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Volume 171, Issue 6 November 30, 2017

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      Leading Edge

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    • Abstract Image

      The Ferrous Awakens

      Andrew J. Rennekamp
      DOI: http://dx.doi.org/10.1016/j.cell.2017.11.029
      Recent discoveries provide a new hope that relapses of several types of cancer can be prevented by inducing ferroptosis.
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      • Benchmarks

    • Abstract Image

      How Cryo-EM Became so Hot

      Yifan Cheng, Robert M. Glaeser, Eva Nogales
      DOI: http://dx.doi.org/10.1016/j.cell.2017.11.016
      The Royal Swedish Academy of Sciences awarded the 2017 Nobel Prize for Chemistry to Jacques Dubochet, Joachim Frank, and Richard Henderson for “developing cryoelectron microscopy for the high-resolution structure determination of biomolecules in solution.” Achieving this goal, which required innovation, persistence, and uncommon physical insight, has broadened horizons for structural studies in molecular and cell biology.
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    • Abstract Image

      Physiology Flies with Time

      Amita Sehgal
      DOI: http://dx.doi.org/10.1016/j.cell.2017.11.028
      The 2017 Nobel Prize in Medicine or Physiology has been awarded to Jeffrey Hall, Michael Rosbash, and Michael Young for elucidating molecular mechanisms of the circadian clock. From studies beginning in fruit flies, we now know that circadian regulation pervades most biological processes and has strong ties to human health and disease.
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      • Stories

    • Abstract Image

      As Time Flew By

      Michael W. Young
      DOI: http://dx.doi.org/10.1016/j.cell.2017.11.022
      My earliest work on circadian rhythms came by chance, when I was a graduate student with Burke Judd at the University of Texas in the early ‘70s. Burke had offered me a place in his lab for summer undergraduate research, and when that went well, I asked to stay. The lab had been trying to use saturation mutagenesis to identify every gene in a region of the X chromosome that represented ∼0.5 percent of the Drosophila genome. The average gene density was turning out to be only about 1/25,000 base pairs.
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    • Abstract Image

      Life Is an N of 1

      Michael Rosbash
      DOI: http://dx.doi.org/10.1016/j.cell.2017.11.027
      It is a strange feeling not to anticipate begging, pleading, sweating, or getting angry at a rejection letter/email when crafting a manuscript for Cell. This manuscript will presumably escape that torture as it is a brief, personal story invited by the Cell editor Marta Koch. I was sorely tempted to tell the tale of my long and colorful history with Cell. However, it cannot be brief, so here is a different piece of personal history.
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      • Conversations

    • Abstract Image

      A Nobel Pursuit May Not Run like Clockwork

      DOI: http://dx.doi.org/10.1016/j.cell.2017.11.030
      Living in rural Maine, Jeffrey Hall’s own rhythm has been thrown upside down after he received a very unexpected call communicating he, together with Michael Rosbash and Mike Young, had been awarded this year’s Nobel Prize in Physiology or Medicine for their “for their discoveries of molecular mechanisms controlling the circadian rhythm.” Cell editor Marta Koch was fortunate to catch Jeff Hall on a calm Sunday morning, when electricity was back on despite recent storms, and chat about behavior, misbehavior, and the challenges and joys of working with fruit flies. Annotated excerpts from this conversation are presented below, and the full conversation is available with the article online.
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      • Previews

    • Abstract Image

      Tumor Evolution: A Problem of Histocompatibility

      Natalie I. Vokes, Eliezer M. Van Allen
      DOI: http://dx.doi.org/10.1016/j.cell.2017.11.012
      In this issue of Cell, two articles show that tumor-specific changes in HLA-mediated antigen presentation affect tumor immunogenicity and may play a role in shaping cancer cell survival.
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    • Abstract Image

      Phytochromes: Where to Start?

      Sookyung Oh, Beronda L. Montgomery
      DOI: http://dx.doi.org/10.1016/j.cell.2017.11.020
      Phytochrome signaling allows plants to sense and respond to light through gene regulation. Ushijima et al. (2017) demonstrate a role for phytochromes in widespread regulation of alternative promoter usage, resulting in light-dependent protein isoforms with altered subcellular localization that help the plant respond metabolically to fluctuating light conditions.
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    • Abstract Image

      Platelets, On Your Marks, Get Set, Migrate!

      Sarah K. Bambach, Tim Lämmermann
      DOI: http://dx.doi.org/10.1016/j.cell.2017.11.026
      The idea that anucleate platelets display autonomous migration has long been viewed with skepticism. Gaertner et al. provide in vivo evidence that platelets undergo active migration at sites of thrombus formation and in inflamed liver sinusoids. Integrin-dependent migration allows platelets to scavenge and bundle fibrin-bound material, including intravascular bacteria.
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      • Articles

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      Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

      Video AbstractOnline Extra
      Nicholas McGranahan, Rachel Rosenthal, Crispin T. Hiley, Andrew J. Rowan, Thomas B.K. Watkins, Gareth A. Wilson, Nicolai J. Birkbak, Selvaraju Veeriah, Peter Van Loo, Javier Herrero, Charles Swanton, the TRACERx Consortium
      DOI: http://dx.doi.org/10.1016/j.cell.2017.10.001
      Open Access
      Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer.
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    • Abstract Image

      MHC-I Genotype Restricts the Oncogenic Mutational Landscape

      Online Extra
      Rachel Marty, Saghar Kaabinejadian, David Rossell, Michael J. Slifker, Joris van de Haar, Hatice Billur Engin, Nicola de Prisco, Trey Ideker, William H. Hildebrand, Joan Font-Burgada, Hannah Carter
      DOI: http://dx.doi.org/10.1016/j.cell.2017.09.050
      HLA genotype-restricted immunoediting during tumor formation shapes the landscape of oncogenic mutations observed in clinically diagnosed tumors.
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    • Abstract Image

      Epigenetic Therapy Ties MYC Depletion to Reversing Immune Evasion and Treating Lung Cancer

      Online Extra
      Michael J. Topper, Michelle Vaz, Katherine B. Chiappinelli, Christina E. DeStefano Shields, Noushin Niknafs, Ray-Whay Chiu Yen, Alyssa Wenzel, Jessica Hicks, Matthew Ballew, Meredith Stone, Phuoc T. Tran, Cynthia A. Zahnow, Matthew D. Hellmann, Valsamo Anagnostou, Pamela L. Strissel, Reiner Strick, Victor E. Velculescu, Stephen B. Baylin
      DOI: http://dx.doi.org/10.1016/j.cell.2017.10.022
      Myc depletion through combined epigenetic therapy reverses immune evasion and enables effective treatment of lung cancer.
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    • Abstract Image

      Myc Cooperates with Ras by Programming Inflammation and Immune Suppression

      Online Extra
      Roderik M. Kortlever, Nicole M. Sodir, Catherine H. Wilson, Deborah L. Burkhart, Luca Pellegrinet, Lamorna Brown Swigart, Trevor D. Littlewood, Gerard I. Evan
      DOI: http://dx.doi.org/10.1016/j.cell.2017.11.013
      Open Access
      Oncogenic Myc activity orchestrates an immune suppressive tumor microenvironment.
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    • Abstract Image

      Light Controls Protein Localization through Phytochrome-Mediated Alternative Promoter Selection

      Online Extra
      Tomokazu Ushijima, Kousuke Hanada, Eiji Gotoh, Wataru Yamori, Yutaka Kodama, Hiroyuki Tanaka, Miyako Kusano, Atsushi Fukushima, Mutsutomo Tokizawa, Yoshiharu Y. Yamamoto, Yasuomi Tada, Yutaka Suzuki, Tomonao Matsushita
      DOI: http://dx.doi.org/10.1016/j.cell.2017.10.018
      Light signaling through phytochrome receptors changes protein localization through alternative promoter selection, allowing plants to metabolically respond to changing light conditions.
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    • Abstract Image

      Composition and Regulation of the Cellular Repertoire of SCF Ubiquitin Ligases

      Online Extra
      Justin M. Reitsma, Xing Liu, Kurt M. Reichermeier, Annie Moradian, Michael J. Sweredoski, Sonja Hess, Raymond J. Deshaies
      DOI: http://dx.doi.org/10.1016/j.cell.2017.10.016
      A cell’s repertoire of SCF ubiquitin ligases, which target proteins for degradation, is directly shaped by the substrates that are present.
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    • Abstract Image

      An Unexpectedly Complex Architecture for Skin Pigmentation in Africans

      Online Extra
      Alicia R. Martin, Meng Lin, Julie M. Granka, Justin W. Myrick, Xiaomin Liu, Alexandra Sockell, Elizabeth G. Atkinson, Cedric J. Werely, Marlo Möller, Manjinder S. Sandhu, David M. Kingsley, Eileen G. Hoal, Xiao Liu, Mark J. Daly, Marcus W. Feldman, Christopher R. Gignoux, Carlos D. Bustamante, Brenna M. Henn
      DOI: http://dx.doi.org/10.1016/j.cell.2017.11.015
      The genetic architecture of skin pigmentation is highly complex, varies across human populations, and is subject to distinct geographical evolutionary pressures.
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    • Abstract Image

      Membrane Microdomain Disassembly Inhibits MRSA Antibiotic Resistance

      Online Extra
      Esther García-Fernández, Gudrun Koch, Rabea M. Wagner, Agnes Fekete, Stephanie T. Stengel, Johannes Schneider, Benjamin Mielich-Süss, Sebastian Geibel, Sebastian M. Markert, Christian Stigloher, Daniel Lopez
      DOI: http://dx.doi.org/10.1016/j.cell.2017.10.012
      Open Access
      Using statins to disassemble bacterial membrane microdomains can decrease antibiotic resistance and re-sensitize MRSA to antibiotic therapies in vivo.
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    • Abstract Image

      Migrating Platelets Are Mechano-scavengers that Collect and Bundle Bacteria

      Online Extra
      Florian Gaertner, Zerkah Ahmad, Gerhild Rosenberger, Shuxia Fan, Leo Nicolai, Benjamin Busch, Gökce Yavuz, Manja Luckner, Hellen Ishikawa-Ankerhold, Roman Hennel, Alexandre Benechet, Michael Lorenz, Sue Chandraratne, Irene Schubert, Sebastian Helmer, Bianca Striednig, Konstantin Stark, Marek Janko, Ralph T. Böttcher, Admar Verschoor, Catherine Leon, Christian Gachet, Thomas Gudermann, Michael Mederos y Schnitzler, Zachary Pincus, Matteo Iannacone, Rainer Haas, Gerhard Wanner, Kirsten Lauber, Michael Sixt, Steffen Massberg
      DOI: http://dx.doi.org/10.1016/j.cell.2017.11.001
      In addition to their role in thrombosis and hemostasis, platelets can also migrate to sites of infection to help trap bacteria and clear the vascular surface.
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    • Abstract Image

      Epsin-Dependent Ligand Endocytosis Activates Notch by Force

      Online Extra
      Paul D. Langridge, Gary Struhl
      DOI: http://dx.doi.org/10.1016/j.cell.2017.10.048
      Force exerted by Epsin-mediated ligand endocytosis induces ectodomain cleavage of Notch to initiate signaling.
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    • Abstract Image

      Force Triggers YAP Nuclear Entry by Regulating Transport across Nuclear Pores

      Online Extra
      Alberto Elosegui-Artola, Ion Andreu, Amy E.M. Beedle, Ainhoa Lezamiz, Marina Uroz, Anita J. Kosmalska, Roger Oria, Jenny Z. Kechagia, Palma Rico-Lastres, Anabel-Lise Le Roux, Catherine M. Shanahan, Xavier Trepat, Daniel Navajas, Sergi Garcia-Manyes, Pere Roca-Cusachs
      DOI: http://dx.doi.org/10.1016/j.cell.2017.10.008
      Force-dependent changes in nuclear pores control protein access to the nucleus.
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    • Abstract Image

      Ancestral Circuits for the Coordinated Modulation of Brain State

      Online Extra
      Matthew Lovett-Barron, Aaron S. Andalman, William E. Allen, Sam Vesuna, Isaac Kauvar, Vanessa M. Burns, Karl Deisseroth
      DOI: http://dx.doi.org/10.1016/j.cell.2017.10.021
      Registration of brain-wide activity measurements with multiple molecular markers at cellular resolution uncovers multiple diverse neuromodulatory pathways linked to brain state.
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      • Theory

    • Abstract Image

      Efficient Generation of Transcriptomic Profiles by Random Composite Measurements

      Online Extra
      Brian Cleary, Le Cong, Anthea Cheung, Eric S. Lander, Aviv Regev
      DOI: http://dx.doi.org/10.1016/j.cell.2017.10.023
      A roadmap to generate a high-dimensional transcriptomic profile from sequencing a small, random selection of genes.
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      • Resources

    • Abstract Image

      A Next Generation Connectivity Map: L1000 Platform and the First 1,000,000 Profiles

      Online Extra
      Aravind Subramanian, Rajiv Narayan, Steven M. Corsello, David D. Peck, Ted E. Natoli, Xiaodong Lu, Joshua Gould, John F. Davis, Andrew A. Tubelli, Jacob K. Asiedu, David L. Lahr, Jodi E. Hirschman, Zihan Liu, Melanie Donahue, Bina Julian, Mariya Khan, David Wadden, Ian C. Smith, Daniel Lam, Arthur Liberzon, Courtney Toder, Mukta Bagul, Marek Orzechowski, Oana M. Enache, Federica Piccioni, Sarah A. Johnson, Nicholas J. Lyons, Alice H. Berger, Alykhan F. Shamji, Angela N. Brooks, Anita Vrcic, Corey Flynn, Jacqueline Rosains, David Y. Takeda, Roger Hu, Desiree Davison, Justin Lamb, Kristin Ardlie, Larson Hogstrom, Peyton Greenside, Nathanael S. Gray, Paul A. Clemons, Serena Silver, Xiaoyun Wu, Wen-Ning Zhao, Willis Read-Button, Xiaohua Wu, Stephen J. Haggarty, Lucienne V. Ronco, Jesse S. Boehm, Stuart L. Schreiber, John G. Doench, Joshua A. Bittker, David E. Root, Bang Wong, Todd R. Golub
      DOI: http://dx.doi.org/10.1016/j.cell.2017.10.049
      The next generation Connectivity Map, a large-scale compendium of functional perturbations in cultured human cells coupled to a gene-expression readout, facilitates the discovery of connections between genes, drugs, and diseases.
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    • Abstract Image

      Precise Editing at DNA Replication Forks Enables Multiplex Genome Engineering in Eukaryotes

      Online Extra
      Edward M. Barbieri, Paul Muir, Benjamin O. Akhuetie-Oni, Christopher M. Yellman, Farren J. Isaacs
      DOI: http://dx.doi.org/10.1016/j.cell.2017.10.034
      Replication forks can be co-opted to introduce multisite mutations in eukaryotic genomes without the need for DNA double-strand break.
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      • SnapShot

    • SnapShot: Circadian Clock

      Online Extra
      Bryan J. Song, Dragana Rogulja
      DOI: http://dx.doi.org/10.1016/j.cell.2017.11.021
      Most creatures on this planet possess an ability to anticipate upcoming events in the environment, courtesy of their circadian clocks. This allows them to prepare for those changes instead of being caught by surprise, which could mean the difference between life and death. In this SnapShot, we describe the basics of how the clock ticks.
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Select all articles on page to then view abstracts, export citations, email, or add to reading list View abstracts of articles selected in the list View Abstracts | Export citations of articles selected in the list Export Citations | Email articles selected in the list Email a Colleague Add the articles selected in the list to your reading list | Add to Reading List
Cover image volume 171, Issue 6 Enlarge Cover

On the cover: Immune evasion is a hallmark of cancer. One mechanism of immune evasion involves disrupting the antigen presenting machinery. In this issue of Cell, McGranahan et al. (1259–1271) presented LOHHLA (Loss of Heterozygosity in Human Leukocyte Antigen), a tool to systematically evaluate the prevalence and importance of HLA loss in cancer. By applying this tool to analyze samples from patients with non-small-cell lung cancer, the authors demonstrated that HLA loss is a common subclonal mechanism of immune evasion, subject to strong selection pressures, and associated with an elevated mutation burden and immune activation. The cover image shows a cell surface with HLA class I from both maternal and paternal lineages (in green and pink), presenting brightly colored neoantigen peptides. One of the parental HLA alleles is subject to loss, illustrated by the green HLA class I proteins gradually disappearing from the cell surface. Cover artwork by Jeroen Claus with Phospho Biomedical Animation.

30 November 2017
Volume 171, Issue 6
On the cover: Immune evasion is a hallmark of cancer. One mechanism of immune evasion involves disrupting the antigen presenting machinery. In this issue of Cell, McGranahan et al. (1259–1271) presented LOHHLA (Loss of Heterozygosity in Human Leukocyte Antigen), a tool to systematically evaluate the prevalence and importance of HLA loss in cancer. By applying this tool to analyze samples from patients with non-small-cell lung cancer, the authors demonstrated that HLA loss is a common subclonal mechanism of immune evasion, subject to strong selection pressures, and associated with an elevated mutation burden and immune activation. The cover image shows a cell surface with HLA class I from both maternal and paternal lineages (in green and pink), presenting brightly colored neoantigen peptides. One of the parental HLA alleles is subject to loss, illustrated by the green HLA class I proteins gradually disappearing from the cell surface. Cover artwork by Jeroen Claus with Phospho Biomedical Animation.

Cell ISSN: 0092-8674

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