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Table of Contents

February 2019 | Volume 2, No. 1

Research Articles

  • A C/EBPα–Wnt connection in gut homeostasis and carcinogenesis
    Open Access
    A C/EBPα–Wnt connection in gut homeostasis and carcinogenesis

    Julian Heuberger, Undine Hill, Susann Förster, Karin Zimmermann, Victoria Malchin, Anja A Kühl, Ulrike Stein, Michael Vieth, Walter Birchmeier, Achim Leutz

    Julian Heuberger ... Achim Leutz

    Published 26 December 2018

    This research reveals an antagonism between C/EBPα expression and activated Wnt signaling in the human and mouse gut and suggests a tumor suppressor function of C/EBPα in human and murine intestinal cancer.

  • Polycomb and Notch signaling regulate cell proliferation potential during <em>Caenorhabditis elegans</em> life cycle
    Open Access
    Polycomb and Notch signaling regulate cell proliferation potential during Caenorhabditis elegans life cycle

    Francesca Coraggio, Ringo Püschel, Alisha Marti, Peter Meister

    Francesca Coraggio ... Peter Meister

    Published 26 December 2018

    Caenorhabditis elegans lineage is invariant between animals. By challenging cell fate in differentiated worms, an unexpected role of Polycomb and Notch signaling in the control of cell proliferation was uncovered, suggesting that the lineage is more flexible than believed.

  • Mechanistic aspects of maltotriose-conjugate translocation to the Gram-negative bacteria cytoplasm
    Open Access
    Mechanistic aspects of maltotriose-conjugate translocation to the Gram-negative bacteria cytoplasm

    Estelle Dumont, Julia Vergalli, Jelena Pajovic, Satya P Bhamidimarri, Koldo Morante, Jiajun Wang, Dmitrijs Lubriks, Edgars Suna, Robert A Stavenger, Mathias Winterhalter, Matthieu Réfrégiers, Jean-Marie Pagès

    Estelle Dumont ... Jean-Marie Pagès

    Published 28 December 2018

    A maltotriose-conjugate can deliver molecules into the cytoplasmic space of Gram-negative bacteria by parasitizing the maltose uptake pathway.

  • Evolution of gene expression levels in the male reproductive organs of <em>Anopheles</em> mosquitoes
    Open Access
    Evolution of gene expression levels in the male reproductive organs of Anopheles mosquitoes

    Abril Izquierdo, Martin Fahrenberger, Tania Persampieri, Mark Q Benedict, Tom Giles, Flaminia Catteruccia, Richard D Emes, Tania Dottorini

    Abril Izquierdo ... Tania Dottorini

    Published 2 January 2019

    Expression patterns of transcripts in reproductive tissues reveal the phylogeny of the An. gambiae complex and are indicative of molecular function, transcription regulatory networks, and protein–protein interaction networks.

  • Rab1b and ARF5 are novel RNA-binding proteins involved in FMDV IRES–driven RNA localization
    Open Access
    Rab1b and ARF5 are novel RNA-binding proteins involved in FMDV IRES–driven RNA localization

    Javier Fernandez-Chamorro, Rosario Francisco-Velilla, Jorge Ramajo, Encarnación Martinez-Salas

    Javier Fernandez-Chamorro ... Encarnación Martinez-Salas

    Published 17 January 2019

    Integration of proteomic data with functional and imaging analysis revealed that Rab1b and ARF5, two ER-Golgi members, are RNA-binding proteins that colocalize with picornavirus IRES-RNA reporters in human cells.

  • KIF18A's neck linker permits navigation of microtubule-bound obstacles within the mitotic spindle
    Open Access
    KIF18A's neck linker permits navigation of microtubule-bound obstacles within the mitotic spindle

    Heidi LH Malaby, Dominique V Lessard, Christopher L Berger, Jason Stumpff

    Heidi LH Malaby ... Jason Stumpff

    Published 17 January 2019

    The length of KIF18A's neck linker permits navigation of obstacles along K-fibers within the mitotic spindle and is required for the timely alignment and segregation of mitotic chromosomes.

  • A junction coverage compatibility score to quantify the reliability of transcript abundance estimates and annotation catalogs
    Open Access
    A junction coverage compatibility score to quantify the reliability of transcript abundance estimates and annotation catalogs

    Charlotte Soneson, Michael I Love, Rob Patro, Shobbir Hussain, Dheeraj Malhotra, Mark D Robinson

    Charlotte Soneson ... Mark D Robinson

    Published 17 January 2019

    Comparison of observed exon–exon junction counts to those predicted from estimated transcript abundances can identify genes with misannotated or misquantified transcripts.

  • Folding–function relationship of the most common cystic fibrosis–causing CFTR conductance mutants
    Open Access
    Folding–function relationship of the most common cystic fibrosis–causing CFTR conductance mutants

    Marcel van Willigen, Annelotte M Vonk, Hui Ying Yeoh, Evelien Kruisselbrink, Bertrand Kleizen, Cornelis K van der Ent, Maarten R Egmond, Hugo R de Jonge, Ineke Braakman, Jeffrey M Beekman, Peter van der Sluijs

    Marcel van Willigen ... Peter van der Sluijs

    Published 18 January 2019

    The tight correlation between folding and function in cystic fibrosis patients with CFTR mutations of the altered-conductance CFTR class provides an attractive paradigm for characterizing mode of action of novel therapeutics.

  • <span class="sc">d</span>-amino acid oxidase promotes cellular senescence via the production of reactive oxygen species
    Open Access
    d-amino acid oxidase promotes cellular senescence via the production of reactive oxygen species

    Taiki Nagano, Shunsuke Yamao, Anju Terachi, Hidetora Yarimizu, Haruki Itoh, Ryoko Katasho, Kosuke Kawai, Akio Nakashima, Tetsushi Iwasaki, Ushio Kikkawa, Shinji Kamada

    Taiki Nagano ... Shinji Kamada

    Published 18 January 2019

    This study reveals a novel role of d-amino acid oxidase in promoting cellular senescence induced by genotoxic stresses via enzymatic generation of reactive oxygen species.

  • <em>Viperin</em> controls chikungunya virus–specific pathogenic T cell IFNγ Th1 stimulation in mice
    Open Access
    Viperin controls chikungunya virus–specific pathogenic T cell IFNγ Th1 stimulation in mice

    Guillaume Carissimo, Teck-Hui Teo, Yi-Hao Chan, Cheryl Yi-Pin Lee, Bernett Lee, Anthony Torres-Ruesta, Jeslin JL Tan, Tze-Kwang Chua, Siew-Wai Fong, Fok-Moon Lum, Lisa FP Ng

    Guillaume Carissimo ... Lisa FP Ng

    Published 21 January 2019

    This study shows that Viperin controls the microenvironment pro-inflammatory response and CD4 T cell–mediated pathogenesis during anti-chikungunya virus immune response in mice.

  • Loss of miR-210 leads to progressive retinal degeneration in <em>Drosophila melanogaster</em>
    Open Access
    Loss of miR-210 leads to progressive retinal degeneration in Drosophila melanogaster

    Carina M Weigelt, Oliver Hahn, Katharina Arlt, Matthias Gruhn, Annika J Jahn, Jacqueline Eßer, Jennifer A Werner, Corinna Klein, Ansgar Büschges, Sebastian Grönke, Linda Partridge

    Carina M Weigelt ... Linda Partridge

    Published 22 January 2019

    Depletion of miRNA-210 disrupts photoreceptor integrity and visual function in Drosophila melanogaster.

  • Mitochondrial stress response triggered by defects in protein synthesis quality control
    Open Access
    Mitochondrial stress response triggered by defects in protein synthesis quality control

    Uwe Richter, Kah Ying Ng, Fumi Suomi, Paula Marttinen, Taina Turunen, Christopher Jackson, Anu Suomalainen, Helena Vihinen, Eija Jokitalo, Tuula A Nyman, Marita A Isokallio, James B Stewart, Cecilia Mancini, Alfredo Brusco, Sara Seneca, Anne Lombès, Robert W Taylor, Brendan J Battersby

    Uwe Richter ... Brendan J Battersby

    Published 25 January 2019

    Quality control defects of mitochondrial nascent chain synthesis trigger a sequential stress response characterized by OMA1 activation and ribosome decay, determining mitochondrial form and function.

  • Reciprocal regulation of STING and TCR signaling by mTORC1 for T-cell activation and function
    Open Access
    Reciprocal regulation of STING and TCR signaling by mTORC1 for T-cell activation and function

    Takayuki Imanishi, Midori Unno, Wakana Kobayashi, Natsumi Yoneda, Satoshi Matsuda, Kazutaka Ikeda, Takayuki Hoshii, Atsushi Hirao, Kensuke Miyake, Glen N Barber, Makoto Arita, Ken J Ishii, Shizuo Akira, Takashi Saito

    Takayuki Imanishi ... Takashi Saito

    Published 25 January 2019

    Costimulation of T cells through both TCR and STING induces growth inhibition by partially blocking the mTORC1 signals, and leads to IFN-I production through sustained activation of IRF3 and mTORC1 activation.

  • Redundant and nonredundant organismal functions of EPS15 and EPS15L1
    Open Access
    Redundant and nonredundant organismal functions of EPS15 and EPS15L1

    Cinzia Milesi, Paola Alberici, Benedetta Pozzi, Amanda Oldani, Galina V Beznoussenko, Andrea Raimondi, Blanche Ekalle Soppo, Stefania Amodio, Giusi Caldieri, Maria Grazia Malabarba, Giovanni Bertalot, Stefano Confalonieri, Dario Parazzoli, Alexander A Mironov, Carlo Tacchetti, Pier Paolo Di Fiore, Sara Sigismund, Nina Offenhäuser

    Cinzia Milesi ... Nina Offenhäuser

    Published 28 January 2019

    This study unveils a redundant function for the endocytic proteins Eps15 and Eps15L1 in mouse embryo development and erythropoiesis, and a unique nonredundant role for Eps15L1 in the nervous system.

  • Chromosome alignment maintenance requires the MAP RECQL4, mutated in the Rothmund–Thomson syndrome
    Open Access
    Chromosome alignment maintenance requires the MAP RECQL4, mutated in the Rothmund–Thomson syndrome

    Hideki Yokoyama, Daniel Moreno-Andres, Susanne A Astrinidis, Yuqing Hao, Marion Weberruss, Anna K Schellhaus, Hongqi Lue, Yoshikazu Haramoto, Oliver J Gruss, Wolfram Antonin

    Hideki Yokoyama ... Wolfram Antonin

    Published 4 February 2019

    RECQL4, which is mutated in the Rothmund–Thomson syndrome characterized by premature aging and cancer susceptibility, is a microtubule-associated protein required for mitotic chromosome alignment.

  • DPP8/DPP9 inhibition elicits canonical Nlrp1b inflammasome hallmarks in murine macrophages
    Open Access
    DPP8/DPP9 inhibition elicits canonical Nlrp1b inflammasome hallmarks in murine macrophages

    Nathalia M de Vasconcelos, Gwendolyn Vliegen, Amanda Gonçalves, Emilie De Hert, Rosa Martín-Pérez, Nina Van Opdenbosch, Anvesh Jallapally, Ruth Geiss-Friedlander, Anne-Marie Lambeir, Koen Augustyns, Pieter Van Der Veken, Ingrid De Meester, Mohamed Lamkanfi

    Nathalia M de Vasconcelos ... Mohamed Lamkanfi

    Published 4 February 2019

    This study shows that caspase-1 autocleavage, ASC speck assembly, and mature IL-1β and IL-18 secretion accompany rapid DPP8/DPP9-regulated pyroptosis induction in macrophages expressing a LeTx-responsive Nlrp1b allele.

  • Somatic recombination underlies frequent revertant mosaicism in loricrin keratoderma
    Open Access
    Somatic recombination underlies frequent revertant mosaicism in loricrin keratoderma

    Shotaro Suzuki, Toshifumi Nomura, Toshinari Miyauchi, Masae Takeda, Yasuyuki Fujita, Wataru Nishie, Masashi Akiyama, Akemi Ishida-Yamamoto, Hiroshi Shimizu

    Shotaro Suzuki ... Hiroshi Shimizu

    Published 4 February 2019

    We demonstrate that revertant mosaicism frequently occurs in loricrin keratoderma and that somatic recombination is the major mechanism underlying this therapeutically important phenomenon.

  • Mitochondrial acetyl-CoA reversibly regulates locus-specific histone acetylation and gene expression
    Open Access
    Mitochondrial acetyl-CoA reversibly regulates locus-specific histone acetylation and gene expression

    Oswaldo A Lozoya, Tianyuan Wang, Dagoberto Grenet, Taylor C Wolfgang, Mack Sobhany, Douglas Ganini da Silva, Gonzalo Riadi, Navdeep Chandel, Richard P Woychik, Janine H Santos

    Oswaldo A Lozoya ... Janine H Santos

    Published 8 February 2019

    This study shows that genetic or pharmacological manipulation of the TCA cycle, when mitochondria are dysfunctional, can modulate histone acetylation and gene expression in the nucleus with physiological outcomes.

  • Centrosome guides spatial activation of Rac to control cell polarization and directed cell migration
    Open Access
    Centrosome guides spatial activation of Rac to control cell polarization and directed cell migration

    Hung-Wei Cheng, Cheng-Te Hsiao, Yin-Quan Chen, Chi-Ming Huang, Seng-I Chan, Arthur Chiou, Jean-Cheng Kuo

    Hung-Wei Cheng ... Jean-Cheng Kuo

    Published 8 February 2019

    The centrosome acts as a controller by balancing the formation of centrosomal and acentrosomal microtubules, the modulation of focal adhesion signaling and the activation of local Rac1 at the cell front, which then coordinates cell polarization during directed cell migration.

  • Vamorolone targets dual nuclear receptors to treat inflammation and dystrophic cardiomyopathy
    Open Access
    Vamorolone targets dual nuclear receptors to treat inflammation and dystrophic cardiomyopathy

    Christopher R Heier, Qing Yu, Alyson A Fiorillo, Christopher B Tully, Asya Tucker, Davi A Mazala, Kitipong Uaesoontrachoon, Sadish Srinivassane, Jesse M Damsker, Eric P Hoffman, Kanneboyina Nagaraju, Christopher F Spurney

    Christopher R Heier ... Christopher F Spurney

    Published 11 February 2019

    Vamorolone is a first-in-class dissociative drug that selectively targets the glucocorticoid receptor to safely treat chronic inflammation and the mineralocorticoid receptor to treat cardiomyopathy, providing efficacy with improved safety in mouse models of Duchenne muscular dystrophy.

  • Mucosa-associated microbiota drives pathogenic functions in IBD-derived intestinal iNKT cells
    Open Access
    Mucosa-associated microbiota drives pathogenic functions in IBD-derived intestinal iNKT cells

    Claudia Burrello, Gabriella Pellegrino, Maria Rita Giuffrè, Giulia Lovati, Ilaria Magagna, Alice Bertocchi, Fulvia Milena Cribiù, Francesca Boggio, Fiorenzo Botti, Elena Trombetta, Laura Porretti, Antonio Di Sabatino, Maurizio Vecchi, Maria Rescigno, Flavio Caprioli, Federica Facciotti

    Claudia Burrello ... Federica Facciotti

    Published 13 February 2019

    Pro-inflammatory iNKT cells are enriched in IBD patients’ lamina propria. Exposure to the mucosa-associated microbiota drives their activation, inducing pathogenic activities against the epithelium.

  • Epithelial polarization in 3D matrix requires DDR1 signaling to regulate actomyosin contractility
    Open Access
    Epithelial polarization in 3D matrix requires DDR1 signaling to regulate actomyosin contractility

    Pia Pernille Søgaard, Noriko Ito, Nanami Sato, Yasuyuki Fujita, Karl Matter, Yoshifumi Itoh

    Pia Pernille Søgaard ... Yoshifumi Itoh

    Published 13 February 2019

    For epithelial cells to establish epithelial polarity in a 3D matrix, signaling of a collagen receptor tyrosine kinase, DDR1, plays a crucial role. DDR1 signaling controls actomyosin contractility at the cell–cell junction through suppression of ROCK activity.

  • An essential role for α4A-tubulin in platelet biogenesis
    Open Access
    An essential role for α4A-tubulin in platelet biogenesis

    Catherine Strassel, Maria M Magiera, Arnaud Dupuis, Morgane Batzenschlager, Agnès Hovasse, Irina Pleines, Paul Guéguen, Anita Eckly, Sylvie Moog, Léa Mallo, Quentin Kimmerlin, Stéphane Chappaz, Jean-Marc Strub, Natarajan Kathiresan, Henri de la Salle, Alain Van Dorsselaer, Claude Ferec, Jean-Yves Py, Christian Gachet, Christine Schaeffer-Reiss, Benjamin T Kile, Carsten Janke, François Lanza

    Catherine Strassel ... François Lanza

    Published 13 February 2019

    Alpha4A-tubulin is the predominant α-tubulin isotype in platelets. Mutations in α4A-tubulin cause abnormal platelet biogenesis and marginal band formation in mice and in a patient, establishing an essential role of this tubulin isotype.

  • Opposing Roles of apolipoprotein E in aging and neurodegeneration
    Open Access
    Opposing Roles of apolipoprotein E in aging and neurodegeneration

    Eloise Hudry, Jacob Klickstein, Claudia Cannavo, Rosemary Jackson, Alona Muzikansky, Sheetal Gandhi, David Urick, Taylie Sargent, Lauren Wrobleski, Allyson D Roe, Steven S Hou, Kishore V Kuchibhotla, Rebecca A Betensky, Tara Spires-Jones, Bradley T Hyman

    Eloise Hudry ... Bradley T Hyman

    Published 13 February 2019

    This study investigates how APOE modulates neuronal function integrity during normal aging and in the context of amyloidosis. This work demonstrates that APOE is a necessary partner of Aβ-dependent neuronal dysfunction and synaptotoxicity but also preserves neuronal network during aging.

  • MiR-146a wild-type 3′ sequence identity is dispensable for proper innate immune function in vivo
    Open Access
    MiR-146a wild-type 3′ sequence identity is dispensable for proper innate immune function in vivo

    Grant Bertolet, Natee Kongchan, Rebekah Miller, Ravi K Patel, Antrix Jain, Jong Min Choi, Alexander B Saltzman, Amber Christenson, Sung Yun Jung, Anna Malovannaya, Andrew Grimson, Joel R Neilson

    Grant Bertolet ... Joel R Neilson

    Published 18 February 2019

    Mice engineered to express an allele of a mammalian microRNA in which the 3′ paring specificity of the mature miRNA is robustly altered are phenotypically indistinguishable from mice with the wild-type allele.

  • Main constraints for RNAi induced by expressed long dsRNA in mouse cells
    Open Access
    Main constraints for RNAi induced by expressed long dsRNA in mouse cells

    Tomas Demeter, Michaela Vaskovicova, Radek Malik, Filip Horvat, Josef Pasulka, Eliska Svobodova, Matyas Flemr, Petr Svoboda

    Tomas Demeter ... Petr Svoboda

    Published 26 February 2019

    A systematic survey of dsRNA expression in mouse fibroblasts and embryonic stem cells shows main constraints for RNAi. RNAi activity depends on the initial Dicer cleavage of dsRNA, having implications for the evolution of mammalian RNAi functions.

Methods

  • Optimized ChIP-seq method facilitates transcription factor profiling in human tumors
    Open Access
    Optimized ChIP-seq method facilitates transcription factor profiling in human tumors

    Abhishek A Singh, Karianne Schuurman, Ekaterina Nevedomskaya, Suzan Stelloo, Simon Linder, Marjolein Droog, Yongsoo Kim, Joyce Sanders, Henk van der Poel, Andries M Bergman, Lodewyk FA Wessels, Wilbert Zwart

    Abhishek A Singh ... Wilbert Zwart

    Published 28 December 2018

    This study presents an optimized ChIP-seq protocol to enhance transcription factor profiling in human tumours, enabling the analysis of highly challenging samples, including core needle biopsies.

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Volume 2, No. 1
February 2019
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