There is life after academia p.5

With high numbers of postdocs emerging from universities, prospective PhD students must be prepared for the fact that they will probably not end up with a career in research.

doi: 10.1038/513005a

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The digital toolbox p.6

A new section of Nature examines the software and websites that make research easier.

doi: 10.1038/513006b

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Heavenly homes p.6

The discovery of our Galaxy’s place in the Universe adds detail to our address.

doi: 10.1038/513006a

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Ebola drug trials set to begin amid crisis p.13

Testing drugs in the middle of deadly disease outbreak is challenging but can be done.

doi: 10.1038/513013a

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Stalled El Niño poised to resurge p.15

Studies of brewing weather event test understanding of past and future climate.

doi: 10.1038/513015a

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Switzerland braces for Alpine lake tsunami p.16

Authorities in Swiss canton blaze a trail by factoring the risk into hazard planning.

doi: 10.1038/513016a

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California quake puts warning system in the spotlight p.18

Scientists, politicians and business leaders will discuss practicalities of a regional network.

doi: 10.1038/513018a

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News Features


Life outside the lab: The ones who got away p.20


doi: 10.1038/513020a

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E-cigarettes: The lingering questions p.24


doi: 10.1038/513024a

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News & Views


Geodynamics: How plumes help to break plates p.36


doi: 10.1038/513036a

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Evolutionary developmental biology: Dynasty of the plastic fish p.37


doi: 10.1038/nature13743

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Cell biology: A guardian angel of cell integrity p.38


doi: 10.1038/513038a

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Biological techniques: Edit the genome to understand it p.40


doi: 10.1038/nature13659

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Cosmology: Meet the Laniakea supercluster p.41


doi: 10.1038/513041a

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Structural biology: How fluorescent RNA gets its glow p.42


doi: 10.1038/513042a

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Migrations and dynamics of the intertropical convergence zone p.45

The intertropical convergence zone, where global rainfall is greatest, is a narrow belt of clouds usually centred about six degrees north of the Equator; this Review links its migrations on various timescales to the atmospheric energy balance.

doi: 10.1038/nature13636

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Developmental plasticity and the origin of tetrapods p.54

The most primitive extant bony fish, Polypterus, exhibits adaptive plasticity for life on land when raised on land rather than in water, suggesting that environmentally induced phenotypic plasticity might have facilitated the macroevolutionary transition to life on land.

doi: 10.1038/nature13708

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Alterations of the human gut microbiome in liver cirrhosis p.59

Invasion of the gut by oral bacteria in liver cirrhosis.

doi: 10.1038/nature13568

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RNA G-quadruplexes cause eIF4A-dependent oncogene translation in cancer p.65

The translation of many messenger RNAs that encode important oncogenes and transcription factors depends on the eIF4A RNA helicase to resolve G-quadruplex structures, implying eIF4A inhibition as an effective cancer therapy.

doi: 10.1038/nature13485

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The Laniakea supercluster of galaxies p.71

Examination of a three-dimensional map of galaxies and their velocities shows a surface bounding the motions of galaxies that are inward after removal of the mean cosmic expansion and long-range flows; the galaxies within this surface lie within our home supercluster.

doi: 10.1038/nature13674

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A 400-solar-mass black hole in the galaxy M82 p.74

The discovery of two stable peaks at frequencies with a ratio of 3:2 in the power spectrum of X-ray emission from the brightest X-ray source in galaxy M82 suggests that, if the relationship between frequency and mass that holds for stellar-mass black holes can be extended to intermediate masses, the black hole believed to be the source of the emission has a mass approximately 400 times that of the Sun.

doi: 10.1038/nature13710

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Hierarchical organization of chiral rafts in colloidal membranes p.77

Inclusions dissolved in a colloidal membrane assemble into highly uniform finite-sized liquid droplets or rafts consisting of thousands of molecules.

doi: 10.1038/nature13694

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Temperature sensitivity of soil respiration rates enhanced by microbial community response p.81

Microbial community responses in soils from the Arctic to the Amazon often enhance the longer-term temperature sensitivity of respiration, particularly in soils with high carbon-to-nitrogen ratios and in soils from cold regions, suggesting that carbon stored in Arctic and boreal soils could be more vulnerable to climate warming than currently predicted.

doi: 10.1038/nature13604

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Asymmetric three-dimensional topography over mantle plumes p.85

Three-dimensional numerical models of the interaction of a mantle plume with a rheologically realistic lithosphere predict complex surface evolution very different from the smooth, radially symmetric patterns usually assumed to be the signature of a mantle upwelling, with strongly asymmetric small-scale three-dimensional features such as rifts and linear fault structures.

doi: 10.1038/nature13703

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RIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis p.90

RIPK1 is shown to have a crucial role—independent of its known kinase function—in suppressing epithelial cell apoptosis and necroptosis in mice, thereby regulating homeostasis and preventing inflammation in barrier tissues.

doi: 10.1038/nature13608

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RIPK1 ensures intestinal homeostasis by protecting the epithelium against apoptosis p.95

This study provides evidence for a critical role of RIPK1 in suppressing caspase-8-mediated cell death and maintaining intestinal homeostasis independently of its kinase activity.

doi: 10.1038/nature13706

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Tumour-derived PTH-related protein triggers adipose tissue browning and cancer cachexia p.100

Many patients with cancer experience cachexia, a wasting disorder of adipose tissue and skeletal muscle that leads to weight loss and frailty; now, tumour-derived parathyroid-hormone-related protein has been shown to stimulate the expression of genes involved in heat production in adipose tissues and to have an important role in tissue wasting.

doi: 10.1038/nature13528

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eIF4F is a nexus of resistance to anti-BRAF and anti-MEK cancer therapies p.105

BRAF mutations occur frequently in melanomas, but patients generally develop resistance to agents targeting mutant BRAF; now, the persistent formation of the translation initiation complex eIF4F has been described as an indicator of multiple mechanisms of resistance that arise in BRAF-mutated tumours and as a promising therapeutic target.

doi: 10.1038/nature13572

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Mutant IDH inhibits HNF-4α to block hepatocyte differentiation and promote biliary cancer p.110

Mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 are among the most common genetic alterations in intrahepatic cholangiocarcinoma (IHCC), a deadly liver cancer. Mutant IDH proteins in IHCC and other malignancies acquire an abnormal enzymatic activity allowing them to convert α-ketoglutarate (αKG) to 2-hydroxyglutarate (2HG), which inhibits the activity of multiple αKG-dependent dioxygenases, and results in alterations in cell differentiation, survival, and extracellular matrix maturation. However, the molecular pathways by which IDH mutations lead to tumour formation remain unclear. Here we show that mutant IDH blocks liver progenitor cells from undergoing hepatocyte differentiation through the production of 2HG and suppression of HNF-4α, a master regulator of hepatocyte identity and quiescence. Correspondingly, genetically engineered mouse models expressing mutant IDH in the adult liver show an aberrant response to hepatic injury, characterized by HNF-4α silencing, impaired hepatocyte differentiation, and markedly elevated levels of cell proliferation. Moreover, IDH and Kras mutations, genetic alterations that co-exist in a subset of human IHCCs, cooperate to drive the expansion of liver progenitor cells, development of premalignant biliary lesions, and progression to metastatic IHCC. These studies provide a functional link between IDH mutations, hepatic cell fate, and IHCC pathogenesis, and present a novel genetically engineered mouse model of IDH-driven malignancy.

doi: 10.1038/nature13441

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Dynamic and static maintenance of epigenetic memory in pluripotent and somatic cells p.115

Using a new method to estimate DNA methylation turnover rate, embryonic stem cells are shown to lack clonal transmission of methylation but still maintain a stable epigenetic state, whereas somatic cells transmit methylation clonally but lose epigenetic state coherence owing to the persistence of accumulated methylation errors.

doi: 10.1038/nature13458

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Saturation editing of genomic regions by multiplex homology-directed repair p.120

The authors perform saturation mutagenesis of genomic regions in their native endogenous chromosomal context by using CRISPR/Cas9 RNA-guided cleavage and multiplex homology-directed repair; its utility is demonstrated by measuring the effects of hundreds to thousands of genomic edits to BRCA1 and DBR1 on splicing and cellular fitness, respectively.

doi: 10.1038/nature13695

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High-resolution structure of the human GPR40 receptor bound to allosteric agonist TAK-875 p.124

The X-ray crystal structure of human GPR40 receptor in the presence of TAK-875, an orally available, potent and selective human GPR40 agonist.

doi: 10.1038/nature13494

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