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Cracking the regulatory code p.190

A collection of papers catalogues the associations between genetic variation and gene expression in healthy tissues – the largest analysis of this kind so far. See Article p.204 & Letters p.239, p.244 & p.249

Michelle C. Ward & Yoav Gilad

doi: 10.1038/550190a

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A pariah finds a home p.191

Pariahs are fundamental building blocks in a branch of mathematics called group theory, but seem to be unconnected from both physics and other areas of mathematics. Such a connection has now been identified.

Terry Gannon

doi: 10.1038/nature24147

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Tumours addicted to drugs are vulnerable p.192

Cancer cells can develop an 'addiction' to the drugs they are treated with, so that they need the drugs to survive. Analysis of the underlying mechanism reveals a potential clinical strategy for harnessing this phenomenon. See Letter p.270

Rebecca J. Lee & Richard Marais

doi: 10.1038/nature24148

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Liquid metal pumped at a record temperature p.194

Although liquid metals are effective fluids for heat transfer, pumping them at high temperatures is limited by their corrosiveness to solid metals. A clever pump design addresses this challenge using only ceramics. See Article p.199

Konstantina Lambrinou

doi: 10.1038/550194b

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Receptors identified for a weight regulator p.195

The discovery of the receptors for the protein GDF15 suggests that it regulates food uptake through the emergency pathway — a neuronal circuit that causes weight loss in response to cancer, tissue damage and stress. See Letter p.255

Mart Saarma & Adrian Goldman

doi: 10.1038/nature24143

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Ring detected around a dwarf planet p.197

Observations of the distant dwarf planet Haumea constrain its size, shape and density, and reveal an encircling planetary ring. The discovery suggests that rings are not as rare in the Solar System as previously thought. See Letter p.219

Amanda A. Sickafoose

doi: 10.1038/550197a

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Articles

Pumping liquid metal at high temperatures up to 1,673 kelvin p.199

By using ceramics for the mechanical and sealing components of a mechanical pump, liquid metal can be circulated continuously at temperatures at least as high as 1,673 kelvin.

C. Amy, D. Budenstein, M. Bagepalli, D. England, F. DeAngelis, G. Wilk, C. Jarrett, C. Kelsall, J. Hirschey, H. Wen + et al.

doi: 10.1038/nature24054

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The transcription fidelity factor GreA impedes DNA break repair p.214

In Escherichia coli, the control of RNA polymerase backtracking by transcription elongation factors impairs DNA break repair by affecting RecBCD resection and consequently RecA loading at sites far removed from the original DNA break.

Priya Sivaramakrishnan, Leonardo A. Sepúlveda, Jennifer A. Halliday, Jingjing Liu, María Angélica Bravo Núñez, Ido Golding, Susan M. Rosenberg & Christophe Herman

doi: 10.1038/nature23907

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Letters

The size, shape, density and ring of the dwarf planet Haumea from a stellar occultation p.219

Observations of a stellar occultation of Haumea, one of the four known trans-Neptunian dwarf planets, constrain its size, shape and density, and reveal a ring coplanar with Haumea’s largest moon.

J. L. Ortiz, P. Santos-Sanz, B. Sicardy, G. Benedetti-Rossi, D. Bérard, N. Morales, R. Duffard, F. Braga-Ribas, U. Hopp, C. Ries + et al.

doi: 10.1038/nature24051

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Light-field-driven currents in graphene p.224

Light-field-driven control of electrons in a conductor is demonstrated by inducing a current by laser pulses in graphene that is sensitive to the carrier-envelope phase.

Takuya Higuchi, Christian Heide, Konrad Ullmann, Heiko B. Weber & Peter Hommelhoff

doi: 10.1038/nature23900

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Layer-by-layer assembly of two-dimensional materials into wafer-scale heterostructures p.229

High-performance semiconductor films with vertical compositions that are designed to atomic-scale precision provide the foundation for modern integrated circuitry and novel materials discovery. One approach to realizing such films is sequential layer-by-layer assembly, whereby atomically thin two-dimensional building blocks are vertically stacked, and held together by van der Waals interactions. With this approach, graphene and transition-metal dichalcogenides—which represent one- and three-atom-thick two-dimensional building blocks, respectively—have been used to realize previously inaccessible heterostructures with interesting physical properties. However, no large-scale assembly method exists at present that maintains the intrinsic properties of these two-dimensional building blocks while producing pristine interlayer interfaces, thus limiting the layer-by-layer assembly method to small-scale proof-of-concept demonstrations. Here we report the generation of wafer-scale semiconductor films with a very high level of spatial uniformity and pristine interfaces. The vertical composition and properties of these films are designed at the atomic scale using layer-by-layer assembly of two-dimensional building blocks under vacuum. We fabricate several large-scale, high-quality heterostructure films and devices, including superlattice films with vertical compositions designed layer-by-layer, batch-fabricated tunnel device arrays with resistances that can be tuned over four orders of magnitude, band-engineered heterostructure tunnel diodes, and millimetre-scale ultrathin membranes and windows. The stacked films are detachable, suspendable and compatible with water or plastic surfaces, which will enable their integration with advanced optical and mechanical systems.

Kibum Kang, Kan-Heng Lee, Yimo Han, Hui Gao, Saien Xie, David A. Muller & Jiwoong Park

doi: 10.1038/nature23905

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Patchy particles made by colloidal fusion p.234

By exploiting geometric constraints and interfacial forces instead of chemistry, colloidal clusters can be controllably coalesced into particles with uniformly distributed surface patches.

Zhe Gong, Theodore Hueckel, Gi-Ra Yi & Stefano Sacanna

doi: 10.1038/nature23901

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The impact of rare variation on gene expression across tissues OPEN p.239

The authors show that rare genetic variants contribute to large gene expression changes across diverse human tissues and provide an integrative method for interpretation of rare variants in individual genomes.

Xin Li, Yungil Kim, Emily K. Tsang, Joe R. Davis, Farhan N. Damani, Colby Chiang, Gaelen T. Hess, Zachary Zappala, Benjamin J. Strober, Alexandra J. Scott + et al.

doi: 10.1038/nature24267

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Landscape of X chromosome inactivation across human tissues OPEN p.244

Multiple transcriptome approaches, including single-cell sequencing, demonstrate that escape from X chromosome inactivation is widespread and occasionally variable between cells, chromosomes, and tissues, resulting in sex-biased expression of at least 60 genes and potentially contributing to sex-specific differences in health and disease.

Taru Tukiainen, Alexandra-Chloé Villani, Angela Yen, Manuel A. Rivas, Jamie L. Marshall, Rahul Satija, Matt Aguirre, Laura Gauthier, Mark Fleharty, Andrew Kirby + et al.

doi: 10.1038/nature24265

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Dynamic landscape and regulation of RNA editing in mammals p.249

Using the GTEx data and others, a comprehensive analysis of adenosine-to-inosine RNA editing in mammals is presented; targets of the various ADAR enzymes are identified, as are several potential regulators of editing, such as AIMP2.

Meng How Tan, Qin Li, Raghuvaran Shanmugam, Robert Piskol, Jennefer Kohler, Amy N. Young, Kaiwen Ivy Liu, Rui Zhang, Gokul Ramaswami, Kentaro Ariyoshi + et al.

doi: 10.1038/nature24041

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Non-homeostatic body weight regulation through a brainstem-restricted receptor for GDF15 p.255

GDNF receptor alpha-like is a brainstem-restricted receptor for growth and differentiation factor 15, regulating appetite and body weight in non-homeostatic conditions by activating the emergency circuit response to disease and toxin stresses.

Jer-Yuan Hsu, Suzanne Crawley, Michael Chen, Dina A. Ayupova, Darrin A. Lindhout, Jared Higbee, Alan Kutach, William Joo, Zhengyu Gao, Diana Fu + et al.

doi: 10.1038/nature24042

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Hippo pathway deficiency reverses systolic heart failure after infarction p.260

Deletion of the Hippo pathway component Salvador in mouse hearts with established ischaemic heart failure after myocardial infarction induces a reparative genetic program with increased scar border vascularity, reduced fibrosis, and recovery of pumping function.

John P. Leach, Todd Heallen, Min Zhang, Mahdis Rahmani, Yuka Morikawa, Matthew C. Hill, Ana Segura, James T. Willerson & James F. Martin

doi: 10.1038/nature24045

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TORC1 organized in inhibited domains (TOROIDs) regulate TORC1 activity p.265

In budding yeast, glucose withdrawal, via the Rag GTPases, leads to TORC1 inhibition through its re-organization into a giant, vacuole-associated helix named a TOROID (TORC1 organized in inhibited domain).

Manoël Prouteau, Ambroise Desfosses, Christian Sieben, Clélia Bourgoint, Nour Lydia Mozaffari, Davide Demurtas, Alok K. Mitra, Paul Guichard, Suliana Manley & Robbie Loewith

doi: 10.1038/nature24021

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Cancer drug addiction is relayed by an ERK2-dependent phenotype switch p.270

The identification of an ERK2–JUNB–FRA1 signalling pathway that drives addiction to therapeutic drugs in cancer cells, and an ERK2-dependent phenotype switch that precedes cell death after drug withdrawal, may help to guide therapies that exploit the addiction phenotype.

Xiangjun Kong, Thomas Kuilman, Aida Shahrabi, Julia Boshuizen, Kristel Kemper, Ji-Ying Song, Hans W. M. Niessen, Elisa A. Rozeman, Marnix H. Geukes Foppen, Christian U. Blank + et al.

doi: 10.1038/nature24037

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RNA targeting with CRISPR–Cas13 p.280

The class 2 type VI RNA-guided RNA-targeting CRISPR–Cas effector Cas13 can be engineered for RNA knockdown and binding, expanding the CRISPR toolset with a flexible platform for studying RNA in mammalian cells and therapeutic development.

Omar O. Abudayyeh, Jonathan S. Gootenberg, Patrick Essletzbichler, Shuo Han, Julia Joung, Joseph J. Belanto, Vanessa Verdine, David B. T. Cox, Max J. Kellner, Aviv Regev + et al.

doi: 10.1038/nature24049

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