Editorial
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
Return to nuclear energy is part of a plan that is not in line with global climate target.
doi: 10.1038/524143a
Anti-poverty programme seeks to gauge success after ten years in Africa.
doi: 10.1038/524144a
Activist group compels records from 40 researchers at US public universities.
doi: 10.1038/nature.2015.18146
International public-health officials discuss how to maximize research benefits of a widely dispersed collection.
doi: 10.1038/524146a
A graphical guide to four giant experiments spread across the world.
doi: 10.1038/524148a
News Features
A new generation of economists is trying to transform global development policy through the power of randomized controlled trials.
doi: 10.1038/524150a
News & Views
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
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
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
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
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
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
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
In the uninjured liver, a population of self-renewing, diploid hepatocytes is identified near the central vein; these cells respond to Wnt signals that are provided by the adjacent central vein endothelial cells, and can give rise to all other hepatocytes to maintain liver homeostasis.
doi: 10.1038/nature14863
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 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
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
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
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
A method of supplying exactly the amounts of air- and moisture-sensitive catalysts and ligands needed for three commonly used syntheses in a stable, storable form in a sealed capsule is described; it should reduce the unnecessary waste of chemicals, money and time.
doi: 10.1038/nature14654
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
Analysis of DNA from a 37,000–42,000-year-old modern human from Romania reveals that 6–9% of the genome is derived from Neanderthals, with the individual having a Neanderthal ancestor as recently as four to six generations back.
doi: 10.1038/nature14558
Octopus bimaculoides genome and transcriptome sequencing demonstrated that a core gene repertoire broadly similar to that of other invertebrate bilaterians is accompanied by expansions in the protocadherin and C2H2 zinc-finger transcription factor families and large-scale genome rearrangements closely associated with octopus-specific transposable elements.
doi: 10.1038/nature14668
Patterns of amino acid conservation have been used to guide the interpretation of the disease-causing potential of genetic variants in patients; now, an appreciable fraction of pathogenic alleles are shown to be fixed in the genomes of other species, suggesting that the genomic context has an important role in allele pathogenicity.
doi: 10.1038/nature14497
Zebrafish embryos injected with egfl7 morpholino exhibit severe vascular defects but egfl7 mutants do not show any obvious phenotypes, illustrating the power of comparing mutants and morphants to identify modifier genes.
doi: 10.1038/nature14580
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
A high-content phenotypic screening method has been developed allowing the first systematic RNA interference screen for nearly 800 genes mediating mammalian meiosis.
doi: 10.1038/nature14568
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
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
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