Volume 525 Number 7569



Too close for comfort? p.289

Relationships between industry and researchers can be hard to define, but universities and other institutions must do more to scrutinize the work of their scientists for conflicts of interest.

doi: 10.1038/525289a


Mind meld p.289

Interdisciplinary science must break down barriers between fields to build common ground.

doi: 10.1038/525289b


Protection priority p.290

All involved in animal research must ensure that rules for ethical experiments are observed.

doi: 10.1038/525290a



Crowdsourcing digs up an early human species p.297

Palaeoanthropologist invites excavators and anatomists to study richest fossil trove in Africa.

doi: 10.1038/nature.2015.18305


Africa braced for snakebite crisis p.299

Health specialists warn that stocks of antivenom will run out in 2016.

doi: 10.1038/525299a


NIH disclosure rules falter p.300

Regulations that require researchers to disclose conflicts of interest yield questionable data and cost universities millions.

doi: 10.1038/525300a


Hunt for gravitational waves to resume after massive upgrade p.301

LIGO experiment now has better chance of detecting ripples in space-time.

doi: 10.1038/525301a


Newfound meteor showers expand astronomical calendar p.302

Sky-watching cameras spot 86 previously unknown events.

doi: 10.1038/525302a

News Features


Why interdisciplinary research matters p.305


doi: 10.1038/525305a


Interdisciplinary research by the numbers p.306


doi: 10.1038/525306a


How to solve the world's biggest problems p.308


doi: 10.1038/525308a

News & Views


Neuroscience: Forgetfulness illuminated p.324


doi: 10.1038/nature15211


Catalysis: Tens of thousands of atoms replaced by one p.325


doi: 10.1038/525325a


Evolutionary biology: Perplexing effects of phenotypic plasticity p.326


doi: 10.1038/nature15214


Cancer: Repositioned to kill stem cells p.328


doi: 10.1038/nature15213


Condensed-matter physics: Charge topology in superconductors p.329


doi: 10.1038/525329a


Atmospheric science: The death toll from air-pollution sources p.330


doi: 10.1038/525330a



Labelling and optical erasure of synaptic memory traces in the motor cortex p.333

A new light-activated probe that targets recently active neuronal spines for manipulation induces shrinkage of recently potentiated spines following a motor learning task; spine shrinkage disrupted learning, suggesting a causal relationship between the specific subset of targeted spines and the learned behaviour.

doi: 10.1038/nature15257


Panorama of ancient metazoan macromolecular complexes p.339

Using biochemical fractionation and mass spectrometry, animal protein complexes are identified from nine species in parallel, and, along with genome sequence information, complex conservation is investigated and over one million protein–protein interactions are predicted in 122 eukaryotes.

doi: 10.1038/nature14877


The mechanism of DNA replication termination in vertebrates p.345

This study describes a new model of eukaryotic replication termination in which converging leading strands pass each other unhindered and the replicative DNA helicase is unloaded late, after all strands have been ligated.

doi: 10.1038/nature14887



Relativistic boost as the cause of periodicity in a massive black-hole binary candidate p.351

The amplitude and sinusoid-like shape of the optical variability of the light curve of PG 1302-102 is best fitted by relativistic Doppler boosting of emission from a compact, steadily accreting, unequal-mass binary, which is consistent with archival ultraviolet data, and suggests the existence of a binary black hole in the relativistic regime.

doi: 10.1038/nature15262


Spawning rings of exceptional points out of Dirac cones p.354

Exceptional points are singularities in non-Hermitian systems that can produce unusual effects, and it is shown that a Dirac cone in a photonic crystal can generate a continuous ring of exceptional points through flattening the tip of the cone.

doi: 10.1038/nature14889


Inhomogeneity of charge-density-wave order and quenched disorder in a high-Tc superconductor p.359

Micro X-ray diffraction imaging of the spatial distribution of charge-density-wave puddles and quenched disorder in HgBa2CuO4 + y reveals a complex, inhomogeneous spatial landscape due to the interplay between charge and dopant order.

doi: 10.1038/nature14987


Designing switchable polarization and magnetization at room temperature in an oxide p.363

Ferroelectricity and ferromagnetism are combined in a bulk perovskite oxide at room temperature by constructing a percolating network of interacting magnetic ions within a complex polar solid.

doi: 10.1038/nature14881


The contribution of outdoor air pollution sources to premature mortality on a global scale p.367

Investigation of premature mortality by seven emission sources of atmospheric pollutants shows that outdoor air pollution, mostly by fine particulate matter, leads to more than three million premature deaths per year worldwide, which could double by 2050.

doi: 10.1038/nature15371


Non-adaptive plasticity potentiates rapid adaptive evolution of gene expression in nature p.372

Experimentally transplanting guppies to evolve in a novel, predator-free environment reveals that the direction of plasticity in gene expression is usually opposite to the direction of adaptive evolution; that is, those genes whose expression changes are disadvantageous are more strongly selected upon than those whose changes are advantageous.

doi: 10.1038/nature15256


A new cyanogenic metabolite in Arabidopsis required for inducible pathogen defence p.376

Untargeted metabolomics and coexpression analysis uncovers the complete biosynthetic pathway of a previously unknown Arabidopsis metabolite, 4-hydroxyindole-3-carbonyl nitrile (4-OH-ICN), which harbours cyanogenic functionality.

doi: 10.1038/nature14907


Erosion of the chronic myeloid leukaemia stem cell pool by PPARγ agonists p.380

Whether cancer is maintained by a small number of stem cells or is composed of proliferating cells with approximate phenotypic equivalency is a central question in cancer biology. In the stem cell hypothesis, relapse after treatment may occur by failure to eradicate cancer stem cells. Chronic myeloid leukaemia (CML) is quintessential to this hypothesis. CML is a myeloproliferative disorder that results from dysregulated tyrosine kinase activity of the fusion oncoprotein BCR–ABL. During the chronic phase, this sole genetic abnormality (chromosomal translocation Ph+: t(9;22)(q34;q11)) at the stem cell level causes increased proliferation of myeloid cells without loss of their capacity to differentiate. Without treatment, most patients progress to the blast phase when additional oncogenic mutations result in a fatal acute leukaemia made of proliferating immature cells. Imatinib mesylate and other tyrosine kinase inhibitors (TKIs) that target the kinase activity of BCR–ABL have improved patient survival markedly. However, fewer than 10% of patients reach the stage of complete molecular response (CMR), defined as the point when BCR-ABL transcripts become undetectable in blood cells. Failure to reach CMR results from the inability of TKIs to eradicate quiescent CML leukaemia stem cells (LSCs). Here we show that the residual CML LSC pool can be gradually purged by the glitazones, antidiabetic drugs that are agonists of peroxisome proliferator-activated receptor-γ (PPARγ). We found that activation of PPARγ by the glitazones decreases expression of STAT5 and its downstream targets HIF2α and CITED2, which are key guardians of the quiescence and stemness of CML LSCs. When pioglitazone was given temporarily to three CML patients in chronic residual disease in spite of continuous treatment with imatinib, all of them achieved sustained CMR, up to 4.7 years after withdrawal of pioglitazone. This suggests that clinically relevant cancer eradication may become a generally attainable goal by combination therapy that erodes the cancer stem cell pool.

doi: 10.1038/nature15248


The spliceosome is a therapeutic vulnerability in MYC-driven cancer p.384

Splicing factors such as BUD31 are identified in a synthetic-lethal screen with cells overexpressing the transcription factor MYC; oncogenic MYC leads to an increase in pre-mRNA synthesis, and spliceosome inhibition impairs the growth and tumorigenicity of MYC-dependent breast cancers, suggesting that spliceosome components may be potential therapeutic targets for MYC-driven cancers.

doi: 10.1038/nature14985


Tet2 is required to resolve inflammation by recruiting Hdac2 to specifically repress IL-6 p.389

The Tet2 enzyme, which catalyses de novo hydroxymethylation of DNA, is shown here to act as a transcriptional repressor by recruiting the histone deacetylase Hdac2 to the Il6 promoter in the course of resolution of the LPS-induced inflammatory response.

doi: 10.1038/nature15252


Replisome speed determines the efficiency of the Tus−Ter replication termination barrier p.394

In all domains of life, DNA synthesis occurs bidirectionally from replication origins. Despite variable rates of replication fork progression, fork convergence often occurs at specific sites. Escherichia coli sets a ‘replication fork trap’ that allows the first arriving fork to enter but not to leave the terminus region. The trap is set by oppositely oriented Tus-bound Ter sites that block forks on approach from only one direction. However, the efficiency of fork blockage by Tus–Ter does not exceed 50% in vivo despite its apparent ability to almost permanently arrest replication forks in vitro. Here we use data from single-molecule DNA replication assays and structural studies to show that both polarity and fork-arrest efficiency are determined by a competition between rates of Tus displacement and rearrangement of Tus–Ter interactions that leads to blockage of slower moving replisomes by two distinct mechanisms. To our knowledge this is the first example where intrinsic differences in rates of individual replisomes have different biological outcomes.

doi: 10.1038/nature14866


Integrator mediates the biogenesis of enhancer RNAs p.399

This study demonstrates a role for the Integrator complex in the stimulus-dependent induction of eRNAs and their 3′ processing; together with previously known roles of Integrator in transcription elongation and RNA processing, these results indicate that Integrator has broad functions in the regulation of eukaryotic gene expression.

doi: 10.1038/nature14906


Crystal structure of the dynamin tetramer p.404

The crystal structure of the large GTPase dynamin tetramer is presented, suggesting a mechanism by which oligomerization of dynamin is regulated, and revealing how mutations that interfere with tetramer formation and autoinhibition are of relevance to understanding the congenital muscle disorders Charcot–Marie–Tooth neuropathy and centronuclear myopathy.

doi: 10.1038/nature14880

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