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  • Molecular basis of crosstalk between oncogenic Ras and the master regulator of hematopoiesis GATA‐2
    1. Koichi R Katsumura1,
    2. Chenxi Yang2,
    3. Meghan E Boyer1,
    4. Lingjun Li2,3 and
    5. Emery H Bresnick*,1
    1. 1UW‐Madison Blood Research Program, Department of Cell and Regenerative Biology, Carbone Cancer Center, Wisconsin Institutes for Medical Research, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
    2. 2Department of Chemistry, University of Wisconsin, Madison, WI, USA
    3. 3University of Wisconsin School of Pharmacy, Madison, WI, USA
    1. *Corresponding author. Tel: +1 608 265 6446; E‐mail: ehbresni{at}wisc.edu

    This study shows that p38α increases GATA‐2 activity at endogenous target genes by inducing GATA‐2 multi‐site phosphorylation. Oncogenic Ras is found to amplify this mechanism, which provides a potential molecular explanation for the cooperative promotion of cancer development by Ras and GATA‐2.

    Synopsis

    This study shows that p38α increases GATA‐2 activity at endogenous target genes by inducing GATA‐2 multi‐site phosphorylation. Oncogenic Ras is found to amplify this mechanism, which provides a potential molecular explanation for the cooperative promotion of cancer development by Ras and GATA‐2.

    • p38α promotes multi‐site GATA‐2 phosphorylation, increasing its localization in nuclear foci enriched in an active form of RNA polymerase II and its capacity to regulate endogenous target genes.

    • A single serine residue within GATA‐2, Ser192, mediates p38α‐dependent multisite phosphorylation and enhanced GATA‐2 activity.

    • Oncogenic Ras amplifies p38α‐ and Ser192‐dependent GATA‐2 multi‐site phosphorylation and function, thus providing a framework for understanding Ras–GATA‐2 interactions in the development and progression of cancer.

    • GATA factor
    • GATA‐2
    • p38
    • Ras
    • transcription
    • Received March 21, 2014.
    • Revision received June 19, 2014.
    • Accepted June 23, 2014.
    Koichi R Katsumura, Chenxi Yang, Meghan E Boyer, Lingjun Li, Emery H Bresnick
  • On the resilience of remote traumatic memories against exposure therapy‐mediated attenuation
    1. Li‐Huei Tsai*,1,2 and
    2. Johannes Gräff*,3
    1. 1Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA
    2. 2Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, USA
    3. 3Brain Mind Institute, School of Life Sciences Ecole Polytechnique Fédérale Lausanne (EPFL), Lausanne, Switzerland
    1. * Corresponding author. Tel: +1 617 324 1660; E‐mail: lhtsai{at}mit.edu

      Corresponding author. Tel: +41 21 693 0713; E‐mail: johannes.graeff{at}epfl.ch

    Remote traumatic memories are resistant to exposure therapy‐based attenuation. This review focuses on the molecular basis for this resilience and shows how pharmacological intervention can eradicate even remote fear memories.

    • epigenetic
    • extinction
    • fear
    • histone acetylation
    • remote memories
    • Received April 14, 2014.
    • Revision received June 4, 2014.
    • Accepted June 4, 2014.
    Li‐Huei Tsai, Johannes Gräff
  • Getting ready for building: signaling and autophagosome biogenesis
    1. Adi Abada1 and
    2. Zvulun Elazar*,1
    1. 1Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel
    1. *Corresponding author. Tel: +972 8 934 3682; Fax: +972 8 934 4112; E‐mail: zvulun.elazar{at}weizmann.ac.il

    Autophagy degrades organelles and large protein aggregates and must be tightly regulated to ensure cell survival. The signaling pathways that regulate this process and recent insights into autophagosome biogenesis are discussed in this Review.

    • Atgs
    • autophagosome biogenesis
    • autophagy
    • mTOR
    • signaling
    • Received May 21, 2014.
    • Revision received June 17, 2014.
    • Accepted June 17, 2014.
    Adi Abada, Zvulun Elazar
  • Printing organs cell‐by‐cell3‐D printing is growing in popularity, but how should we regulate the application of this new technology to health care?

    3‐D printing is growing in popularity, but how should we regulate the application of this new technology to health care?

    1. Howard Wolinsky (howard.wolinsky{at}gmail.com) 1
    1. 1Freelance writer, Chicago, IL, USA

    3‐D bioprinting of tissues and organs is becoming more feasible, but its widespread use raises legal and ethical challenges for which the regulators seem currently unprepared.

    Howard Wolinsky
  • Peer review: rigor? Or rigor mortis?
    1. Vytas A Bankaitis (vytas{at}tamhsc.edu) 1
    1. 1Department of Molecular and Cellular Medicine, Texas A&M University Health Science Center, College Station, TX, USA

    Has the focus of peer‐review on “significant advances in molecular mechanism” provided the illusion of progress in place of candour and measured author discussions of the experimental and interpretive caveats of their work?

    Vytas A Bankaitis
  • Thinking outside the ‘knowledge deficit’ boxScientists could achieve more fulfilled professional lives by embracing the skills needed for effective interaction with the public

    Scientists could achieve more fulfilled professional lives by embracing the skills needed for effective interaction with the public

    1. Chantal Pouliot (chantal.pouliot{at}fse.ulaval.ca) 1 and
    2. Julie Godbout2
    1. 1Département d'études sur l'enseignement et l'apprentissage, Faculté des sciences de l'éducation, Pavillon des Sciences de l'éducation Université Laval, Québec, Canada
    2. 2Natural Resources Canada, Canadian Forest Service Laurentian Forestry Centre, Sainte‐Foy Québec, Canada

    Scientists are often asked to interact with the public, but a lack of training and knowledge of the latest research and ideas about science communication can make them both reluctant and ill‐equipped to do so.

    Chantal Pouliot, Julie Godbout
  • Mitochondrial apoptosis is dispensable for NLRP3 inflammasome activation but non‐apoptotic caspase‐8 is required for inflammasome priming
    1. Ramanjaneyulu Allam1,,
    2. Kate E Lawlor2,3,,
    3. Eric Chi‐Wang Yu1,
    4. Alison L Mildenhall2,3,
    5. Donia M Moujalled2,3,
    6. Rowena S Lewis2,3,
    7. Francine Ke2,3,
    8. Kylie D Mason2,3,
    9. Michael J White2,3,
    10. Katryn J Stacey4,
    11. Andreas Strasser2,3,
    12. Lorraine A O'Reilly2,3,
    13. Warren Alexander2,3,
    14. Benjamin T Kile2,3,
    15. David L Vaux2,3 and
    16. James E Vince*,2,3
    1. 1Department of Biochemistry, University of Lausanne, Epalinges, Switzerland
    2. 2The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
    3. 3Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia
    4. 4School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Qld, Australia
    1. *Corresponding author. Tel: + 61 3 93452524; Fax: + 61 3 93470852; E‐mail: vince{at}wehi.edu.au
    1. These authors contributed equally to this work.

    Mitochondria are believed to have an important role in NLRP3 activation. Using 14 strains of knockout mice, this study finds no evidence for the involvement of mitochondrial damage in NLRP3 function, but shows that caspase‐8 is needed for inflammasome priming.

    Synopsis

    Mitochondria are believed to have an important role in NLRP3 activation. Using 14 strains of knockout mice, this study finds no evidence for the involvement of mitochondrial damage in NLRP3 function, but shows that caspase‐8 is needed for inflammasome priming.

    • The essential mitochondrial apoptosis executioners, BAX and BAK are not required for NLRP3 activation.

    • Genetic deletion of the mitochondrial permeability transition pore component cyclophilin D, the mitochondrial anti‐viral signalling protein (MAVS) or the mitophagy regulator Parkin does not impact on NLRP3 activity.

    • Caspase‐8 expression is required for efficient inflammasome priming and Toll‐like‐receptor‐induced cytokine production.

    • apoptosis
    • caspase‐8
    • inflammasome
    • mitochondria
    • NLRP3
    • Received January 13, 2014.
    • Revision received May 23, 2014.
    • Accepted May 24, 2014.
    Ramanjaneyulu Allam, Kate E Lawlor, Eric Chi‐Wang Yu, Alison L Mildenhall, Donia M Moujalled, Rowena S Lewis, Francine Ke, Kylie D Mason, Michael J White, Katryn J Stacey, Andreas Strasser, Lorraine A O'Reilly, Warren Alexander, Benjamin T Kile, David L Vaux, James E Vince