Volume 503 Issue 7476


Climate negotiations soldier on p.311

As the Warsaw conference on the climate wraps up this week, there is reason for hope despite several well-publicized setbacks.

doi: 10.1038/503311a

The new zoo p.311

Changes to the international zoological code are to be welcomed, despite continuing dissent.

doi: 10.1038/503311b

Space spectacular p.312

Nature doesn’t usually do film reviews, but Gravity is a true great.

doi: 10.1038/503312a


News Features

The quest for supercarbon p.327

Graphene's dazzling properties promise a technological revolution, but Europe may have to spend a billion euros to overcome some fundamental problems.

doi: 10.1038/503327a

Sex, cancer and a virus p.330

Human papillomavirus is causing a new form of head and neck cancer— leaving researchers scrambling to understand risk factors, tests and treatments.

doi: 10.1038/503330a

News & Views

An infernal Earth p.344

Orbiting less than two stellar radii above the visible surface of a Sun-like star, the Earth-sized exoplanet Kepler-78b is a hellish world. But its existence bodes well for the discovery and characterization of habitable planets. See Letters p.377 & p.381

doi: 10.1038/nature12702

High-endurance algae p.345

Breaking waves place repeated loading on marine algae, which can lead to death by fatigue. But observations of one alga suggest that its joint structure, which lacks transverse connections, confers fatigue resistance.

doi: 10.1038/503345a

Conduits of the carbon cycle p.346

Emissions of carbon dioxide from inland waters to the atmosphere are a crucial link in the global carbon cycle. A comprehensive analysis reveals that this connection is much stronger than was previously thought. See Article p.355

doi: 10.1038/503346a

Killing the survivors p.347

Antibiotic-tolerant, dormant variants of otherwise antibiotic-sensitive bacteria underlie many chronic and relapsing infections. A small molecule has been identified that can efficiently eradicate these persister cells. See Article p.365

doi: 10.1038/nature12834

The challenge of hot drought p.350

An analysis of North American drought variability over the past millennium shows that it is not unusual for widespread drought to persist for years, prompting fresh thinking about our ability to deal with such climate conditions.

doi: 10.1038/503350a

Group size determines cultural complexity p.351

Many animals use culture, the ability to learn from others, but only humans create complex culture. A laboratory experiment tests which characteristics of our social networks give us this capacity. See Letter p.389

doi: 10.1038/nature12708

Slipping under the radar p.352

HIV avoids triggering the cell receptors that initiate the host's innate immune responses. It seems that the virus achieves this evasion by using its protein coat to hide its nucleic acids until they are beyond detection. See Letter p.402

doi: 10.1038/nature12707


Global carbon dioxide emissions from inland waters p.355

An analysis of regional variations in global inland water surface area, dissolved CO2 and gas transfer velocity yields a global CO2 evasion rate of 2.1×1015 grams of carbon per year, which is higher than previous estimates owing to a larger contribution from streams and rivers.

doi: 10.1038/nature12760

Activated ClpP kills persisters and eradicates a chronic biofilm infection p.365

Dormant bacterial persister cells evade antibiotic destruction and their survival gives rise to some chronic infections; this study reveals that persister cells can be eradicated with a compound activating the bacterial protease ClpP, providing an effective biofilm treatment in vitro and in mouse chronic infection models.

doi: 10.1038/nature12790


An Earth-sized planet with an Earth-like density p.377

Recent analyses of data from the NASA Kepler spacecraft have established that planets with radii within 25 per cent of the Earth’s () are commonplace throughout the Galaxy, orbiting at least 16.5 per cent of Sun-like stars. Because these studies were sensitive to the sizes of the planets but not their masses, the question remains whether these Earth-sized planets are indeed similar to the Earth in bulk composition. The smallest planets for which masses have been accurately determined are Kepler-10b (1.42) and Kepler-36b (1.49), which are both significantly larger than the Earth. Recently, the planet Kepler-78b was discovered and found to have a radius of only 1.16. Here we report that the mass of this planet is 1.86 Earth masses. The resulting mean density of the planet is 5.57 g cm−3, which is similar to that of the Earth and implies a composition of iron and rock.

doi: 10.1038/nature12768

A rocky composition for an Earth-sized exoplanet p.381

Planets with sizes between that of Earth (with radius ) and Neptune (about 4) are now known to be common around Sun-like stars. Most such planets have been discovered through the transit technique, by which the planet’s size can be determined from the fraction of starlight blocked by the planet as it passes in front of its star. Measuring the planet’s mass—and hence its density, which is a clue to its composition—is more difficult. Planets of size 2–4 have proved to have a wide range of densities, implying a diversity of compositions, but these measurements did not extend to planets as small as Earth. Here we report Doppler spectroscopic measurements of the mass of the Earth-sized planet Kepler-78b, which orbits its host star every 8.5 hours (ref. 6). Given a radius of 1.20 ± 0.09 and a mass of 1.69 ± 0.41, the planet’s mean density of 5.3 ± 1.8 g cm−3 is similar to Earth’s, suggesting a composition of rock and iron.

doi: 10.1038/nature12767

Reducing the contact time of a bouncing drop p.385

Surfaces designed so that drops do not adhere to them but instead bounce off have received substantial attention because of their ability to stay dry, self-clean and resist icing. A drop striking a non-wetting surface of this type will spread out to a maximum diameter and then recoil to such an extent that it completely rebounds and leaves the solid material. The amount of time that the drop is in contact with the solid—the ‘contact time’—depends on the inertia and capillarity of the drop, internal dissipation and surface–liquid interactions. And because contact time controls the extent to which mass, momentum and energy are exchanged between drop and surface, it is often advantageous to minimize it. The conventional approach has been to minimize surface–liquid interactions that can lead to contact line pinning; but even in the absence of any surface interactions, drop hydrodynamics imposes a minimum contact time that was conventionally assumed to be attained with axisymmetrically spreading and recoiling drops. Here we demonstrate that it is possible to reduce the contact time below this theoretical limit by using superhydrophobic surfaces with a morphology that redistributes the liquid mass and thereby alters the drop hydrodynamics. We show theoretically and experimentally that this approach allows us to reduce the overall contact time between a bouncing drop and a surface below what was previously thought possible.

doi: 10.1038/nature12740

Experimental evidence for the influence of group size on cultural complexity p.389

The remarkable ecological and demographic success of humanity is largely attributed to our capacity for cumulative culture. The accumulation of beneficial cultural innovations across generations is puzzling because transmission events are generally imperfect, although there is large variance in fidelity. Events of perfect cultural transmission and innovations should be more frequent in a large population. As a consequence, a large population size may be a prerequisite for the evolution of cultural complexity, although anthropological studies have produced mixed results and empirical evidence is lacking. Here we use a dual-task computer game to show that cultural evolution strongly depends on population size, as players in larger groups maintained higher cultural complexity. We found that when group size increases, cultural knowledge is less deteriorated, improvements to existing cultural traits are more frequent, and cultural trait diversity is maintained more often. Our results demonstrate how changes in group size can generate both adaptive cultural evolution and maladaptive losses of culturally acquired skills. As humans live in habitats for which they are ill-suited without specific cultural adaptations, it suggests that, in our evolutionary past, group-size reduction may have exposed human societies to significant risks, including societal collapse.

doi: 10.1038/nature12774

A canonical to non-canonical Wnt signalling switch in haematopoietic stem-cell ageing p.392

Many organs with a high cell turnover (for example, skin, intestine and blood) are composed of short-lived cells that require continuous replenishment by somatic stem cells. Ageing results in the inability of these tissues to maintain homeostasis and it is believed that somatic stem-cell ageing is one underlying cause of tissue attrition with age or age-related diseases. Ageing of haematopoietic stem cells (HSCs) is associated with impaired haematopoiesis in the elderly. Despite a large amount of data describing the decline of HSC function on ageing, the molecular mechanisms of this process remain largely unknown, which precludes rational approaches to attenuate stem-cell ageing. Here we report an unexpected shift from canonical to non-canonical Wnt signalling in mice due to elevated expression of Wnt5a in aged HSCs, which causes stem-cell ageing. Wnt5a treatment of young HSCs induces ageing-associated stem-cell apolarity, reduction of regenerative capacity and an ageing-like myeloid–lymphoid differentiation skewing via activation of the small Rho GTPase Cdc42. Conversely, Wnt5a haploinsufficiency attenuates HSC ageing, whereas stem-cell-intrinsic reduction of Wnt5a expression results in functionally rejuvenated aged HSCs. Our data demonstrate a critical role for stem-cell-intrinsic non-canonical Wnt5a signalling in HSC ageing.

doi: 10.1038/nature12631

Staphylococcus δ-toxin induces allergic skin disease by activating mast cells p.397

Atopic dermatitis is a chronic inflammatory skin disease that affects 15–30% of children and approximately 5% of adults in industrialized countries. Although the pathogenesis of atopic dermatitis is not fully understood, the disease is mediated by an abnormal immunoglobulin-E immune response in the setting of skin barrier dysfunction. Mast cells contribute to immunoglobulin-E-mediated allergic disorders including atopic dermatitis. Upon activation, mast cells release their membrane-bound cytosolic granules leading to the release of several molecules that are important in the pathogenesis of atopic dermatitis and host defence. More than 90% of patients with atopic dermatitis are colonized with Staphylococcus aureus in the lesional skin whereas most healthy individuals do not harbour the pathogen. Several staphylococcal exotoxins can act as superantigens and/or antigens in models of atopic dermatitis. However, the role of these staphylococcal exotoxins in disease pathogenesis remains unclear. Here we report that culture supernatants of S. aureus contain potent mast-cell degranulation activity. Biochemical analysis identified δ-toxin as the mast cell degranulation-inducing factor produced by S. aureus. Mast cell degranulation induced by δ-toxin depended on phosphoinositide 3-kinase and calcium (Ca2+) influx; however, unlike that mediated by immunoglobulin-E crosslinking, it did not require the spleen tyrosine kinase. In addition, immunoglobulin-E enhanced δ-toxin-induced mast cell degranulation in the absence of antigen. Furthermore, S. aureus isolates recovered from patients with atopic dermatitis produced large amounts of δ-toxin. Skin colonization with S. aureus, but not a mutant deficient in δ-toxin, promoted immunoglobulin-E and interleukin-4 production, as well as inflammatory skin disease. Furthermore, enhancement of immunoglobulin-E production and dermatitis by δ-toxin was abrogated in KitW-sh/W-sh mast-cell-deficient mice and restored by mast cell reconstitution. These studies identify δ-toxin as a potent inducer of mast cell degranulation and suggest a mechanistic link between S. aureus colonization and allergic skin disease.

doi: 10.1038/nature12655

HIV-1 evades innate immune recognition through specific cofactor recruitment p.402

Human immunodeficiency virus (HIV)-1 is able to replicate in primary human macrophages without stimulating innate immunity despite reverse transcription of genomic RNA into double-stranded DNA, an activity that might be expected to trigger innate pattern recognition receptors. We reasoned that if correctly orchestrated HIV-1 uncoating and nuclear entry is important for evasion of innate sensors then manipulation of specific interactions between HIV-1 capsid and host factors that putatively regulate these processes should trigger pattern recognition receptors and stimulate type 1 interferon (IFN) secretion. Here we show that HIV-1 capsid mutants N74D and P90A, which are impaired for interaction with cofactors cleavage and polyadenylation specificity factor subunit 6 (CPSF6) and cyclophilins (Nup358 and CypA), respectively, cannot replicate in primary human monocyte-derived macrophages because they trigger innate sensors leading to nuclear translocation of NF-κB and IRF3, the production of soluble type 1 IFN and induction of an antiviral state. Depletion of CPSF6 with short hairpin RNA expression allows wild-type virus to trigger innate sensors and IFN production. In each case, suppressed replication is rescued by IFN-receptor blockade, demonstrating a role for IFN in restriction. IFN production is dependent on viral reverse transcription but not integration, indicating that a viral reverse transcription product comprises the HIV-1 pathogen-associated molecular pattern. Finally, we show that we can pharmacologically induce wild-type HIV-1 infection to stimulate IFN secretion and an antiviral state using a non-immunosuppressive cyclosporine analogue. We conclude that HIV-1 has evolved to use CPSF6 and cyclophilins to cloak its replication, allowing evasion of innate immune sensors and induction of a cell-autonomous innate immune response in primary human macrophages.

doi: 10.1038/nature12769

Antigen-specific B-cell receptor sensitizes B cells to infection by influenza virus p.406

Influenza A virus-specific B lymphocytes and the antibodies they produce protect against infection. However, the outcome of interactions between an influenza haemagglutinin-specific B cell via its receptor (BCR) and virus is unclear. Through somatic cell nuclear transfer we generated mice that harbour B cells with a BCR specific for the haemagglutinin of influenza A/WSN/33 virus (FluBI mice). Their B cells secrete an immunoglobulin gamma 2b that neutralizes infectious virus. Whereas B cells from FluBI and control mice bind equivalent amounts of virus through interaction of haemagglutinin with surface-disposed sialic acids, the A/WSN/33 virus infects only the haemagglutinin-specific B cells. Mere binding of virus is not sufficient for infection of B cells: this requires interactions of the BCR with haemagglutinin, causing both disruption of antibody secretion and FluBI B-cell death within 18 h. In mice infected with A/WSN/33, lung-resident FluBI B cells are infected by the virus, thus delaying the onset of protective antibody release into the lungs, whereas FluBI cells in the draining lymph node are not infected and proliferate. We propose that influenza targets and kills influenza-specific B cells in the lung, thus allowing the virus to gain purchase before the initiation of an effective adaptive response.

doi: 10.1038/nature12637

The nuclear receptor Rev-erbα controls circadian thermogenic plasticity p.410

Circadian oscillation of body temperature is a basic, evolutionarily conserved feature of mammalian biology. In addition, homeostatic pathways allow organisms to protect their core temperatures in response to cold exposure. However, the mechanism responsible for coordinating daily body temperature rhythm and adaptability to environmental challenges is unknown. Here we show that the nuclear receptor Rev-erbα (also known as Nr1d1), a powerful transcriptional repressor, links circadian and thermogenic networks through the regulation of brown adipose tissue (BAT) function. Mice exposed to cold fare considerably better at 05:00 (Zeitgeber time 22) when Rev-erbα is barely expressed than at 17:00 (Zeitgeber time 10) when Rev-erbα is abundant. Deletion of Rev-erbα markedly improves cold tolerance at 17:00, indicating that overcoming Rev-erbα-dependent repression is a fundamental feature of the thermogenic response to cold. Physiological induction of uncoupling protein 1 (Ucp1) by cold temperatures is preceded by rapid downregulation of Rev-erbα in BAT. Rev-erbα represses Ucp1 in a brown-adipose-cell-autonomous manner and BAT Ucp1 levels are high in Rev-erbα-null mice, even at thermoneutrality. Genetic loss of Rev-erbα also abolishes normal rhythms of body temperature and BAT activity. Thus, Rev-erbα acts as a thermogenic focal point required for establishing and maintaining body temperature rhythm in a manner that is adaptable to environmental demands.

doi: 10.1038/nature12642

Temperature-dependent regulation of flowering by antagonistic FLM variants p.414

The appropriate timing of flowering is crucial for plant reproductive success. It is therefore not surprising that intricate genetic networks have evolved to perceive and integrate both endogenous and environmental signals, such as carbohydrate and hormonal status, photoperiod and temperature. In contrast to our detailed understanding of the vernalization pathway, little is known about how flowering time is controlled in response to changes in the ambient growth temperature. In Arabidopsis thaliana, the MADS-box transcription factor genes FLOWERING LOCUS M (FLM) and SHORT VEGETATIVE PHASE (SVP) have key roles in this process. FLM is subject to temperature-dependent alternative splicing. Here we report that the two main FLM protein splice variants, FLM-β and FLM-δ, compete for interaction with the floral repressor SVP. The SVP–FLM-β complex is predominately formed at low temperatures and prevents precocious flowering. By contrast, the competing SVP–FLM-δ complex is impaired in DNA binding and acts as a dominant-negative activator of flowering at higher temperatures. Our results show a new mechanism that controls the timing of the floral transition in response to changes in ambient temperature. A better understanding of how temperature controls the molecular mechanisms of flowering will be important to cope with current changes in global climate.

doi: 10.1038/nature12633

Precision is essential for efficient catalysis in an evolved Kemp eliminase p.418

Linus Pauling established the conceptual framework for understanding and mimicking enzymes more than six decades ago. The notion that enzymes selectively stabilize the rate-limiting transition state of the catalysed reaction relative to the bound ground state reduces the problem of design to one of molecular recognition. Nevertheless, past attempts to capitalize on this idea, for example by using transition state analogues to elicit antibodies with catalytic activities, have generally failed to deliver true enzymatic rates. The advent of computational design approaches, combined with directed evolution, has provided an opportunity to revisit this problem. Starting from a computationally designed catalyst for the Kemp elimination—a well-studied model system for proton transfer from carbon—we show that an artificial enzyme can be evolved that accelerates an elementary chemical reaction 6 × 108-fold, approaching the exceptional efficiency of highly optimized natural enzymes such as triosephosphate isomerase. A 1.09 Å resolution crystal structure of the evolved enzyme indicates that familiar catalytic strategies such as shape complementarity and precisely placed catalytic groups can be successfully harnessed to afford such high rate accelerations, making us optimistic about the prospects of designing more sophisticated catalysts.

doi: 10.1038/nature12623

Structural basis for ligase-specific conjugation of linear ubiquitin chains by HOIP p.422

Linear ubiquitin chains are important regulators of cellular signalling pathways that control innate immunity and inflammation through nuclear factor (NF)-κB activation and protection against tumour necrosis factor-α-induced apoptosis. They are synthesized by HOIP, which belongs to the RBR (RING-between-RING) family of E3 ligases and is the catalytic component of LUBAC (linear ubiquitin chain assembly complex), a multisubunit E3 ligase. RBR family members act as RING/HECT hybrids, employing RING1 to recognize ubiquitin-loaded E2 while a conserved cysteine in RING2 subsequently forms a thioester intermediate with the transferred or ‘donor’ ubiquitin. Here we report the crystal structure of the catalytic core of HOIP in its apo form and in complex with ubiquitin. The carboxy-terminal portion of HOIP adopts a novel fold that, together with a zinc-finger, forms a ubiquitin-binding platform that orients the acceptor ubiquitin and positions its α-amino group for nucleophilic attack on the E3∼ubiquitin thioester. The C-terminal tail of a second ubiquitin molecule is located in close proximity to the catalytic cysteine, providing a unique snapshot of the ubiquitin transfer complex containing both donor and acceptor ubiquitin. These interactions are required for activation of the NF-κB pathway in vivo, and they explain the determinants of linear ubiquitin chain specificity by LUBAC.

doi: 10.1038/nature12638