Volume 514 Issue 7523

Editorials

The ice bucket p.403

Social-media fun for medical research bypasses animal sensitivities.

doi: 10.1038/514403b

A ripe time for gaining ground p.403

After three years of heated debate, the advocates and critics of gain-of-function research must work to agree on how best to regulate the work.

doi: 10.1038/514403a

Toxic influence p.404

Europe must act to stop livestock drugs from wiping out its vulture populations.

doi: 10.1038/514404a

News

News Features

The ethics squad p.418

Bioethicists are setting up consultancies for research — but some scientists question whether they are needed.

doi: 10.1038/514418a

Tales of the hobbit p.422

In 2004, researchers announced the discovery of Homo floresiensis, a small relative of modern humans that lived as recently as 18,000 years ago. The ‘hobbit’ is now considered the most important hominin fossil in a generation. Here, the scientists behind the find tell its story.

doi: 10.1038/514422a

News & Views

A crack in the natural-gas bridge p.436

Integrated assessment models show that, without new climate policies, abundant supplies of natural gas will have little impact on greenhouse-gas emissions and climate change. See Letter p.482

doi: 10.1038/nature13927

A stamp on the envelope p.437

A high-resolution crystal structure of the HIV-1 Env trimer proteins, in their form before they fuse with target cells, will aid the design of vaccines that elicit protective immune responses to this protein complex. See Article p.455

doi: 10.1038/nature13926

Treatment by cell transplant p.438

Transplanting gene-corrected macrophage cells directly into the lungs of mice has been shown to effectively treat their pulmonary alveolar proteinosis, a hereditary lung disease also found in humans. See Article p.450

doi: 10.1038/nature13758

Hurling comets around a planetary nursery p.440

An analysis of hundreds of star-grazing comets in a young planetary system shows that they form two families: a group of old, dried-out comets and a younger group probably related to the break-up of a larger planetary body. See Letter p.462

doi: 10.1038/514440a

Relax and come in p.441

During inflammation, lymph nodes swell with an influx of immune cells. New findings identify a signalling pathway that induces relaxation in the contractile cells that give structure to these organs. See Letter p.498

doi: 10.1038/514441a

Potency needs constancy p.442

In a finding that highlights ways to optimize the efficacy of antibody-based therapeutics and vaccines, the activity of potent HIV-1-neutralizing antibodies has been confirmed to depend on cellular binding to the antibodies' Fc regions.

doi: 10.1038/514442a

Articles

Genome sequence of a 45,000-year-old modern human from western Siberia p.445

The high-quality genome sequence of a 45,000-year-old modern human from Siberia reveals that gene flow from Neanderthals into the ancestors of this individual had already occurred about 7,000 to 13,000 years earlier; genomic comparisons show that he belonged to a population that lived close in time to the separation of populations in east and west Eurasia and that may represent an early modern human radiation out of Africa that has no direct descendants today.

doi: 10.1038/nature13810

Pulmonary macrophage transplantation therapy p.450

This study reports the correction of pulmonary alveolar proteinosis (PAP) in Csf2rb–/– mice by a single transfer of either wild-type or gene-corrected macrophages directly to the lungs — the transplanted macrophages persisted for at least 1 year; this transplantation strategy obviated the need for myeloablation and immunosuppression and should be a feasible therapy for humans with hereditary PAP.

doi: 10.1038/nature13807

Structure and immune recognition of trimeric pre-fusion HIV-1 Env p.455

A crystal structure of the human immunodeficiency virus Env trimer, used by the virus to infect cells, is determined here; the new structure, which shows the pre-fusion form of Env, increases our understanding of the fusion mechanism and of how the conformation of Env allows the virus to evade the immune response.

doi: 10.1038/nature13808

Letters

Two families of exocomets in the β Pictoris system p.462

The young planetary system surrounding the star β Pictoris harbours active minor bodies. These asteroids and comets produce a large amount of dust and gas through collisions and evaporation, as happened early in the history of our Solar System. Spectroscopic observations of β Pictoris reveal a high rate of transits of small evaporating bodies, that is, exocomets. Here we report an analysis of more than 1,000 archival spectra gathered between 2003 and 2011, which provides a sample of about 6,000 variable absorption signatures arising from exocomets transiting the disk of the parent star. Statistical analysis of the observed properties of these exocomets allows us to identify two populations with different physical properties. One family consists of exocomets producing shallow absorption lines, which can be attributed to old exhausted (that is, strongly depleted in volatiles) comets trapped in a mean motion resonance with a massive planet. Another family consists of exocomets producing deep absorption lines, which may be related to the recent fragmentation of one or a few parent bodies. Our results show that the evaporating bodies observed for decades in the β Pictoris system are analogous to the comets in our own Solar System.

doi: 10.1038/nature13849

Producing more grain with lower environmental costs p.486

In an experiment across China to test integrated soil–crop system management for rice, wheat and maize against current practice, improvements in grain yield are equivalent to high-input techniques, but nutrient use, nutrient loss and greenhouse gas emissions are lower than current practice.

doi: 10.1038/nature13609

Diabetes recovery by age-dependent conversion of pancreatic δ-cells into insulin producers p.503

Total or near-total loss of insulin-producing β-cells occurs in type 1 diabetes. Restoration of insulin production in type 1 diabetes is thus a major medical challenge. We previously observed in mice in which β-cells are completely ablated that the pancreas reconstitutes new insulin-producing cells in the absence of autoimmunity. The process involves the contribution of islet non-β-cells; specifically, glucagon-producing α-cells begin producing insulin by a process of reprogramming (transdifferentiation) without proliferation. Here we show the influence of age on β-cell reconstitution from heterologous islet cells after near-total β-cell loss in mice. We found that senescence does not alter α-cell plasticity: α-cells can reprogram to produce insulin from puberty through to adulthood, and also in aged individuals, even a long time after β-cell loss. In contrast, before puberty there is no detectable α-cell conversion, although β-cell reconstitution after injury is more efficient, always leading to diabetes recovery. This process occurs through a newly discovered mechanism: the spontaneous en masse reprogramming of somatostatin-producing δ-cells. The juveniles display ‘somatostatin-to-insulin’ δ-cell conversion, involving dedifferentiation, proliferation and re-expression of islet developmental regulators. This juvenile adaptability relies, at least in part, upon the combined action of FoxO1 and downstream effectors. Restoration of insulin producing-cells from non-β-cell origins is thus enabled throughout life via δ- or α-cell spontaneous reprogramming. A landscape with multiple intra-islet cell interconversion events is emerging, offering new perspectives for therapy.

doi: 10.1038/nature13633

Contrasting roles of histone 3 lysine 27 demethylases in acute lymphoblastic leukaemia p.513

T-cell acute lymphoblastic leukaemia (T-ALL) is a haematological malignancy with a poor prognosis and no available targeted therapies; now two histone H3 lysine 27 demethylases, JMJD3 and UTX, are shown to have contrasting roles in human T-ALL cells and a mouse model of the disease, and a small molecule demethylase inhibitor is found to inhibit the growth of T-ALL cell lines, introducing a potential therapeutic avenue for acute leukaemia.

doi: 10.1038/nature13605

Structure and mechanism of Zn2+-transporting P-type ATPases p.518

Zinc is an essential micronutrient for all living organisms. It is required for signalling and proper functioning of a range of proteins involved in, for example, DNA binding and enzymatic catalysis. In prokaryotes and photosynthetic eukaryotes, Zn2+-transporting P-type ATPases of class IB (ZntA) are crucial for cellular redistribution and detoxification of Zn2+ and related elements. Here we present crystal structures representing the phosphoenzyme ground state (E2P) and a dephosphorylation intermediate (E2·Pi) of ZntA from Shigella sonnei, determined at 3.2 Å and 2.7 Å resolution, respectively. The structures reveal a similar fold to Cu+-ATPases, with an amphipathic helix at the membrane interface. A conserved electronegative funnel connects this region to the intramembranous high-affinity ion-binding site and may promote specific uptake of cellular Zn2+ ions by the transporter. The E2P structure displays a wide extracellular release pathway reaching the invariant residues at the high-affinity site, including C392, C394 and D714. The pathway closes in the E2·Pi state, in which D714 interacts with the conserved residue K693, which possibly stimulates Zn2+ release as a built-in counter ion, as has been proposed for H+-ATPases. Indeed, transport studies in liposomes provide experimental support for ZntA activity without counter transport. These findings suggest a mechanistic link between PIB-type Zn2+-ATPases and PIII-type H+-ATPases and at the same time show structural features of the extracellular release pathway that resemble PII-type ATPases such as the sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) and Na+, K+-ATPase. These findings considerably increase our understanding of zinc transport in cells and represent new possibilities for biotechnology and biomedicine.

doi: 10.1038/nature13618