Volume 505 Number 7484


Don’t rush to rehabilitate Hwang p.453

Nature’s profile of a former fraudster’s attempts to regain respectability should not be taken as an endorsement of the researcher’s claims.

doi: 10.1038/505453a

A return to order p.453

Members of the US Congress have taken a much-needed step to restore credibility.

doi: 10.1038/505453b

A question of time p.454

Timekeeping is boosted by the advent of an optical clock based on strontium atoms.

doi: 10.1038/505454a


Sea drilling project launches p.466

International expedition hopes to unravel mysteries of the South China Sea, one of the world’s most geologically important seas.

doi: 10.1038/505466a

News Features

Cloning comeback p.468

Ten years ago, Woo Suk Hwang rose to the top of his field before fraud and dodgy bioethical practices derailed his career. Can a scientific pariah redeem himself?

doi: 10.1038/505468a

Flawed to perfection p.472

Ultra-pure synthetic diamonds offer advances in fields from quantum computing to cancer diagnostics.

doi: 10.1038/505472a

News & Views

Good dirt with good friends p.486

An analysis of data from forests across the planet reveals that the types of beneficial fungus with which tree roots associate determine the amount of carbon stored in soils. See Letter p.543

doi: 10.1038/nature12849

Evaporating asteroid p.487

The asteroid Ceres has been thought to contain abundant water. Observations acquired with the Herschel Space Observatory now show that this Solar System object is spewing water vapour from its surface. See Letter p.525

doi: 10.1038/505487a

Sex specificity in the blood p.488

Haematopoietic stem cells, from which blood cells originate, are shown to respond to oestrogen and divide more frequently in female mice than in males, probably preparing females for the increased demand for blood in pregnancy. See Letter p.555

doi: 10.1038/505488a

Protecting the weak from the strong p.490

A thin engineered surface has been developed that can protect sensitive electronic systems from strong signal interference, allowing them to communicate effectively with external antennas.

doi: 10.1038/nature12852

A resolution of the Antarctic paradox p.491

A combination of observational data and modelling reveals the potential significance of the north and tropical Atlantic Ocean in driving change in Antarctic winds and sea ice on decadal timescales and longer. See Letter p.538

doi: 10.1038/505491a

Not-so-innocent bystanders p.492

The discovery that most CD4+ T cells killed during HIV infection die through a process known as pyroptosis may provide long-sought explanations for HIV-associated T-cell depletion and inflammation. See Article p.509

doi: 10.1038/505492a


Discovery and saturation analysis of cancer genes across 21 tumour types p.495

Large-scale genomic analysis of somatic point mutations in exomes from tumour–normal pairs across 21 cancer types identifies most known cancer genes in these tumour types as well as 33 genes not known to be significantly mutated, and down-sampling analysis indicates that larger sample sizes will reveal many more genes mutated at clinically important frequencies.

doi: 10.1038/nature12912

Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection p.509

Quiescent CD4 T cells in lymphoid tissues are shown to die after HIV-1 infection by caspase-1-mediated pyroptosis, a highly inflammatory form of programmed cell death; caspase 1 inhibitors, which are safe for human use, can rescue the cell death in vitro raising the possibility of new therapeutics targeting the host instead of the virus.

doi: 10.1038/nature12940

Architecture of the large subunit of the mammalian mitochondrial ribosome p.515

Cryo-electron microscopy combined with chemical crosslinking and mass spectrometry is used to determine the structure of the large subunit of the mammalian mitoribosome; this structure provides detailed structural insight, particularly of the molecular architecture of the polypeptide exit site, which has been structurally remodelled during evolution, presumably to help facilitate the membrane insertion of the highly hydrophobic proteins encoded by the mitochondrial genome.

doi: 10.1038/nature12890


A millisecond pulsar in a stellar triple system p.520

Gravitationally bound three-body systems have been studied for hundreds of years and are common in our Galaxy. They show complex orbital interactions, which can constrain the compositions, masses and interior structures of the bodies and test theories of gravity, if sufficiently precise measurements are available. A triple system containing a radio pulsar could provide such measurements, but the only previously known such system, PSR B1620-26 (refs 7, 8; with a millisecond pulsar, a white dwarf, and a planetary-mass object in an orbit of several decades), shows only weak interactions. Here we report precision timing and multiwavelength observations of PSR J0337+1715, a millisecond pulsar in a hierarchical triple system with two other stars. Strong gravitational interactions are apparent and provide the masses of the pulsar (1.4378(13), where is the solar mass and the parentheses contain the uncertainty in the final decimal places) and the two white dwarf companions (0.19751(15) and 0.4101(3)), as well as the inclinations of the orbits (both about 39.2°). The unexpectedly coplanar and nearly circular orbits indicate a complex and exotic evolutionary past that differs from those of known stellar systems. The gravitational field of the outer white dwarf strongly accelerates the inner binary containing the neutron star, and the system will thus provide an ideal laboratory in which to test the strong equivalence principle of general relativity.

doi: 10.1038/nature12917

Localized sources of water vapour on the dwarf planet (1) Ceres p.525

The ‘snowline’ conventionally divides Solar System objects into dry bodies, ranging out to the main asteroid belt, and icy bodies beyond the belt. Models suggest that some of the icy bodies may have migrated into the asteroid belt. Recent observations indicate the presence of water ice on the surface of some asteroids, with sublimation a potential reason for the dust activity observed on others. Hydrated minerals have been found on the surface of the largest object in the asteroid belt, the dwarf planet (1) Ceres, which is thought to be differentiated into a silicate core with an icy mantle. The presence of water vapour around Ceres was suggested by a marginal detection of the photodissociation product of water, hydroxyl (ref. 12), but could not be confirmed by later, more sensitive observations. Here we report the detection of water vapour around Ceres, with at least 1026 molecules being produced per second, originating from localized sources that seem to be linked to mid-latitude regions on the surface. The water evaporation could be due to comet-like sublimation or to cryo-volcanism, in which volcanoes erupt volatiles such as water instead of molten rocks.

doi: 10.1038/nature12918

Tunable symmetry breaking and helical edge transport in a graphene quantum spin Hall state p.528

Low-dimensional electronic systems have traditionally been obtained by electrostatically confining electrons, either in heterostructures or in intrinsically nanoscale materials such as single molecules, nanowires and graphene. Recently, a new method has emerged with the recognition that symmetry-protected topological (SPT) phases, which occur in systems with an energy gap to quasiparticle excitations (such as insulators or superconductors), can host robust surface states that remain gapless as long as the relevant global symmetry remains unbroken. The nature of the charge carriers in SPT surface states is intimately tied to the symmetry of the bulk, resulting in one- and two-dimensional electronic systems with novel properties. For example, time reversal symmetry endows the massless charge carriers on the surface of a three-dimensional topological insulator with helicity, fixing the orientation of their spin relative to their momentum. Weakly breaking this symmetry generates a gap on the surface, resulting in charge carriers with finite effective mass and exotic spin textures. Analogous manipulations have yet to be demonstrated in two-dimensional topological insulators, where the primary example of a SPT phase is the quantum spin Hall state. Here we demonstrate experimentally that charge-neutral monolayer graphene has a quantum spin Hall state when it is subjected to a very large magnetic field angled with respect to the graphene plane. In contrast to time-reversal-symmetric systems, this state is protected by a symmetry of planar spin rotations that emerges as electron spins in a half-filled Landau level are polarized by the large magnetic field. The properties of the resulting helical edge states can be modulated by balancing the applied field against an intrinsic antiferromagnetic instability, which tends to spontaneously break the spin-rotation symmetry. In the resulting canted antiferromagnetic state, we observe transport signatures of gapped edge states, which constitute a new kind of one-dimensional electronic system with a tunable bandgap and an associated spin texture.

doi: 10.1038/nature12800

Dislocations in bilayer graphene p.533

Dislocations represent one of the most fascinating and fundamental concepts in materials science. Most importantly, dislocations are the main carriers of plastic deformation in crystalline materials. Furthermore, they can strongly affect the local electronic and optical properties of semiconductors and ionic crystals. In materials with small dimensions, they experience extensive image forces, which attract them to the surface to release strain energy. However, in layered crystals such as graphite, dislocation movement is mainly restricted to the basal plane. Thus, the dislocations cannot escape, enabling their confinement in crystals as thin as only two monolayers. To explore the nature of dislocations under such extreme boundary conditions, the material of choice is bilayer graphene, the thinnest possible quasi-two-dimensional crystal in which such linear defects can be confined. Homogeneous and robust graphene membranes derived from high-quality epitaxial graphene on silicon carbide provide an ideal platform for their investigation. Here we report the direct observation of basal-plane dislocations in freestanding bilayer graphene using transmission electron microscopy and their detailed investigation by diffraction contrast analysis and atomistic simulations. Our investigation reveals two striking size effects. First, the absence of stacking-fault energy, a unique property of bilayer graphene, leads to a characteristic dislocation pattern that corresponds to an alternating AB  AC change of the stacking order. Second, our experiments in combination with atomistic simulations reveal a pronounced buckling of the bilayer graphene membrane that results directly from accommodation of strain. In fact, the buckling changes the strain state of the bilayer graphene and is of key importance for its electronic properties. Our findings will contribute to the understanding of dislocations and of their role in the structural, mechanical and electronic properties of bilayer and few-layer graphene.

doi: 10.1038/nature12780

Impacts of the north and tropical Atlantic Ocean on the Antarctic Peninsula and sea ice p.538

In recent decades, Antarctica has experienced pronounced climate changes. The Antarctic Peninsula exhibited the strongest warming of any region on the planet, causing rapid changes in land ice. Additionally, in contrast to the sea-ice decline over the Arctic, Antarctic sea ice has not declined, but has instead undergone a perplexing redistribution. Antarctic climate is influenced by, among other factors, changes in radiative forcing and remote Pacific climate variability, but none explains the observed Antarctic Peninsula warming or the sea-ice redistribution in austral winter. However, in the north and tropical Atlantic Ocean, the Atlantic Multidecadal Oscillation (a leading mode of sea surface temperature variability) has been overlooked in this context. Here we show that sea surface warming related to the Atlantic Multidecadal Oscillation reduces the surface pressure in the Amundsen Sea and contributes to the observed dipole-like sea-ice redistribution between the Ross and Amundsen–Bellingshausen–Weddell seas and to the Antarctic Peninsula warming. Support for these findings comes from analysis of observational and reanalysis data, and independently from both comprehensive and idealized atmospheric model simulations. We suggest that the north and tropical Atlantic is important for projections of future climate change in Antarctica, and has the potential to affect the global thermohaline circulation and sea-level change.

doi: 10.1038/nature12945

Mycorrhiza-mediated competition between plants and decomposers drives soil carbon storage p.543

Soil contains more carbon than the atmosphere and vegetation combined. Understanding the mechanisms controlling the accumulation and stability of soil carbon is critical to predicting the Earth’s future climate. Recent studies suggest that decomposition of soil organic matter is often limited by nitrogen availability to microbes and that plants, via their fungal symbionts, compete directly with free-living decomposers for nitrogen. Ectomycorrhizal and ericoid mycorrhizal (EEM) fungi produce nitrogen-degrading enzymes, allowing them greater access to organic nitrogen sources than arbuscular mycorrhizal (AM) fungi. This leads to the theoretical prediction that soil carbon storage is greater in ecosystems dominated by EEM fungi than in those dominated by AM fungi. Using global data sets, we show that soil in ecosystems dominated by EEM-associated plants contains 70% more carbon per unit nitrogen than soil in ecosystems dominated by AM-associated plants. The effect of mycorrhizal type on soil carbon is independent of, and of far larger consequence than, the effects of net primary production, temperature, precipitation and soil clay content. Hence the effect of mycorrhizal type on soil carbon content holds at the global scale. This finding links the functional traits of mycorrhizal fungi to carbon storage at ecosystem-to-global scales, suggesting that plant–decomposer competition for nutrients exerts a fundamental control over the terrestrial carbon cycle.

doi: 10.1038/nature12901

The genome of the recently domesticated crop plant sugar beet (Beta vulgaris) OPEN p.546

Sugar beet (Beta vulgaris ssp. vulgaris) is an important crop of temperate climates which provides nearly 30% of the world’s annual sugar production and is a source for bioethanol and animal feed. The species belongs to the order of Caryophylalles, is diploid with 2n = 18 chromosomes, has an estimated genome size of 714–758 megabases and shares an ancient genome triplication with other eudicot plants. Leafy beets have been cultivated since Roman times, but sugar beet is one of the most recently domesticated crops. It arose in the late eighteenth century when lines accumulating sugar in the storage root were selected from crosses made with chard and fodder beet. Here we present a reference genome sequence for sugar beet as the first non-rosid, non-asterid eudicot genome, advancing comparative genomics and phylogenetic reconstructions. The genome sequence comprises 567 megabases, of which 85% could be assigned to chromosomes. The assembly covers a large proportion of the repetitive sequence content that was estimated to be 63%. We predicted 27,421 protein-coding genes supported by transcript data and annotated them on the basis of sequence homology. Phylogenetic analyses provided evidence for the separation of Caryophyllales before the split of asterids and rosids, and revealed lineage-specific gene family expansions and losses. We sequenced spinach (Spinacia oleracea), another Caryophyllales species, and validated features that separate this clade from rosids and asterids. Intraspecific genomic variation was analysed based on the genome sequences of sea beet (Beta vulgaris ssp. maritima; progenitor of all beet crops) and four additional sugar beet accessions. We identified seven million variant positions in the reference genome, and also large regions of low variability, indicating artificial selection. The sugar beet genome sequence enables the identification of genes affecting agronomically relevant traits, supports molecular breeding and maximizes the plant’s potential in energy biotechnology.

doi: 10.1038/nature12817

Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer’s disease p.550

Genome-wide association studies (GWAS) have identified several risk variants for late-onset Alzheimer's disease (LOAD). These common variants have replicable but small effects on LOAD risk and generally do not have obvious functional effects. Low-frequency coding variants, not detected by GWAS, are predicted to include functional variants with larger effects on risk. To identify low-frequency coding variants with large effects on LOAD risk, we carried out whole-exome sequencing (WES) in 14 large LOAD families and follow-up analyses of the candidate variants in several large LOAD case–control data sets. A rare variant in PLD3 (phospholipase D3; Val232Met) segregated with disease status in two independent families and doubled risk for Alzheimer’s disease in seven independent case–control series with a total of more than 11,000 cases and controls of European descent. Gene-based burden analyses in 4,387 cases and controls of European descent and 302 African American cases and controls, with complete sequence data for PLD3, reveal that several variants in this gene increase risk for Alzheimer’s disease in both populations. PLD3 is highly expressed in brain regions that are vulnerable to Alzheimer’s disease pathology, including hippocampus and cortex, and is expressed at significantly lower levels in neurons from Alzheimer’s disease brains compared to control brains. Overexpression of PLD3 leads to a significant decrease in intracellular amyloid-β precursor protein (APP) and extracellular Aβ42 and Aβ40 (the 42- and 40-residue isoforms of the amyloid-β peptide), and knockdown of PLD3 leads to a significant increase in extracellular Aβ42 and Aβ40. Together, our genetic and functional data indicate that carriers of PLD3 coding variants have a twofold increased risk for LOAD and that PLD3 influences APP processing. This study provides an example of how densely affected families may help to identify rare variants with large effects on risk for disease or other complex traits.

doi: 10.1038/nature12825

Oestrogen increases haematopoietic stem-cell self-renewal in females and during pregnancy p.555

Sexually dimorphic mammalian tissues, including sexual organs and the brain, contain stem cells that are directly or indirectly regulated by sex hormones. An important question is whether stem cells also exhibit sex differences in physiological function and hormonal regulation in tissues that do not show sex-specific morphological differences. The terminal differentiation and function of some haematopoietic cells are regulated by sex hormones, but haematopoietic stem-cell function is thought to be similar in both sexes. Here we show that mouse haematopoietic stem cells exhibit sex differences in cell-cycle regulation by oestrogen. Haematopoietic stem cells in female mice divide significantly more frequently than in male mice. This difference depends on the ovaries but not the testes. Administration of oestradiol, a hormone produced mainly in the ovaries, increased haematopoietic stem-cell division in males and females. Oestrogen levels increased during pregnancy, increasing haematopoietic stem-cell division, haematopoietic stem-cell frequency, cellularity, and erythropoiesis in the spleen. Haematopoietic stem cells expressed high levels of oestrogen receptor-α (ERα). Conditional deletion of ERα from haematopoietic stem cells reduced haematopoietic stem-cell division in female, but not male, mice and attenuated the increases in haematopoietic stem-cell division, haematopoietic stem-cell frequency, and erythropoiesis during pregnancy. Oestrogen/ERα signalling promotes haematopoietic stem-cell self-renewal, expanding splenic haematopoietic stem cells and erythropoiesis during pregnancy.

doi: 10.1038/nature12932

Diet rapidly and reproducibly alters the human gut microbiome p.559

Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut, but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals, reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids and the outgrowth of microorganisms capable of triggering inflammatory bowel disease. In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles.

doi: 10.1038/nature12820

Glutamine methylation in histone H2A is an RNA-polymerase-I-dedicated modification p.564

Nucleosomes are decorated with numerous post-translational modifications capable of influencing many DNA processes. Here we describe a new class of histone modification, methylation of glutamine, occurring on yeast histone H2A at position 105 (Q105) and human H2A at Q104. We identify Nop1 as the methyltransferase in yeast and demonstrate that fibrillarin is the orthologue enzyme in human cells. Glutamine methylation of H2A is restricted to the nucleolus. Global analysis in yeast, using an H2AQ105me-specific antibody, shows that this modification is exclusively enriched over the 35S ribosomal DNA transcriptional unit. We show that the Q105 residue is part of the binding site for the histone chaperone FACT (facilitator of chromatin transcription) complex. Methylation of Q105 or its substitution to alanine disrupts binding to FACT in vitro. A yeast strain mutated at Q105 shows reduced histone incorporation and increased transcription at the ribosomal DNA locus. These features are phenocopied by mutations in FACT complex components. Together these data identify glutamine methylation of H2A as the first histone epigenetic mark dedicated to a specific RNA polymerase and define its function as a regulator of FACT interaction with nucleosomes.

doi: 10.1038/nature12819

Structural basis of the alternating-access mechanism in a bile acid transporter p.569

Bile acids are synthesized from cholesterol in hepatocytes and secreted through the biliary tract into the small intestine, where they aid in absorption of lipids and fat-soluble vitamins. Through a process known as enterohepatic recirculation, more than 90% of secreted bile acids are then retrieved from the intestine and returned to the liver for resecretion. In humans, there are two Na+-dependent bile acid transporters involved in enterohepatic recirculation, the Na+-taurocholate co-transporting polypeptide (NTCP; also known as SLC10A1) expressed in hepatocytes, and the apical sodium-dependent bile acid transporter (ASBT; also known as SLC10A2) expressed on enterocytes in the terminal ileum. In recent years, ASBT has attracted much interest as a potential drug target for treatment of hypercholesterolaemia, because inhibition of ASBT reduces reabsorption of bile acids, thus increasing bile acid synthesis and consequently cholesterol consumption. However, a lack of three-dimensional structures of bile acid transporters hampers our ability to understand the molecular mechanisms of substrate selectivity and transport, and to interpret the wealth of existing functional data. The crystal structure of an ASBT homologue from Neisseria meningitidis (ASBTNM) in detergent was reported recently, showing the protein in an inward-open conformation bound to two Na+ and a taurocholic acid. However, the structural changes that bring bile acid and Na+ across the membrane are difficult to infer from a single structure. To understand the structural changes associated with the coupled transport of Na+ and bile acids, here we solved two structures of an ASBT homologue from Yersinia frederiksenii (ASBTYf) in a lipid environment, which reveal that a large rigid-body rotation of a substrate-binding domain gives the conserved ‘crossover’ region, where two discontinuous helices cross each other, alternating accessibility from either side of the cell membrane. This result has implications for the location and orientation of the bile acid during transport, as well as for the translocation pathway for Na+.

doi: 10.1038/nature12811