Table of Contents

Volume 515 Number 7526 pp163-304

13 November 2014

About the cover

Clinical depression is the most common major mental health disorder and by some measures, it is responsible for a greater burden of disability than any other cause. In this special issue, Nature asks why the burden is so great, how science is helping, where today’s research is headed and what the future may hold. Cover image: Carl De Torres.

This Week

Editorials

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World View

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Seven Days

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News in Focus

Features

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Books and Arts

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  • Film: Enigma variations

    Robert P. Crease ponders a brace of biopics on Alan Turing and Stephen Hawking.

    • Review of The Imitation Game and The Theory of Everything
      Morten Tyldum & James Marsh
  • Q&A: Space-time visionary

    Thanks to theoretical physicist Kip Thorne, real science is embedded in Christopher Nolan's film Interstellar, in which explorers seek a new home for humankind. Thorne talks about what he learned from the film's unprecedented visualizations of black holes and wormholes, what it and his accompanying book can teach, and the likelihood of humans escaping the Solar System.

    • Review of Interstellar and The Science of Interstellar
      Christopher Nolan & Kip Thorne
  • Books in brief

    Barbara Kiser reviews five of the week's best science picks.

Careers

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Q&As

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Futures

Specials

Technology Feature

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  • A deep look at synaptic dynamics

    The processes behind neuronal communication have not yet been resolved in detail, but dyes, microscopy and protein analysis are beginning to fill in the gaps.

    • Vivien Marx

Outlook: Sickle-cell desease

research

Articles

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  • Synaptic, transcriptional and chromatin genes disrupted in autism

    • Silvia De Rubeis
    • Xin He
    • Arthur P. Goldberg
    • Christopher S. Poultney
    • Kaitlin Samocha
    • A. Ercument Cicek
    • Yan Kou
    • Li Liu
    • Menachem Fromer
    • Susan Walker
    • Tarjinder Singh
    • Lambertus Klei
    • Jack Kosmicki
    • Shih-Chen Fu
    • Branko Aleksic
    • Monica Biscaldi
    • Patrick F. Bolton
    • Jessica M. Brownfeld
    • Jinlu Cai
    • Nicholas G. Campbell
    • Angel Carracedo
    • Maria H. Chahrour
    • Andreas G. Chiocchetti
    • Hilary Coon
    • Emily L. Crawford
    • Lucy Crooks
    • Sarah R. Curran
    • Geraldine Dawson
    • Eftichia Duketis
    • Bridget A. Fernandez
    • Louise Gallagher
    • Evan Geller
    • Stephen J. Guter
    • R. Sean Hill
    • Iuliana Ionita-Laza
    • Patricia Jimenez Gonzalez
    • Helena Kilpinen
    • Sabine M. Klauck
    • Alexander Kolevzon
    • Irene Lee
    • Jing Lei
    • Terho Lehtimäki
    • Chiao-Feng Lin
    • Avi Ma’ayan
    • Christian R. Marshall
    • Alison L. McInnes
    • Benjamin Neale
    • Michael J. Owen
    • Norio Ozaki
    • Mara Parellada
    • Jeremy R. Parr
    • Shaun Purcell
    • Kaija Puura
    • Deepthi Rajagopalan
    • Karola Rehnström
    • Abraham Reichenberg
    • Aniko Sabo
    • Michael Sachse
    • Stephan J. Sanders
    • Chad Schafer
    • Martin Schulte-Rüther
    • David Skuse
    • Christine Stevens
    • Peter Szatmari
    • Kristiina Tammimies
    • Otto Valladares
    • Annette Voran
    • Li-San Wang
    • Lauren A. Weiss
    • A. Jeremy Willsey
    • Timothy W. Yu
    • Ryan K. C. Yuen
    • The DDD Study
    • Homozygosity Mapping Collaborative for Autism
    • UK10K Consortium
    • The Autism Sequencing Consortium
    • Edwin H. Cook
    • Christine M. Freitag
    • Michael Gill
    • Christina M. Hultman
    • Thomas Lehner
    • Aarno Palotie
    • Gerard D. Schellenberg
    • Pamela Sklar
    • Matthew W. State
    • James S. Sutcliffe
    • Christopher A. Walsh
    • Stephen W. Scherer
    • Michael E. Zwick
    • Jeffrey C. Barrett
    • David J. Cutler
    • Kathryn Roeder
    • Bernie Devlin
    • Mark J. Daly
    • Joseph D. Buxbaum

    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.

  • The contribution of de novo coding mutations to autism spectrum disorder

    • Ivan Iossifov
    • Brian J. O’Roak
    • Stephan J. Sanders
    • Michael Ronemus
    • Niklas Krumm
    • Dan Levy
    • Holly A. Stessman
    • Kali T. Witherspoon
    • Laura Vives
    • Karynne E. Patterson
    • Joshua D. Smith
    • Bryan Paeper
    • Deborah A. Nickerson
    • Jeanselle Dea
    • Shan Dong
    • Luis E. Gonzalez
    • Jeffrey D. Mandell
    • Shrikant M. Mane
    • Michael T. Murtha
    • Catherine A. Sullivan
    • Michael F. Walker
    • Zainulabedin Waqar
    • Liping Wei
    • A. Jeremy Willsey
    • Boris Yamrom
    • Yoon-ha Lee
    • Ewa Grabowska
    • Ertugrul Dalkic
    • Zihua Wang
    • Steven Marks
    • Peter Andrews
    • Anthony Leotta
    • Jude Kendall
    • Inessa Hakker
    • Julie Rosenbaum
    • Beicong Ma
    • Linda Rodgers
    • Jennifer Troge
    • Giuseppe Narzisi
    • Seungtai Yoon
    • Michael C. Schatz
    • Kenny Ye
    • W. Richard McCombie
    • Jay Shendure
    • Evan E. Eichler
    • Matthew W. State
    • Michael Wigler

    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.

  • Evolution of mosquito preference for humans linked to an odorant receptor

    • Carolyn S. McBride
    • Felix Baier
    • Aman B. Omondi
    • Sarabeth A. Spitzer
    • Joel Lutomiah
    • Rosemary Sang
    • Rickard Ignell
    • Leslie B. Vosshall

    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.

  • Clathrin regenerates synaptic vesicles from endosomes

    • Shigeki Watanabe
    • Thorsten Trimbuch
    • Marcial Camacho-Pérez
    • Benjamin R. Rost
    • Bettina Brokowski
    • Berit Söhl-Kielczynski
    • Annegret Felies
    • M. Wayne Davis
    • Christian Rosenmund
    • Erik M. Jorgensen

    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.

    See also

Letters

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  • The expanding fireball of Nova Delphini 2013

    • G. H. Schaefer
    • T. ten Brummelaar
    • D. R. Gies
    • C. D. Farrington
    • B. Kloppenborg
    • O. Chesneau
    • J. D. Monnier
    • S. T. Ridgway
    • N. Scott
    • I. Tallon-Bosc
    • H. A. McAlister
    • T. Boyajian
    • V. Maestro
    • D. Mourard
    • A. Meilland
    • N. Nardetto
    • P. Stee
    • J. Sturmann
    • N. Vargas
    • F. Baron
    • M. Ireland
    • E. K. Baines
    • X. Che
    • J. Jones
    • N. D. Richardson
    • R. M. Roettenbacher
    • L. Sturmann
    • N. H. Turner
    • P. Tuthill
    • G. van Belle
    • K. von Braun
    • R. T. Zavala
    • D. P. K. Banerjee
    • N. M. Ashok
    • V. Joshi
    • J. Becker
    • P. S. Muirhead

    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.

  • Observation of topological transitions in interacting quantum circuits

    • P. Roushan
    • C. Neill
    • Yu Chen
    • M. Kolodrubetz
    • C. Quintana
    • N. Leung
    • M. Fang
    • R. Barends
    • B. Campbell
    • Z. Chen
    • B. Chiaro
    • A. Dunsworth
    • E. Jeffrey
    • J. Kelly
    • A. Megrant
    • J. Mutus
    • P. J. J. O’Malley
    • D. Sank
    • A. Vainsencher
    • J. Wenner
    • T. White
    • A. Polkovnikov
    • A. N. Cleland
    • J. M. Martinis

    Superconducting quantum circuits are used to directly observe and characterize topological phase transitions; this approach promises to be a powerful and general platform for characterizing topological phenomena in quantum systems.

    See also
    See also
  • Subduction-driven recycling of continental margin lithosphere

    • A. Levander
    • M. J. Bezada
    • F. Niu
    • E. D. Humphreys
    • I. Palomeras
    • S. M. Thurner
    • J. Masy
    • M. Schmitz
    • J. Gallart
    • R. Carbonell
    • M. S. Miller

    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.

  • Comparative population genomics in animals uncovers the determinants of genetic diversity

    • J. Romiguier
    • P. Gayral
    • M. Ballenghien
    • A. Bernard
    • V. Cahais
    • A. Chenuil
    • Y. Chiari
    • R. Dernat
    • L. Duret
    • N. Faivre
    • E. Loire
    • J. M. Lourenco
    • B. Nabholz
    • C. Roux
    • G. Tsagkogeorga
    • A. A.-T. Weber
    • L. A. Weinert
    • K. Belkhir
    • N. Bierne
    • S. Glémin
    • N. Galtier

    Genome-wide DNA polymorphism analysis across 76 animal species reveals a strong effect of ecological strategies, and particularly parental investment, on species levels of genetic diversity.

  • A three-dimensional human neural cell culture model of Alzheimer’s disease

    • Se Hoon Choi
    • Young Hye Kim
    • Matthias Hebisch
    • Christopher Sliwinski
    • Seungkyu Lee
    • Carla D’Avanzo
    • Hechao Chen
    • Basavaraj Hooli
    • Caroline Asselin
    • Julien Muffat
    • Justin B. Klee
    • Can Zhang
    • Brian J. Wainger
    • Michael Peitz
    • Dora M. Kovacs
    • Clifford J. Woolf
    • Steven L. Wagner
    • Rudolph E. Tanzi
    • Doo Yeon Kim

    Early-onset familial Alzheimer’s disease mutations induce both amyloid-β and tau pathologies in differentiated human neural stem cells in 3D cultures.

  • Piezo1 integration of vascular architecture with physiological force

    • Jing Li
    • Bing Hou
    • Sarka Tumova
    • Katsuhiko Muraki
    • Alexander Bruns
    • Melanie J. Ludlow
    • Alicia Sedo
    • Adam J. Hyman
    • Lynn McKeown
    • Richard S. Young
    • Nadira Y. Yuldasheva
    • Yasser Majeed
    • Lesley A. Wilson
    • Baptiste Rode
    • Marc A. Bailey
    • Hyejeong R. Kim
    • Zhaojun Fu
    • Deborah A. L. Carter
    • Jan Bilton
    • Helen Imrie
    • Paul Ajuh
    • T. Neil Dear
    • Richard M. Cubbon
    • Mark T. Kearney
    • K. Raj Prasad
    • Paul C. Evans
    • Justin F. X. Ainscough
    • David J. Beech

    The Piezo1 calcium-permeable channel is revealed to have a role in the vascular cellular response to shear stress; a mouse knockout reveals that this channel is also important for normal vascular development.

  • The complete structure of the large subunit of the mammalian mitochondrial ribosome

    • Basil J. Greber
    • Daniel Boehringer
    • Marc Leibundgut
    • Philipp Bieri
    • Alexander Leitner
    • Nikolaus Schmitz
    • Ruedi Aebersold
    • Nenad Ban

    The structure of the 39S large mitoribosome subunit is solved by cryo-electron microscopy at an impressive 3.4 Å resolution, revealing the location of 50 ribosomal proteins, the peptidyl transferase centre, the tRNAs within this active site, and the nascent peptide chain within the exit tunnel.

  • Structural basis for the assembly of the Sxl–Unr translation regulatory complex

    • Janosch Hennig
    • Cristina Militti
    • Grzegorz M. Popowicz
    • Iren Wang
    • Miriam Sonntag
    • Arie Geerlof
    • Frank Gabel
    • Fátima Gebauer
    • Michael Sattler

    The crystal structure of the RNA binding domains of Sxl and Unr with msl2 RNA shows that interwoven interactions establish cooperative assembly of the ternary complex, highlighting how binding of relatively general RNA binding domains to RNA can result in a unique and specific protein–RNA architecture.