EMBO reports Table of Contents for February 2018; Vol. 19, No. 2

February 2018 | Volume 19, Number 2 Submit Table of Contents Opinion News & Views Science & Society Review Scientific Reports Articles Volume 19, Number 2 Opinion A unified reviewing format for grant applications and evaluations Many scientists are struggling with a deluge of requests to review grant applications that they increasingly have to refuse. A simple and well‐structured application format would make it easier to recruit reviewers and improve the quality and reliability of peer review. Carsten Janke Published online 27.12.2017 A witness protection program for science Research integrity can no longer rely on the sacrifice of whistleblowers reporting misconduct. Various policies could lead to a witness protection program in science. David Shaw Published online 21.12.2017 News & Views Stretching the arms of the type VI secretion sheath protein The bacterial type VI secretion system translocates effectors into the external milieu. Modifications of the sheath subunits lock the system in the pre‐secretion state, allowing for the first time the purification and structural analysis of the extended complex. Petr G Leiman Published online 22.01.2018 Science & Society The dilemmas of science for policy: Scientific evidence and the consequences of regulatory options in risk and benefit assessment The aim of obtaining the most accurate and complete scientific information as input for regulatory decision making is not always the most suitable one, due to the consequences on the population level of alternative regulatory options. José Luis Luján and Oliver Todt Published online 05.01.2018 Mind the gaps!: Towards an ethical framework for genome editing The use of CRISPR/Cas genome editing in agriculture and medicine develops in a state of vagueness regarding regulation, trust and responsible research. The precautionary principle could provide a way for handling these uncertainties when developing safe and socially acceptable applications. Matthias Braun and Peter Dabrock Published online 27.12.2017 The genetics of domestication: Research into the domestication of livestock and companion animals sheds light both on their “evolution” and human history Genetic, archeological and historical studies of the evolution of livestock and companion animals yields new insights into the history of both animal domestication and the rise of human civilizations. Philip Hunter Published online 15.01.2018 Review The bright and the dark side of human antibody responses to flaviviruses: lessons for vaccine design Infection by flaviviruses can lead to non‐neutralizing cross‐reactions with patient antibodies, aggravating disease by antibody‐dependent enhancement. This review analyses the molecular determinants of dual antibody responses, and proposes epitope‐focused strategies to produce protective antibodies only. Félix A Rey, Karin Stiasny, Marie‐Christine Vaney, Mariano Dellarole and Franz X Heinz Published online 27.12.2017 Scientific Reports Type VI secretion system sheath inter‐subunit interactions modulate its contraction The bacterial type VI secretion system translocates effectors by contracting a helical sheath polymer of interconnected subunits. A single residue and a specific subunit linker are critical for sheath contraction, and if mutated lock the T6SS in a pre‐firing state. Maximilian Brackmann, Jing Wang and Marek Basler Published online 08.12.2017 E2F1 interacts with BCL‐xL and regulates its subcellular localization dynamics to trigger cell death E2F1 interacts with BCL‐xL, independently from its BH3 binding groove, and decreases the subcellular mobility of BCL‐xL. This interferes with its ability to inhibit mitochondrial outer membrane permeabilisation and accounts for transcription‐independent E2F1‐induced apoptosis. Céline Vuillier, Steven Lohard, Aurélie Fétiveau, Jennifer Allègre, Cémile Kayaci, Louise E King, Frédérique Braun, Sophie Barillé‐Nion, Fabien Gautier, Laurence Dubrez, Andrew P Gilmore, Philippe P Juin and Laurent Maillet Published online 12.12.2017 CDK9‐mediated phosphorylation controls the interaction of TIP60 with the transcriptional machinery The phosphorylation of TIP60 by CDK9 provides the priming for GSK‐3‐mediated phosphorylation of TIP60 and regulates the interaction of TIP60 with chromatin. Prisca Brauns‐Schubert, Florian Schubert, Manuela Wissler, Martina Weiss, Lisa Schlicher, Simon Bessler, Mariam Safavi, Cornelius Miething, Christoph Borner, Tilman Brummer and Ulrich Maurer Published online 15.01.2018 The unique histidine in OSCP subunit of F‐ATP synthase mediates inhibition of the permeability transition pore by acidic pH The unique histidine of the OSCP subunit of F‐ATP synthase mediates inhibition of the mitochondrial permeability transition pore by acidic pH, providing evidence that the pore forms from F‐ATP synthase through a mechanism involving its peripheral stalk. Manuela Antoniel, Kristen Jones, Salvatore Antonucci, Barbara Spolaore, Federico Fogolari, Valeria Petronilli, Valentina Giorgio, Michela Carraro, Fabio Di Lisa, Michael Forte, Ildikó Szabó, Giovanna Lippe and Paolo Bernardi Published online 07.12.2017 Articles WDR11‐mediated Hedgehog signalling defects underlie a new ciliopathy related to Kallmann syndrome WDR11, the causative gene for congenital hypogonadotrophic hypogonadism and Kallmann syndrome, promotes Hedgehog singaling and ciliogenesis, linking these diseases to the human ciliopathy spectrum. Yeon‐Joo Kim, Daniel PS Osborn, Ji‐Young Lee, Masatake Araki, Kimi Araki, Timothy Mohun, Johanna Känsäkoski, Nina Brandstack, Hyun‐Taek Kim, Francesc Miralles, Cheol‐Hee Kim, Nigel A Brown, Hyung‐Goo Kim, Juan Pedro Martinez‐Barbera, Paris Ataliotis, Taneli Raivio, Lawrence C Layman and Soo‐Hyun Kim Published online 20.12.2017 Myosin‐1C uses a novel phosphoinositide‐dependent pathway for nuclear localization Nuclear import of the motor protein Myosin‐1C does not require soluble factors, but is dependent on phosphoinositide‐binding. This shows that membrane association and nuclear retention are sufficient to drive nuclear localization of also soluble proteins. Ilja Nevzorov, Ekaterina Sidorenko, Weihuan Wang, Hongxia Zhao and Maria K Vartiainen Published online 12.01.2018 Regulation of the Mdm2–p53 pathway by the ubiquitin E3 ligase MARCH7 The ubiqutin E3 ligase MARCH7 catalyzes Lys63‐linked polyubiquitination of Mdm2, which impedes Mdm2 autoubiquitination and degradation, thereby leading to the stabilization of Mdm2. Kailiang Zhao, Yang Yang, Guang Zhang, Chenfeng Wang, Decai Wang, Mian Wu and Yide Mei Published online 02.01.2018 Metabolic stress regulates ERK activity by controlling KSR‐RAF heterodimerization Somatic RAF/RAS mutations result in deregulated ERK signaling in melanomas. Metabolic stress impacts differently on ERK activation in BRAF‐ and NRAS‐mutant cells, indicating that targeting of energy metabolism is not a general therapeutic strategy for melanoma. Amandine Verlande, Michaela Krafčíková, David Potěšil, Lukáš Trantírek, Zbyněk Zdráhal, Moustafa Elkalaf, Jan Trnka, Karel Souček, Nora Rauch, Jens Rauch, Walter Kolch and Stjepan Uldrijan Published online 20.12.2017 TRIP6 inhibits Hippo signaling in response to tension at adherens junctions Mechanical tension regulates Hippo signaling via the mechanosensor vinculin at adherens junctions. Tension‐activated vinculin stimulates binding of LATS1/2 to TRIP6, which blocks the association of LATS1/2 with its activator MOB1, thereby increasing YAP activity. Shubham Dutta, Sebastian Mana‐Capelli, Murugan Paramasivam, Ishani Dasgupta, Heather Cirka, Kris Billiar and Dannel McCollum Published online 08.12.2017 Rad9/53BP1 protects stalled replication forks from degradation in Mec1/ATR‐defective cells The yeast checkpoint protein Rad9 and its human ortholog 53BP1 are known to inhibit resection of DSBs. This study shows that Rad9 supports viability of Mec1‐defective cells under replication stress by protecting stalled replication forks from Dna2‐mediated degradation. Matteo Villa, Diego Bonetti, Massimo Carraro and Maria Pia Longhese Published online 04.01.2018 Shifting meiotic to mitotic spindle assembly in oocytes disrupts chromosome alignment Meiotic spindles in mouse oocytes form ‘inside‐out’, ending with a barrel‐shaped pole. Shifting spindles towards a mitotic‐like ‘outside‐in’ mode leads to severe chromosome alignment defects, indicating that ‘inside‐out’ spindle assembly is essential to prevent aneuploid gametes. Isma Bennabi, Isabelle Quéguiner, Agnieszka Kolano, Thomas Boudier, Philippe Mailly, Marie‐Hélène Verlhac and Marie‐Emilie Terret Published online 12.01.2018   Unsubscribe from or edit your subscription for this service. Or by mail: Customer Service * 973 University Avenue * Los Gatos, CA 95032 * U.S.A. Copyright © 2017 by the European Molecular Biology Organisation.