Table of Contents

Volume 496 Number 7446 pp397-542

25 April 2013

About the cover

A macrophage attacking bacteria. Macrophages are phagocytic cells found in blood, lymph and in all mammalian tissue types. They have many and diverse roles in normal development, homeostasis, tissue repair and the immune response to pathogens. Their diversity means that they are involved in almost every human disease and are prime therapeutic targets because their function can be augmented or inhibited to alter disease outcome. A Review in this issue discusses macrophage physiology in terms of the homeostatic mechanisms by which macrophages contribute to physiological and pathophysiologic adaptations in mammals. Cover: SCIEPRO/SCIENCE PHOTO LIBRARY

This Week



World View


Seven Days

  • Seven days: 19–25 April 2013

    This week in science: Ricin-laced letters sent to politicians; Antares rocket completes its maiden test flight; and Nobel laureate François Jacob dies.

News in Focus


  • Firearms research: The gun fighter

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    There are almost as many firearms in the United States as there are citizens. Garen Wintemute is one of few people studying the consequences.

    • Meredith Wadman
  • Mental health: On the spectrum

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    Research suggests that mental illnesses lie along a spectrum — but the field's latest diagnostic manual still splits them apart.

    • David Adam


  • DNA: Celebrate the unknowns

    On the 60th anniversary of the double helix, we should admit that we don't fully understand how evolution works at the molecular level, suggests Philip Ball.

Spring Books

  • Cognitive science: Mind as mirror

    Philip Ball gets under the skin of a treatise on the brain as an analogy machine.

    • Review of Surfaces and Essences: Analogy as the Fuel and Fire of Thinking
      Douglas Hofstadter & Emmanuel Sander
  • Gastronomy: The kitchen revolution

    Michael Pollan's latest book will be eaten up by the conscious consumers he created, says Nathan Myhrvold.

    • Review of Cooked: A Natural History of Transformation
      Michael Pollan
  • Biology: Vive la différence

    Suzanne Alonzo relishes a synthesis of the extraordinary variations among males and females of the same species.

    • Review of Odd Couples: Extraordinary Differences Between the Sexes in the Animal Kingdom
      Daphne J. Fairbairn
  • Geology: Written in stone

    Ted Nield relishes a deft tracing of the relationship between the rise of geology and the novel in the turbulent nineteenth century.

    • Review of Novel Science: Fiction and the Invention of Nineteenth-Century Geology
      Adelene Buckland
  • Physics: Clockwork cosmos

    Pedro Ferreira ponders a vision of the Universe in which time is paramount.

    • Review of Time Reborn: From the Crisis in Physics to the Future of the Universe
      Lee Smolin
  • Neuroscience: Drugs to build a better brain

    Anjan Chatterjee probes a cognitive-enhancement primer.

    • Review of Bad Moves: How Decision Making goes Wrong, and the Ethics of Smart Drugs
      Barbara J. Sahakian & Jamie Nicole Labuzetta
  • Culture: Of Genesis and genetics

    Tim Radford revels in a masterly take on science invoked by the Bible.

    • Review of The Serpent's Promise: The Bible Retold As Science
      Steve Jones






Career Briefs


naturejobs job listings and advertising features




  • Macrophage biology in development, homeostasis and disease

    • Thomas A. Wynn
    • Ajay Chawla
    • Jeffrey W. Pollard

    A discussion of progress in macrophage biology, examining their classification, diverse lineages, identities and regulation, their roles in regulating normal physiology and development, and their identification as therapeutic targets in human diseases.


  • Classical command of quantum systems

    • Ben W. Reichardt
    • Falk Unger
    • Umesh Vazirani

    A scheme is described that enables characterization and classical command of large quantum systems; it provides a test of whether a claimed quantum computer is truly quantum, and also advances towards a goal of quantum cryptography, namely the use of untrusted devices to establish a shared random key, with security based on the validity of quantum physics.

    See also
  • Dynamic regulatory network controlling TH17 cell differentiation

    • Nir Yosef
    • Alex K. Shalek
    • Jellert T. Gaublomme
    • Hulin Jin
    • Youjin Lee
    • Amit Awasthi
    • Chuan Wu
    • Katarzyna Karwacz
    • Sheng Xiao
    • Marsela Jorgolli
    • David Gennert
    • Rahul Satija
    • Arvind Shakya
    • Diana Y. Lu
    • John J. Trombetta
    • Meenu R. Pillai
    • Peter J. Ratcliffe
    • Mathew L. Coleman
    • Mark Bix
    • Dean Tantin
    • Hongkun Park
    • Vijay K. Kuchroo
    • Aviv Regev

    A global view of the genetic networks regulating the differentiation of TH17 cells is presented, based on temporal expression profiling, computational network reconstruction and validation of predicted interactions by nanowire-mediated siRNA perturbation.

  • Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus

    • Hua-Xin Liao
    • Rebecca Lynch
    • Tongqing Zhou
    • Feng Gao
    • S. Munir Alam
    • Scott D. Boyd
    • Andrew Z. Fire
    • Krishna M. Roskin
    • Chaim A. Schramm
    • Zhenhai Zhang
    • Jiang Zhu
    • Lawrence Shapiro
    • NISC Comparative Sequencing Program
    • James C. Mullikin
    • S. Gnanakaran
    • Peter Hraber
    • Kevin Wiehe
    • Garnett Kelsoe
    • Guang Yang
    • Shi-Mao Xia
    • David C. Montefiori
    • Robert Parks
    • Krissey E. Lloyd
    • Richard M. Scearce
    • Kelly A. Soderberg
    • Myron Cohen
    • Gift Kamanga
    • Mark K. Louder
    • Lillian M. Tran
    • Yue Chen
    • Fangping Cai
    • Sheri Chen
    • Stephanie Moquin
    • Xiulian Du
    • M. Gordon Joyce
    • Sanjay Srivatsan
    • Baoshan Zhang
    • Anqi Zheng
    • George M. Shaw
    • Beatrice H. Hahn
    • Thomas B. Kepler
    • Bette T. M. Korber
    • Peter D. Kwong
    • John R. Mascola
    • Barton F. Haynes

    Longitudinal sampling is used to map the evolution of an HIV-1 virus from the time of infection, and the co-evolution of a broadly neutralizing antibody in the same infected patient; the findings have important implications for HIV vaccine development.

    See also
  • Accurate assessment of mass, models and resolution by small-angle scattering

    • Robert P. Rambo
    • John A. Tainer

    Small-angle scattering of X-rays or neutrons is more readily applied to macromolecular complexes than is X-ray crystallography, and is particularly useful for protein complexes with high flexibility; here new quantitative metrics are presented that will allow solution-derived structures to be validated and assessed for mass, resolution and accuracy.


  • Experimental realization of non-Abelian non-adiabatic geometric gates

    • A. A. Abdumalikov Jr
    • J. M. Fink
    • K. Juliusson
    • M. Pechal
    • S. Berger
    • A. Wallraff
    • S. Filipp

    Microwave stimulation of a superconducting artificial three-level atom is used to demonstrate high-fidelity, non-Abelian geometric transformations, the results of which depend on the order in which they are performed.

  • Anomalous sulphur isotopes in plume lavas reveal deep mantle storage of Archaean crust

    • Rita A. Cabral
    • Matthew G. Jackson
    • Estelle F. Rose-Koga
    • Kenneth T. Koga
    • Martin J. Whitehouse
    • Michael A. Antonelli
    • James Farquhar
    • James M. D. Day
    • Erik H. Hauri

    Mass-independent fractionation of sulphur isotopes in basalts from the oceanic island of Mangaia (Cook Islands) indicates ancient subducted Archaean (>2.45 Gyr) oceanic crust and lithosphere survives in the mantle to be sampled beneath hotspot volcanoes.

  • A systematic genome-wide analysis of zebrafish protein-coding gene function

    • Ross N. W. Kettleborough
    • Elisabeth M. Busch-Nentwich
    • Steven A. Harvey
    • Christopher M. Dooley
    • Ewart de Bruijn
    • Freek van Eeden
    • Ian Sealy
    • Richard J. White
    • Colin Herd
    • Isaac J. Nijman
    • Fruzsina Fényes
    • Selina Mehroke
    • Catherine Scahill
    • Richard Gibbons
    • Neha Wali
    • Samantha Carruthers
    • Amanda Hall
    • Jennifer Yen
    • Edwin Cuppen
    • Derek L. Stemple

    A project to identify the phenotypes of disruptive mutations in every zebrafish protein-coding gene has so far revealed potentially disruptive mutations in more than 38% of the protein-coding genes, and the phenotypic consequences of each allele can be assessed using a novel multi-allelic phenotyping scheme.

    See also
  • The zebrafish reference genome sequence and its relationship to the human genomeOpen

    • Kerstin Howe
    • Matthew D. Clark
    • Carlos F. Torroja
    • James Torrance
    • Camille Berthelot
    • Matthieu Muffato
    • John E. Collins
    • Sean Humphray
    • Karen McLaren
    • Lucy Matthews
    • Stuart McLaren
    • Ian Sealy
    • Mario Caccamo
    • Carol Churcher
    • Carol Scott
    • Jeffrey C. Barrett
    • Romke Koch
    • Gerd-Jörg Rauch
    • Simon White
    • William Chow
    • Britt Kilian
    • Leonor T. Quintais
    • José A. Guerra-Assunção
    • Yi Zhou
    • Yong Gu
    • Jennifer Yen
    • Jan-Hinnerk Vogel
    • Tina Eyre
    • Seth Redmond
    • Ruby Banerjee
    • Jianxiang Chi
    • Beiyuan Fu
    • Elizabeth Langley
    • Sean F. Maguire
    • Gavin K. Laird
    • David Lloyd
    • Emma Kenyon
    • Sarah Donaldson
    • Harminder Sehra
    • Jeff Almeida-King
    • Jane Loveland
    • Stephen Trevanion
    • Matt Jones
    • Mike Quail
    • Dave Willey
    • Adrienne Hunt
    • John Burton
    • Sarah Sims
    • Kirsten McLay
    • Bob Plumb
    • Joy Davis
    • Chris Clee
    • Karen Oliver
    • Richard Clark
    • Clare Riddle
    • David Eliott
    • Glen Threadgold
    • Glenn Harden
    • Darren Ware
    • Beverly Mortimer
    • Giselle Kerry
    • Paul Heath
    • Benjamin Phillimore
    • Alan Tracey
    • Nicole Corby
    • Matthew Dunn
    • Christopher Johnson
    • Jonathan Wood
    • Susan Clark
    • Sarah Pelan
    • Guy Griffiths
    • Michelle Smith
    • Rebecca Glithero
    • Philip Howden
    • Nicholas Barker
    • Christopher Stevens
    • Joanna Harley
    • Karen Holt
    • Georgios Panagiotidis
    • Jamieson Lovell
    • Helen Beasley
    • Carl Henderson
    • Daria Gordon
    • Katherine Auger
    • Deborah Wright
    • Joanna Collins
    • Claire Raisen
    • Lauren Dyer
    • Kenric Leung
    • Lauren Robertson
    • Kirsty Ambridge
    • Daniel Leongamornlert
    • Sarah McGuire
    • Ruth Gilderthorp
    • Coline Griffiths
    • Deepa Manthravadi
    • Sarah Nichol
    • Gary Barker
    • Siobhan Whitehead
    • Michael Kay
    • Jacqueline Brown
    • Clare Murnane
    • Emma Gray
    • Matthew Humphries
    • Neil Sycamore
    • Darren Barker
    • David Saunders
    • Justene Wallis
    • Anne Babbage
    • Sian Hammond
    • Maryam Mashreghi-Mohammadi
    • Lucy Barr
    • Sancha Martin
    • Paul Wray
    • Andrew Ellington
    • Nicholas Matthews
    • Matthew Ellwood
    • Rebecca Woodmansey
    • Graham Clark
    • James Cooper
    • Anthony Tromans
    • Darren Grafham
    • Carl Skuce
    • Richard Pandian
    • Robert Andrews
    • Elliot Harrison
    • Andrew Kimberley
    • Jane Garnett
    • Nigel Fosker
    • Rebekah Hall
    • Patrick Garner
    • Daniel Kelly
    • Christine Bird
    • Sophie Palmer
    • Ines Gehring
    • Andrea Berger
    • Christopher M. Dooley
    • Zübeyde Ersan-Ürün
    • Cigdem Eser
    • Horst Geiger
    • Maria Geisler
    • Lena Karotki
    • Anette Kirn
    • Judith Konantz
    • Martina Konantz
    • Martina Oberländer
    • Silke Rudolph-Geiger
    • Mathias Teucke
    • Kazutoyo Osoegawa
    • Baoli Zhu
    • Amanda Rapp
    • Sara Widaa
    • Cordelia Langford
    • Fengtang Yang
    • Nigel P. Carter
    • Jennifer Harrow
    • Zemin Ning
    • Javier Herrero
    • Steve M. J. Searle
    • Anton Enright
    • Robert Geisler
    • Ronald H. A. Plasterk
    • Charles Lee
    • Monte Westerfield
    • Pieter J. de Jong
    • Leonard I. Zon
    • John H. Postlethwait
    • Christiane Nüsslein-Volhard
    • Tim J. P. Hubbard
    • Hugues Roest Crollius
    • Jane Rogers
    • Derek L. Stemple

    A high-quality sequence assembly of the zebrafish genome reveals the largest gene set of any vertebrate and provides information on key genomic features, and comparison to the human reference genome shows that approximately 70% of human protein-coding genes have at least one clear zebrafish orthologue.

    See also
  • The global distribution and burden of dengue

    • Samir Bhatt
    • Peter W. Gething
    • Oliver J. Brady
    • Jane P. Messina
    • Andrew W. Farlow
    • Catherine L. Moyes
    • John M. Drake
    • John S. Brownstein
    • Anne G. Hoen
    • Osman Sankoh
    • Monica F. Myers
    • Dylan B. George
    • Thomas Jaenisch
    • G. R. William Wint
    • Cameron P. Simmons
    • Thomas W. Scott
    • Jeremy J. Farrar
    • Simon I. Hay

    The public health burden of dengue is unknown; here cartographic approaches are used to provide insight into the global, regional and national burden of dengue, with the finding that the global number of infections per year is around 390 million, more than three times the estimate of the World Health Organization.

  • Diverse type VI secretion phospholipases are functionally plastic antibacterial effectors

    • Alistair B. Russell
    • Michele LeRoux
    • Krisztina Hathazi
    • Danielle M. Agnello
    • Takahiko Ishikawa
    • Paul A. Wiggins
    • Sun Nyunt Wai
    • Joseph D. Mougous

    A functionally diverse superfamily of bacterial phospholipase enzymes that mediate antagonisitc interactions as effectors of the type VI secretion system is uncovered; these enzymes degrade the bacterial membrane, representing a novel mechanism of bacterial competition.

  • Induction of pathogenic TH17 cells by inducible salt-sensing kinase SGK1

    • Chuan Wu
    • Nir Yosef
    • Theresa Thalhamer
    • Chen Zhu
    • Sheng Xiao
    • Yasuhiro Kishi
    • Aviv Regev
    • Vijay K. Kuchroo

    Transcriptional profiling of developing TH17 cells identifies serum glucocorticoid kinase 1 (SGK1) as an essential node downstream of IL-23 signalling, and transcriptional analysis shows that a modest increase in salt concentration induces SGK1 expression, promotes IL-23 receptor expression and enhances TH17 cell differentiation, accelerating the development of autoimmunity.

    See also
  • Sodium chloride drives autoimmune disease by the induction of pathogenic TH17 cells

    • Markus Kleinewietfeld
    • Arndt Manzel
    • Jens Titze
    • Heda Kvakan
    • Nir Yosef
    • Ralf A. Linker
    • Dominik N. Muller
    • David A. Hafler

    Increased salt concentrations are shown to induce murine and human TH17 cells by a mechanism that depends on activation of p38/MAPK, NFAT5 and SGK1; mice kept on a high-salt diet develop a more severe experimental autoimmune encephalomyelitis due to increased induction of TH17 cells.

    See also
  • High-level semi-synthetic production of the potent antimalarial artemisinin

    • C. J. Paddon
    • P. J. Westfall
    • D. J. Pitera
    • K. Benjamin
    • K. Fisher
    • D. McPhee
    • M. D. Leavell
    • A. Tai
    • A. Main
    • D. Eng
    • D. R. Polichuk
    • K. H. Teoh
    • D. W. Reed
    • T. Treynor
    • J. Lenihan
    • H. Jiang
    • M. Fleck
    • S. Bajad
    • G. Dang
    • D. Dengrove
    • D. Diola
    • G. Dorin
    • K. W. Ellens
    • S. Fickes
    • J. Galazzo
    • S. P. Gaucher
    • T. Geistlinger
    • R. Henry
    • M. Hepp
    • T. Horning
    • T. Iqbal
    • L. Kizer
    • B. Lieu
    • D. Melis
    • N. Moss
    • R. Regentin
    • S. Secrest
    • H. Tsuruta
    • R. Vazquez
    • L. F. Westblade
    • L. Xu
    • M. Yu
    • Y. Zhang
    • L. Zhao
    • J. Lievense
    • P. S. Covello
    • J. D. Keasling
    • K. K. Reiling
    • N. S. Renninger
    • J. D. Newman

    Saccharomyces cerevisiae is engineered to produce high concentrations of artemisinic acid, a precursor of the artemisinin used in combination therapies for malaria treatment; an efficient and practical chemical process to convert artemisinic acid to artemisinin is also developed.

  • Crystal structure of a eukaryotic phosphate transporter

    • Bjørn P. Pedersen
    • Hemant Kumar
    • Andrew B. Waight
    • Aaron J. Risenmay
    • Zygy Roe-Zurz
    • Bryant H. Chau
    • Avner Schlessinger
    • Massimiliano Bonomi
    • William Harries
    • Andrej Sali
    • Atul K. Johri
    • Robert M. Stroud

    The X-ray crystal structure of a high-affinity phosphate importer in an inward-facing, occluded state in the presence of phosphate is reported; this is the first structure of a membrane protein involved in inorganic phosphate uptake and the first crystal structure of a eukaryotic MFS transporter.