Table of Contents

Volume 516 Number 7531 pp287-444

18 December 2014

About the cover

The 2014 edition of Nature’s 10 — a list of 10 people who mattered in science this year selected by Nature’s team of editors — looks behind the major events and discoveries to the human endeavour that makes science work. This year’s picks include Andrea Accomazzo, flight director of the Rosetta mission that landed the Philae spacecraft on comet 67P/Churyumov–Gerasimenko; Radhika Nagpal, who contributed to the rapid advances being made in artificial intelligence and robotics and Sjors Scheres wins a spot on the list for his work on cryo-electron microscopy. Nature’s list also includes: Pete Frates, the retired baseball player who has amyotrophic lateral sclerosis (ALS) and is credited with turning the Ice Bucket Challenge into the social media phenomenon of the year; Sheik Humarr Khan, who dedicated himself to understanding and fighting the Ebola virus disease in Sierra Leone, and who died from the disease in July; Masayo Takahashi, who led the first clinical trial of cells derived from induced pluripotent stem (iPS) cells; Kopillil Radhakrishnan, head of the Indian Space Research Organization; David Spergel, who identified problems with the reported discovery of gravitational waves from the infant universe; Maryam Mirzakhani, the mathematician who became the first female winner of the prestigious Fields Medal prize for mathematics; and Suzanne Topalian, whose work has been crucial in bringing a technique known as cancer immunotherapy from laboratory to clinic. Cover: CGI illustration by Peter Crowther Associates/ Début Art.

This Week


  • Keep asking the question

    Scientists must push to preserve a small part of a large US survey that provides essential information on the ever-changing scientific workforce.

  • Spin cycle

    Pressures in all stages of the news-making process can lead to hype in science reporting.

  • Honest brokers

    Climate negotiations in Lima stumbled on transparency, but there is time to adjust.

World View


Seven Days

  • Seven days: 12–18 December 2014

    The week in science: Activists harm Nazca lines; Large Hadron Collider heads towards reboot; and Russia promises nuclear reactors for India.

    News in Focus

    • 365 days: 2014 in science

      No Alt text available for this image

      Comets, stem cells and cosmic dust are among the year's top stories.

      • Lauren Morello
      • Alison Abbott
      • Declan Butler
      • Ewen Callaway
      • David Cyranoski
      • Sara Reardon
      • Quirin Schiermeier
      • Alexandra Witze




    Books and Arts

    • In retrospect: Between Pacific Tides

      Aaron Hirsh celebrates the 75th anniversary of the marine-biology classic by Ed Ricketts, the bohemian scientist who inspired John Steinbeck.

      • Review of Between Pacific Tides
        Edward F. Ricketts & Jack Calvin






    naturejobs job listings and advertising features






    • The exclusion of a significant range of ages in a massive star cluster

      • Chengyuan Li
      • Richard de Grijs
      • Licai Deng

      Hubble Space Telescope observations of the stellar cluster NGC 1651, which is approximately two billion years old, show that the colour–brightness distribution of stars old enough to have left the main sequence can be explained only by a single-age population, despite having a feature usually interpreted to indicate an age spread of more than 300 million years.

    • Deterministic switching of ferromagnetism at room temperature using an electric field

      • J. T. Heron
      • J. L. Bosse
      • Q. He
      • Y. Gao
      • M. Trassin
      • L. Ye
      • J. D. Clarkson
      • C. Wang
      • Jian Liu
      • S. Salahuddin
      • D. C. Ralph
      • D. G. Schlom
      • J. Íñiguez
      • B. D. Huey
      • R. Ramesh

      Multiferroic devices that can switch magnetization with electric field at room temperature are desirable, but in BiFeO3 the required direct 180-degree switch is thermodynamically forbidden; here it is shown that such switching is possible because the kinetics of the switching process favours a two-step sequence of partial switching.

      See also
    • Reconstruction and control of a time-dependent two-electron wave packet

      • Christian Ott
      • Andreas Kaldun
      • Luca Argenti
      • Philipp Raith
      • Kristina Meyer
      • Martin Laux
      • Yizhu Zhang
      • Alexander Blättermann
      • Steffen Hagstotz
      • Thomas Ding
      • Robert Heck
      • Javier Madroñero
      • Fernando Martín
      • Thomas Pfeifer

      The dynamics of two correlated electrons can be reconstructed from the quantum interference of low-lying doubly excited states in helium, as observed in attosecond transient-absorption spectra, and can be controlled by tuning the interaction with a visible laser field of variable intensity.

    • Global protected area expansion is compromised by projected land-use and parochialism

      • Federico Montesino Pouzols
      • Tuuli Toivonen
      • Enrico Di Minin
      • Aija S. Kukkala
      • Peter Kullberg
      • Johanna Kuusterä
      • Joona Lehtomäki
      • Henrikki Tenkanen
      • Peter H. Verburg
      • Atte Moilanen

      Internationally coordinated expansion of the global protected area network to 17% could triple the average protection of species ranges and ecoregions; if projected land-use changes and consequent habitat loss until 2040 occur, currently feasible protection levels will not be achievable, and more than 1,000 threatened species face reductions in the range of over 50%.

      See also
    • Signatures of aestivation and migration in Sahelian malaria mosquito populations

      • A. Dao
      • A. S. Yaro
      • M. Diallo
      • S. Timbiné
      • D. L. Huestis
      • Y. Kassogué
      • A. I. Traoré
      • Z. L. Sanogo
      • D. Samaké
      • T. Lehmann

      Malaria-carrying mosquitoes nearly disappear in the dry season, yet they reappear suddenly following the first rains; using surveys of mosquito densities, the authors characterize the population dynamics of the three main vector species and use these to infer persistence by long-distance migration in two species and aestivation in the third.

      See also
    • A relative shift in cloacal location repositions external genitalia in amniote evolution

      • Patrick Tschopp
      • Emma Sherratt
      • Thomas J. Sanger
      • Anna C. Groner
      • Ariel C. Aspiras
      • Jimmy K. Hu
      • Olivier Pourquié
      • Jérôme Gros
      • Clifford J. Tabin

      It has been known for some time that limbs share at least some of their molecular patterning mechanism with external genitalia; here, this connection is examined in a variety of species, revealing that once-shared developmental trajectories could help to explain the observed patterning similarities.

    • Adenosine activates brown adipose tissue and recruits beige adipocytes via A2A receptors

      • Thorsten Gnad
      • Saskia Scheibler
      • Ivar von Kügelgen
      • Camilla Scheele
      • Ana Kilić
      • Anja Glöde
      • Linda S. Hoffmann
      • Laia Reverte-Salisa
      • Philipp Horn
      • Samet Mutlu
      • Ali El-Tayeb
      • Mathias Kranz
      • Winnie Deuther-Conrad
      • Peter Brust
      • Martin E. Lidell
      • Matthias J. Betz
      • Sven Enerbäck
      • Jürgen Schrader
      • Gennady G. Yegutkin
      • Christa E. Müller
      • Alexander Pfeifer

      Cold exposure activates brown adipose tissue (BAT) through the sympathetic nervous system, and previous studies have reported inhibitory effects of the purinergic transmitter adenosine in BAT from hamster or rat; here adenosine/A2A signalling is shown to be involved in sympathetic activation of human and murine brown adipocytes to allow protection of mice from diet-induced obesity.

    • Modelling human development and disease in pluripotent stem-cell-derived gastric organoids

      • Kyle W. McCracken
      • Emily M. Catá
      • Calyn M. Crawford
      • Katie L. Sinagoga
      • Michael Schumacher
      • Briana E. Rockich
      • Yu-Hwai Tsai
      • Christopher N. Mayhew
      • Jason R. Spence
      • Yana Zavros
      • James M. Wells

      The in vitro generation, from pluripotent stem cells, of three-dimensional human gastric organoids (hGOs) that contain a physiological gastric epithelium comprising both progenitor and differentiated cell types, and have expected functional characteristics is described, as is modelling the pathophysiological response of the human stomach to Helicobacter pylori using these hGOs.

    • Primate-specific endogenous retrovirus-driven transcription defines naive-like stem cells

      • Jichang Wang
      • Gangcai Xie
      • Manvendra Singh
      • Avazeh T. Ghanbarian
      • Tamás Raskó
      • Attila Szvetnik
      • Huiqiang Cai
      • Daniel Besser
      • Alessandro Prigione
      • Nina V. Fuchs
      • Gerald G. Schumann
      • Wei Chen
      • Matthew C. Lorincz
      • Zoltán Ivics
      • Laurence D. Hurst
      • Zsuzsanna Izsvák

      An extensive analysis of HERVH (a primate-specific endogenous retrovirus) expression in human pluripotent stem cells is presented, identifying a sub-population of cells within cultured human embryonic stem cells and induced pluripotent stem cells that has characteristics of naive-state cells — the study provides evidence for a new primate-specific transcriptional circuitry regulating pluripotency.

    • Protein quality control at the inner nuclear membrane

      • Anton Khmelinskii
      • Ewa Blaszczak
      • Marina Pantazopoulou
      • Bernd Fischer
      • Deike J. Omnus
      • Gaëlle Le Dez
      • Audrey Brossard
      • Alexander Gunnarsson
      • Joseph D. Barry
      • Matthias Meurer
      • Daniel Kirrmaier
      • Charles Boone
      • Wolfgang Huber
      • Gwenaël Rabut
      • Per O. Ljungdahl
      • Michael Knop

      A protein degradation pathway is found at the inner nuclear membrane that is distinct from, but complementary to, endoplasmic-reticulum-associated protein degradation, and which is mediated by the Asi protein complex; a genome-wide library screening of yeast identifies more than 20 substrates of this pathway, which is shown to target mislocalized integral membrane proteins for degradation.

    • Mitochondrial UPR-regulated innate immunity provides resistance to pathogen infection

      • Mark W. Pellegrino
      • Amrita M. Nargund
      • Natalia V. Kirienko
      • Reba Gillis
      • Christopher J. Fiorese
      • Cole M. Haynes

      A link between an intracellular stress response, bacterial infection and triggering of the innate immune response is shown in Caenorhabditis elegans; exposure to the pathogen Pseudomonas aeruginosa caused activation of the transcription factor ATFS-1 and innate immunity that is regulated by the mitochondrial unfolded protein response.

    • Rapid development of broadly influenza neutralizing antibodies through redundant mutations

      • Leontios Pappas
      • Mathilde Foglierini
      • Luca Piccoli
      • Nicole L. Kallewaard
      • Filippo Turrini
      • Chiara Silacci
      • Blanca Fernandez-Rodriguez
      • Gloria Agatic
      • Isabella Giacchetto-Sasselli
      • Gabriele Pellicciotta
      • Federica Sallusto
      • Qing Zhu
      • Elisa Vicenzi
      • Davide Corti
      • Antonio Lanzavecchia

      The main pathway of somatic mutations leading to the generation of high affinity broadly neutralizing antibodies against the influenza haemagglutinin stem is defined.

    • In vivo engineering of oncogenic chromosomal rearrangements with the CRISPR/Cas9 system

      • Danilo Maddalo
      • Eusebio Manchado
      • Carla P. Concepcion
      • Ciro Bonetti
      • Joana A. Vidigal
      • Yoon-Chi Han
      • Paul Ogrodowski
      • Alessandra Crippa
      • Natasha Rekhtman
      • Elisa de Stanchina
      • Scott W. Lowe
      • Andrea Ventura

      The CRISPR/Cas system has been used to induce the Eml4Alk chromosomal inversion in mice, a characteristic chromosomal rearrangement seen in human non-small cell lung cancers; the mice developed lung cancer and responded to the ALK inhibitor crizotinib, which is used to treat lung cancer patients with the EML4–ALK rearrangement; this general strategy can be used to engineer other disease-associated chromosomal rearrangements in mice and potentially in other organisms.

    • Rapid modelling of cooperating genetic events in cancer through somatic genome editing

      • Francisco J. Sánchez-Rivera
      • Thales Papagiannakopoulos
      • Rodrigo Romero
      • Tuomas Tammela
      • Matthew R. Bauer
      • Arjun Bhutkar
      • Nikhil S. Joshi
      • Lakshmipriya Subbaraj
      • Roderick T. Bronson
      • Wen Xue
      • Tyler Jacks

      The CRISPR/Cas system has been used in mice for genome editing to introduce genetic alterations found in human lung tumours, and these genome modifications resulted in mouse lung tumours showing different histopathologies depending on the genes altered; the CRISPR/Cas system offers improved and faster ways to create animal models of human diseases such as cancer.

    • Cohesin-dependent globules and heterochromatin shape 3D genome architecture in S. pombe

      • Takeshi Mizuguchi
      • Geoffrey Fudenberg
      • Sameet Mehta
      • Jon-Matthew Belton
      • Nitika Taneja
      • Hernan Diego Folco
      • Peter FitzGerald
      • Job Dekker
      • Leonid Mirny
      • Jemima Barrowman
      • Shiv I. S. Grewal

      Genome-wide chromatin conformation capture (Hi-C) is used to investigate three-dimensional genome organization in Schizosaccharomyces pombe; small domains of chromatin interact locally on chromosome arms to form globules, which depend on cohesin but not heterochromatin for formation, and heterochromatin at centromeres and telomeres provides crucial structural constraints to shape genome architecture.

    • R-loops induce repressive chromatin marks over mammalian gene terminators

      • Konstantina Skourti-Stathaki
      • Kinga Kamieniarz-Gdula
      • Nicholas J. Proudfoot

      R-loops, which have been considered to be rare and potentially harmful transcriptional by-products, are now shown to be needed for antisense transcription and to induce repressive chromatin marks that reinforce pausing of transcription and thereby enhance its termination.