Table of Contents

Volume 527 Number 7577 pp133-268

12 November 2015

About the cover

A hollow log hive in the Cévennes mountains, France, showing circular honeycomb architecture characteristic of the honeybee Apis mellifera. Bees and humans have enjoyed a long association, as evidenced by bee iconography in rock art and ancient Egyptian paintings and carvings, and a few isolated reports of beeswax in archeological contexts. But when did this association become common? Mélanie Roffet-Salque et al. use the telltale gas chromatographic signature of beeswax from lipid residues preserved in pottery vessels to plot the use of beeswax across Neolithic Europe, the Middle East and North Africa. They demonstrate its extensive and possibly continuous use in some places for 8,000 years or more. The association, therefore, goes back to the beginnings of agriculture and possibly earlier. Cover photo: Eric Tourneret (

This Week


  • A breath of fresh air

    The decision to use the Montreal Protocol to reduce the impact of refrigerants on global warming is a step forward ahead of the Paris climate summit.

  • Universities’ value

    Proposals for UK higher education contain some positive points amid the financial gloom.

  • Radio interference

    Conflict at the Arecibo Observatory highlights the need for funders to become more flexible.

World View


Seven Days


    News in Focus




    • Biological research: Rethink biosafety

      Tim Trevan calls on those working with organisms that are hazardous, or could be so, to take lessons from the nuclear industries, hospitals and other sectors that have established a safety culture.

    • CRISPR: A path through the thicket

      As various advisory bodies, scientific organizations and funding agencies deliberate on genome editing in humans, Debra J. H. Mathews, Robin Lovell-Badge and colleagues lay out some key points for consideration.

    Books and Arts

    • Cancer therapy: Up close and personalized

      Gerard Evan reviews an inspiring, at times frustrating, chronicle of the war on cancer by one of its generals.

      • Review of The Death of Cancer
        Vincent T. DeVita & Elizabeth DeVita-Raeburn
    • Books in brief

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

    • History of science: Trial by gender

      Jennifer Rampling applauds an account of how Johannes Kepler saved his mother from being burned as a witch.

      • Review of The Astronomer and the Witch: Johannes Kepler's Fight for his Mother
        Ulinka Rublack








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    • Basomedial amygdala mediates top-down control of anxiety and fear

      • Avishek Adhikari
      • Talia N. Lerner
      • Joel Finkelstein
      • Sally Pak
      • Joshua H. Jennings
      • Thomas J. Davidson
      • Emily Ferenczi
      • Lisa A. Gunaydin
      • Julie J. Mirzabekov
      • Li Ye
      • Sung-Yon Kim
      • Anna Lei
      • Karl Deisseroth

      Activation of the ventral medial prefrontal cortex–basomedial amygdala pathway is shown to suppress anxiety and fear-related freezing in mice, thus identifying the basomedial amygdala (and not intercalated cells, as posited by earlier models) as a novel target of top-down control.

    • Oxidative stress inhibits distant metastasis by human melanoma cells

      • Elena Piskounova
      • Michalis Agathocleous
      • Malea M. Murphy
      • Zeping Hu
      • Sara E. Huddlestun
      • Zhiyu Zhao
      • A. Marilyn Leitch
      • Timothy M. Johnson
      • Ralph J. DeBerardinis
      • Sean J. Morrison

      Human melanoma cells grown in mice experience high levels of oxidative stress in the bloodstream such that few metastasizing cells survive to form tumours; the rare melanoma cells that successfully metastasize undergo metabolic changes that increase their capacity to withstand this stress, and antioxidant treatments increase metastasis formation by human melanoma cells, while inhibiting antioxidant pathways had the reverse effect.

      See also
    • BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis

      • Matthew C. Canver
      • Elenoe C. Smith
      • Falak Sher
      • Luca Pinello
      • Neville E. Sanjana
      • Ophir Shalem
      • Diane D. Chen
      • Patrick G. Schupp
      • Divya S. Vinjamur
      • Sara P. Garcia
      • Sidinh Luc
      • Ryo Kurita
      • Yukio Nakamura
      • Yuko Fujiwara
      • Takahiro Maeda
      • Guo-Cheng Yuan
      • Feng Zhang
      • Stuart H. Orkin
      • Daniel E. Bauer

      A CRISPR-Cas9 approach is used to perform saturating mutagenesis of the human and mouse BCL11A enhancers, producing a map that reveals critical regions and specific vulnerabilities; BCL11A enhancer disruption is validated by CRISPR-Cas9 as a therapeutic strategy for inducing fetal haemoglobin by applying it in both mice and primary human erythroblast cells.


    • A rocky planet transiting a nearby low-mass star

      • Zachory K. Berta-Thompson
      • Jonathan Irwin
      • David Charbonneau
      • Elisabeth R. Newton
      • Jason A. Dittmann
      • Nicola Astudillo-Defru
      • Xavier Bonfils
      • Michaël Gillon
      • Emmanuël Jehin
      • Antony A. Stark
      • Brian Stalder
      • Francois Bouchy
      • Xavier Delfosse
      • Thierry Forveille
      • Christophe Lovis
      • Michel Mayor
      • Vasco Neves
      • Francesco Pepe
      • Nuno C. Santos
      • Stéphane Udry
      • Anaël Wünsche

      A low-mass star that is just 12 parsecs away from Earth is shown to be transited by an Earth-sized planet, GJ 1132b, which probably has a rock/iron composition and might support a substantial atmosphere.

      See also
    • Entangling two transportable neutral atoms via local spin exchange

      • A. M. Kaufman
      • B. J. Lester
      • M. Foss-Feig
      • M. L. Wall
      • A. M. Rey
      • C. A. Regal

      Spin-entangled states between two neutral atoms in different optical tweezers are prepared by combining them in the same optical tweezer and allowing for controlled interactions, after which the particles are dynamically separated in space and their entanglement is maintained.

    • Large anomalous Hall effect in a non-collinear antiferromagnet at room temperature

      • Satoru Nakatsuji
      • Naoki Kiyohara
      • Tomoya Higo

      The Hall effect is sometimes encountered in ferromagnetic materials in the absence of an external magnetic field; this so-called anomalous Hall effect is now reported in the antiferromagnetic material Mn3Sn, where it occurs as a consequence of the unusual and complex arrangement of the constituent magnetic moments.

    • Liquids with permanent porosity

      • Nicola Giri
      • Mario G. Del Pópolo
      • Gavin Melaugh
      • Rebecca L. Greenaway
      • Klaus Rätzke
      • Tönjes Koschine
      • Laure Pison
      • Margarida F. Costa Gomes
      • Andrew I. Cooper
      • Stuart L. James

      Porous materials find use in applications such as gas separation, drug delivery and energy storage, but have hitherto been solid rather than liquid; now a combination of cage molecules and a crown-ether solvent that cannot enter the cage molecules is used to create a porous liquid that can solubilize methane gas better than non-porous liquids.

      See also
    • Widespread exploitation of the honeybee by early Neolithic farmers

      • Mélanie Roffet-Salque
      • Martine Regert
      • Richard P. Evershed
      • Alan K. Outram
      • Lucy J. E. Cramp
      • Orestes Decavallas
      • Julie Dunne
      • Pascale Gerbault
      • Simona Mileto
      • Sigrid Mirabaud
      • Mirva Pääkkönen
      • Jessica Smyth
      • Lucija Šoberl
      • Helen L. Whelton
      • Alfonso Alday-Ruiz
      • Henrik Asplund
      • Marta Bartkowiak
      • Eva Bayer-Niemeier
      • Lotfi Belhouchet
      • Federico Bernardini
      • Mihael Budja
      • Gabriel Cooney
      • Miriam Cubas
      • Ed M. Danaher
      • Mariana Diniz
      • László Domboróczki
      • Cristina Fabbri
      • Jesus E. González-Urquijo
      • Jean Guilaine
      • Slimane Hachi
      • Barrie N. Hartwell
      • Daniela Hofmann
      • Isabel Hohle
      • Juan J. Ibáñez
      • Necmi Karul
      • Farid Kherbouche
      • Jacinta Kiely
      • Kostas Kotsakis
      • Friedrich Lueth
      • James P. Mallory
      • Claire Manen
      • Arkadiusz Marciniak
      • Brigitte Maurice-Chabard
      • Martin A. Mc Gonigle
      • Simone Mulazzani
      • Mehmet Özdoğan
      • Olga S. Perić
      • Slaviša R. Perić
      • Jörg Petrasch
      • Anne-Marie Pétrequin
      • Pierre Pétrequin
      • Ulrike Poensgen
      • C. Joshua Pollard
      • François Poplin
      • Giovanna Radi
      • Peter Stadler
      • Harald Stäuble
      • Nenad Tasić
      • Dushka Urem-Kotsou
      • Jasna B. Vuković
      • Fintan Walsh
      • Alasdair Whittle
      • Sabine Wolfram
      • Lydia Zapata-Peña
      • Jamel Zoughlami

      Detection of molecular biomarkers characteristic of beeswax in pottery vessels at archaeological sites reveals that humans have exploited bee products (such as beeswax and honey) at least 9,000 years ago since the beginnings of agriculture.

    • Deep-time evolution of regeneration and preaxial polarity in tetrapod limb development

      • Nadia B. Fröbisch
      • Constanze Bickelmann
      • Jennifer C. Olori
      • Florian Witzmann

      Salamanders are the only tetrapod that can fully regenerate their limbs and tail, a capacity that might be linked to their unique preaxial mode of limb development; here, data from fossils reveal the existence of preaxial polarity in various amphibians from the Carboniferous and Permian periods, suggesting that salamander-like regeneration is an ancient feature of tetrapods that was subsequently lost at least once in the lineage leading to amniotes.

    • Resensitizing daclatasvir-resistant hepatitis C variants by allosteric modulation of NS5A

      • Jin-Hua Sun
      • Donald R. O’Boyle II
      • Robert A. Fridell
      • David R. Langley
      • Chunfu Wang
      • Susan B. Roberts
      • Peter Nower
      • Benjamin M. Johnson
      • Frederic Moulin
      • Michelle J. Nophsker
      • Ying-Kai Wang
      • Mengping Liu
      • Karen Rigat
      • Yong Tu
      • Piyasena Hewawasam
      • John Kadow
      • Nicholas A. Meanwell
      • Mark Cockett
      • Julie A. Lemm
      • Melissa Kramer
      • Makonen Belema
      • Min Gao

      The drug daclatasvir (DCV), which inhibits the hepatitis C virus (HCV) non-structural protein 5A (NS5A), can successfully reduce viral load in patients; here, a combination of DCV and an NS5A analogue is shown to enhance DCV potency on multiple genotypes and overcome resistance in vitro and in a mouse model.

    • Epigenetic silencing of TH1-type chemokines shapes tumour immunity and immunotherapy

      • Dongjun Peng
      • Ilona Kryczek
      • Nisha Nagarsheth
      • Lili Zhao
      • Shuang Wei
      • Weimin Wang
      • Yuqing Sun
      • Ende Zhao
      • Linda Vatan
      • Wojciech Szeliga
      • Jan Kotarski
      • Rafał Tarkowski
      • Yali Dou
      • Kathleen Cho
      • Sharon Hensley-Alford
      • Adnan Munkarah
      • Rebecca Liu
      • Weiping Zou

      Treating ovarian cancer in mouse models with inhibitors for the epigenetic regulators EZH2 and DNMT1 increases the expression of the inflammatory chemokines CXCL9 and CXCL10, resulting in enhanced tumour infiltration by effector T cells, and slowed tumour progression.

    • The DNA glycosylase AlkD uses a non-base-flipping mechanism to excise bulky lesions

      • Elwood A. Mullins
      • Rongxin Shi
      • Zachary D. Parsons
      • Philip K. Yuen
      • Sheila S. David
      • Yasuhiro Igarashi
      • Brandt F. Eichman

      Crystal structures of the DNA glycosylase AlkD with DNA containing various modified bases show that neither substrate recognition nor catalysis use a base-flipping mechanism; instead, AlkD scans the phosphodeoxyribose backbone for increased cationic charge imparted by the alkylated base, and then uses the positive charge to facilitate cleavage of the glycosidic bond, thus explaining the specificity of AlkD for cationic lesions.

      See also
    • Structure of a eukaryotic SWEET transporter in a homotrimeric complex

      • Yuyong Tao
      • Lily S. Cheung
      • Shuo Li
      • Joon-Seob Eom
      • Li-Qing Chen
      • Yan Xu
      • Kay Perry
      • Wolf B. Frommer
      • Liang Feng

      The X-ray crystal structure is presented of a seven-transmembrane eukaryotic SWEET glucose transporter, revealing the link between seven-transmembrane eukaryotic SWEETs and their three-transmembrane bacterial homologues and providing insight into eukaryotic sugar transport mechanisms.