Volume 524 Number 7564

Editorial

Science in the community p.135

Randomized controlled trials are providing evidence about interventions in health, education and international development, but they are only part of a suite of useful tools.

doi: 10.1038/524135a

News

News Features

News & Views

A cure for catalyst poisoning p.164

Compounds that are sensitive to the components of air are difficult to use in chemical reactions, requiring conditions that are tedious to set up. A simple, practical solution to this problem has finally been devised. See Letter p.208

doi: 10.1038/524164a

Maintaining liver mass p.165

A previously under-appreciated subset of liver cells has been found to contribute to the day-to-day maintenance of liver mass in mice. The cells are induced and supported by signals from an adjacent vein. See Article p.180

doi: 10.1038/nature15201

Strand separation unravelled p.166

The DNA double helix must be separated into single strands to be duplicated. A structure of the Mcm2–7 helicase enzyme responsible for this activity yields unprecedented insight into how the process is initiated. See Article p.186

doi: 10.1038/nature14643

Matter and antimatter scrutinized p.168

A search for differences in the charge-to-mass ratio of protons and antiprotons, conducted at unprecedented levels of precision, results in stringent limits to the validity of fundamental physical symmetries. See Letter p.196

doi: 10.1038/524168a

It takes two to untangle p.169

Yeast require the enzyme Hsp104 to untangle protein aggregates, which arise in stressed or aged cells. Animals lack Hsp104, but it emerges that proteins of the DNAJ family of molecular chaperones can fulfil this role. See Letter p.251

doi: 10.1038/nature14640

Mapping the path to a longer life p.170

Inhibiting the PI3K branch of the cell signalling induced by insulin and insulin-like growth factor can extend lifespan. The finding that inhibiting the RAS branch also extends lifespan in flies suggests a new target for anti-ageing drugs.

doi: 10.1038/524170a

Analysis

Universal allosteric mechanism for Gα activation by GPCRs p.173

There are ~800 human GPCRs and 16 different Gα proteins; this study revealed the molecular details of Gα activation by GPCRs and suggests that a universal activation mechanism governs Gα activation—the details of this mechanism can explain how the GPCR–Gα system diversified rapidly, while conserving the allosteric activation mechanism.

doi: 10.1038/nature14663

Articles

Structure of the eukaryotic MCM complex at 3.8 Å p.186

Cryo-electron microscopy is used to visualize the double hexamer of the eukaryotic minichromosome maintenance complex (MCM), which is assembled during the G1 phase of DNA replication; two interdigitated hexamers have a central channel that tightly fits a DNA duplex, and the orientation of the tilted single hexamers sheds light on many functional aspects, particularly in the initial origin DNA melting.

doi: 10.1038/nature14685

Letters

A giant protogalactic disk linked to the cosmic web p.192

A two-dimensional spectroscopic investigation of a large, luminous filament of the cosmic web near QSO UM287 reveals that the brightest emission region is an extended rotating hydrogen disk with a velocity profile that is characteristic of gas in a 1013-solar-mass dark-matter halo, with a geometry that is strongly suggestive of cold flow accretion.

doi: 10.1038/nature14616

High-precision comparison of the antiproton-to-proton charge-to-mass ratio OPEN p.196

The CPT theorem (the assumption that physical laws are invariant under simultaneous charge conjugation, parity transformation and time reversal) is central to the standard model of particle physics; here the charge-to-mass ratio of the antiproton is compared to that of the proton, with a precision of 69 parts per trillion, and the result supports the CPT theorem at the atto-electronvolt scale.

doi: 10.1038/nature14861

Rejuvenation of metallic glasses by non-affine thermal strain p.200

This study shows that metallic glasses can be rejuvenated (taken to higher energy states with more plasticity) by thermally cycling them at relatively low temperatures (well below the glass transition temperature); this is attributed to the effect of intrinsic structural inhomogeneities in the glassy state, which translate into localized internal strains as the temperature is cycled and the different regions expand and contract by different amounts.

doi: 10.1038/nature14674

Graphene kirigami p.204

The ratio of in-plane stiffness to out-of-plane bending stiffness of graphene is shown to be similar to that of a piece of paper, which allows ideas from kirigami (a variation of origami that allows cutting) to be applied to micrometre-scale graphene sheets to build mechanically stretchable yet robust electrodes, springs and hinges.

doi: 10.1038/nature14588

The role of ridges in the formation and longevity of flat slabs p.212

Flat-slab subduction is often proposed to cause deformation of continental crust far from plate boundaries as well as unusual patterns of volcanism; a study of the largest-known flat slab, located in Peru, now shows that the ridge is necessary for the formation and longevity of the flat slab, whereas other contributing factors such as trench retreat and suction alone will not suffice.

doi: 10.1038/nature14648

Metabolic rescue in pluripotent cells from patients with mtDNA disease p.234

Mutations in mitochondrial (mt)DNA are associated with severe disorders for which treatment is currently limited; this study shows that mtDNA mutations can be genetically corrected and normal metabolic function restored in cells derived from patients with mtDNA disease and reprogrammed to pluripotency through factor-mediated reprogramming or via a somatic cell nuclear transfer approach.

doi: 10.1038/nature14546

The CREB coactivator CRTC2 controls hepatic lipid metabolism by regulating SREBP1 p.243

Studies in mice reveal that CREB regulated transcription coactivator 2 (CRTC2) acts as a mediator of mTOR signalling in the liver to regulate SREBP1-controlled lipid homeostasis during feeding and diabetes; overexpression of a CRTC2 mutant defective for mTOR regulation improves the lipogenic program and insulin sensitivity in obese mice.

doi: 10.1038/nature14557

Crucial HSP70 co-chaperone complex unlocks metazoan protein disaggregation p.247

An efficient protein disaggregation system uncovered in metazoan cells requires transient interactions between J-protein co-chaperones of classes A and B, which synergistically boost HSP70-dependent disaggregation activity, providing a flexible further level of regulation for metazoan protein quality control, with direct relevance to human diseases such as age-related neurodegeneration.

doi: 10.1038/nature14884

X-ray structure of a mammalian stearoyl-CoA desaturase p.252

The crystal structure of mouse SCD1 bound to fatty acid stearoyl-CoA is solved at 2.6 Å resolution; the structure reveals a novel geometry for the dimetal centre, and the acyl chain of the bound fatty acid is shown to be shielded and shaped to a particular conformation by the enzyme, providing a structural basis for the selectivity of fatty acid metabolism.

doi: 10.1038/nature14549