Volume 517 Issue 7536, 29 January 2015

Perception, a ‘face built out of many lines� by Norwegian artist Espen Kluge. Squamous cell head and neck cancer is one of the most common and deadly cancers. Despite initial responses to combinations of surgery, radiation and chemotherapy, approximately half of all tumours recur, usually within two years of initial diagnosis. Molecular markers and targeted therapies have had little impact on this disease to date. Here, The Cancer Genome Atlas team presents a detailed genome-wide overview of alterations and highlights critical genetic events of potential biological and clinical significance in head and neck squamous cell carcinomas (HNSCCs) with different human papillomavirus (HPV) status. Mutational profiles reveal distinct subgroups of HNSCCs. Mutations in EGFR, FGFRs, PIK3CA and cyclin-dependent kinases represent candidate targets for therapeutic intervention in the majority of HNSCCs. Cover : www.espen-kluge.com

Editorial

  • Editorial |

    The discovery of part of a 55,000-year-old human skull in Israel will help to answer some questions about our species’ evolution — but it shows that the tale is complicated.

  • Editorial |

    A few Republicans agreeing with basic climate research is not an environmental victory.

  • Editorial |

    Technicians are often under appreciated, but without them there could be no research.

World View

Research Highlights

Social Selection

Seven Days

  • Seven Days |

    The week in science: Obama announces precision-medicine push, marijuana research endorsed by paediatric group, and Israel frees jailed Palestinian physicist.

News

Correction

News Feature

  • News Feature |

    Research relies on unsung heroes working behind the scenes — and some of them have rather unusual jobs.

Comment

Books & Arts

  • Books & Arts |

    Herbert Gintis applauds two books that powerfully enrich the dialogue on behavioural science.

    • Herbert Gintis
  • Books & Arts |

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

    • Barbara Kiser

Correspondence

Correction

Obituary

News & Views

  • News & Views |

    Influenza virus severely damages the epithelial tissue that lines the lung. Findings suggest that, in mice, activation of a back-up population of stem cells mediates effective repair of the injured lung. See Letters p.616 & p.621

    • Emma L. Rawlins
  • News & Views |

    A link between rotation and age for Sun-like stars has long been known, but a stringent test of it for older stars has been lacking. The Kepler mission helps to fill this gap with observations of an old star cluster. See Letter p.589

    • David Soderblom
  • News & Views |

    The identification of the gene regulatory network that controls the formation of xylem — the major component of wood — opens up new avenues for manipulating plant biomass. See Article p.571

    • Anthony Bishopp
    •  & Malcolm J. Bennett
  • News & Views |

    Splitting and recombining an electron wave packet has been used to test relativity at a record sensitivity. The result heralds an era of precision measurements of relativity using quantum-information methods. See Letter p.592

    • V. Alan Kostelecký
  • News & Views |

    The repurposing of a bacterial defence system known as CRISPR into a potent activator of gene expression in human cells enables powerful studies of gene function, as exemplified in cancer cells. See Article p.583

    • Seung Woo Cho
    •  & Howard Y. Chang

    Special:

  • News & Views |

    A combination of simulations and data shows that short-term climate trends are dominated by natural internal variations, providing a basis for climate forecasting, but not for assessing sensitivity to forced changes. See Article p.565

    • James Risbey
  • News & Views |

    The discovery that the estimated number of stem-cell divisions in a tissue correlates with cancer incidence suggests that the varying probability of developing cancer in different tissues is mostly down to random mutations.

    • Dominik Wodarz
    •  & Ann G. Zauber

Article

  • Article |

    A study of the effect of radiative forcing, climate feedback and ocean heat uptake on global-mean surface temperature indicates that overestimation of the response of climate models to radiative forcing from increasing greenhouse gas concentrations is not responsible for the post-1998 discrepancy between model simulations and observations.

    • Jochem Marotzke
    •  & Piers M. Forster
  • Article |

    The full complement of transcriptional regulators that affect synthesis of the plant secondary cell wall remains largely undetermined; here, the network of protein–DNA interactions controlling secondary cell wall synthesis of Arabidopsis thaliana is determined, showing that gene expression is regulated by a series of feed-forward loops to ensure that the secondary cell wall is deposited at the right time and in the right place.

    • M. Taylor-Teeples
    • , L. Lin
    • , M. de Lucas
    • , G. Turco
    • , T. W. Toal
    • , A. Gaudinier
    • , N. F. Young
    • , G. M. Trabucco
    • , M. T. Veling
    • , R. Lamothe
    • , P. P. Handakumbura
    • , G. Xiong
    • , C. Wang
    • , J. Corwin
    • , A. Tsoukalas
    • , L. Zhang
    • , D. Ware
    • , M. Pauly
    • , D. J. Kliebenstein
    • , K. Dehesh
    • , I. Tagkopoulos
    • , G. Breton
    • , J. L. Pruneda-Paz
    • , S. E. Ahnert
    • , S. A. Kay
    • , S. P. Hazen
    •  & S. M. Brady
  • Article | | Open Access

    The Cancer Genome Atlas presents an integrative genome-wide analysis of genetic alterations in 279 head and neck squamous cell carcinomas (HNSCCs), which are classified by human papillomavirus (HPV) status; alterations in EGFR, FGFR, PIK3CA and cyclin-dependent kinases are shown to represent candidate targets for therapeutic intervention in most HNSCCs.

    • Michael S. Lawrence
    • , Carrie Sougnez
    • , Lee Lichtenstein
    • , Kristian Cibulskis
    • , Eric Lander
    • , Stacey B. Gabriel
    • , Gad Getz
    • , Adrian Ally
    • , Miruna Balasundaram
    • , Inanc Birol
    • , Reanne Bowlby
    • , Denise Brooks
    • , Yaron S. N. Butterfield
    • , Rebecca Carlsen
    • , Dean Cheng
    • , Andy Chu
    • , Noreen Dhalla
    • , Ranabir Guin
    • , Robert A. Holt
    • , Steven J. M. Jones
    • , Darlene Lee
    • , Haiyan I. Li
    • , Marco A. Marra
    • , Michael Mayo
    • , Richard A. Moore
    • , Andrew J. Mungall
    • , A. Gordon Robertson
    • , Jacqueline E. Schein
    • , Payal Sipahimalani
    • , Angela Tam
    • , Nina Thiessen
    • , Tina Wong
    • , Alexei Protopopov
    • , Netty Santoso
    • , Semin Lee
    • , Michael Parfenov
    • , Jianhua Zhang
    • , Harshad S. Mahadeshwar
    • , Jiabin Tang
    • , Xiaojia Ren
    • , Sahil Seth
    • , Psalm Haseley
    • , Dong Zeng
    • , Lixing Yang
    • , Andrew W. Xu
    • , Xingzhi Song
    • , Angeliki Pantazi
    • , Christopher A. Bristow
    • , Angela Hadjipanayis
    • , Jonathan Seidman
    • , Lynda Chin
    • , Peter J. Park
    • , Raju Kucherlapati
    • , Rehan Akbani
    • , Tod Casasent
    • , Wenbin Liu
    • , Yiling Lu
    • , Gordon Mills
    • , Thomas Motter
    • , John Weinstein
    • , Lixia Diao
    • , Jing Wang
    • , You Hong Fan
    • , Jinze Liu
    • , Kai Wang
    • , J. Todd Auman
    • , Saianand Balu
    • , Thomas Bodenheimer
    • , Elizabeth Buda
    • , D. Neil Hayes
    • , Katherine A. Hoadley
    • , Alan P. Hoyle
    • , Stuart R. Jefferys
    • , Corbin D. Jones
    • , Patrick K. Kimes
    • , Yufeng Liu
    • , J. S. Marron
    • , Shaowu Meng
    • , Piotr A. Mieczkowski
    • , Lisle E. Mose
    • , Joel S. Parker
    • , Charles M. Perou
    • , Jan F. Prins
    • , Jeffrey Roach
    • , Yan Shi
    • , Janae V. Simons
    • , Darshan Singh
    • , Matthew G. Soloway
    • , Donghui Tan
    • , Umadevi Veluvolu
    • , Vonn Walter
    • , Scot Waring
    • , Matthew D. Wilkerson
    • , Junyuan Wu
    • , Ni Zhao
    • , Andrew D. Cherniack
    • , Peter S. Hammerman
    • , Aaron D. Tward
    • , Chandra Sekhar Pedamallu
    • , Gordon Saksena
    • , Joonil Jung
    • , Akinyemi I. Ojesina
    • , Scott L. Carter
    • , Travis I. Zack
    • , Steven E. Schumacher
    • , Rameen Beroukhim
    • , Samuel S. Freeman
    • , Matthew Meyerson
    • , Juok Cho
    • , Lynda Chin
    • , Gad Getz
    • , Michael S. Noble
    • , Daniel DiCara
    • , Hailei Zhang
    • , David I. Heiman
    • , Nils Gehlenborg
    • , Doug Voet
    • , Pei Lin
    • , Scott Frazer
    • , Petar Stojanov
    • , Yingchun Liu
    • , Lihua Zou
    • , Jaegil Kim
    • , Carrie Sougnez
    • , Stacey B. Gabriel
    • , Michael S. Lawrence
    • , Donna Muzny
    • , HarshaVardhan Doddapaneni
    • , Christie Kovar
    • , Jeff Reid
    • , Donna Morton
    • , Yi Han
    • , Walker Hale
    • , Hsu Chao
    • , Kyle Chang
    • , Jennifer A. Drummond
    • , Richard A. Gibbs
    • , Nipun Kakkar
    • , David Wheeler
    • , Liu Xi
    • , Giovanni Ciriello
    • , Marc Ladanyi
    • , William Lee
    • , Ricardo Ramirez
    • , Chris Sander
    • , Ronglai Shen
    • , Rileen Sinha
    • , Nils Weinhold
    • , Barry S. Taylor
    • , B. Arman Aksoy
    • , Gideon Dresdner
    • , Jianjiong Gao
    • , Benjamin Gross
    • , Anders Jacobsen
    • , Boris Reva
    • , Nikolaus Schultz
    • , S. Onur Sumer
    • , Yichao Sun
    • , Timothy A. Chan
    • , Luc G. Morris
    • , Joshua Stuart
    • , Stephen Benz
    • , Sam Ng
    • , Christopher Benz
    • , Christina Yau
    • , Stephen B. Baylin
    • , Leslie Cope
    • , Ludmila Danilova
    • , James G. Herman
    • , Moiz Bootwalla
    • , Dennis T. Maglinte
    • , Peter W. Laird
    • , Timothy Triche Jr
    • , Daniel J. Weisenberger
    • , David J. Van Den Berg
    • , Nishant Agrawal
    • , Justin Bishop
    • , Paul C. Boutros
    • , Jeff P. Bruce
    • , Lauren Averett Byers
    • , Joseph Califano
    • , Thomas E. Carey
    • , Zhong Chen
    • , Hui Cheng
    • , Simion I. Chiosea
    • , Ezra Cohen
    • , Brenda Diergaarde
    • , Ann Marie Egloff
    • , Adel K. El-Naggar
    • , Robert L. Ferris
    • , Mitchell J. Frederick
    • , Jennifer R. Grandis
    • , Yan Guo
    • , Robert I. Haddad
    • , Peter S. Hammerman
    • , Thomas Harris
    • , D. Neil Hayes
    • , Angela B. Y. Hui
    • , J. Jack Lee
    • , Scott M. Lippman
    • , Fei-Fei Liu
    • , Jonathan B. McHugh
    • , Jeff Myers
    • , Patrick Kwok Shing Ng
    • , Bayardo Perez-Ordonez
    • , Curtis R. Pickering
    • , Michael Prystowsky
    • , Marjorie Romkes
    • , Anthony D. Saleh
    • , Maureen A. Sartor
    • , Raja Seethala
    • , Tanguy Y. Seiwert
    • , Han Si
    • , Aaron D. Tward
    • , Carter Van Waes
    • , Daryl M. Waggott
    • , Maciej Wiznerowicz
    • , Wendell G. Yarbrough
    • , Jiexin Zhang
    • , Zhixiang Zuo
    • , Ken Burnett
    • , Daniel Crain
    • , Johanna Gardner
    • , Kevin Lau
    • , David Mallery
    • , Scott Morris
    • , Joseph Paulauskis
    • , Robert Penny
    • , Candace Shelton
    • , Troy Shelton
    • , Mark Sherman
    • , Peggy Yena
    • , Aaron D. Black
    • , Jay Bowen
    • , Jessica Frick
    • , Julie M. Gastier-Foster
    • , Hollie A. Harper
    • , Kristen Leraas
    • , Tara M. Lichtenberg
    • , Nilsa C. Ramirez
    • , Lisa Wise
    • , Erik Zmuda
    • , Julien Baboud
    • , Mark A. Jensen
    • , Ari B. Kahn
    • , Todd D. Pihl
    • , David A. Pot
    • , Deepak Srinivasan
    • , Jessica S. Walton
    • , Yunhu Wan
    • , Robert A. Burton
    • , Tanja Davidsen
    • , John A. Demchok
    • , Greg Eley
    • , Martin L. Ferguson
    • , Kenna R. Mills Shaw
    • , Bradley A. Ozenberger
    • , Margi Sheth
    • , Heidi J. Sofia
    • , Roy Tarnuzzer
    • , Zhining Wang
    • , Liming Yang
    • , Jean Claude Zenklusen
    • , Charles Saller
    • , Katherine Tarvin
    • , Chu Chen
    • , Roni Bollag
    • , Paul Weinberger
    • , Wojciech Golusiński
    • , Paweł Golusiński
    • , Matthew Ibbs
    • , Konstanty Korski
    • , Andrzej Mackiewicz
    • , Wiktoria Suchorska
    • , Bartosz Szybiak
    • , Maciej Wiznerowicz
    • , Ken Burnett
    • , Erin Curley
    • , Johanna Gardner
    • , David Mallery
    • , Robert Penny
    • , Troy Shelton
    • , Peggy Yena
    • , Christina Beard
    • , Colleen Mitchell
    • , George Sandusky
    • , Nishant Agrawal
    • , Julie Ahn
    • , Justin Bishop
    • , Joseph Califano
    • , Zubair Khan
    • , Jeff P. Bruce
    • , Angela B. Y. Hui
    • , Jonathan Irish
    • , Fei-Fei Liu
    • , Bayardo Perez-Ordonez
    • , John Waldron
    • , Paul C. Boutros
    • , Daryl M. Waggott
    • , Jeff Myers
    • , William N. William Jr
    • , Scott M. Lippman
    • , Sophie Egea
    • , Carmen Gomez-Fernandez
    • , Lynn Herbert
    • , Carol R. Bradford
    • , Thomas E. Carey
    • , Douglas B. Chepeha
    • , Andrea S. Haddad
    • , Tamara R. Jones
    • , Christine M. Komarck
    • , Mayya Malakh
    • , Jonathan B. McHugh
    • , Jeffrey S. Moyer
    • , Ariane Nguyen
    • , Lisa A. Peterson
    • , Mark E. Prince
    • , Laura S. Rozek
    • , Maureen A. Sartor
    • , Evan G. Taylor
    • , Heather M. Walline
    • , Gregory T. Wolf
    • , Lori Boice
    • , Bhishamjit S. Chera
    • , William K. Funkhouser
    • , Margaret L. Gulley
    • , Trevor G. Hackman
    • , D. Neil Hayes
    • , Michele C. Hayward
    • , Mei Huang
    • , W. Kimryn Rathmell
    • , Ashley H. Salazar
    • , William W. Shockley
    • , Carol G. Shores
    • , Leigh Thorne
    • , Mark C. Weissler
    • , Sylvia Wrenn
    • , Adam M. Zanation
    • , Simion I. Chiosea
    • , Brenda Diergaarde
    • , Ann Marie Egloff
    • , Robert L. Ferris
    • , Marjorie Romkes
    • , Raja Seethala
    • , Brandee T. Brown
    • , Yan Guo
    • , Michelle Pham
    •  & Wendell G. Yarbrough
  • Article |

    The CRISPR-Cas9 system, a powerful tool for genome editing, has been engineered to activate endogenous gene transcription specifically and potently on a genome-wide scale and applied to a large-scale gain-of-function screen for studying melanoma drug resistance.

    • Silvana Konermann
    • , Mark D. Brigham
    • , Alexandro E. Trevino
    • , Julia Joung
    • , Omar O. Abudayyeh
    • , Clea Barcena
    • , Patrick D. Hsu
    • , Naomi Habib
    • , Jonathan S. Gootenberg
    • , Hiroshi Nishimasu
    • , Osamu Nureki
    •  & Feng Zhang

Letter

  • Letter |

    The measurement of the rotational periods of 30 cool stars in the 2.5-billion-year-old cluster NGC 6819 allows the calibration of gyrochronology — the determination of a star’s age on the basis of its rotation period — over a much broader age range than hitherto, meaning that it might be possible to determine the ages of many cool stars in the Galactic field with a precision of roughly 10 per cent.

    • Søren Meibom
    • , Sydney A. Barnes
    • , Imants Platais
    • , Ronald L. Gilliland
    • , David W. Latham
    •  & Robert D. Mathieu
  • Letter |

    An electronic analogue of a Michelson–Morley experiment, in which an electron wave packet bound inside a calcium ion is split into two parts and subsequently recombined, demonstrates that the relative change in orientation of the two parts that results from the Earth’s rotation reveals no anisotropy in the electron dispersion; this verification of Lorentz symmetry improves on the precision of previous tests by a factor of 100.

    • T. Pruttivarasin
    • , M. Ramm
    • , S. G. Porsev
    • , I. I. Tupitsyn
    • , M. S. Safronova
    • , M. A. Hohensee
    •  & H. Häffner
  • Letter |

    Micrometre-sized particles covered with stiff, nanoscale spikes are shown to exhibit long-term colloidal stability in both hydrophilic and hydrophobic media, without the need for chemical coating, owing to the effect of the spikes on the contact area and, consequently, the force between the particles.

    • Joong Hwan Bahng
    • , Bongjun Yeom
    • , Yichun Wang
    • , Siu On Tung
    • , J. Damon Hoff
    •  & Nicholas Kotov
  • Letter |

    Based on first-principles resistivity calculations, it was recently concluded that the thermal conductivity of iron in Earth’s core was too high to sustain thermal convection, thus invalidating such geodynamo models; new calculations including electron correlations find that electron–electron scattering is comparable to the electron–phonon scattering at high temperatures in iron, doubling the expected resistivity, and reviving conventional geodynamo models.

    • Peng Zhang
    • , R. E. Cohen
    •  & K. Haule
  • Letter |

    Single-molecule, real-time DNA sequencing is used to analyse a haploid human genome (CHM1), thus closing or extending more than half of the remaining 164 euchromatic gaps in the human genome; the complete sequences of euchromatic structural variants (including inversions, complex insertions and tandem repeats) are resolved at the base-pair level, suggesting that a greater complexity of the human genome can now be accessed.

    • Mark J. P. Chaisson
    • , John Huddleston
    • , Megan Y. Dennis
    • , Peter H. Sudmant
    • , Maika Malig
    • , Fereydoun Hormozdiari
    • , Francesca Antonacci
    • , Urvashi Surti
    • , Richard Sandstrom
    • , Matthew Boitano
    • , Jane M. Landolin
    • , John A. Stamatoyannopoulos
    • , Michael W. Hunkapiller
    • , Jonas Korlach
    •  & Evan E. Eichler
  • Letter |

    Using a model of tuberculosis in zebrafish, granuloma formation is shown to coincide with hypoxia and angiogenesis; furthermore, the pharmacological inhibition of the pro-angiogenic VEGF pathway reduces infection burden, suggesting a possible treatment strategy in patients with the disease.

    • Stefan H. Oehlers
    • , Mark R. Cronan
    • , Ninecia R. Scott
    • , Monica I. Thomas
    • , Kazuhide S. Okuda
    • , Eric M. Walton
    • , Rebecca W. Beerman
    • , Philip S. Crosier
    •  & David M. Tobin
  • Letter |

    Many patients experiencing sudden loss of lung tissue somehow undergo full recovery; here this recovery is traced to a discrete population of lung stem cells that are not only essential for lung regeneration but can be cloned and then transplanted to other mice to contribute new lung tissue.

    • Wei Zuo
    • , Ting Zhang
    • , Daniel Zheng'An Wu
    • , Shou Ping Guan
    • , Audrey-Ann Liew
    • , Yusuke Yamamoto
    • , Xia Wang
    • , Siew Joo Lim
    • , Matthew Vincent
    • , Mark Lessard
    • , Christopher P. Crum
    • , Wa Xian
    •  & Frank McKeon
  • Letter |

    Lineage-tracing experiments identify a rare, undifferentiated population of quiescent cells in the mouse distal lung that are activated through a Notch signalling pathway to repair the epithelium after bleomycin- or influenza-mediated injury; inappropriate Notch signalling may be a major contributor to failed regeneration within the lungs of patients with chronic lung disease.

    • Andrew E. Vaughan
    • , Alexis N. Brumwell
    • , Ying Xi
    • , Jeffrey E. Gotts
    • , Doug G. Brownfield
    • , Barbara Treutlein
    • , Kevin Tan
    • , Victor Tan
    • , Feng Chun Liu
    • , Mark R. Looney
    • , Michael A. Matthay
    • , Jason R. Rock
    •  & Harold A. Chapman
  • Letter |

    p53 is often mutated or lost in cancer; here inactivation of ΔNp63 and ΔNp73 in the absence of p53 is shown to result in metabolic reprogramming and tumour regression via activation of IAPP (islet amyloid polypeptide or amylin), and IAPP-based anti-diabetes therapeutic strategies show potential for the treatment of p53-deficient and mutant tumours.

    • Avinashnarayan Venkatanarayan
    • , Payal Raulji
    • , William Norton
    • , Deepavali Chakravarti
    • , Cristian Coarfa
    • , Xiaohua Su
    • , Santosh K. Sandur
    • , Marc S. Ramirez
    • , Jaehuk Lee
    • , Charles V. Kingsley
    • , Eliot F. Sananikone
    • , Kimal Rajapakshe
    • , Katherine Naff
    • , Jan Parker-Thornburg
    • , James A. Bankson
    • , Kenneth Y. Tsai
    • , Preethi H. Gunaratne
    •  & Elsa R. Flores
  • Letter |

    By binding and inhibiting a second CDC20 molecule, the mitotic checkpoint complex can convert a local ‘wait’ signal from unattached kinetochores to inhibit the anaphase promoting complex/cyclosome throughout the cell and avoid premature cell division.

    • Daisuke Izawa
    •  & Jonathon Pines

Feature

Career Brief

Futures

  • Futures |

    Is this the real life?

    • Michael Adam Robson
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