Table of Contents
01 December 2013; volume 14, issue 12
Upfront
Editorial
- Science is the drug
- Howy Jacobs
… in which Howy confesses to some eccentric proclivities.
- Copyright © 2013 European Molecular Biology Organization
- Three sides of a coin
- Holger Breithaupt
The ‘Drugs & Science’ series in EMBO reports will highlight the therapeutic, the risky and the societal aspects of drug use and abuse.
- Copyright © 2013 European Molecular Biology Organization
Opinion
- Thirteen follies and fallacies about alternative medicine
- Edzard Ernst1
Thirteen common misunderstandings about alternative medicine and the consequences for health.
- Copyright © 2013 European Molecular Biology Organization
Correspondence
Hot off the Press
- MxB/Mx2: the latest piece in HIV's interferon puzzle
Three groups have recently shown in Nature and Cell Host & Microbe that MxB/Mx2 is an interferon‐inducible HIV restriction factor, adding to the innate arsenal of the cell against the virus and paving the way for the possible development of new antiviral strategies.
- Copyright © 2013 European Molecular Biology Organization
- Remodelling without a power stroke
Although chromatin remodellers are thought to exert power strokes to move nucleosomes along DNA, two studies in this issue show that a power stroke is not required for efficient remodelling, indicating that the DNA binding domain primarily tethers remodellers to nucleosomes.
- Copyright © 2013 European Molecular Biology Organization
- Human Primpol1: a novel guardian of stalled replication forks
- 1 Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia, USA
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↵† These authors contributed equally to this work.
Huang and colleagues identify a human primase‐polymerase that is required for stalled replication fork restart and the maintenance of genome integrity.
- Copyright © 2013 European Molecular Biology Organization
Science & Society
- From promise to practiceThe role of synthetic biology in green chemistry
The role of synthetic biology in green chemistry
Synthetic biology has the potential to profoundly change the way we produce many chemicals, as well as to reduce the environmental impact of the chemical industry.
- Copyright © 2013 European Molecular Biology Organization
- Complex diseases require complex therapies
- Ravi Iyengar1
Understanding disease causes and drug action at the molecular and systems levels could help to identify combinations of drugs that are more effective than individual drugs alone.
- Copyright © 2013 European Molecular Biology Organization
- Tapping the crowds for research fundingCrowdfunding, a common practice to support projects in the arts, music or gaming, has also attracted the attention of scientists
Crowdfunding, a common practice to support projects in the arts, music or gaming, has also attracted the attention of scientists
- Katrin Weigmann1
Scientists are exploring crowdfunding as a potential new source of cash for their research.
- Copyright © 2013 European Molecular Biology Organization
- EU‐LIFE revives funding debateA group of mid‐level life science research institutes is reopening the debate on how to fund research at the EU level calling for a stronger emphasis on excellence
A group of mid‐level life science research institutes is reopening the debate on how to fund research at the EU level calling for a stronger emphasis on excellence
- Philip Hunter1
EU‐LIFE, which represents 10 European life science research institutes, has reopened the debate about how to fund research at the European level by calling for the budget of the European Research Council to be drastically increased.
- Copyright © 2013 European Molecular Biology Organization
Review
- Building and remodelling Cullin–RING E3 ubiquitin ligases
- 1 Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, 02115, USA
- 2 Departments of Structural Biology and Tumour Cell Biology, Howard Hughes Medical Institute, St Jude Children's Research Hospital, Memphis, Tennessee, 38105, USA
- ↵*Corresponding author. Tel: (617) 432‐6590; Fax: (617) 432‐6591; E-mail: wade_harper{at}hms.harvard.edu
Cullin‐RING E3 ubiquitin ligases (CRLs) are multiprotein complexes that ubiquitylate a plethora of signalling proteins, thereby broadly affecting cellular processes. This review is focused on how CRLs are dynamically controlled, with an emphasis on neddylation cycles and substrate receptor exchange.
- Received September 3, 2013.
- Accepted October 8, 2013.
- Copyright © 2013 European Molecular Biology Organization
- Cellular dynamics in the muscle satellite cell niche
- 1 Sprott Center for Stem Cell Research, Ottawa Hospital Research Institute, 501 Smyth Road, Ottawa, Ontario, K1H 8L6, Canada
- 2 Faculty of Medicine, Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, K1H 8M5, Canada
- ↵*Corresponding author. Tel: 00 1 (613) 739 6740; Fax: 00 1 (613) 739 6294; E-mail: mrudnicki{at}ohri.ca
Multiple, functionally diverse cell types have been shown to contribute to skeletal muscle regeneration. This Review discusses the cellular dynamics and the roles of immune, fibrogenic, vessel‐associated and myogenic cells in the response of the satellite cell niche to muscle injury and disease.
- Received September 5, 2013.
- Accepted October 21, 2013.
- Copyright © 2013 European Molecular Biology Organization
- Three wise centromere functions: see no error, hear no break, speak no delay
- 1 Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, UK
- 2 Present address: Molecular Function Laboratory, Centre for Frontier Research, National Institute of Genetics, Mishima, Shizuoka, Japan
- ↵*Corresponding author. Tel: +44‐1382‐385814; Fax: +44‐1382‐386375; E-mail: t.tanaka{at}dundee.ac.uk
Centromeres are known to promote kinetochore assembly. However, two other roles—facilitating robust sister chromatid cohesion and advancing the replication timing of centromeric regions—have recently emerged. The three are analysed in this Review.
- Received September 5, 2013.
- Accepted October 18, 2013.
- Copyright © 2013 European Molecular Biology Organization
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Scientific Reports
- PARP1 orchestrates variant histone exchange in signal‐mediated transcriptional activation
- ↵*Corresponding author. Tel:+44 (0)161 275 5979; Fax:+44 (0)161 275 5082; E-mail: a.d.sharrocks{at}man.ac.uk
This study reveals an essential role for PARP1 in the exchange of the histone variant H2A.Z by H2A at the ‐1 nucleosome of the FOS promoter, which promotes signal‐induced transcriptional activation.
- Received August 2, 2013.
- Accepted September 16, 2013.
- Copyright © 2013 European Molecular Biology Organization
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- No need for a power stroke in ISWI‐mediated nucleosome sliding
- 1 Adolf‐Butenandt‐Institute, Ludwig‐Maximilians‐Universität, 80336, Munich, Germany
- 2 Center for Integrated Protein Science Munich, Ludwig‐Maximilians‐Universität, Munich, Germany
- ↵*Corresponding author. Tel:+089 2180 75 431; Fax:+089 2180 75 425; E-mail: felix.mueller-planitz{at}med.uni-muenchen.de
Nucleosome remodellers are thought to mechanically pull extranucleosomal DNA into the nucleosome. Surprisingly, even when the mechanical step is experimentally prevented, ISWI can still reposition nucleosomes. The authors discuss alternative models to explain the mechanism.
- Received July 23, 2013.
- Revision received September 4, 2013.
- Accepted September 16, 2013.
- Copyright © 2013 European Molecular Biology Organization
- Nucleosome sliding by Chd1 does not require rigid coupling between DNA‐binding and ATPase domains
- ↵*Corresponding author. Tel:+1 410 516 7850; Fax:+1 410 516 4118; E-mail: gdbowman{at}jhu.edu
Chromatin remodellers are thought to require a rigid connection between ATPase and DNA‐binding domain to reposition nucleosomes. However, the linking segment of Chd1 can accommodate large changes in length and flexibility, showing that current models for remodeller activity must be revised.
- Received July 24, 2013.
- Revision received September 11, 2013.
- Accepted September 17, 2013.
- Copyright © 2013 European Molecular Biology Organization
- hPrimpol1/CCDC111 is a human DNA primase‐polymerase required for the maintenance of genome integrity
- Li Wan1,†,
- Jiangman Lou1,†,
- Yisui Xia2,†,
- Bei Su1,
- Ting Liu1,
- Jiamin Cui2,
- Yingying Sun1,
- Huiqiang Lou*,2 and
- Jun Huang*,1
- 1 Life Sciences Institute, Zhejiang University, Hangzhou, Zhejiang, 310058, China
- 2 State key laboratory of Agro‐Biotechnology, College of Biological Sciences, Agricultural University, Beijing, 100193, China
- ↵*Corresponding authors. Tel:+86 10 6273 4504; Fax:+86 10 6273 4504; E-mail: lou{at}cau.edu.cn or Tel:+86 571 8898 1391; Fax:+86 571 8898 1391; E-mail: jhuang{at}zju.edu.cn
-
↵† These authors contributed equally to this work.
This study identifies the first human DNA primase‐polymerase, which is required for stalled replication fork restart and the maintenance of genome integrity.
- Received July 25, 2013.
- Revision received September 17, 2013.
- Accepted September 17, 2013.
- Copyright © 2013 European Molecular Biology Organization
- Tpo1‐mediated spermine and spermidine export controls cell cycle delay and times antioxidant protein expression during the oxidative stress response
- Antje Krüger1,2,
- Jakob Vowinckel1,
- Michael Mülleder1,
- Phillip Grote2,
- Floriana Capuano1,
- Katharina Bluemlein1,† and
- Markus Ralser*,1,3
- 1 Cambridge Systems Biology Centre and Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, CB2 1GA, Cambridge, UK
- 2 Max Planck Institute for Molecular Genetics, 14195, Berlin, Germany
- 3 Division of Physiology and Metabolism, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK
- ↵*Corresponding author. Tel:+44 (0)1223 761346; Fax:+44 (0)1223 766002; E-mail: mr559{at}cam.ac.uk
Cellular export of the metabolites spermine and spermidine is induced under oxidative stress to control the timing of antioxidant gene expression and cell cycle delay and to promote cell survival.
- Received August 29, 2013.
- Revision received September 20, 2013.
- Accepted September 20, 2013.
- Copyright © 2013 European Molecular Biology Organization
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Interaction with both ZNRF3 and LGR4 is required for the signalling activity of R‐spondin
- Yang Xie1,†,
- Raffaella Zamponi1,
- Olga Charlat1,
- Melissa Ramones1,
- Susanne Swalley1,
- Xiaomo Jiang1,
- Daniel Rivera1,
- William Tschantz1,
- Bo Lu1,
- Lisa Quinn1,
- Chris Dimitri1,
- Jefferson Parker1,
- Doug Jeffery1,
- Sheri K Wilcox2,
- Mike Watrobka2,
- Peter LeMotte1,
- Brian Granda1,
- Jeffrey A Porter1,
- Vic E Myer1,
- Andreas Loew1 and
- Feng Cong*,1
- 1 Novartis Institutes for Biomedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts, 02139, USA
- 2 SomaLogic, Inc., 2945 Wilderness Place, Boulder Colorado, 80301, USA
- ↵*Corresponding author. Tel:+1 617 871 7510; Fax:+1 617 871 7262; E-mail: feng.cong{at}novartis.com
This study shows that both ZNRF3‐ and LGR4‐binding motifs of R‐spondin are required for its Wnt‐promoting activity. These results support a dual receptor model of R‐spondin signalling, where LGR4 serves as the engagement receptor while ZNRF3 functions as the effector receptor.
- Received June 18, 2013.
- Revision received October 1, 2013.
- Accepted October 1, 2013.
- Copyright © 2013 European Molecular Biology Organization
- Loss of iron triggers PINK1/Parkin‐independent mitophagy
- 1 MRC‐Protein Phosphorylation and Ubiquitylation Unit
- 2 Cell Signalling and Immunology, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK
- ↵*Corresponding author. Tel:+01382 388905; Fax:+01382 223778; E-mail: i.ganley{at}dundee.ac.uk
A novel mitophagy assay uncovers a new PINK1/Parkin‐independent mitophagy pathway induced by a decrease in iron levels. This pathway is active in fibroblasts of Parkinson patients with Parkin mutations and could be exploited as a potential therapy.
- Received June 4, 2013.
- Revision received September 30, 2013.
- Accepted October 1, 2013.
- Copyright © 2013 European Molecular Biology Organization
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- Tightly controlled WRKY23 expression mediates Arabidopsis embryo development
- Wim Grunewald*,1,2,†,
- Ive De Smet*,1,2,3,†,
- Bert De Rybel4,
- Helene S Robert1,2,
- Brigitte van de Cotte1,2,
- Viola Willemsen5,
- Godelieve Gheysen6,
- Dolf Weijers4,
- Jiří Friml1,2 and
- Tom Beeckman1,2
- 1 Department of Plant Systems Biology, VIB, and Bioinformatics, Ghent University, 9052, Ghent, Belgium
- 2 Department of Plant Biotechnology and Bioinformatics, Ghent University, 9052, Ghent, Belgium
- 3 Plant and Crop Sciences Division, School of Biosciences, University of Nottingham, LE12 5RD, Loughborough, UK
- 4 Laboratory of Biochemistry, Wageningen University, 6703 HA, Wageningen, The Netherlands
- 5 Plant Developmental Biology Wageningen University, 6700 AP, Wageningen, The Netherlands
- 6 Department Molecular Biotechnology, Faculty of Bioscience Engineering, Ghent University, 9000, Ghent, Belgium
- ↵*Corresponding authors. Tel:+32 92446611; Fax:+32 92446610; E-mail: wim.grunewald{at}vib.be or Tel:+32 93313890; Fax:+32 93313809; E-mail: ive.desmet{at}psb.vib-ugent.be
-
↵† These authors contributed equally to this work.
This study presents evidence that the tightly controlled expression of the transcription factor WRKY23 regulates both auxin‐dependent and auxin‐independent signalling pathways leading to root stem cell niche specification in Arabidopsis.
- Received March 21, 2013.
- Revision received October 4, 2013.
- Accepted October 4, 2013.
- Copyright © 2013 European Molecular Biology Organization
- Piezo1‐dependent stretch‐activated channels are inhibited by Polycystin‐2 in renal tubular epithelial cells
- Rémi Peyronnet1,†,
- Joana R Martins1,†,
- Fabrice Duprat1,
- Sophie Demolombe1,
- Malika Arhatte1,
- Martine Jodar1,
- Michel Tauc2,
- Christophe Duranton2,
- Marc Paulais3,
- Jacques Teulon3,
- Eric Honoré*,1 and
- Amanda Patel1
- 1 Institut de Pharmacologie Moléculaire et Cellulaire, LabEx ICST, UMR 7275 CNRS, Université de Nice Sophia Antipolis, Valbonne, France
- 2 CNRS‐FRE 472, Laboratoire de Physiomédecine Moléculaire, Université de Nice Sophia Antipolis, Nice, France
- 3 UPMC Université Paris 06, UMR 872 CNRS, Laboratoire de Génomique, Physiologie et Physiopathologie Rénales, Paris, France
- ↵*Corresponding author. Tel:+33 493 957745; Fax:+33 493 957704; E-mail: honore{at}ipmc.cnrs.fr
-
↵† These authors contributed equally to this work.
This study provides evidence that the activity of renal non‐selective stretch‐activated ion channels (SACs) depends on Piezo1 but is negatively regulated by Polycystin‐2 (PC2). PC2 co‐immunoprecipitates with Piezo1 and deletion of its N‐terminal domain prevents both this interaction and inhibition of SAC activity.
- Received May 6, 2013.
- Revision received October 7, 2013.
- Accepted October 7, 2013.
- Copyright © 2013 European Molecular Biology Organization