네이처 컨텐츠

Editorials

Applied prestige p.389

The UK research assessment should inspire everybody to reward excellent societal impacts.

doi: 10.1038/519389b

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Rethinking the brain p.389

Critics of the European Human Brain Project were justified, says an independent report on the project. Both its governance and its scientific direction need to be adjusted.

doi: 10.1038/519389a

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About time p.390

The next few years will see NASA missions probe the innermost secrets of gas giants.

doi: 10.1038/519390a

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News

News Features

Biotech boot camp p.402

US funding agencies are turning to a Silicon Valley entrepreneur to focus fledgling biomedical companies on success — even when that means making a scientific course correction.

Heidi Ledford

doi: 10.1038/519402a

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News & Views

A big-hearted molecule p.416

Blockade of the enzyme PDE9 prevents degradation of the molecule cyclic GMP, which has been shown to protect against heart failure. The finding indicates that PDE9 inhibition might be a drug target for treating this condition. See Letter p.472

Michaela Kuhn

doi: 10.1038/nature14373

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Square ice in a graphene sandwich p.417

Films of ice less than 1 nanometre thick, sandwiched between sheets of graphene, have been observed to adopt a square lattice structure quite different from the widely occurring hexagonal structure of bulk ice. See Letter p.443

Alan K. Soper

doi: 10.1038/519417a

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DNA replication reconstructed p.418

Genetically identical cells can have many variable properties. A study of correlations between cells in a lineage explains paradoxical inheritance laws, in which mother and daughter cells seem less similar than cousins. See Letter p.431

Michael Weinreich

doi: 10.1038/519418a

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Atomic doughnuts from single photons p.420

Analysis of the interaction between a photon and an ensemble of some 3,000 atoms trapped between two mirrors has revealed a form of multi-atom quantum entanglement that has no counterpart in classical mechanics. See Letter p.439

James K. Thompson

doi: 10.1038/519420b

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Defiant daughters and coordinated cousins p.422

Genetically identical cells can have many variable properties. A study of correlations between cells in a lineage explains paradoxical inheritance laws, in which mother and daughter cells seem less similar than cousins. See Letter p.468

Andreas Hilfinger & Johan Paulsson

doi: 10.1038/nature14210

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When the wind blows p.423

Astronomical observations of a luminous galaxy that has a central, mass-accreting supermassive black hole reveal how such entities launch and propel gas through galaxies at high speeds. See Letter p.436

James E. Geach

doi: 10.1038/519423a

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Articles

MAP4K4 regulates integrin-FERM binding to control endothelial cell motility p.425

A new MAP4K4–moesin–talin–β1-integrin pathway regulating endothelial cell motility was discovered through chemical and siRNA screens; loss of Map4k4 or inhibition of MAP4K4 kinase activity altered the sprout morphology of endothelial cells during angiogenesis by blocking moesin phosphorylation, which regulates the disassembly of focal adhesions, demonstrating that this pathway is involved in both normal and pathological angiogenesis.

Philip Vitorino, Stacey Yeung, Ailey Crow, Jesse Bakke, Tanya Smyczek, Kristina West, Erin McNamara, Jeffrey Eastham-Anderson, Stephen Gould, Seth F. Harris + et al.

doi: 10.1038/nature14323

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Regulated eukaryotic DNA replication origin firing with purified proteins p.431

It has long been a goal to reconstitute eukaryotic DNA replication; here a purified in vitro system from budding yeast containing 16 factors, themselves composed of 42 polypeptides, fulfils the staged process of origin-dependent initiation, including its regulation by kinases.

Joseph T. P. Yeeles, Tom D. Deegan, Agnieszka Janska, Anne Early & John F. X. Diffley

doi: 10.1038/nature14285

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Letters

Entanglement with negative Wigner function of almost 3,000 atoms heralded by one photon p.439

The detection of a single photon from a laser interacting with an atomic ensemble is shown to produce entanglement of almost 3,000 atoms; in contrast to previous production of multi-atom entanglement, the highly non-classical nature of the present entangled state is verified by measurement of a negative quasiprobability distribution.

Robert McConnell, Hao Zhang, Jiazhong Hu, Senka Ćuk & Vladan Vuletić

doi: 10.1038/nature14293

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Square ice in graphene nanocapillaries p.443

The structure of the low-dimensional water confined in hydrophobic pores is shown, using electron microscopy and supported by molecular dynamics simulations, to be ‘square ice’, which does not have the conventional tetrahedral hydrogen bonding.

G. Algara-Siller, O. Lehtinen, F. C. Wang, R. R. Nair, U. Kaiser, H. A. Wu, A. K. Geim & I. V. Grigorieva

doi: 10.1038/nature14295

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Vapour-mediated sensing and motility in two-component droplets p.446

Droplets of mixed water and propylene glycol deposited on clean glass exhibit a contact angle but do not suffer from contact line pinning; their motion can be controlled by the vapour emitted from neighbouring droplets to create a variety of autonomous fluidic machines with integrated sensing and motility capabilities.

N. J. Cira, A. Benusiglio & M. Prakash

doi: 10.1038/nature14272

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The paraventricular thalamus controls a central amygdala fear circuit p.455

Inhibiting projections from the paraventricular nucleus of the thalamus to a specific division of the amygdala prevents fear conditioning in mice, indicating an important role for the thalamus–amygdala circuit in establishing and maintaining fear responses.

Mario A. Penzo, Vincent Robert, Jason Tucciarone, Dimitri De Bundel, Minghui Wang, Linda Van Aelst, Martin Darvas, Luis F. Parada, Richard D. Palmiter, Miao He + et al.

doi: 10.1038/nature13978

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A temporal shift in the circuits mediating retrieval of fear memory p.460

Dissociating early from late fear memory retrieval in rats reveals that while the projection from the prelimbic prefrontal cortex to the amygdala is critical for fear memory retrieval at early time points, a separate circuit involving the paraventricular region of the dorsal midline thalamus is critical for fear memory retrieval at late time points, establishing the paraventricular region as a critical maintenance/retrieval node during the transition from short- to long-term fear memory.

Fabricio H. Do-Monte, Kelvin Quiñones-Laracuente & Gregory J. Quirk

doi: 10.1038/nature14030

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Two insulin receptors determine alternative wing morphs in planthoppers p.464

Some insects have alternative wing morphs, one that is long-winged and changes habitat to follow resources, and one that is short-winged and flightless but has high fertility; here, the molecular details of this switch are revealed, with opposite effects of two insulin receptors controlling the development of different wing morphs in the planthopper.

Hai-Jun Xu, Jian Xue, Bo Lu, Xue-Chao Zhang, Ji-Chong Zhuo, Shu-Fang He, Xiao-Fang Ma, Ya-Qin Jiang, Hai-Wei Fan, Ji-Yu Xu + et al.

doi: 10.1038/nature14286

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Lineage correlations of single cell division time as a probe of cell-cycle dynamics p.468

Precise measurement of cell-cycle duration in thousands of mammalian cells reveals correlations among cousin cells, but no such correlations between mother and daughter cells; recapitulating this finding using a deterministic model suggests that observed cellular heterogeneities in cell-cycle duration may be attributable to deterministic processes, and eventually be controlled.

Oded Sandler, Sivan Pearl Mizrahi, Noga Weiss, Oded Agam, Itamar Simon & Nathalie Q. Balaban

doi: 10.1038/nature14318

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Phosphodiesterase 9A controls nitric-oxide-independent cGMP and hypertrophic heart disease p.472

The inhibition, in mice, of the phosphodiesterase PDE9A, which specifically regulates natriuretic-peptide-coupled cGMP signalling, is independent of nitric oxide and is upregulated in failing human hearts, and can reverse pre-established stress-induced heart disease.

Dong I. Lee, Guangshuo Zhu, Takashi Sasaki, Gun-Sik Cho, Nazha Hamdani, Ronald Holewinski, Su-Hyun Jo, Thomas Danner, Manling Zhang, Peter P. Rainer + et al.

doi: 10.1038/nature14332

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SLC38A9 is a component of the lysosomal amino acid sensing machinery that controls mTORC1 p.477

The mTORC1 protein kinase complex integrates nutrient and growth stimuli to modulate signalling pathways that regulate cellular metabolism and physiology, but the molecular nature of the amino acid sensing mechanism at the lysosome is unknown; here, an orphan member of the human solute carrier group of proteins, SLC38A9, is shown to be an integral component of the lysosomal machinery that can directly sense amino acids and activate mTORC1.

Manuele Rebsamen, Lorena Pochini, Taras Stasyk, Mariana E. G. de Araújo, Michele Galluccio, Richard K. Kandasamy, Berend Snijder, Astrid Fauster, Elena L. Rudashevskaya, Manuela Bruckner + et al.

doi: 10.1038/nature14107

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N6-methyladenosine marks primary microRNAs for processing p.482

The first step in the biogenesis of microRNAs is the processing of primary microRNAs (pri-miRNAs) by the microprocessor complex, composed of the RNA-binding protein DGCR8 and the type III RNase DROSHA. This initial event requires recognition of the junction between the stem and the flanking single-stranded RNA of the pri-miRNA hairpin by DGCR8 followed by recruitment of DROSHA, which cleaves the RNA duplex to yield the pre-miRNA product. While the mechanisms underlying pri-miRNA processing have been determined, the mechanism by which DGCR8 recognizes and binds pri-miRNAs, as opposed to other secondary structures present in transcripts, is not understood. Here we find in mammalian cells that methyltransferase-like 3 (METTL3) methylates pri-miRNAs, marking them for recognition and processing by DGCR8. Consistent with this, METTL3 depletion reduced the binding of DGCR8 to pri-miRNAs and resulted in the global reduction of mature miRNAs and concomitant accumulation of unprocessed pri-miRNAs. In vitro processing reactions confirmed the sufficiency of the N6-methyladenosine (m6A) mark in promoting pri-miRNA processing. Finally, gain-of-function experiments revealed that METTL3 is sufficient to enhance miRNA maturation in a global and non-cell-type-specific manner. Our findings reveal that the m6A mark acts as a key post-transcriptional modification that promotes the initiation of miRNA biogenesis.

Claudio R. Alarcón, Hyeseung Lee, Hani Goodarzi, Nils Halberg & Sohail F. Tavazoie

doi: 10.1038/nature14281

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Structural imprints in vivo decode RNA regulatory mechanisms p.486

The single-stranded nature of RNAs synthesized in the cell gives them great scope to form different structures, but current methods to measure RNA structure in vivo are limited; now, a new methodology allows researchers to examine all four nucleotides in mouse embryonic stem cells.

Robert C. Spitale, Ryan A. Flynn, Qiangfeng Cliff Zhang, Pete Crisalli, Byron Lee, Jong-Wha Jung, Hannes Y. Kuchelmeister, Pedro J. Batista, Eduardo A. Torre, Eric T. Kool + et al.

doi: 10.1038/nature14263

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hiCLIP reveals the in vivo atlas of mRNA secondary structures recognized by Staufen 1 p.491

A method, termed hiCLIP, has been developed to determine the RNA duplexes bound by RNA-binding proteins, revealing an unforeseen prevalence of long-range duplexes in 3′ untranslated regions (UTRs), and a decreased incidence of SNPs in duplex-forming regions; the results also show that RNA structure is able to regulate gene expression.

Yoichiro Sugimoto, Alessandra Vigilante, Elodie Darbo, Alexandra Zirra, Cristina Militti, Andrea D’Ambrogio, Nicholas M. Luscombe & Jernej Ule

doi: 10.1038/nature14280

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