Volume 540 Issue 7631, 1 December 2016

Malignant germ cells with loss of heterozygosity undergoing apoptosis. Tumours formed from germ cells � those cells that develop in the embryo to become the cells of the reproductive system � tend to be more sensitive to chemotherapy than are many other adult cancers. To establish the basis for this chemosensitivity and the drivers of clinical resistance, Eliezer Van Allen, Christopher Sweeney and colleagues performed clinical whole-exome and transcriptome sequencing of germ-cell tumours from patients with various clinical outcomes, including the very rare case of death from germ-cell tumours. They find that primary germ-cell tumours are highly enriched for chromosomal reciprocal loss of heterozygosity, and for mutations in KRAS, and have high mitochondrial priming. This work provides insights into chemosensitivity and the evolution of chemoresistance in germ-cell tumours. Cover: Ella Marushchenko & Elina Korobenko (Ella Maru Studio, Inc.)

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  • Brief Communications Arising |

    • Zhaleh Safikhani
    • , Nehme El-Hachem
    • , Petr Smirnov
    • , Mark Freeman
    • , Anna Goldenberg
    • , Nicolai J. Birkbak
    • , Andrew H. Beck
    • , Hugo J. W. L. Aerts
    • , John Quackenbush
    •  & Benjamin Haibe-Kains
  • Brief Communications Arising |

    • John Patrick Mpindi
    • , Bhagwan Yadav
    • , Päivi Östling
    • , Prson Gautam
    • , Disha Malani
    • , Astrid Murumägi
    • , Akira Hirasawa
    • , Sara Kangaspeska
    • , Krister Wennerberg
    • , Olli Kallioniemi
    •  & Tero Aittokallio
  • Brief Communications Arising |

    • Zhaleh Safikhani
    • , Nehme El-Hachem
    • , Petr Smirnov
    • , Mark Freeman
    • , Anna Goldenberg
    • , Nicolai J. Birkbak
    • , Andrew H. Beck
    • , Hugo J. W. L. Aerts
    • , John Quackenbush
    •  & Benjamin Haibe-Kains
  • Brief Communications Arising |

    • Mehdi Bouhaddou
    • , Matthew S. DiStefano
    • , Eric A. Riesel
    • , Emilce Carrasco
    • , Hadassa Y. Holzapfel
    • , DeAnalisa C. Jones
    • , Gregory R. Smith
    • , Alan D. Stern
    • , Sulaiman S. Somani
    • , T. Victoria Thompson
    •  & Marc R. Birtwistle
  • Brief Communications Arising |

    • Zhaleh Safikhani
    • , Nehme El-Hachem
    • , Petr Smirnov
    • , Mark Freeman
    • , Anna Goldenberg
    • , Nicolai J. Birkbak
    • , Andrew H. Beck
    • , Hugo J. W. L. Aerts
    • , John Quackenbush
    •  & Benjamin Haibe-Kains
  • News & Views

  • News & Views |

    Studies of a large frost-filled basin on Pluto show that this feature altered the dwarf planet's spin axis, driving tectonic activity on its surface, and hint at the presence of a subsurface ocean. See Letters p.86, p.90, p.94 & p.97

    • Amy C. Barr
  • News & Views |

    Mitochondrial organelles — the energy powerhouses of the cell — must divide and fuse dynamically to function. It emerges that two distinct dynamin enzymes enable mitochondrial division. See Letter p.139

    • Heidi M. McBride
    •  & Adam Frost
  • News & Views |

    Dealing with errors in a quantum computer typically requires complex programming and many additional quantum bits. A technique for controlling errors has been proposed that alleviates both of these problems.

    • Daniel Gottesman
  • News & Views |

    To reach the cell surface, membrane proteins are first targeted to an organelle called the endoplasmic reticulum. Several targeting pathways are known, but it now emerges that there is yet another pathway. See Letter p.134

    • Martin R. Pool
  • News & Views |

    Changes in the amount of carbon stored in soil might be a crucial feedback to climate change. Experimental field studies show that warming-induced soil carbon losses are greatest where carbon stocks are largest. See Letter p.104

    • Eric A. Davidson
  • News & Views |

    In the 1980s, the gas surrounding a black hole in a nearby galaxy began to emit much more radiation than before. This change has unexpectedly reversed in the past five years, questioning our understanding of these extreme phenomena.

    • Stephanie LaMassa
  • News & Views |

    Little is known about the biological rhythms that emerge from social behaviours in the wild. A study of shorebird pairs shows that rhythms of nest-incubation duties are mainly governed by strategies to avoid predators. See Letter p.109

    • C. Loren Buck
  • Reviews

  • Review Article |

    A comprehensive review into mammalian interspecies chimaeras, documenting the advances that have occurred alongside developments in stem-cell biology and assessing the future of the field, including any possible ethical and legal issues.

    • Jun Wu
    • , Henry T. Greely
    • , Rudolf Jaenisch
    • , Hiromitsu Nakauchi
    • , Janet Rossant
    •  & Juan Carlos Izpisua Belmonte
  • Review Article |

    This Review discusses current knowledge of the structure, function and interactions of the metabotropic glutamate and GABAB receptors and the potential to target receptor subunits for future therapeutic intervention in neurological and mental health disorders.

    • Jean-Philippe Pin
    •  & Bernhard Bettler
  • Articles

  • Article | | open

    Genomic and molecular analyses of Clunio marinus timing strains suggest that modulation of alternative splicing of Ca2+/calmodulin-dependent kinase II represents a mechanism for evolutionary adaptation of circadian timing.

    • Tobias S. Kaiser
    • , Birgit Poehn
    • , David Szkiba
    • , Marco Preussner
    • , Fritz J. Sedlazeck
    • , Alexander Zrim
    • , Tobias Neumann
    • , Lam-Tung Nguyen
    • , Andrea J. Betancourt
    • , Thomas Hummel
    • , Heiko Vogel
    • , Silke Dorner
    • , Florian Heyd
    • , Arndt von Haeseler
    •  & Kristin Tessmar-Raible
  • Article |

    Specific intramolecular interactions of mitofusin 2 amino acid sequences either constrain or permit mitochondrial fusion and the addition of short peptides matching these sequences stabilize the fusion-constrained or fusion-permissive form, thus inhibiting or promoting mitochondrial fusion.

    • Antonietta Franco
    • , Richard N. Kitsis
    • , Julie A. Fleischer
    • , Evripidis Gavathiotis
    • , Opher S. Kornfeld
    • , Guohua Gong
    • , Nikolaos Biris
    • , Ann Benz
    • , Nir Qvit
    • , Sara K. Donnelly
    • , Yun Chen
    • , Steven Mennerick
    • , Louis Hodgson
    • , Daria Mochly-Rosen
    •  & Gerald W. Dorn II
  • Article |

    The structures of several states on the pathway of SelB-mediated delivery of selenocysteine-specific tRNA to the ribosome in Escherichia coli reveal the mechanism of UGA stop codon recoding to selenocysteine and show how codon recognition triggers activation of translational GTPases.

    • Niels Fischer
    • , Piotr Neumann
    • , Lars V. Bock
    • , Cristina Maracci
    • , Zhe Wang
    • , Alena Paleskava
    • , Andrey L. Konevega
    • , Gunnar F Schröder
    • , Helmut Grubmüller
    • , Ralf Ficner
    • , Marina V. Rodnina
    •  & Holger Stark
  • Letters

  • Letter |

    To explain the position of the Sputnik Planitia basin on Pluto, the feature would need to have formed via impact and Pluto would need to have a subsurface ocean.

    • F. Nimmo
    • , D. P. Hamilton
    • , W. B. McKinnon
    • , P. M. Schenk
    • , R. P. Binzel
    • , C. J. Bierson
    • , R. A. Beyer
    • , J. M. Moore
    • , S. A. Stern
    • , H. A. Weaver
    • , C. B. Olkin
    • , L. A. Young
    • , K. E. Smith
    • , New Horizons Geology, Geophysics & Imaging Theme Team
    • , J. M. Moore
    • , W. B. McKinnon
    • , J. R. Spencer
    • , R. Beyer
    • , R. P. Binzel
    • , M. Buie
    • , B. Buratti
    • , A. Cheng
    • , D. Cruikshank
    • , C. Dalle Ore
    • , A. Earle
    • , R. Gladstone
    • , W. Grundy
    • , A. D. Howard
    • , T. Lauer
    • , I. Linscott
    • , F. Nimmo
    • , J. Parker
    • , S. Porter
    • , H. Reitsema
    • , D. Reuter
    • , J. H. Roberts
    • , S. Robbins
    • , P. M. Schenk
    • , M. Showalter
    • , K. Singer
    • , D. Strobel
    • , M. Summers
    • , L. Tyler
    • , O. L. White
    • , O. M. Umurhan
    • , M. Banks
    • , O. Barnouin
    • , V. Bray
    • , B. Carcich
    • , A. Chaikin
    • , C. Chavez
    • , C. Conrad
    • , D. P. Hamilton
    • , C. Howett
    • , J. Hofgartner
    • , J. Kammer
    • , C. Lisse
    • , A. Marcotte
    • , A. Parker
    • , K. Retherford
    • , M. Saina
    • , K. Runyon
    • , E. Schindhelm
    • , J. Stansberry
    • , A. Steffl
    • , T. Stryk
    • , H. Throop
    • , C. Tsang
    • , A. Verbiscer
    • , H. Winters
    • , A. Zangari
    • , S. A. Stern
    • , H. A. Weaver
    • , C. B. Olkin
    • , L. A. Young
    •  & K. E. Smith
  • Letter |

    Modelling suggests that the icy region on Pluto known as Sputnik Planitia formed shortly after Charon did and has since been stable, with its latitude corresponding to a minimum in annual solar illumination and its longitude determined by tidal forces from Charon.

    • Douglas P. Hamilton
    • , S. A. Stern
    • , J. M. Moore
    • , L. A. Young
    • , the New Horizons Geology, Geophysics & Imaging Theme Team
    • , R. P. Binzel
    • , M. W. Buie
    • , B. J. Buratti
    • , A. F. Cheng
    • , K. Ennico
    • , W. M. Grundy
    • , I. R. Linscott
    • , W. B. McKinnon
    • , C. B. Olkin
    • , H. J. Reitsema
    • , D. C. Reuter
    • , P. Schenk
    • , M. R. Showalter
    • , J. R. Spencer
    • , G. L. Tyler
    •  & H. A. Weaver
  • Letter |

    Ghost imaging is demonstrated using beams of correlated pairs of ultracold helium atoms, rather than photons, yielding a reconstructed image with submillimetre resolution.

    • R. I. Khakimov
    • , B. M. Henson
    • , D. K. Shin
    • , S. S. Hodgman
    • , R. G. Dall
    • , K. G. H. Baldwin
    •  & A. G. Truscott
  • Letter |

    A compilation of global soil carbon data from field experiments provides empirical evidence that warming-induced net losses of soil carbon could accelerate climate change.

    • T. W. Crowther
    • , K. E. O. Todd-Brown
    • , C. W. Rowe
    • , W. R. Wieder
    • , J. C. Carey
    • , M. B. Machmuller
    • , B. L. Snoek
    • , S. Fang
    • , G. Zhou
    • , S. D. Allison
    • , J. M. Blair
    • , S. D. Bridgham
    • , A. J. Burton
    • , Y. Carrillo
    • , P. B. Reich
    • , J. S. Clark
    • , A. T. Classen
    • , F. A. Dijkstra
    • , B. Elberling
    • , B. A. Emmett
    • , M. Estiarte
    • , S. D. Frey
    • , J. Guo
    • , J. Harte
    • , L. Jiang
    • , B. R. Johnson
    • , G. Kröel-Dulay
    • , K. S. Larsen
    • , H. Laudon
    • , J. M. Lavallee
    • , Y. Luo
    • , M. Lupascu
    • , L. N. Ma
    • , S. Marhan
    • , A. Michelsen
    • , J. Mohan
    • , S. Niu
    • , E. Pendall
    • , J. Peñuelas
    • , L. Pfeifer-Meister
    • , C. Poll
    • , S. Reinsch
    • , L. L. Reynolds
    • , I. K. Schmidt
    • , S. Sistla
    • , N. W. Sokol
    • , P. H. Templer
    • , K. K. Treseder
    • , J. M. Welker
    •  & M. A. Bradford
  • Letter |

    Socially synchronized rhythms in shorebirds were assessed during biparental incubation under natural circumstances and were exceptionally diverse, often not following the 24-h day, whereby risk of predation, not starvation, determined some of the variation in incubation rhythms.

    • Martin Bulla
    • , Mihai Valcu
    • , Adriaan M. Dokter
    • , Alexei G. Dondua
    • , András Kosztolányi
    • , Anne L. Rutten
    • , Barbara Helm
    • , Brett K. Sandercock
    • , Bruce Casler
    • , Bruno J. Ens
    • , Caleb S. Spiegel
    • , Chris J. Hassell
    • , Clemens Küpper
    • , Clive Minton
    • , Daniel Burgas
    • , David B. Lank
    • , David C. Payer
    • , Egor Y. Loktionov
    • , Erica Nol
    • , Eunbi Kwon
    • , Fletcher Smith
    • , H. River Gates
    • , Hana Vitnerová
    • , Hanna Prüter
    • , James A. Johnson
    • , James J. H. St Clair
    • , Jean-François Lamarre
    • , Jennie Rausch
    • , Jeroen Reneerkens
    • , Jesse R. Conklin
    • , Joanna Burger
    • , Joe Liebezeit
    • , Joël Bêty
    • , Jonathan T. Coleman
    • , Jordi Figuerola
    • , Jos C. E. W. Hooijmeijer
    • , José A. Alves
    • , Joseph A. M. Smith
    • , Karel Weidinger
    • , Kari Koivula
    • , Ken Gosbell
    • , Klaus-Michael Exo
    • , Larry Niles
    • , Laura Koloski
    • , Laura McKinnon
    • , Libor Praus
    • , Marcel Klaassen
    • , Marie-Andrée Giroux
    • , Martin Sládeček
    • , Megan L. Boldenow
    • , Michael I. Goldstein
    • , Miroslav Šálek
    • , Nathan Senner
    • , Nelli Rönkä
    • , Nicolas Lecomte
    • , Olivier Gilg
    • , Orsolya Vincze
    • , Oscar W. Johnson
    • , Paul A. Smith
    • , Paul F. Woodard
    • , Pavel S. Tomkovich
    • , Phil F. Battley
    • , Rebecca Bentzen
    • , Richard B. Lanctot
    • , Ron Porter
    • , Sarah T. Saalfeld
    • , Scott Freeman
    • , Stephen C. Brown
    • , Stephen Yezerinac
    • , Tamás Székely
    • , Tomás Montalvo
    • , Theunis Piersma
    • , Vanessa Loverti
    • , Veli-Matti Pakanen
    • , Wim Tijsen
    •  & Bart Kempenaers
  • Letter |

    Genomic analyses show that primary germ-cell tumours are highly enriched for chromosomal reciprocal loss of heterozygosity, mutations in KRAS and have high mitochondrial priming, providing insight into chemosensitivity and the evolution of chemoresistance in this disease.

    • Amaro Taylor-Weiner
    • , Travis Zack
    • , Elizabeth O’Donnell
    • , Jennifer L. Guerriero
    • , Brandon Bernard
    • , Anita Reddy
    • , G. Celine Han
    • , Saud AlDubayan
    • , Ali Amin-Mansour
    • , Steven E. Schumacher
    • , Kevin Litchfield
    • , Clare Turnbull
    • , Stacey Gabriel
    • , Rameen Beroukhim
    • , Gad Getz
    • , Scott L. Carter
    • , Michelle S. Hirsch
    • , Anthony Letai
    • , Christopher Sweeney
    •  & Eliezer M Van Allen
  • Letter |

    Inhibition of mechanistic target of rapamycin (mTOR) suspends mouse blastocyst development and the cells remain ‘paused’ in a reversible pluripotent state, allowing prolonged culture.

    • Aydan Bulut-Karslioglu
    • , Steffen Biechele
    • , Hu Jin
    • , Trisha A. Macrae
    • , Miroslav Hejna
    • , Marina Gertsenstein
    • , Jun S. Song
    •  & Miguel Ramalho-Santos
  • Letter |

    The enzyme RIPK1 functions through its RHIM domain to prevent ZBP1-mediated activation of RIPK3–MLKL-dependent necroptosis, thus preventing perinatal lethality and skin inflammation in adult mice.

    • Juan Lin
    • , Snehlata Kumari
    • , Chun Kim
    • , Trieu-My Van
    • , Laurens Wachsmuth
    • , Apostolos Polykratis
    •  & Manolis Pasparakis
  • Letter |

    In the absence of RIPK1, ZBP1 engages RIPK3 in a RHIM-dependent manner and acts as a critical activator of RIPK3/MLKL-dependent necroptosis.

    • Kim Newton
    • , Katherine E. Wickliffe
    • , Allie Maltzman
    • , Debra L. Dugger
    • , Andreas Strasser
    • , Victoria C. Pham
    • , Jennie R. Lill
    • , Merone Roose-Girma
    • , Søren Warming
    • , Margaret Solon
    • , Hai Ngu
    • , Joshua D. Webster
    •  & Vishva M. Dixit
  • Letter |

    Experiments in yeast cells show that three proteins—Snd1, Snd2 and Snd3—provide an alternative pathway for targeting of cellular proteins to the endoplasmic reticulum.

    • Naama Aviram
    • , Tslil Ast
    • , Elizabeth A. Costa
    • , Eric C. Arakel
    • , Silvia G. Chuartzman
    • , Calvin H. Jan
    • , Sarah Haßdenteufel
    • , Johanna Dudek
    • , Martin Jung
    • , Stefan Schorr
    • , Richard Zimmermann
    • , Blanche Schwappach
    • , Jonathan S. Weissman
    •  & Maya Schuldiner
  • Letter |

    A method for CRISPR-based genome editing that harnesses cellular non-homologous end joining activity to achieve targeted DNA knock-in in non-dividing tissues.

    • Keiichiro Suzuki
    • , Yuji Tsunekawa
    • , Reyna Hernandez-Benitez
    • , Jun Wu
    • , Jie Zhu
    • , Euiseok J. Kim
    • , Fumiyuki Hatanaka
    • , Mako Yamamoto
    • , Toshikazu Araoka
    • , Zhe Li
    • , Masakazu Kurita
    • , Tomoaki Hishida
    • , Mo Li
    • , Emi Aizawa
    • , Shicheng Guo
    • , Song Chen
    • , April Goebl
    • , Rupa Devi Soligalla
    • , Jing Qu
    • , Tingshuai Jiang
    • , Xin Fu
    • , Maryam Jafari
    • , Concepcion Rodriguez Esteban
    • , W. Travis Berggren
    • , Jeronimo Lajara
    • , Estrella Nuñez-Delicado
    • , Pedro Guillen
    • , Josep M. Campistol
    • , Fumio Matsuzaki
    • , Guang-Hui Liu
    • , Pierre Magistretti
    • , Kun Zhang
    • , Edward M. Callaway
    • , Kang Zhang
    •  & Juan Carlos Izpisua Belmonte

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