Volume 530 Number 7589

Editorials

Benefits of sharing p.129

A swift and effective response to emerging infectious diseases demands that researchers have ready access to the latest data on the pathogens responsible. There is still a long way to go to ensure this.

doi: 10.1038/530129a

A good precedent p.129

Jimmy Carter’s efforts to eradicate Guinea worm should be applauded.

doi: 10.1038/530130a

Outside the bubble p.130

Governments must stop proposing solutions and invest in large-scale removal of carbon dioxide.

doi: 10.1038/530130b

News

News Features

News & Views

From genetics to physiology at last p.162

The identification of a set of genetic variations that are strongly associated with the risk of developing schizophrenia provides insights into the neurobiology of this destructive disease. See Article p.177

doi: 10.1038/nature16874

A great Arctic ice shelf p.163

Newly mapped features on the floor of the Arctic Ocean suggest that the Arctic basin was once covered by a one-kilometre-thick, flowing ice shelf derived from large ice sheets in eastern Siberia, Arctic Canada and the Barents Sea.

doi: 10.1038/nature16878

Out with the old p.164

The selective elimination of cells that have adopted an irreversible, senescent state has now been shown to extend the lifespan of mice and to ameliorate some age-related disease processes. See Article p.184

doi: 10.1038/nature16875

Compact coupling for a two-stage accelerator p.165

Injecting electrons that have been accelerated by a laser-powered plasma wave into a second plasma wave represents a two-step electron accelerator. With 100 such steps, collider applications become possible. See Letter p.190

doi: 10.1038/530165a

Asymmetric breaks in DNA cause sterility p.167

The part that the mouse gene Prdm9 plays in generating double-strand breaks in DNA has now been linked to its putative role in speciation, thanks to experiments that use a 'humanized' version of the gene. See Article p.171

doi: 10.1038/nature16870

Resolution beyond the diffraction limit p.168

A method has been devised that extends the resolution of X-ray crystal structures beyond the diffraction limit. This might help to improve the visualization of structures of proteins that form 'poorly diffracting' crystals. See Letter p.202

doi: 10.1038/530168a

Exoplanets hidden in the gaps p.169

Planets develop from the disk of dust and gas that surrounds a newly formed star. Observations of gaps in the disks of four such systems have allowed us to start unravelling the processes by which planets form.

doi: 10.1038/530169a

Articles

Re-engineering the zinc fingers of PRDM9 reverses hybrid sterility in mice p.171

PRDM9 is a DNA-binding protein that controls the position of double-strand breaks in meiosis, and the gene that encodes it is responsible for hybrid infertility between closely related mouse species; this hybrid infertility is eliminated by introducing the zinc-finger domain sequence from the human version of the PRDM9 gene, a change which alters both the position of double-strand breaks and the symmetry of PRDM9 binding and suggests that PRDM9 may have a more general but transient role in the early stages of speciation.

doi: 10.1038/nature16931

Schizophrenia risk from complex variation of complement component 4 p.177

Schizophrenia is associated with genetic variation at the major histocompatibility complex locus; this study reveals that alleles at this locus associate with schizophrenia in proportion to their tendency to generate greater expression of complement component 4 (C4A) genes and that C4 promotes the elimination of synapses.

doi: 10.1038/nature16549

Naturally occurring p16Ink4a-positive cells shorten healthy lifespan p.184

When senescent cells accumulate during adulthood they negatively influence lifespan and promote age-dependent changes in several organs; clearance of these cells delayed tumorigenesis in mice and attenuated age-related deterioration of several organs without overt side effects, suggesting that the therapeutic removal of senescent cells may be able to extend healthy lifespan.

doi: 10.1038/nature16932

Letters

Observing the Rosensweig instability of a quantum ferrofluid p.194

Spontaneous translational symmetry breaking is experimentally observed in a dipolar Bose–Einstein condensate of dysprosium atoms, whereby an instability causes a spontaneous transition from an unstructured superfluid to an ordered arrangement of droplet crystals, which is surprisingly long-lived.

doi: 10.1038/nature16485

Observation of polar vortices in oxide superlattices p.198

In material systems with several interacting degrees of freedom, the complex interplay between these factors can give rise to exotic phases; now superlattices consisting of alternating layers of PbTiO3 and SrTiO3 are found to exhibit an unusual form of ferroelectric ordering in the PbTiO3 layers, in which the electric dipoles arrange themselves into regular, ordered arrays of vortex–antivortex structures.

doi: 10.1038/nature16463

Macromolecular diffractive imaging using imperfect crystals p.202

Crystal lattice disorder, which gives rise to a continuous diffraction pattern, is exploited to determine the structure of the integral membrane protein complex photosystem II to a higher resolution than could be achieved using Bragg diffraction alone.

doi: 10.1038/nature16949

Covariation of deep Southern Ocean oxygenation and atmospheric CO2 through the last ice age p.207

A reconstruction of changes in ocean oxygenation throughout the last glacial cycle shows that respired carbon was removed from the deep Southern Ocean during deglaciation and Antarctic warm events, consistent with a prominent role of reduced iron fertilization and enhanced ocean ventilation, modifying atmospheric carbon dioxide concentrations over the past 80,000 years.

doi: 10.1038/nature16514

Hoxb5 marks long-term haematopoietic stem cells and reveals a homogenous perivascular niche p.223

Until recently, complex multi-parameters were required for the isolation and identification of haematopoietic stem cells, complicating study of their biology in situ; here the authors have found that expression of a single gene, Hoxb5, defines haematopoietic stem cells with long-term reconstitution capacity, and that these cells are mainly found in direct contact with endothelial cells.

doi: 10.1038/nature16943

Real-time, portable genome sequencing for Ebola surveillance p.228

A nanopore DNA sequencer is used for real-time genomic surveillance of the Ebola virus epidemic in the field in Guinea; the authors demonstrate that it is possible to pack a genomic surveillance laboratory in a suitcase and transport it to the field for on-site virus sequencing, generating results within 24 hours of sample collection.

doi: 10.1038/nature16996

Backbone NMR reveals allosteric signal transduction networks in the β1-adrenergic receptor p.237

G protein-coupled receptors (GPCRs) are physiologically important transmembrane signalling proteins that trigger intracellular responses upon binding of extracellular ligands. Despite recent breakthroughs in GPCR crystallography, the details of ligand-induced signal transduction are not well understood owing to missing dynamical information. In principle, such information can be provided by NMR, but so far only limited data of functional relevance on few side-chain sites of eukaryotic GPCRs have been obtained. Here we show that receptor motions can be followed at virtually any backbone site in a thermostabilized mutant of the turkey β1-adrenergic receptor (β1AR). Labelling with [15N]valine in a eukaryotic expression system provides over twenty resolved resonances that report on structure and dynamics in six ligand complexes and the apo form. The response to the various ligands is heterogeneous in the vicinity of the binding pocket, but gets transformed into a homogeneous readout at the intracellular side of helix 5 (TM5), which correlates linearly with ligand efficacy for the G protein pathway. The effect of several pertinent, thermostabilizing point mutations was assessed by reverting them to the native sequence. Whereas the response to ligands remains largely unchanged, binding of the G protein mimetic nanobody NB80 and G protein activation are only observed when two conserved tyrosines (Y227 and Y343) are restored. Binding of NB80 leads to very strong spectral changes throughout the receptor, including the extracellular ligand entrance pocket. This indicates that even the fully thermostabilized receptor undergoes activating motions in TM5, but that the fully active state is only reached in presence of Y227 and Y343 by stabilization with a G protein-like partner. The combined analysis of chemical shift changes from the point mutations and ligand responses identifies crucial connections in the allosteric activation pathway, and presents a general experimental method to delineate signal transmission networks at high resolution in GPCRs.

doi: 10.1038/nature16577