Table of Contents

Volume 509 Number 7501 pp399-526

22 May 2014

About the cover

A conjugating pair of Paramecium cells visualized by confocal microscopy: the mating-type O cell was transformed to express fluorescent-labelled ciliary protein (shown in yellow), and both O and E cells are decorated with the TAP952 anti-monoglycylated tubulin antibody (shown in red). The protozoan Paramecium, widely studied as a typical ciliate, multiplies asexually by binary fission much of the time, but under certain conditions will reproduce sexually. Two mating types, E and O, were discovered in 1937 but only now has the molecular basis for maternal inheritance of mating type been elucidated. Eric Meyer and colleagues show in Paramecium tetraurelia that mating type E depends on expression of the transmembrane protein mtA, and the default type O is determined during development by excision of the mtA promoter by scnRNAs, a class of small ‘scan’ RNA that reprograms the Paramecium genome during sexual reproduction by recognizing and excising transposable elements. A similar switch mechanism, involving a different gene, mtB, has evolved independently in a sibling species P. septaurelia, implying that exaptation of the scnRNA pathway may be a general mechanism for transgenerational epigenetic inheritance of differentiated states in Paramecium. Cover: Anne Aubusson-Fleury /Centre de Génétique Moléculaire Gif-sur-Yvette.

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World View


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  • Seven days: 16–22 May 2014

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  • Trials

    An experimental direction.

    • John Frizell



  • The role of senescent cells in ageing

    • Jan M. van Deursen

    Cellular senescence has recently been shown to have roles in complex biological processes other than protection against cancer, and to represent a series of progressive and diverse cellular states after initial growth arrest; better understanding of mechanisms underlying its progression and of acute and chronic senescent cells may lead to new therapeutic strategies for age-related pathologies.


  • Genome-defence small RNAs exapted for epigenetic mating-type inheritance

    • Deepankar Pratap Singh
    • Baptiste Saudemont
    • Gérard Guglielmi
    • Olivier Arnaiz
    • Jean-François Goût
    • Malgorzata Prajer
    • Alexey Potekhin
    • Ewa Przybòs
    • Anne Aubusson-Fleury
    • Simran Bhullar
    • Khaled Bouhouche
    • Maoussi Lhuillier-Akakpo
    • Véronique Tanty
    • Corinne Blugeon
    • Adriana Alberti
    • Karine Labadie
    • Jean-Marc Aury
    • Linda Sperling
    • Sandra Duharcourt
    • Eric Meyer

    The molecular basis for mating-type determination in the ciliate Paramecium has been elucidated, revealing a novel function for a class of small RNAs — these scnRNAs are typically involved in reprogramming the Paramecium genome during sexual reproduction by recognizing and excising transposable elements, but they are now found to be co-opted to switch off expression of the newly identified mating-type gene mtA by excising its promoter, and to mediate epigenetic inheritance of mating types across sexual generations.

    See also
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    • Steffen B. E. Wolff
    • Jan Gründemann
    • Philip Tovote
    • Sabine Krabbe
    • Gilad A. Jacobson
    • Christian Müller
    • Cyril Herry
    • Ingrid Ehrlich
    • Rainer W. Friedrich
    • Johannes J. Letzkus
    • Andreas Lüthi

    Plasticity within neuronal microcircuits is believed to be the substrate of learning, and this study identifies two distinct disinhibitory mechanisms involving interactions between PV+ and SOM+ interneurons that dynamically regulate principal neuron activity in the amygdala and thereby control auditory fear learning.

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    • Vera C. Martins
    • Katrin Busch
    • Dilafruz Juraeva
    • Carmen Blum
    • Carolin Ludwig
    • Volker Rasche
    • Felix Lasitschka
    • Sergey E. Mastitsky
    • Benedikt Brors
    • Thomas Hielscher
    • Hans Joerg Fehling
    • Hans-Reimer Rodewald

    T cells develop from thymic precursor cells that are constantly replaced with newly arriving bone marrow progenitor cells, and the ‘old’ and ‘new’ cells are shown here to compete; in the absence of cell competition, when the influx of new bone marrow progenitor cells is blocked, the old cells acquire the ability to self-renew and eventually become transformed, leading to the development of a form of leukaemia.

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  • A Wolf–Rayet-like progenitor of SN2013cu from spectral observations of a stellar wind

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    • D. Tal
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    • D. Perley
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    • J. C. Wheeler

    The detection of strong emission lines in an early-time spectrum of typeIIb supernova SN2013cu reveals Wolf–Rayet-like wind signatures, suggesting that the supernova’s progenitor may have been a Wolf–Rayet star with a wind dominated by helium and nitrogen, with traces of hydrogen.

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    Conventional quantum cryptography relies on monitoring signal disturbance to make sure that information leakage is negligible; here a new quantum method of achieving security is described, in which little information is leaked to the eavesdropper regardless of the signal disturbance.

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    • Matthew S. Crowe
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    • Apirat Chaikuad
    • Stefan Knapp
    • Kunhong Xiao
    • Sharon L. Campbell
    • Dennis J. Thiele
    • Christopher M. Counter

    Tumorigenesis driven by the oncogene BRAFV600E is shown both to depend on the BRAF substrates MEK1/2 associating with copper, and to be sensitive to copper-chelating drugs, suggesting merit in testing such drugs for the treatment of BRAF mutation-positive cancers.

  • Protective mucosal immunity mediated by epithelial CD1d and IL-10

    • Torsten Olszak
    • Joana F. Neves
    • C. Marie Dowds
    • Kristi Baker
    • Jonathan Glickman
    • Nicholas O. Davidson
    • Chyuan-Sheng Lin
    • Christian Jobin
    • Stephan Brand
    • Karl Sotlar
    • Koichiro Wada
    • Kazufumi Katayama
    • Atsushi Nakajima
    • Hiroyuki Mizuguchi
    • Kunito Kawasaki
    • Kazuhiro Nagata
    • Werner Müller
    • Scott B. Snapper
    • Stefan Schreiber
    • Arthur Kaser
    • Sebastian Zeissig
    • Richard S. Blumberg

    Here, the presentation of lipid antigens by CD1d is shown to induce retrograde anti-inflammatory signalling in intestinal epithelial cells, resulting in the production of IL-10.

  • Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid

    • Long N. Nguyen
    • Dongliang Ma
    • Guanghou Shui
    • Peiyan Wong
    • Amaury Cazenave-Gassiot
    • Xiaodong Zhang
    • Markus R. Wenk
    • Eyleen L. K. Goh
    • David L. Silver

    Mfsd2a is the major transporter of the omega-3 fatty acid docosahexaenoic acid (DHA) into brain, with Mfsd2a-knockout mice showing reduced DHA in brain, neuronal cell loss in hippocampus and cerebellum, behavioural disorders and reduced brain size; DHA is transported in a sodium-dependent manner, in the form of lysophosphatidylcholines (LPCs) carrying long-chain fatty acids.

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    • Esther Kur
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    • Chenghua Gu

    Mfsd2a is a key regulator of blood–brain barrier (BBB) formation and function in mice: Mfsd2a is selectively expressed in BBB-containing blood vessels in the CNS; Mfsd2a−/− mice have a leaky BBB and increased vesicular transcytosis in CNS endothelial cells; and Mfsd2a endothelial expression is regulated by pericytes to facilitate BBB integrity.

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    • Nathan R. James
    • Jarrod E. Voss
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    • Ben F. Luisi

    Many bacteria are able to survive in the presence of antibiotics in part because they possess pumps that can remove a broad range of small molecules; here, the structure of one such pump, AcrAB–TolC, is determined using X-ray crystallography and cryo-electron microscopy.

  • Structural basis of Sec-independent membrane protein insertion by YidC

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    The crystal structure of the bacterial protein YidC is reported, together with a structure-based functional analysis, providing insight into the role of YidC in inserting single-spanning membrane proteins into the membrane.