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The power of prediction markets p.308

Scientists are beginning to understand why these ‘mini Wall Streets’ work so well at forecasting election results — and how they sometimes fail.

Adam Mann

doi: 10.1038/538308a

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News & Views

A matched set of frog sequences p.320

A whole-genome duplication that occurred around 34 million years ago in the frog Xenopus laevis made generating a genome sequence for this valuable model organism a challenge. This obstacle has finally been overcome. See Article p.336

Shawn Burgess

doi: 10.1038/538320a

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Unexpected X-ray flares p.321

Two sources of highly energetic flares have been discovered in archival X-ray data of 70 nearby galaxies. These flares have an undetermined origin and might represent previously unknown astrophysical phenomena. See Letter p.356

Sergio Campana

doi: 10.1038/538321a

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A shocking protein complex p.322

Heat-shock proteins have been found to form part of a large protein complex, called the epichaperome, that improves the survival of some cancer cells. This complex might offer a new target for cancer treatment. See Letter p.397

Kai Bartkowiak & Klaus Pantel

doi: 10.1038/nature19476

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Chemical diversity targets malaria p.323

A molecule selected from a library of compounds that have structures similar to natural products targets several stages of the malarial parasite's life cycle, offering single-dose treatment of the disease in mouse models. See Article p.344

David A. Fidock

doi: 10.1038/nature19481

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Speedy electrons exposed in a flash p.325

A link has been established between high-frequency light emissions and electron oscillations induced in an insulator by a laser. This is a key step in efforts to make electronic devices that work faster than is currently possible. See Letter p.359

Michael Chini

doi: 10.1038/538325a

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The organelle replication connection p.326

Live-cell imaging reveals that a functional interaction occurs between two different organelles: contact between the endoplasmic reticulum and mitochondria is needed for mitochondrial DNA replication and division.

Elena Ziviani & Luca Scorrano

doi: 10.1038/538326b

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Articles

Accurate de novo design of hyperstable constrained peptides p.329

Computational methods for the de novo design of conformationally restricted peptides produce exceptionally stable short peptides stabilized by backbone cyclization and/or internal disulfide bonds that are promising starting points for a new generation of peptide-based drugs.

Gaurav Bhardwaj, Vikram Khipple Mulligan, Christopher D. Bahl, Jason M. Gilmore, Peta J. Harvey, Olivier Cheneval, Garry W. Buchko, Surya V. S. R. K. Pulavarti, Quentin Kaas, Alexander Eletsky + et al.

doi: 10.1038/nature19791

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Genome evolution in the allotetraploid frog Xenopus laevis OPEN p.336

The two homoeologous subgenomes in the allotetraploid frog Xenopus laevis evolved asymmetrically; one often retained the ancestral state, whereas the other experienced gene loss, deletion, rearrangement and reduced gene expression.

Adam M. Session, Yoshinobu Uno, Taejoon Kwon, Jarrod A. Chapman, Atsushi Toyoda, Shuji Takahashi, Akimasa Fukui, Akira Hikosaka, Atsushi Suzuki, Mariko Kondo + et al.

doi: 10.1038/nature19840

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Diversity-oriented synthesis yields novel multistage antimalarial inhibitors p.344

The bicyclic azetidines, a class of potent, well-tolerated antimalarial compounds that is active against multiple stages of the Plasmodium life-cycle, has been discovered following screens against libraries of compounds reminiscent of natural products.

Nobutaka Kato, Eamon Comer, Tomoyo Sakata-Kato, Arvind Sharma, Manmohan Sharma, Micah Maetani, Jessica Bastien, Nicolas M. Brancucci, Joshua A. Bittker, Victoria Corey + et al.

doi: 10.1038/nature19804

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Frizzled proteins are colonic epithelial receptors for C. difficile toxin B p.350

Here, a genome-wide CRISPR–Cas9 screen is used to identify the Wnt receptors frizzled as physiologically relevant Clostridium difficile toxin B receptors, providing new therapeutic targets for treating C. difficile infections.

Liang Tao, Jie Zhang, Paul Meraner, Alessio Tovaglieri, Xiaoqian Wu, Ralf Gerhard, Xinjun Zhang, William B. Stallcup, Ji Miao, Xi He + et al.

doi: 10.1038/nature19799

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Letters

Ultraluminous X-ray bursts in two ultracompact companions to nearby elliptical galaxies p.356

A search of archival X-ray data for 70 nearby galaxies yielded two flaring sources in globular clusters or ultracompact dwarf companions of parent elliptical galaxies.

Jimmy A. Irwin, W. Peter Maksym, Gregory R. Sivakoff, Aaron J. Romanowsky, Dacheng Lin, Tyler Speegle, Ian Prado, David Mildebrath, Jay Strader, Jifeng Liu + et al.

doi: 10.1038/nature19822

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Multi-petahertz electronic metrology p.359

Investigations using single-cycle intense optical fields to drive electron motion in bulk silicon dioxide show that the light-induced electric currents extend in frequency up to about 8 petahertz.

M. Garg, M. Zhan, T. T. Luu, H. Lakhotia, T. Klostermann, A. Guggenmos & E. Goulielmakis

doi: 10.1038/nature19821

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A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns p.378

Pancreatic cancer is not caused by a specific series of genetic alterations that occur sequentially but by one, or few, catastrophic events that result in simultaneous oncogenic genetic rearrangements, giving rise to highly aggressive tumours.

Faiyaz Notta, Michelle Chan-Seng-Yue, Mathieu Lemire, Yilong Li, Gavin W. Wilson, Ashton A. Connor, Robert E. Denroche, Sheng-Ben Liang, Andrew M. K. Brown, Jaeseung C. Kim + et al.

doi: 10.1038/nature19823

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Cortico-fugal output from visual cortex promotes plasticity of innate motor behaviour p.383

The mammalian visual cortex massively innervates the brainstem, a phylogenetically older structure, via cortico-fugal axonal projections. Many cortico-fugal projections target brainstem nuclei that mediate innate motor behaviours, but the function of these projections remains poorly understood. A prime example of such behaviours is the optokinetic reflex (OKR), an innate eye movement mediated by the brainstem accessory optic system, that stabilizes images on the retina as the animal moves through the environment and is thus crucial for vision. The OKR is plastic, allowing the amplitude of this reflex to be adaptively adjusted relative to other oculomotor reflexes and thereby ensuring image stability throughout life. Although the plasticity of the OKR is thought to involve subcortical structures such as the cerebellum and vestibular nuclei, cortical lesions have suggested that the visual cortex might also be involved. Here we show that projections from the mouse visual cortex to the accessory optic system promote the adaptive plasticity of the OKR. OKR potentiation, a compensatory plastic increase in the amplitude of the OKR in response to vestibular impairment, is diminished by silencing visual cortex. Furthermore, targeted ablation of a sparse population of cortico-fugal neurons that specifically project to the accessory optic system severely impairs OKR potentiation. Finally, OKR potentiation results from an enhanced drive exerted by the visual cortex onto the accessory optic system. Thus, cortico-fugal projections to the brainstem enable the visual cortex, an area that has been principally studied for its sensory processing function, to plastically adapt the execution of innate motor behaviours.

Bao-hua Liu, Andrew D. Huberman & Massimo Scanziani

doi: 10.1038/nature19818

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Allogeneic transplantation of iPS cell-derived cardiomyocytes regenerates primate hearts p.388

Allogenic induced pluripotent stem cell-derived cardiomyocytes transplanted directly into infarcted cynomolgus monkey hearts show electrical coupling with host cardiomyocytes improve cardiac contractile function after mild immunosuppression.

Yuji Shiba, Toshihito Gomibuchi, Tatsuichiro Seto, Yuko Wada, Hajime Ichimura, Yuki Tanaka, Tatsuki Ogasawara, Kenji Okada, Naoko Shiba, Kengo Sakamoto + et al.

doi: 10.1038/nature19815

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Fetal liver endothelium regulates the seeding of tissue-resident macrophages p.392

PLVAP selectively controls the seeding of fetal liver monocyte-derived tissue-resident macrophages, seemingly by interacting with chemotactic and adhesive molecules at the diaphragms of liver sinusoidal endothelium.

Pia Rantakari, Norma Jäppinen, Emmi Lokka, Elias Mokkala, Heidi Gerke, Emilia Peuhu, Johanna Ivaska, Kati Elima, Kaisa Auvinen & Marko Salmi

doi: 10.1038/nature19814

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The epichaperome is an integrated chaperome network that facilitates tumour survival p.397

Chaperomes are dynamic assemblies of proteins that regulate cellular homeostasis but specific cellular stresses remodel chaperome components into a stable chaperome network called the epichaperome, which might offer a new cancer target.

Anna Rodina, Tai Wang, Pengrong Yan, Erica DaGama Gomes, Mark P. S. Dunphy, Nagavarakishore Pillarsetty, John Koren, John F. Gerecitano, Tony Taldone, Hongliang Zong + et al.

doi: 10.1038/nature19807

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Molecular basis of Lys11-polyubiquitin specificity in the deubiquitinase Cezanne p.402

The structures of the deubiquitinating enzyme Cezanne alone or in complex with its substrate or product are solved, showing how Cezanne specifically targets Lys11-linked polyubiquitin.

Tycho E. T. Mevissen, Yogesh Kulathu, Monique P.C. Mulder, Paul P. Geurink, Sarah L. Maslen, Malte Gersch, Paul R. Elliott, John E. Burke, Bianca D. M. van Tol, Masato Akutsu + et al.

doi: 10.1038/nature19836

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Atomic structure of the entire mammalian mitochondrial complex I p.406

The atomic structure of ovine mitochondrial complex I is solved at 3.9 Å resolution, revealing that supernumerary subunits stabilize the complex and providing insight into the molecular basis of its function and regulation.

Karol Fiedorczuk, James A. Letts, Gianluca Degliesposti, Karol Kaszuba, Mark Skehel & Leonid A. Sazanov

doi: 10.1038/nature19794

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X-ray structure of the human α4β2 nicotinic receptor p.411

Nicotinic acetylcholine receptors are ligand-gated ion channels that mediate fast chemical neurotransmission at the neuromuscular junction and have diverse signalling roles in the central nervous system. The nicotinic receptor has been a model system for cell-surface receptors, and specifically for ligand-gated ion channels, for well over a century. In addition to the receptors’ prominent roles in the development of the fields of pharmacology and neurobiology, nicotinic receptors are important therapeutic targets for neuromuscular disease, addiction, epilepsy and for neuromuscular blocking agents used during surgery. The overall architecture of the receptor was described in landmark studies of the nicotinic receptor isolated from the electric organ of Torpedo marmorata. Structures of a soluble ligand-binding domain have provided atomic-scale insights into receptor–ligand interactions, while high-resolution structures of other members of the pentameric receptor superfamily provide touchstones for an emerging allosteric gating mechanism. All available high-resolution structures are of homopentameric receptors. However, the vast majority of pentameric receptors (called Cys-loop receptors in eukaryotes) present physiologically are heteromeric. Here we present the X-ray crystallographic structure of the human α4β2 nicotinic receptor, the most abundant nicotinic subtype in the brain. This structure provides insights into the architectural principles governing ligand recognition, heteromer assembly, ion permeation and desensitization in this prototypical receptor class.

Claudio L. Morales-Perez, Colleen M. Noviello & Ryan E. Hibbs

doi: 10.1038/nature19785

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