Table of Contents

Volume 502 Number 7471 pp271-402

17 October 2013

About the cover

Every research funding agency wants to support science that makes a difference, but there is no simple formula for identifying truly important research. And as funding gets squeezed, scientists face ever-stiffer competition for resources and jobs, and it becomes even more important to identify the best work. In a series of features and opinion pieces in this issue, we examine how the impact of research is measured — and ask whether today’s evaluation systems promote the most influential science. Cover by Lorenzo Petrantoni.

This Week


  • The maze of impact metrics

    In deciding how to judge the impact of research, evaluators must take into account the effects of emphasizing particular measures — and be open about their methods.

  • High hopes

    Care must be taken not to raise unrealistic expectations for RTS,S malaria vaccine.

  • Searching for life

    A look into the past frames our attempts to find extraterrestrial intelligence.

World View


Seven Days

  • Seven days: 11–17 October

    The week in science: Nobel Peace Prize goes to chemical-weapons watchdog, Russia replaces space chief, and Italy ends controversial stem-cell trial.

News in Focus




  • Publishing: Open citations

    Make bibliographic citation data freely available and substantial benefits will flow, says David Shotton, director of the Open Citations Corpus.

  • Referencing: The reuse factor

    The reference is not dead — it is exploding to encompass the full spectrum of research outputs from lines of code to video frames, explains Mark Hahnel.

Books and Arts

  • Quantum physics: Packet man

    Graham Farmelo delights in a study of Albert Einstein's under-appreciated contributions to quantum theory.

    • Review of Einstein and the Quantum: The Quest of the Valiant Swabian
      A. Douglas Stone
  • Geoengineering: One cool solution

    Nicola Jones finds a treatise on a proposed global-warming fix intriguing, but isn't converted to the cause.

    • Review of A Case for Climate Engineering
      David Keith







  • Impact: Pack a punch

    Grant reviewers are increasingly focusing on the scientific and social impact of proposed research projects.

    • Amber Dance


  • Birth and rebirth

    Even if one PhD experience turns sour, another could offer the right opportunity, says Susie Crowe.

    • Susie Crowe

Career Briefs


naturejobs job listings and advertising features



Outlook: Chemistry Masterclass

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  • Criteria for the use of omics-based predictors in clinical trialsOpen

    • Lisa M. McShane
    • Margaret M. Cavenagh
    • Tracy G. Lively
    • David A. Eberhard
    • William L. Bigbee
    • P. Mickey Williams
    • Jill P. Mesirov
    • Mei-Yin C. Polley
    • Kelly Y. Kim
    • James V. Tricoli
    • Jeremy M. G. Taylor
    • Deborah J. Shuman
    • Richard M. Simon
    • James H. Doroshow
    • Barbara A. Conley

    A checklist of criteria to determine the readiness of high-throughput ‘omics’-based tests for guiding patient therapy in clinical trials is discussed; the checklist, developed by the US National Cancer Institute in collaboration with additional scientists with relevant expertise, provides a framework to evaluate the strength of evidence for a test and outlines practical issues to consider before using the test in a clinical setting, with an aim to avoid premature advancement of omics-based tests in clinical trials.


  • Olivine crystals align during diffusion creep of Earth’s upper mantle

    • Tomonori Miyazaki
    • Kenta Sueyoshi
    • Takehiko Hiraga

    In Earth’s mantle, the shape change of olivine grains depending on temperature and the presence of melt can result in the development of olivine crystallographic preferred orientation during diffusion creep, meaning that the process may be the principal mechanism of mantle flow.

  • A regenerative approach to the treatment of multiple sclerosis

    • Vishal A. Deshmukh
    • Virginie Tardif
    • Costas A. Lyssiotis
    • Chelsea C. Green
    • Bilal Kerman
    • Hyung Joon Kim
    • Krishnan Padmanabhan
    • Jonathan G. Swoboda
    • Insha Ahmad
    • Toru Kondo
    • Fred H. Gage
    • Argyrios N. Theofilopoulos
    • Brian R. Lawson
    • Peter G. Schultz
    • Luke L. Lairson

    Multiple sclerosis is associated with a deficiency in generation of mature oligodendroctyes; an image-based screen for oligodendrocyte differentiation inducers identified the compound benztropine, which enhances remyelination acting through muscarinic receptors and decreases clinical severity in a multiple sclerosis model system.

    See also
  • Mutational landscape and significance across 12 major cancer typesOpen

    • Cyriac Kandoth
    • Michael D. McLellan
    • Fabio Vandin
    • Kai Ye
    • Beifang Niu
    • Charles Lu
    • Mingchao Xie
    • Qunyuan Zhang
    • Joshua F. McMichael
    • Matthew A. Wyczalkowski
    • Mark D. M. Leiserson
    • Christopher A. Miller
    • John S. Welch
    • Matthew J. Walter
    • Michael C. Wendl
    • Timothy J. Ley
    • Richard K. Wilson
    • Benjamin J. Raphael
    • Li Ding

    As part of The Cancer Genome Atlas Pan-Cancer effort, data analysis for point mutations and small indels from 3,281 tumours and 12 tumour types is presented; among the findings are 127 significantly mutated genes from cellular processes with both established and emerging links in cancer, and an indication that the number of driver mutations required for oncogenesis is relatively small.

    See also
  • Reprogramming in vivo produces teratomas and iPS cells with totipotency features

    • María Abad
    • Lluc Mosteiro
    • Cristina Pantoja
    • Marta Cañamero
    • Teresa Rayon
    • Inmaculada Ors
    • Osvaldo Graña
    • Diego Megías
    • Orlando Domínguez
    • Dolores Martínez
    • Miguel Manzanares
    • Sagrario Ortega
    • Manuel Serrano

    Induced pluripotent stem cells (iPS cells) have been created in vivo by reprogramming mouse somatic cells with Oct4, Sox2, Klf4 and c-Myc; these cells have totipotent features that are missing from in vitro created iPS cells or embryonic stem cells.

    See also


  • Slowly fading super-luminous supernovae that are not pair-instability explosions

    • M. Nicholl
    • S. J. Smartt
    • A. Jerkstrand
    • C. Inserra
    • M. McCrum
    • R. Kotak
    • M. Fraser
    • D. Wright
    • T.-W. Chen
    • K. Smith
    • D. R. Young
    • S. A. Sim
    • S. Valenti
    • D. A. Howell
    • F. Bresolin
    • R. P. Kudritzki
    • J. L. Tonry
    • M. E. Huber
    • A. Rest
    • A. Pastorello
    • L. Tomasella
    • E. Cappellaro
    • S. Benetti
    • S. Mattila
    • E. Kankare
    • T. Kangas
    • G. Leloudas
    • J. Sollerman
    • F. Taddia
    • E. Berger
    • R. Chornock
    • G. Narayan
    • C. W. Stubbs
    • R. J. Foley
    • R. Lunnan
    • A. Soderberg
    • N. Sanders
    • D. Milisavljevic
    • R. Margutti
    • R. P. Kirshner
    • N. Elias-Rosa
    • A. Morales-Garoffolo
    • S. Taubenberger
    • M. T. Botticella
    • S. Gezari
    • Y. Urata
    • S. Rodney
    • A. G. Riess
    • D. Scolnic
    • W. M. Wood-Vasey
    • W. S. Burgett
    • K. Chambers
    • H. A. Flewelling
    • E. A. Magnier
    • N. Kaiser
    • N. Metcalfe
    • J. Morgan
    • P. A. Price
    • W. Sweeney
    • C. Waters

    Observations of two slow-to-fade super-luminous supernovae are reported; both show relatively fast rise times and blue colours, which are incompatible with pair-instability models.

    See also
  • Deterministic entanglement of superconducting qubits by parity measurement and feedback

    • D. Ristè
    • M. Dukalski
    • C. A. Watson
    • G. de Lange
    • M. J. Tiggelman
    • Ya. M. Blanter
    • K. W. Lehnert
    • R. N. Schouten
    • L. DiCarlo

    A time-resolved, continuous parity measurement of two superconducting qubits in a three-dimensional circuit quantum electrodynamics architecture is reported; by further implementing feedback control, entanglement is generated ‘on demand’.

  • Molecular understanding of sulphuric acid–amine particle nucleation in the atmosphereOpen

    • João Almeida
    • Siegfried Schobesberger
    • Andreas Kürten
    • Ismael K. Ortega
    • Oona Kupiainen-Määttä
    • Arnaud P. Praplan
    • Alexey Adamov
    • Antonio Amorim
    • Federico Bianchi
    • Martin Breitenlechner
    • André David
    • Josef Dommen
    • Neil M. Donahue
    • Andrew Downard
    • Eimear Dunne
    • Jonathan Duplissy
    • Sebastian Ehrhart
    • Richard C. Flagan
    • Alessandro Franchin
    • Roberto Guida
    • Jani Hakala
    • Armin Hansel
    • Martin Heinritzi
    • Henning Henschel
    • Tuija Jokinen
    • Heikki Junninen
    • Maija Kajos
    • Juha Kangasluoma
    • Helmi Keskinen
    • Agnieszka Kupc
    • Theo Kurtén
    • Alexander N. Kvashin
    • Ari Laaksonen
    • Katrianne Lehtipalo
    • Markus Leiminger
    • Johannes Leppä
    • Ville Loukonen
    • Vladimir Makhmutov
    • Serge Mathot
    • Matthew J. McGrath
    • Tuomo Nieminen
    • Tinja Olenius
    • Antti Onnela
    • Tuukka Petäjä
    • Francesco Riccobono
    • Ilona Riipinen
    • Matti Rissanen
    • Linda Rondo
    • Taina Ruuskanen
    • Filipe D. Santos
    • Nina Sarnela
    • Simon Schallhart
    • Ralf Schnitzhofer
    • John H. Seinfeld
    • Mario Simon
    • Mikko Sipilä
    • Yuri Stozhkov
    • Frank Stratmann
    • Antonio Tomé
    • Jasmin Tröstl
    • Georgios Tsagkogeorgas
    • Petri Vaattovaara
    • Yrjo Viisanen
    • Annele Virtanen
    • Aron Vrtala
    • Paul E. Wagner
    • Ernest Weingartner
    • Heike Wex
    • Christina Williamson
    • Daniela Wimmer
    • Penglin Ye
    • Taina Yli-Juuti
    • Kenneth S. Carslaw
    • Markku Kulmala
    • Joachim Curtius
    • Urs Baltensperger
    • Douglas R. Worsnop
    • Hanna Vehkamäki
    • Jasper Kirkby

    Amines at typical atmospheric concentrations of a only few molecules per trillion air molecules combine with sulphuric acid to form highly stable aerosol particles at rates similar to those observed in the lower atmosphere.

  • Chelicerate neural ground pattern in a Cambrian great appendage arthropod

    • Gengo Tanaka
    • Xianguang Hou
    • Xiaoya Ma
    • Gregory D. Edgecombe
    • Nicholas J. Strausfeld

    Cambrian great appendage arthropods had heads that bore a claw-like appendage pair; neuroanatomical and phylogenetic analysis of a well-preserved Alalcomenaeus fossil reveals the relationship of great appendage arthropods to Chelicerata.

  • A juvenile mouse pheromone inhibits sexual behaviour through the vomeronasal system

    • David M. Ferrero
    • Lisa M. Moeller
    • Takuya Osakada
    • Nao Horio
    • Qian Li
    • Dheeraj S. Roy
    • Annika Cichy
    • Marc Spehr
    • Kazushige Touhara
    • Stephen D. Liberles

    ESP22, a new pheromone produced by juvenile mice before puberty and released through the tears, activates neurons in the vomeronasal organ and inhibits mating behaviour in adult males towards animals expressing this signal.

  • Diabetic hyperglycaemia activates CaMKII and arrhythmias by O-linked glycosylation

    • Jeffrey R. Erickson
    • Laetitia Pereira
    • Lianguo Wang
    • Guanghui Han
    • Amanda Ferguson
    • Khanha Dao
    • Ronald J. Copeland
    • Florin Despa
    • Gerald W. Hart
    • Crystal M. Ripplinger
    • Donald M. Bers

    CaMKII is known to be pathologically activated in heart failure and arrhythmias; here it is shown that glucose-induced CaMKII activation via O-linked glycosylation might contribute to cardiac pathology in diabetes.

  • A statin-dependent QTL for GATM expression is associated with statin-induced myopathy

    • Lara M. Mangravite
    • Barbara E. Engelhardt
    • Marisa W. Medina
    • Joshua D. Smith
    • Christopher D. Brown
    • Daniel I. Chasman
    • Brigham H. Mecham
    • Bryan Howie
    • Heejung Shim
    • Devesh Naidoo
    • QiPing Feng
    • Mark J. Rieder
    • Yii.-Der I. Chen
    • Jerome I. Rotter
    • Paul M. Ridker
    • Jemma C. Hopewell
    • Sarah Parish
    • Jane Armitage
    • Rory Collins
    • Russell A. Wilke
    • Deborah A. Nickerson
    • Matthew Stephens
    • Ronald M. Krauss

    Exploration of the interacting effect of statin exposure and genetic variation on gene expression identifies acis-eQTL that is differentially associated with expression of the GATM gene, which encodes a rate-limiting enzyme involved in creatine synthesis, and thatis associated with incidence of statin-induced myopathy, the major adverse effect of statin treatment.

  • HELQ promotes RAD51 paralogue-dependent repair to avert germ cell loss and tumorigenesis

    • Carrie A. Adelman
    • Rafal L. Lolo
    • Nicolai J. Birkbak
    • Olga Murina
    • Kenichiro Matsuzaki
    • Zuzana Horejsi
    • Kalindi Parmar
    • Valérie Borel
    • J. Mark Skehel
    • Gordon Stamp
    • Alan D’Andrea
    • Alessandro A. Sartori
    • Charles Swanton
    • Simon J. Boulton

    Interstrand crosslink (ICL) repair involves proteins whose mutation results in the disorder Fanconi anaemia: here gene knockdown studies in mice show that the absence of HELQ, a protein previously implicated in ICL repair, compromises germ cell development and results in tumour predisposition due to defective recombination at damaged replication forks.

  • Hidden specificity in an apparently nonspecific RNA-binding protein

    • Ulf-Peter Guenther
    • Lindsay E. Yandek
    • Courtney N. Niland
    • Frank E. Campbell
    • David Anderson
    • Vernon E. Anderson
    • Michael E. Harris
    • Eckhard Jankowsky

    A novel high-throughput sequencing kinetics approach is used to measure functional binding of the apparently nonspecific RNA-binding protein C5 to all possible sequence variants in its substrate binding site; C5 binds different substrate variants with affinities varying widely, and with a similar affinity distribution to that of highly specific nucleic-acid-binding proteins, but it does not bind its physiological RNA targets with the highest affinity.

  • Migrating bubble during break-induced replication drives conservative DNA synthesis

    • Natalie Saini
    • Sreejith Ramakrishnan
    • Rajula Elango
    • Sandeep Ayyar
    • Yu Zhang
    • Angela Deem
    • Grzegorz Ira
    • James E. Haber
    • Kirill S. Lobachev
    • Anna Malkova

    This paper demonstrates that the mechanism of break-induced replication (BIR) is significantly different from S-phase replication, as it proceeds via a migrating bubble driven by Pif1 helicase, results in conservative inheritance of newly synthesized DNA, and is inherently mutagenic.

  • Pif1 helicase and Polδ promote recombination-coupled DNA synthesis via bubble migration

    • Marenda A. Wilson
    • YoungHo Kwon
    • Yuanyuan Xu
    • Woo-Hyun Chung
    • Peter Chi
    • Hengyao Niu
    • Ryan Mayle
    • Xuefeng Chen
    • Anna Malkova
    • Patrick Sung
    • Grzegorz Ira

    This paper demonstrates that Pif1 helicase works with polymerase d to promote DNA synthesis through a migrating D-loop, a mechanism used to copy tens of kilobases during repair of chromosome breaks by break-induced replication (BIR).