Volume 516 Number 7531

Editorials

Spin cycle p.287

Pressures in all stages of the news-making process can lead to hype in science reporting.

doi: 10.1038/516287b

Keep asking the question p.287

Scientists must push to preserve a small part of a large US survey that provides essential information on the ever-changing scientific workforce.

doi: 10.1038/516287a

Honest brokers p.288

Climate negotiations in Lima stumbled on transparency, but there is time to adjust.

doi: 10.1038/516288a

News

News Features

News & Views

Better chemistry through radicals p.332

An iron catalyst has been developed that mediates bond formation between a wide range of alkene reactants, opening up short synthetic routes to compounds that were previously accessible only through arduous pathways. See Article p.343

doi: 10.1038/516332a

Toehold gene switches make big footprints p.333

The development of RNA-based devices called toehold switches that regulate translation might usher in an era in which protein production can be linked to almost any RNA input and provide precise, low-cost diagnostics.

doi: 10.1038/516333a

How vector mosquitoes beat the heat p.334

Intensive longitudinal sampling of malaria mosquitoes in the African semi-desert reveals that three morphologically indistinguishable species have distinctive strategies for surviving the dry season.

doi: 10.1038/nature14073

Mind the gaps p.336

New analysis reveals the conservation gains that could be achieved by expanding the global network of protected areas — but also how this may be undermined by land-use change and a lack of international coordination. See Letter p.383

doi: 10.1038/516336a

Two steps for a magnetoelectric switch p.337

Magnetoelectric materials allow magnetism to be controlled by an electric field. The discovery of an indirect path for switching electrical polarization in one such material brings this idea close to practical use. See Letter p.370

doi: 10.1038/516337a

An RNA-synthesizing machine p.338

Crystal structures of the complete RNA polymerases from influenza A and B viruses provide insight into how these enzymes initiate RNA synthesis, and reveal targets for antiviral drug design. See Articles p.355 & p.361

doi: 10.1038/516338a

Articles

An AUTS2–Polycomb complex activates gene expression in the CNS p.349

Polycomb group proteins are known to maintain gene repression during development; however, when autism susceptibility candidate 2 (AUTS2) associates with some Polycomb group complexes, these complexes have an unexpected gene activation role, offering new insight into the role of AUTS2 in neurological disorders.

doi: 10.1038/nature13921

Letters

The exclusion of a significant range of ages in a massive star cluster p.367

Hubble Space Telescope observations of the stellar cluster NGC 1651, which is approximately two billion years old, show that the colour–brightness distribution of stars old enough to have left the main sequence can be explained only by a single-age population, despite having a feature usually interpreted to indicate an age spread of more than 300 million years.

doi: 10.1038/nature13969

Global protected area expansion is compromised by projected land-use and parochialism p.383

Internationally coordinated expansion of the global protected area network to 17% could triple the average protection of species ranges and ecoregions; if projected land-use changes and consequent habitat loss until 2040 occur, currently feasible protection levels will not be achievable, and more than 1,000 threatened species face reductions in the range of over 50%.

doi: 10.1038/nature14032

Signatures of aestivation and migration in Sahelian malaria mosquito populations p.387

Malaria-carrying mosquitoes nearly disappear in the dry season, yet they reappear suddenly following the first rains; using surveys of mosquito densities, the authors characterize the population dynamics of the three main vector species and use these to infer persistence by long-distance migration in two species and aestivation in the third.

doi: 10.1038/nature13987

Adenosine activates brown adipose tissue and recruits beige adipocytes via A2A receptors p.395

Cold exposure activates brown adipose tissue (BAT) through the sympathetic nervous system, and previous studies have reported inhibitory effects of the purinergic transmitter adenosine in BAT from hamster or rat; here adenosine/A2A signalling is shown to be involved in sympathetic activation of human and murine brown adipocytes to allow protection of mice from diet-induced obesity.

doi: 10.1038/nature13816

Modelling human development and disease in pluripotent stem-cell-derived gastric organoids p.400

The in vitro generation, from pluripotent stem cells, of three-dimensional human gastric organoids (hGOs) that contain a physiological gastric epithelium comprising both progenitor and differentiated cell types, and have expected functional characteristics is described, as is modelling the pathophysiological response of the human stomach to Helicobacter pylori using these hGOs.

doi: 10.1038/nature13863

Primate-specific endogenous retrovirus-driven transcription defines naive-like stem cells p.405

An extensive analysis of HERVH (a primate-specific endogenous retrovirus) expression in human pluripotent stem cells is presented, identifying a sub-population of cells within cultured human embryonic stem cells and induced pluripotent stem cells that has characteristics of naive-state cells — the study provides evidence for a new primate-specific transcriptional circuitry regulating pluripotency.

doi: 10.1038/nature13804

Protein quality control at the inner nuclear membrane p.410

A protein degradation pathway is found at the inner nuclear membrane that is distinct from, but complementary to, endoplasmic-reticulum-associated protein degradation, and which is mediated by the Asi protein complex; a genome-wide library screening of yeast identifies more than 20 substrates of this pathway, which is shown to target mislocalized integral membrane proteins for degradation.

doi: 10.1038/nature14096

In vivo engineering of oncogenic chromosomal rearrangements with the CRISPR/Cas9 system p.423

Chromosomal rearrangements have a central role in the pathogenesis of human cancers and often result in the expression of therapeutically actionable gene fusions. A recently discovered example is a fusion between the genes echinoderm microtubule-associated protein like 4 (EML4) and anaplastic lymphoma kinase (ALK), generated by an inversion on the short arm of chromosome 2: inv(2)(p21p23). The EML4–ALK oncogene is detected in a subset of human non-small cell lung cancers (NSCLC) and is clinically relevant because it confers sensitivity to ALK inhibitors. Despite their importance, modelling such genetic events in mice has proven challenging and requires complex manipulation of the germ line. Here we describe an efficient method to induce specific chromosomal rearrangements in vivo using viral-mediated delivery of the CRISPR/Cas9 system to somatic cells of adult animals. We apply it to generate a mouse model of Eml4–Alk-driven lung cancer. The resulting tumours invariably harbour the Eml4–Alk inversion, express the Eml4–Alk fusion gene, display histopathological and molecular features typical of ALK+ human NSCLCs, and respond to treatment with ALK inhibitors. The general strategy described here substantially expands our ability to model human cancers in mice and potentially in other organisms.

doi: 10.1038/nature13902

Rapid modelling of cooperating genetic events in cancer through somatic genome editing p.428

The CRISPR/Cas system has been used in mice for genome editing to introduce genetic alterations found in human lung tumours, and these genome modifications resulted in mouse lung tumours showing different histopathologies depending on the genes altered; the CRISPR/Cas system offers improved and faster ways to create animal models of human diseases such as cancer.

doi: 10.1038/nature13906

Cohesin-dependent globules and heterochromatin shape 3D genome architecture in S. pombe p.432

Genome-wide chromatin conformation capture (Hi-C) is used to investigate three-dimensional genome organization in Schizosaccharomyces bombe; small domains of chromatin interact locally on chromosome arms to form globules, which depend on cohesin but not heterochromatin for formation, and heterochromatin at centromeres and telomeres provides crucial structural constraints to shape genome architecture.

doi: 10.1038/nature13833