네이처 컨텐츠

Editorials

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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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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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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News

News Features

The ones who got away p.20

Sometimes, the brightest stars in science decide to leave. Nature finds out where they go.

Ewen Callaway

doi: 10.1038/513020a

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The lingering questions p.24

In the haze of incomplete data, scientists are divided over the risks and benefits of electronic cigarettes.

Daniel Cressey

doi: 10.1038/513024a

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News & Views

How plumes help to break plates p.36

Computer models show how hot material that rises from Earth's interior is affected by plate tectonics, producing unexpected irregularities in Earth's topography and assisting in the break-up of continental plates. See Letter p.85

Susanne Buiter

doi: 10.1038/513036a

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Dynasty of the plastic fish p.37

Ambitious experimental and morphological studies of a modern fish show how developmental flexibility may have helped early 'fishapods' to make the transition from finned aquatic animals to tetrapods that walk on land. See Article p.54

John Hutchinson

doi: 10.1038/nature13743

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A guardian angel of cell integrity p.38

The finding that RIPK1, an integral protein in cell-death pathways, also functions to preserve the body's epithelial-cell barriers challenges the idea that cell death and survival are regulated by distinct factors. See Letters p.90 & p.95

Francis Ka-Ming Chan

doi: 10.1038/513038a

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Edit the genome to understand it p.40

Genome editing followed by sequencing has now been used to engineer and analyse every variation of several stretches of human DNA in living cells, providing insight into the function of each constituent nucleotide molecule. See Letter p.120

Fyodor D. Urnov

doi: 10.1038/nature13659

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Meet the Laniakea supercluster p.41

An analysis of a three-dimensional map of galaxies and their velocities reveals the hitherto unknown edges of the large system of galaxies in which we live — dubbed the Laniakea supercluster. See Letter p.71

Elmo Tempel

doi: 10.1038/513041a

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How fluorescent RNA gets its glow p.42

Fluorescent tags are proving invaluable for tracking RNA molecules in cells. Two sets of crystal structures for one such tag — an RNA motif that fluoresces when bound to a dye — will aid the development of even better markers.

William G. Scott

doi: 10.1038/513042a

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Review

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.

Tapio Schneider, Tobias Bischoff & Gerald H. Haug

doi: 10.1038/nature13636

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Articles

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.

Emily M. Standen, Trina Y. Du & Hans C. E. Larsson

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.

Nan Qin, Fengling Yang, Ang Li, Edi Prifti, Yanfei Chen, Li Shao, Jing Guo, Emmanuelle Le Chatelier, Jian Yao, Lingjiao Wu + et al.

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.

Andrew L. Wolfe, Kamini Singh, Yi Zhong, Philipp Drewe, Vinagolu K. Rajasekhar, Viraj R. Sanghvi, Konstantinos J. Mavrakis, Man Jiang, Justine E. Roderick, Joni Van der Meulen + et al.

doi: 10.1038/nature13485

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Letters

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.

R. Brent Tully, Hélène Courtois, Yehuda Hoffman & Daniel Pomarède

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.

Dheeraj R. Pasham, Tod E. Strohmayer & Richard F. Mushotzky

doi: 10.1038/nature13710

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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.

Kristiina Karhu, Marc D. Auffret, Jennifer A. J. Dungait, David W. Hopkins, James I. Prosser, Brajesh K. Singh, Jens-Arne Subke, Philip A. Wookey, Göran I. Ågren, Maria-Teresa Sebastià + et al.

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.

Evgueni Burov & Taras Gerya

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.

Marius Dannappel, Katerina Vlantis, Snehlata Kumari, Apostolos Polykratis, Chun Kim, Laurens Wachsmuth, Christina Eftychi, Juan Lin, Teresa Corona, Nicole Hermance + et al.

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.

Nozomi Takahashi, Lars Vereecke, Mathieu J. M. Bertrand, Linde Duprez, Scott B. Berger, Tatyana Divert, Amanda Gonçalves, Mozes Sze, Barbara Gilbert, Stephanie Kourula + et al.

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.

Serkan Kir, James P. White, Sandra Kleiner, Lawrence Kazak, Paul Cohen, Vickie E. Baracos & Bruce M. Spiegelman

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.

Lise Boussemart, Hélène Malka-Mahieu, Isabelle Girault, Delphine Allard, Oskar Hemmingsson, Gorana Tomasic, Marina Thomas, Christine Basmadjian, Nigel Ribeiro, Frédéric Thuaud + et al.

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.

Supriya K. Saha, Christine A. Parachoniak, Krishna S. Ghanta, Julien Fitamant, Kenneth N. Ross, Mortada S. Najem, Sushma Gurumurthy, Esra A. Akbay, Daniela Sia, Helena Cornella + et al.

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.

Zohar Shipony, Zohar Mukamel, Netta Mendelson Cohen, Gilad Landan, Elad Chomsky, Shlomit Reich Zeliger, Yael Chagit Fried, Elena Ainbinder, Nir Friedman & Amos Tanay

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.

Gregory M. Findlay, Evan A. Boyle, Ronald J. Hause, Jason C. Klein & Jay Shendure

doi: 10.1038/nature13695

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