Volume 522 Issue 7557, 25 June 2015

An adapted image showing condensed mitotic chromosomes (blue); co-localization between telomeric TTAGGG repeats (green) and a DNA damage marker (red) indicates that telomeres are recognized as damage in cells that spontaneously arrest in mitosis during crisis. Cells forming a tumour must overcome two barriers before becoming cancerous. The first is senescence and the second is a proliferative block known as crisis. Cells that escape senescence usually succumb during crisis, but it has not been clear what triggers cell death at that stage. Jan Karlseder and colleagues now demonstrate that cells that bypass senescence in the absence of p53 have shortened telomeres that undergo fusion, and these fusions trigger mitotic delay. During mitotic arrest telomeres are further deprotected and detected by the DNA damage machinery, which leads to cell death. These findings might offer a clinical opportunity, as exacerbation of mitotic telomere deprotection sensitizes cancer cells to mitotic drugs � but mitotic arrest has also been associated with genome instability and tumorigenesis in checkpoint-compromised cells. (Cover illustration by Jamie Simon, The Salk Institute)


  • Editorial |

    The Vatican has produced a timely and valuable warning on the threat of climate change that will reach a wide audience.

  • Editorial |

    Draft European rules governing privacy threaten to hamper medical research.

  • Editorial |

    Antarctica’s apparent barrenness hides an abundance of living organisms.

World View

  • World View |

    Sexist comments made by my former boss Tim Hunt are not an indication that he is biased against women, argues Alessia Errico.

    • Alessia Errico

Research Highlights

Social Selection

Seven Days

  • Seven Days |

    High seas to receive legal protection; US national-security lab appoints first woman head; and Europe’s Earth-observation satellite launches.



News Feature

  • News Feature |

    When the Francis Crick Institute opens in London this year, it will be Europe’s largest biomedical research centre. Can director Paul Nurse make this gamble pay off for UK science?

    • Ewen Callaway


  • Comment |

    Democratically weighing up the benefits and risks of gene editing and artificial intelligence is a political endeavour, not an academic one, says Daniel Sarewitz.

    • Daniel Sarewitz


  • Comment |

    Researchers and ethicists need to see past what can seem to be gendered debates when it comes to the governance of biotechnology, says Charis Thompson.

    • Charis Thompson

Books & Arts



News & Views

  • News & Views |

    Observations of galaxies that formed early in the Universe's history reveal much lower dust levels than are found in sources from a slightly later era. It seems that galaxies underwent rapid change during a relatively short period. See Letter p.455

    • Veronique Buat
  • News & Views |

    A genetic variant of PrP, the protein that forms prions, confers protection against the human prion disease kuru by inhibiting the conversion of functional isoforms to the abnormal, disease-causing conformation. See Letter p.478

    • Glenn Telling
  • News & Views |

    Two related peptides compete for binding to the same receptor to regulate the spacing of cells on the lower surfaces of leaves. This discovery highlights the complexity of cell signalling in plants. See Article p.439

    • Sacco de Vries
  • News & Views |

    Changes in the occurrence of atmospheric circulation patterns are not well understood. A study finds that these have been a big factor in observed changes in regional temperature extremes during recent decades. See Letter p.465

    • Theodore G. Shepherd
  • News & Views |

    An enzyme has been found that alters the molecular structure of vitamin B2, adding a fourth ring to its existing three-ring system. The product catalyses new types of chemistry in concert with certain other enzymes. See Letters p.497 & p.502

    • Catherine F. Clarke
    •  & Christopher M. Allan
  • News & Views |

    Retinitis pigmentosa causes the death of cone cells, leading to blindness. A factor secreted from rod cells, RdCVF, promotes cone survival in a mouse model of the disease. It now emerges that RdCVF works by increasing glucose uptake in cones.

    • Connie Cepko
    •  & Claudio Punzo


Review Article

  • Review Article |

    Recent research has shown that while large fauna and flowering plants in the Antarctic are scarce, there are considerable levels of marine and terrestrial biodiversity, particularly the microbiota; what drives it, and how the Antarctic can meet conservation targets, are the subject of this review.

    • Steven L. Chown
    • , Andrew Clarke
    • , Ceridwen I. Fraser
    • , S. Craig Cary
    • , Katherine L. Moon
    •  & Melodie A. McGeoch



  • Article |

    An investigation of the molecular mechanism of stomatal development and patterning finds an unexpected signalling mechanism: two signalling peptides (STOMAGEN, a positive regulator of stomatal development; and EPF2, a negative regulator of this process) use the same receptor kinase, ERECTA, to fine-tune stomatal development.

    • Jin Suk Lee
    • , Marketa Hnilova
    • , Michal Maes
    • , Ya-Chen Lisa Lin
    • , Aarthi Putarjunan
    • , Soon-Ki Han
    • , Julian Avila
    •  & Keiko U. Torii
  • Article |

    Myocardial hypoxia activates HIF1α, which activates the splicing factor SF3B1, which mediates a splice switch of the fructose-metabolising enzyme KHK, so that the C isoform that has superior affinity for fructose is expressed in the heart—pathological heart growth and contractile dysfunction can therefore be suppressed by depleting SF3B1 or deleting KHK.

    • Peter Mirtschink
    • , Jaya Krishnan
    • , Fiona Grimm
    • , Alexandre Sarre
    • , Manuel Hörl
    • , Melis Kayikci
    • , Niklaus Fankhauser
    • , Yann Christinat
    • , Cédric Cortijo
    • , Owen Feehan
    • , Ana Vukolic
    • , Samuel Sossalla
    • , Sebastian N. Stehr
    • , Jernej Ule
    • , Nicola Zamboni
    • , Thierry Pedrazzini
    •  & Wilhelm Krek


  • Letter |

    Measurements of [C ii] emission and dust emission from nine typical star-forming galaxies about one billion years after the Big Bang show that galaxies of this age have dust levels that are significantly lower than those of typical galaxies about two billion years later and comparable with those of local low-metallicity galaxies.

    • P. L. Capak
    • , C. Carilli
    • , G. Jones
    • , C. M. Casey
    • , D. Riechers
    • , K. Sheth
    • , C. M. Carollo
    • , O. Ilbert
    • , A. Karim
    • , O. LeFevre
    • , S. Lilly
    • , N. Scoville
    • , V. Smolcic
    •  & L. Yan
  • Letter |

    In the ultraviolet spectrum, the Neptune-mass exoplanet GJ 436b is shown to have transit depths far greater than those seen in the optical spectrum, indicating that it is surrounded and trailed by a large cloud composed mainly of hydrogen atoms.

    • David Ehrenreich
    • , Vincent Bourrier
    • , Peter J. Wheatley
    • , Alain Lecavelier des Etangs
    • , Guillaume Hébrard
    • , Stéphane Udry
    • , Xavier Bonfils
    • , Xavier Delfosse
    • , Jean-Michel Désert
    • , David K. Sing
    •  & Alfred Vidal-Madjar
  • Letter |

    High-harmonic generation in zinc oxide illuminated by an intense, pulsed, mid-infrared laser is found to involve a recollision effect in which electrons recollide with holes causing harmonics to be emitted, a process similar to that which occurs in atomic systems.

    • G. Vampa
    • , T. J. Hammond
    • , N. Thiré
    • , B. E. Schmidt
    • , F. Légaré
    • , C. R. McDonald
    • , T. Brabec
    •  & P. B. Corkum
  • Letter |

    This study identifies statistically significant trends in mid-atmospheric circulation patterns that partially explain observed changes in extreme temperature occurrence over Eurasia and North America; although the underlying cause of circulation pattern trends remains uncertain, most extreme temperature trends are shown to be consistent with thermodynamic warming.

    • Daniel E. Horton
    • , Nathaniel C. Johnson
    • , Deepti Singh
    • , Daniel L. Swain
    • , Bala Rajaratnam
    •  & Noah S. Diffenbaugh
  • Letter |

    Populations of the flour beetle Tribolium castaneum with histories of strong versus weak sexual selection purge mutation load and resist extinction differently.

    • Alyson J. Lumley
    • , Łukasz Michalczyk
    • , James J. N. Kitson
    • , Lewis G. Spurgin
    • , Catriona A. Morrison
    • , Joanne L. Godwin
    • , Matthew E. Dickinson
    • , Oliver Y. Martin
    • , Brent C. Emerson
    • , Tracey Chapman
    •  & Matthew J. G. Gage
  • Letter |

    Some types of anaemia do not respond to erythropoietin (Epo) treatment because patients do not have sufficient numbers of Epo-sensitive erythroid precursor cells; here, two agonists of PPAR-α are found to synergize with glucocorticoid treatment to promote early erythroid progenitor self-renewal, increasing the production of mature red blood cells in both human and mouse cultures and alleviating anaemia in mouse models.

    • Hsiang-Ying Lee
    • , Xiaofei Gao
    • , M. Inmaculada Barrasa
    • , Hu Li
    • , Russell R. Elmes
    • , Luanne L. Peters
    •  & Harvey F. Lodish
  • Letter |

    This study looks at a polymorphism of the human prion protein gene, which results in a G-to-V substitution at residue 127, in transgenic mice expressing different human prion proteins, finding that mice heterozygous for the G127V polymorphism are resistant to both kuru and classical CJD prions, but there is some transmission of variant CJD prions; most remarkable, however, is that mice homozygous for V127 are completely resistant to all prion strains.

    • Emmanuel A. Asante
    • , Michelle Smidak
    • , Andrew Grimshaw
    • , Richard Houghton
    • , Andrew Tomlinson
    • , Asif Jeelani
    • , Tatiana Jakubcova
    • , Shyma Hamdan
    • , Angela Richard-Londt
    • , Jacqueline M. Linehan
    • , Sebastian Brandner
    • , Michael Alpers
    • , Jerome Whitfield
    • , Simon Mead
    • , Jonathan D. F. Wadsworth
    •  & John Collinge
  • Letter |

    Cell polarity is an important feature of many tissues and is often disrupted in cancer; the TNF receptor Grindelwald is now shown to have an important role in coordinating cell polarity and neoplastic growth in a Drosophila model.

    • Ditte S. Andersen
    • , Julien Colombani
    • , Valentina Palmerini
    • , Krittalak Chakrabandhu
    • , Emilie Boone
    • , Michael Röthlisberger
    • , Janine Toggweiler
    • , Konrad Basler
    • , Marina Mapelli
    • , Anne-Odile Hueber
    •  & Pierre Léopold
  • Letter |

    A phase I study of passive immunization with a CD4 binding-site-directed broadly neutralizing antibody shows that it transiently reduces HIV-1 viral loads in humans.

    • Marina Caskey
    • , Florian Klein
    • , Julio C. C. Lorenzi
    • , Michael S. Seaman
    • , Anthony P. West Jr
    • , Noreen Buckley
    • , Gisela Kremer
    • , Lilian Nogueira
    • , Malte Braunschweig
    • , Johannes F. Scheid
    • , Joshua A. Horwitz
    • , Irina Shimeliovich
    • , Sivan Ben-Avraham
    • , Maggi Witmer-Pack
    • , Martin Platten
    • , Clara Lehmann
    • , Leah A. Burke
    • , Thomas Hawthorne
    • , Robert J. Gorelick
    • , Bruce D. Walker
    • , Tibor Keler
    • , Roy M. Gulick
    • , Gerd Fätkenheuer
    • , Sarah J. Schlesinger
    •  & Michel C. Nussenzweig


  • Letter |

    Cells that bypass senescence in the absence of the p53 tumour suppressor protein have shortened telomeres that undergo fusion, and these fusions trigger mitotic arrest and cell death in crisis.

    • Makoto T. Hayashi
    • , Anthony J. Cesare
    • , Teresa Rivera
    •  & Jan Karlseder
  • Letter |

    The Fdc1 protein from Aspergillus niger (which is homologous to the UbiD enzyme) uses a new prenylated flavin cofactor to achieve 1,3-dipolar cycloaddition chemistry and catalyse the reversible decarboxylation of aromatic carboxylic acids.

    • Karl A. P. Payne
    • , Mark D. White
    • , Karl Fisher
    • , Basile Khara
    • , Samuel S. Bailey
    • , David Parker
    • , Nicholas J. W. Rattray
    • , Drupad K. Trivedi
    • , Royston Goodacre
    • , Rebecca Beveridge
    • , Perdita Barran
    • , Stephen E. J. Rigby
    • , Nigel S. Scrutton
    • , Sam Hay
    •  & David Leys
  • Letter |

    Ubiquinone is an essential component of electron transfer chains found both in bacteria and in mitochondria; the bacterial enzyme UbiX involved in ubiquinone biosynthesis is a flavin prenyltransferase, and the flavin-derived cofactor synthesized by UbiX is used by the UbiD decarboxylase in the ubiquinone biosynthetic pathway.

    • Mark D. White
    • , Karl A. P. Payne
    • , Karl Fisher
    • , Stephen A. Marshall
    • , David Parker
    • , Nicholas J. W. Rattray
    • , Drupad K. Trivedi
    • , Royston Goodacre
    • , Stephen E. J. Rigby
    • , Nigel S. Scrutton
    • , Sam Hay
    •  & David Leys


  • Feature |

    The time spent at a patient's bedside makes nurses the perfect people to pursue potent quality-of-life research.

    • Kendall Powell



  • Futures |

    Mind games.

    • J. J. Roth


  • Outlook |

    Addiction is a devastating disease that alters the brain's circuitry, notably in young adults. But the changes need not be permanent: improved understanding of them will help in developing ways to lessen the burden. By Margaret Munro. See a Nature Video at go.nature.com/e1gqkk .

    • Margaret Munro
  • Outlook |

    Addiction researchers are optimistic that they can create effective medication to treat addictions. But the key question is, will pharmaceutical companies bring them to market?

    • Cassandra Willyard
  • Outlook |

    To treat addiction, people need help to develop psychosocial skills in addition to taking medication, says Kenneth E. Leonard.

    • Kenneth E. Leonard
  • Outlook |

    Giving a gift or a cash incentive to someone to give up an addiction sounds like a prize for behaving badly, but the practice works. The real challenge is deciding who should pay for it.

    • Sujata Gupta
  • Outlook |

    Ingenious pill formulations and the latest manufacturing technologies are helping to stem the tide of painkiller addiction.

    • Elie Dolgin
  • Outlook |

    Research into addiction explores many aspects of how and why this disease develops. Here are four of the toughest questions.

    • David Holmes

Nature Outlook

  • Nature Outlook |


    Addiction is a chronic disease that can destroy the lives of individuals and their families. Researchers are teasing apart the complex neural, genetic and behavioural factors that drive people to lose the ability to resist damaging substances, and are looking for ways to treat, reverse or even prevent addictions.

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