 loci. One Crohn’s disease risk allele is in ATG16L1, a gene homologous to the essential yeast autophagy gene ATG16 (ref. 2). It is not known how ATG16L1 or autophagy contributes to intestinal biology or Crohn’s disease pathogenesis. To address these questions, we generated and characterized mice that are hypomorphic for ATG16L1 protein expression, and validated conclusions on the basis of studies in these mice by analysing intestinal tissues that we collected from Crohn’s disease patients carrying the Crohn’s disease risk allele of ATG16L1. Here we show that ATG16L1 is a bona fide autophagy protein. Within the ileal epithelium, both ATG16L1 and a second essential autophagy protein ATG5 are selectively important for the biology of the Paneth cell, a specialized epithelial cell that functions in part by secretion of granule contents containing antimicrobial peptides and other proteins that alter the intestinal environment. ATG16L1- and ATG5-deficient Paneth cells exhibited notable abnormalities in the granule exocytosis pathway. In addition, transcriptional analysis revealed an unexpected gain of function specific to ATG16L1-deficient Paneth cells including increased expression of genes involved in peroxisome proliferator-activated receptor (PPAR) signalling and lipid metabolism, of acute phase reactants and of two adipocytokines, leptin and adiponectin, known to directly influence intestinal injury responses. Importantly, Crohn’s disease patients homozygous for the ATG16L1 Crohn’s disease risk allele displayed Paneth cell granule abnormalities similar to those observed in autophagy-protein-deficient mice and expressed increased levels of leptin protein. Thus, ATG16L1, and probably the process of autophagy, have a role within the intestinal epithelium of mice and Crohn’s disease patients by selective effects on the cell biology and specialized regulatory properties of Paneth cells.

Nature 456, 264 (2008). doi:10.1038/nature07383

Authors: Tatsuya Saitoh, Naonobu Fujita, Myoung Ho Jang, Satoshi Uematsu, Bo-Gie Yang, Takashi Satoh, Hiroko Omori, Takeshi Noda, Naoki Yamamoto, Masaaki Komatsu, Keiji Tanaka, Taro Kawai, Tohru Tsujimura, Osamu Takeuchi, Tamotsu Yoshimori & Shizuo Akira

Systems for protein degradation are essential for tight control of the inflammatory immune response. Autophagy, a bulk degradation system that delivers cytoplasmic constituents into autolysosomes, controls degradation of long-lived proteins, insoluble protein aggregates and invading microbes, and is suggested to be involved in the regulation of inflammation. However, the mechanism underlying the regulation of inflammatory response by autophagy is poorly understood. Here we show that Atg16L1 (autophagy-related 16-like 1), which is implicated in Crohn's disease, regulates endotoxin-induced inflammasome activation in mice. Atg16L1-deficiency disrupts the recruitment of the Atg12-Atg5 conjugate to the isolation membrane, resulting in a loss of microtubule-associated protein 1 light chain 3 (LC3) conjugation to phosphatidylethanolamine. Consequently, both autophagosome formation and degradation of long-lived proteins are severely impaired in Atg16L1-deficient cells. Following stimulation with lipopolysaccharide, a ligand for Toll-like receptor 4 (refs 8, 9), Atg16L1-deficient macrophages produce high amounts of the inflammatory cytokines IL-1β and IL-18. In lipopolysaccharide-stimulated macrophages, Atg16L1-deficiency causes Toll/IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF)-dependent activation of caspase-1, leading to increased production of IL-1β. Mice lacking Atg16L1 in haematopoietic cells are highly susceptible to dextran sulphate sodium-induced acute colitis, which is alleviated by injection of anti-IL-1β and IL-18 antibodies, indicating the importance of Atg16L1 in the suppression of intestinal inflammation. These results demonstrate that Atg16L1 is an essential component of the autophagic machinery responsible for control of the endotoxin-induced inflammatory immune response.

Nature 456, 269 (2008). doi:10.1038/nature07349

Authors: Yi Liu, Renaud Dentin, Danica Chen, Susan Hedrick, Kim Ravnskjaer, Simon Schenk, Jill Milne, David J. Meyers, Phil Cole, John Yates III, Jerrold Olefsky, Leonard Guarente & Marc Montminy

During early fasting, increases in skeletal muscle proteolysis liberate free amino acids for hepatic gluconeogenesis in response to pancreatic glucagon. Hepatic glucose output diminishes during the late protein-sparing phase of fasting, when ketone body production by the liver supplies compensatory fuel for glucose-dependent tissues. Glucagon stimulates the gluconeogenic program by triggering the dephosphorylation and nuclear translocation of the CREB regulated transcription coactivator 2 (CRTC2; also known as TORC2), while parallel decreases in insulin signalling augment gluconeogenic gene expression through the dephosphorylation and nuclear shuttling of forkhead box O1 (FOXO1). Here we show that a fasting-inducible switch, consisting of the histone acetyltransferase p300 and the nutrient-sensing deacetylase sirtuin 1 (SIRT1), maintains energy balance in mice through the sequential induction of CRTC2 and FOXO1. After glucagon induction, CRTC2 stimulated gluconeogenic gene expression by an association with p300, which we show here is also activated by dephosphorylation at Ser 89 during fasting. In turn, p300 increased hepatic CRTC2 activity by acetylating it at Lys 628, a site that also targets CRTC2 for degradation after its ubiquitination by the E3 ligase constitutive photomorphogenic protein (COP1). Glucagon effects were attenuated during late fasting, when CRTC2 was downregulated owing to SIRT1-mediated deacetylation and when FOXO1 supported expression of the gluconeogenic program. Disrupting SIRT1 activity, by liver-specific knockout of the Sirt1 gene or by administration of a SIRT1 antagonist, increased CRTC2 activity and glucose output, whereas exposure to SIRT1 agonists reduced them. In view of the reciprocal activation of FOXO1 and its coactivator peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1