Volume 515 Number 7526

Editorials

High ambition p.163

The European Space Agency can be proud of its comet mission— whatever happens.

doi: 10.1038/515163b

News

News Features

The great depression p.179

Depression causes more disability than any other disorder. A special issue explores how science can help.

doi: 10.1038/515179a

If depression were cancer p.182

Research into depression has struggled, while studies of cancer have thrived — but the balance could be shifting.

doi: 10.1038/515182a

A change of mind p.185

Cognitive behavioural therapy is the best-studied form of psychotherapy. But researchers are still struggling to understand why it works.

doi: 10.1038/515185a

News & Views

The best way forward p.200

Conventional behavioural mouse models of depression are often used to study the disorder, but cannot capture the full picture of the human disease. Here, scientists present two views about the best research strategies to adopt if treatments are to be improved.

doi: 10.1038/515200a

Magnetic fields without magnetic fields p.202

Exquisite control of quantum systems has allowed researchers to connect reality to ideas of how an exotic form of particle transport known as the quantum Hall effect can occur in the absence of a magnetic field. See Letters p.237 & p.241

doi: 10.1038/515202a

Mystery of the horrible hands solved p.203

A pair of newly discovered 70-million-year-old fossils from Mongolia — including material previously lost to poaching — reveals the true nature of one of the most enigmatic dinosaur species, Deinocheirus mirificus. See Letter p.257

doi: 10.1038/nature13930

Electron mirages in an iron salt p.205

The detection of unusual 'mirage' energy bands in photoemission spectra of single-atom layers of iron selenide reveals the probable cause of high-temperature superconductivity in these artificial structures. See Letter p.245

doi: 10.1038/515205a

Building a bigger brain p.206

An innovative approach to analysing the functions and gene-expression profiles of neural stem cells in developing human and mouse brains sheds light on the differences — and similarities — between the two species. See Letter p.264

doi: 10.1038/515206a

Towards unified vesicle endocytosis p.207

An ultrafast, temperature-dependent mode of endocytosis, a process that is required for neurons to repeatedly fire, challenges current thinking and brings an old model back into the spotlight. See Article p.228

doi: 10.1038/nature13925

Articles

Synaptic, transcriptional and chromatin genes disrupted in autism p.209

Whole-exome sequencing in a large autism study identifies over 100 autosomal genes that are likely to affect risk for the disorder; these genes, which show unusual evolutionary constraint against mutations, carry de novo loss-of-function mutations in over 5% of autistic subjects and many function in synaptic, transcriptional and chromatin-remodelling pathways.

doi: 10.1038/nature13772

The contribution of de novo coding mutations to autism spectrum disorder p.216

Family-based exome sequencing in a large autism study has identified 27 high-confidence gene targets and accurately estimates the contribution of both de novo gene-disrupting and missense mutations to the incidence of simplex autism, with target genes in affected females overlapping those in males of lower but not higher IQ; targets also overlap known targets for intellectual disability and schizophrenia, and are enriched for chromatin modifiers, FMRP-associated genes and embryonically expressed genes.

doi: 10.1038/nature13908

Evolution of mosquito preference for humans linked to an odorant receptor p.222

The mosquito Aedes aegypti includes two subspecies, one of which shows a preference for biting humans, whereas the other prefers to bite non-human animals; genetic analysis reveals that changes in the mosquito odorant receptor Or4 contribute to the behavioural difference—in human-preferring mosquitoes, Or4 is more highly expressed and more sensitive to sulcatone, a compound present at high levels in human odour.

doi: 10.1038/nature13964

Clathrin regenerates synaptic vesicles from endosomes p.228

Ultrastructural analysis of synaptic vesicle recycling reveals that clathrin is not required for the initial rapid step of vesicle recycling by ultrafast endocytosis at the plasma membrane and instead clathrin acts later at an endosome to regenerate synaptic vesicles; however, when ultrafast endocytosis does not occur (for example, in experiments at room temperature rather than physiological temperature), clathrin-mediated endocytosis does happen at the plasma membrane.

doi: 10.1038/nature13846

Letters

The expanding fireball of Nova Delphini 2013 p.234

High spatial resolution is needed to study the early development of a nova; here measurements of the angular size and radial velocity of Nova Delphini 2013 reveal early structures in the ejected material and a geometric distance to the nova of about 4.5 kiloparsecs from the Sun.

doi: 10.1038/nature13834

Interfacial mode coupling as the origin of the enhancement of Tc in FeSe films on SrTiO3 p.245

Films of iron selenide (FeSe) one unit cell thick grown on strontium titanate (SrTiO3 or STO) substrates have recently shown superconducting energy gaps opening at temperatures close to the boiling point of liquid nitrogen (77 kelvin), which is a record for the iron-based superconductors. The gap opening temperature usually sets the superconducting transition temperature Tc, as the gap signals the formation of Cooper pairs, the bound electron states responsible for superconductivity. To understand why Cooper pairs form at such high temperatures, we examine the role of the SrTiO3 substrate. Here we report high-resolution angle-resolved photoemission spectroscopy results that reveal an unexpected characteristic of the single-unit-cell FeSe/SrTiO3 system: shake-off bands suggesting the presence of bosonic modes, most probably oxygen optical phonons in SrTiO3 (refs 5, 6, 7), which couple to the FeSe electrons with only a small momentum transfer. Such interfacial coupling assists superconductivity in most channels, including those mediated by spin fluctuations. Our calculations suggest that this coupling is responsible for raising the superconducting gap opening temperature in single-unit-cell FeSe/SrTiO3.

doi: 10.1038/nature13894

Subduction-driven recycling of continental margin lithosphere p.253

Seismic images of the subducted Atlantic slab under northeastern South America and the Alboran slab beneath the Gibraltar arc region show that subducting oceanic plates viscously entrain and remove the bottom of the continental thermal boundary layer from adjacent continental margins, driving surface tectonics and pre-conditioning the margins for further deformation.

doi: 10.1038/nature13878

Radial glia require PDGFD–PDGFRβ signalling in human but not mouse neocortex p.264

Evolutionary expansion of the human neocortex underlies many of our unique mental abilities. This expansion has been attributed to the increased proliferative potential of radial glia (RG; neural stem cells) and their subventricular dispersion from the periventricular niche during neocortical development. Such adaptations may have evolved through gene expression changes in RG. However, whether or how RG gene expression varies between humans and other species is unknown. Here we show that the transcriptional profiles of human and mouse neocortical RG are broadly conserved during neurogenesis, yet diverge for specific signalling pathways. By analysing differential gene co-expression relationships between the species, we demonstrate that the growth factor PDGFD is specifically expressed by RG in human, but not mouse, corticogenesis. We also show that the expression domain of PDGFRβ, the cognate receptor for PDGFD, is evolutionarily divergent, with high expression in the germinal region of dorsal human neocortex but not in the mouse. Pharmacological inhibition of PDGFD–PDGFRβ signalling in slice culture prevents normal cell cycle progression of neocortical RG in human, but not mouse. Conversely, injection of recombinant PDGFD or ectopic expression of constitutively active PDGFRβ in developing mouse neocortex increases the proportion of RG and their subventricular dispersion. These findings highlight the requirement of PDGFD–PDGFRβ signalling for human neocortical development and suggest that local production of growth factors by RG supports the expanded germinal region and progenitor heterogeneity of species with large brains.

doi: 10.1038/nature13973

The participation of cortical amygdala in innate, odour-driven behaviour p.269

Innate behaviours are observed in naive animals without prior learning or experience, suggesting that the neural circuits that mediate these behaviours are genetically determined and stereotyped. The neural circuits that convey olfactory information from the sense organ to the cortical and subcortical olfactory centres have been anatomically defined, but the specific pathways responsible for innate responses to volatile odours have not been identified. Here we devise genetic strategies that demonstrate that a stereotyped neural circuit that transmits information from the olfactory bulb to cortical amygdala is necessary for innate aversive and appetitive behaviours. Moreover, we use the promoter of the activity-dependent gene arc to express the photosensitive ion channel, channelrhodopsin, in neurons of the cortical amygdala activated by odours that elicit innate behaviours. Optical activation of these neurons leads to appropriate behaviours that recapitulate the responses to innate odours. These data indicate that the cortical amygdala plays a critical role in generating innate odour-driven behaviours but do not preclude its participation in learned olfactory behaviours.

doi: 10.1038/nature13897