Volume 538 Number 7625

Editorials

News

News Features

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.

doi: 10.1038/538308a

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

doi: 10.1038/538320a

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

doi: 10.1038/538321a

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

doi: 10.1038/nature19476

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

doi: 10.1038/nature19481

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

doi: 10.1038/538325a

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.

doi: 10.1038/538326b

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.

doi: 10.1038/nature19791

Letters

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.

doi: 10.1038/nature19821

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.

doi: 10.1038/nature19818

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.

doi: 10.1038/nature19785