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  • The crystal structure of the phosphatidylinositol 4‐kinase IIα
    1. Adriana Baumlova1,
    2. Dominika Chalupska1,
    3. Bartosz Róźycki2,
    4. Marko Jovic3,
    5. Eva Wisniewski3,
    6. Martin Klima1,
    7. Anna Dubankova1,
    8. Daniel P Kloer4,
    9. Radim Nencka1,
    10. Tamas Balla3 and
    11. Evzen Boura*,1
    1. 1Institute of Organic Chemistry and Biochemistry AS CR, Prague, Czech Republic
    2. 2Institute of Physics Polish Academy of Sciences, Warsaw, Poland
    3. 3Section on Molecular Signal Transduction, Program for Developmental Neuroscience, NICHD NIH, Bethesda, MD, USA
    4. 4Syngenta Jealott's Hill Internation Research Centre, Bracknell, UK
    1. *Corresponding author. Tel: +420 220 183 465; Fax: +420 220 183 578; E‐mail: boura{at}uochb.cas.cz

    The crystal structure of PI4K IIα reveals its membrane binding mode and highlights a membrane‐oriented hydrophobic pocket as a potential allosteric regulatory site.

    Synopsis

    The crystal structure of PI4K IIα reveals its membrane binding mode and highlights a membrane‐oriented hydrophobic pocket as a potential allosteric regulatory site.

    • The crystal structure of PI4K IIα was solved at 2.8 Å resolution.

    • The structure highlights important differences between type II and type III PI 4‐kinases.

    • Molecular simulation suggests a membrane binding mode that involves a hydrophobic pocket with allosteric regulatory potential.

    • crystal structure
    • kinase
    • membrane
    • Monte Carlo simulations
    • phosphatidyl inositol
    • Received March 27, 2014.
    • Revision received August 6, 2014.
    • Accepted August 7, 2014.
    Adriana Baumlova, Dominika Chalupska, Bartosz Róźycki, Marko Jovic, Eva Wisniewski, Martin Klima, Anna Dubankova, Daniel P Kloer, Radim Nencka, Tamas Balla, Evzen Boura
  • Pulling teeth from historyDNA from ancient teeth can help to yield information about our ancestors' health, diet and diseases

    DNA from ancient teeth can help to yield information about our ancestors' health, diet and diseases

    1. Philip Hunter (ph{at}philiphunter.com) 1
    1. 1Freelance journalist, London, UK

    Teeth have proven to be an excellence source of ancient DNA. New analytical tools are helping to exploit this treasure trove to address questions about the link between diet and health, and the impact of historical epidemics with clear relevance for human health today.

    Philip Hunter
  • Diversity and convergence in the mechanisms establishing L/R asymmetry in metazoa
    1. Jean‐Baptiste Coutelis1,2,3,
    2. Nicanor González‐Morales1,2,3,
    3. Charles Géminard1,2,3 and
    4. Stéphane Noselli*,1,2,3
    1. 1Institut de Biologie Valrose University of Nice Sophia Antipolis, Nice, France
    2. 2CNRS Institut de Biologie Valrose UMR 7277, Nice, France
    3. 3INSERM Institut de Biologie Valrose U1091, Nice, France
    1. *Corresponding author. Tel: +33 4 9207 6433; E‐mail: noselli{at}unice.fr

    Defects in left/right body asymmetry lead to severe pathologies in human. This review discusses divergent and common mechanisms of how and when symmetry is broken during embryogenesis in vertebrates and invertebrates, both at the cellular and organism level.

    • L/R asymmetry
    • symmetry breaking
    • directional morphogenesis
    • evolution, invertebrates
    • vertebrates
    • Received April 28, 2014.
    • Revision received July 3, 2014.
    • Accepted July 16, 2014.
    Jean‐Baptiste Coutelis, Nicanor González‐Morales, Charles Géminard, Stéphane Noselli
  • Flexibility in crosstalk between H2B ubiquitination and H3 methylation in vivo
    1. Hanneke Vlaming1,
    2. Tibor van Welsem1,
    3. Erik L de Graaf2,
    4. David Ontoso34,
    5. AF Maarten Altelaar2,
    6. Pedro A San‐Segundo3,
    7. Albert JR Heck2 and
    8. Fred van Leeuwen*,1
    1. 1Division of Gene Regulation, Netherlands Cancer Institute, Amsterdam, the Netherlands
    2. 2Biomolecular Mass Spectrometry and Proteomics Group, The Netherlands Proteomics Centre Utrecht University, Utrecht, the Netherlands
    3. 3Instituto de Biología Funcional y Genómica CSIC/University of Salamanca, Salamanca, Spain
    4. 4Howard Hughes Medical Institute, Molecular Biology Program Memorial Sloan‐Kettering Cancer Center, New York, NY, USA
    1. *Corresponding author. Tel: +31 20 5121973; Fax: +31 20 5121989; E‐mail: fred.v.leeuwen{at}nki.nl

    Variously tethered ubiquitins, expressed as linear histone‐ubiquitin fusions, can substitute for native H2BK123ub in the crosstalk to H3 methylation and in the DNA damage response. This reveals a remarkable plasticity in H2Bub signaling in vivo.

    Synopsis

    Variously tethered ubiquitins, expressed as linear histone‐ubiquitin fusions, can substitute for native H2BK123ub in the crosstalk to H3 methylation and in the DNA damage response. This reveals a remarkable plasticity in H2Bub signaling in vivo.

    • Ubiquitins tethered to the N‐terminus of H2A efficiently bypass native H2B ubiquitination in promoting H3K79 and H3K4 methylation.

    • Ubiquitin tethered to the C‐terminus of H2B, on the same region of the nucleosome but in the opposite orientation, confers only modest crosstalk.

    • Tethered ubiquitins support the DNA damage response following UV irradiation.

    • chromatin
    • crosstalk
    • Dot1
    • histone ubiquitination
    • Set1
    • Received March 20, 2014.
    • Revision received July 3, 2014.
    • Accepted July 21, 2014.
    Hanneke Vlaming, Tibor van Welsem, Erik L de Graaf, David Ontoso, AF Maarten Altelaar, Pedro A San‐Segundo, Albert JR Heck, Fred van Leeuwen
  • Cooperative actions of p21WAF1 and p53 induce Slug protein degradation and suppress cell invasion
    1. Jongdoo Kim1,2,
    2. Seunghee Bae3,
    3. Sungkwan An3,
    4. Jong Kuk Park1,
    5. Eun Mi Kim1,
    6. Sang‐Gu Hwang1,
    7. Wun‐Jae Kim4 and
    8. Hong‐Duck Um*,1,2
    1. 1Division of Radiation Cancer Biology, Korea Institute of Radiological & Medical Sciences, Seoul, Korea
    2. 2Department of Radiological Cancer Medicine, University of Science and Technology, Seoul, Korea
    3. 3Molecular‐Targeted Drug Research Center, Konkuk University, Seoul, Korea
    4. 4Department of Urology, Chungbuk National University, Chungju, Korea
    1. *Corresponding author. Tel: +82 2 970 1304; e‐mail: hdum{at}kcch.re.kr

    This study shows that both p53 and p21WAF1 bind to Slug and cooperate to promote the Mdm2‐dependent degradation of Slug, thus suppressing cell invasion.

    Synopsis

    This study shows that both p53 and p21WAF1 bind to Slug and cooperate to promote the Mdm2‐dependent degradation of Slug, thus suppressing cell invasion.

    • p53 and p21WAF1 require each other to suppress cell invasion.

    • Both p53 and p21 bind to Slug and promote its Mdm2‐dependent degradation.

    • This is the first study to elucidate a mechanism involving p53 and p21 cooperation.

    • Cancer
    • invasion
    • p21
    • p53
    • Slug
    • Received February 4, 2014.
    • Revision received July 26, 2014.
    • Accepted July 29, 2014.
    Jongdoo Kim, Seunghee Bae, Sungkwan An, Jong Kuk Park, Eun Mi Kim, Sang‐Gu Hwang, Wun‐Jae Kim, Hong‐Duck Um
  • Taking control over intracellular fatty acid levels is essential for the analysis of thermogenic function in cultured primary brown and brite/beige adipocytes
    1. Yongguo Li1,
    2. Tobias Fromme1,
    3. Sabine Schweizer1,
    4. Theresa Schöttl1 and
    5. Martin Klingenspor*,1
    1. 1Molecular Nutritional Medicine, Else Kröner Fresenius Center for Nutritional Medicine, Technische Universität München, Freising, Germany
    1. *Corresponding author. Tel: +49 8161 71 2386; Fax: +49 8161 71 2366; E‐mail: mk{at}tum.de

    This study provides guidelines and protocols for the accurate quantification of the specific contribution of UCP1 to thermogenesis in brown and brite/beige adipocytes.

    Synopsis

    This study provides guidelines and protocols for the accurate quantification of the specific contribution of UCP1 to thermogenesis in brown and brite/beige adipocytes.

    • Activation of UCP1 is a prerequisite for quantifying UCP1‐mediated leak respiration in cultured primary adipocytes

    • Free fatty acids released by adrenergic‐stimulated lipolysis mask the specific UCP1‐mediated component of uncoupled respiration by inducing unspecific leak respiration in cultured primary adipocytes

    • Scavenging of free fatty acids with BSA enables specific measurement of UCP1‐mediated uncoupled respiration and reveals thermogenic property of brite adipocytes in a similar fashion as in brown adipocytes, with activation being largely dependent on adipose triglyceride lipase (ATGL).

    • brite adipocytes
    • brown adipocytes
    • thermogenesis
    • UCP1
    • uncoupled respiration
    • Received March 17, 2014.
    • Revision received July 12, 2014.
    • Accepted July 23, 2014.
    Yongguo Li, Tobias Fromme, Sabine Schweizer, Theresa Schöttl, Martin Klingenspor
  • The most important application of scienceAs scientists have to justify research funding with potential social benefits, they may well add education to the list

    As scientists have to justify research funding with potential social benefits, they may well add education to the list

    1. Valentí Rull (vrull{at}ibb.csic.es) 1
    1. 1Botanic Institute of Barcelona, Barcelona, Spain

    Science is increasingly expected to deliver economic benefits, sustainable development and human welfare. Embedding real science into education can address these expectations and the grand challenges facing humanity in the 21st century.

    Valentí Rull