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Cell
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Apr 19, 2018

Volume 173Issue 3p531-804
Open Archive
On the cover: The Bajau, an indigenous Southeast Asian group sometimes referred to as the ‘Sea Nomads’, have lived off the bounty of the sea for thousands of years through a lifestyle built around breath-hold diving. More recently, cultural and societal shifts have sedentarized the Bajau. The cover image shows a Bajau diver, hunting fish underwater with a spear gun. In this issue, Ilardo et al. (569–580) discover the remarkable genetic and physiological adaptations that allow the Bajau to survive underwater through breath hold diving....
On the cover: The Bajau, an indigenous Southeast Asian group sometimes referred to as the ‘Sea Nomads’, have lived off the bounty of the sea for thousands of years through a lifestyle built around breath-hold diving. More recently, cultural and societal shifts have sedentarized the Bajau. The cover image shows a Bajau diver, hunting fish underwater with a spear gun. In this issue, Ilardo et al. (569–580) discover the remarkable genetic and physiological adaptations that allow the Bajau to survive underwater through breath hold diving.

Leading Edge

Select

  • Artificial Intelligence Is Becoming Natural

    • Marta Koch
    You don’t have to sit in a self-driving Tesla to feel the impact of artificial intelligence (AI) on your daily life. From voice-powered personal assistants like Alexa or Siri to help you track and organize information to tailored online shopping, AI is no longer in the realm of science fiction.

Commentary

  • Revolutionizing Precision Oncology through Collaborative Proteogenomics and Data Sharing

    • Henry Rodriguez,
    • Stephen R. Pennington
    The integration of proteomics into precision oncology presents opportunities that may transform the molecular analysis of cancer and accelerate basic and clinical cancer research. This Commentary discusses the importance of international collaboration and data sharing inspired by the Cancer Moonshot to accelerate the progress of multi-omic precision medicine–an approach that addresses the global diversity of people and of cancers.

Previews

  • Multi-regional Sequencing Elucidates the Evolution of Clear Cell Renal Cell Carcinoma

    • Christopher J. Ricketts,
    • W. Marston Linehan
    Extensive multi-regional whole-genome and -exome sequencing performed in tumors from patients with localized, as well as metastatic, clear cell renal cell carcinoma provides a comprehensive description of the tumor origin, intratumoral heterogeneity, evolution, and route to metastasis, laying the foundation for the development of precision clinical management.
  • A Mechanosensitive GPCR that Detects the Bloody Force

    • Adam J. Iliff,
    • X.Z. Shawn Xu
    Mechanoreceptors mediate a wide variety of physiological processes, such as hearing, touch, proprioception, and blood flow regulation. It is generally believed that mechanoreceptors are force-gated ion channels. Now, Xu et al. uncover a GPCR that is activated by shear force in endothelial cells of blood vessels.
  • AttrActin’ Attention to Early Mouse Development

    • Tristan Frum,
    • Amy Ralston
    A new study by Zenker et al. uses time-lapse imaging to discover how dynamic actin movements contribute to epithelialization of living mouse embryos. Together with work from other labs, this study presents exciting new ways to think about the emergence of cell fates during mammalian development.
  • Seeing More: A Future of Augmented Microscopy

    • Devin P. Sullivan,
    • Emma Lundberg
    Microscope images are information rich. In this issue of Cell, Christiansen et al. show that label-free images of cells can be used to predict fluorescent labels representing cell type, state, and organelle distribution using a deep-learning framework. This paves the way for computationally multiplexed assays derived from inexpensive label-free microscopy.

Minireview

Review

Articles

  • Physiological and Genetic Adaptations to Diving in Sea Nomads

    • Melissa A. Ilardo,
    • Ida Moltke,
    • Thorfinn S. Korneliussen,
    • Jade Cheng,
    • Aaron J. Stern,
    • Fernando Racimo,
    • Peter de Barros Damgaard,
    • Martin Sikora,
    • Andaine Seguin-Orlando,
    • Simon Rasmussen,
    • Inge C.L. van den Munckhof,
    • Rob ter Horst,
    • Leo A.B. Joosten,
    • Mihai G. Netea,
    • Suhartini Salingkat,
    • Rasmus Nielsen,
    • Eske Willerslev
    Genetic and physiological adaptations enable the remarkable breath-holding ability of marine nomads.
  • Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal

    • Samra Turajlic,
    • Hang Xu,
    • Kevin Litchfield,
    • Andrew Rowan,
    • Tim Chambers,
    • Jose I. Lopez,
    • David Nicol,
    • Tim O’Brien,
    • James Larkin,
    • Stuart Horswell,
    • Mark Stares,
    • Lewis Au,
    • Mariam Jamal-Hanjani,
    • Ben Challacombe,
    • Ashish Chandra,
    • Steve Hazell,
    • Claudia Eichler-Jonsson,
    • Aspasia Soultati,
    • Simon Chowdhury,
    • Sarah Rudman,
    • Joanna Lynch,
    • Archana Fernando,
    • Gordon Stamp,
    • Emma Nye,
    • Faiz Jabbar,
    • Lavinia Spain,
    • Sharanpreet Lall,
    • Rosa Guarch,
    • Mary Falzon,
    • Ian Proctor,
    • Lisa Pickering,
    • Martin Gore,
    • Thomas B.K. Watkins,
    • Sophia Ward,
    • Aengus Stewart,
    • Renzo DiNatale,
    • Maria F. Becerra,
    • Ed Reznik,
    • James J. Hsieh,
    • Todd A. Richmond,
    • George F. Mayhew,
    • Samantha M. Hill,
    • Catherine D. McNally,
    • Carol Jones,
    • Heidi Rosenbaum,
    • Stacey Stanislaw,
    • Daniel L. Burgess,
    • Nelson R. Alexander,
    • Charles Swanton
    • PEACE,
    • the TRACERx Renal Consortium
    A multi-center prospective study and two validation cohorts of matched primary metastasis biopsies from 100 patients with clear-cell renal cell carcinoma provides a comprehensive picture of the genetic underpinnings and the evolutionary patterns of metastasis.
  • Deterministic Evolutionary Trajectories Influence Primary Tumor Growth: TRACERx Renal

    • Samra Turajlic,
    • Hang Xu,
    • Kevin Litchfield,
    • Andrew Rowan,
    • Stuart Horswell,
    • Tim Chambers,
    • Tim O’Brien,
    • Jose I. Lopez,
    • Thomas B.K. Watkins,
    • David Nicol,
    • Mark Stares,
    • Ben Challacombe,
    • Steve Hazell,
    • Ashish Chandra,
    • Thomas J. Mitchell,
    • Lewis Au,
    • Claudia Eichler-Jonsson,
    • Faiz Jabbar,
    • Aspasia Soultati,
    • Simon Chowdhury,
    • Sarah Rudman,
    • Joanna Lynch,
    • Archana Fernando,
    • Gordon Stamp,
    • Emma Nye,
    • Aengus Stewart,
    • Wei Xing,
    • Jonathan C. Smith,
    • Mickael Escudero,
    • Adam Huffman,
    • Nik Matthews,
    • Greg Elgar,
    • Ben Phillimore,
    • Marta Costa,
    • Sharmin Begum,
    • Sophia Ward,
    • Max Salm,
    • Stefan Boeing,
    • Rosalie Fisher,
    • Lavinia Spain,
    • Carolina Navas,
    • Eva Grönroos,
    • Sebastijan Hobor,
    • Sarkhara Sharma,
    • Ismaeel Aurangzeb,
    • Sharanpreet Lall,
    • Alexander Polson,
    • Mary Varia,
    • Catherine Horsfield,
    • Nicos Fotiadis,
    • Lisa Pickering,
    • Roland F. Schwarz,
    • Bruno Silva,
    • Javier Herrero,
    • Nick M. Luscombe,
    • Mariam Jamal-Hanjani,
    • Rachel Rosenthal,
    • Nicolai J. Birkbak,
    • Gareth A. Wilson,
    • Orsolya Pipek,
    • Dezso Ribli,
    • Marcin Krzystanek,
    • Istvan Csabai,
    • Zoltan Szallasi,
    • Martin Gore,
    • Nicholas McGranahan,
    • Peter Van Loo,
    • Peter Campbell,
    • James Larkin,
    • Charles Swanton
    • the TRACERx Renal Consortium
    A multi-center prospective study on 101 patients with clear-cell renal cell carcinoma resolves the evolutionary features and subtypes underpinning the diverse clinical phenotypes of the disease and suggests these features as potential biomarkers for guiding intervention and surveillance.
  • Timing the Landmark Events in the Evolution of Clear Cell Renal Cell Cancer: TRACERx Renal

    • Thomas J. Mitchell,
    • Samra Turajlic,
    • Andrew Rowan,
    • David Nicol,
    • James H.R. Farmery,
    • Tim O’Brien,
    • Inigo Martincorena,
    • Patrick Tarpey,
    • Nicos Angelopoulos,
    • Lucy R. Yates,
    • Adam P. Butler,
    • Keiran Raine,
    • Grant D. Stewart,
    • Ben Challacombe,
    • Archana Fernando,
    • Jose I. Lopez,
    • Steve Hazell,
    • Ashish Chandra,
    • Simon Chowdhury,
    • Sarah Rudman,
    • Aspasia Soultati,
    • Gordon Stamp,
    • Nicos Fotiadis,
    • Lisa Pickering,
    • Lewis Au,
    • Lavinia Spain,
    • Joanna Lynch,
    • Mark Stares,
    • Jon Teague,
    • Francesco Maura,
    • David C. Wedge,
    • Stuart Horswell,
    • Tim Chambers,
    • Kevin Litchfield,
    • Hang Xu,
    • Aengus Stewart,
    • Reza Elaidi,
    • Stéphane Oudard,
    • Nicholas McGranahan,
    • Istvan Csabai,
    • Martin Gore,
    • P. Andrew Futreal,
    • James Larkin,
    • Andy G. Lynch,
    • Zoltan Szallasi,
    • Charles Swanton,
    • Peter J. Campbell
    • the TRACERx Renal Consortium
    Combination of whole-genome sequencing analysis and a multi-region sampling approach provides insights into the nature and timing of key oncogenic events in clear cell renal cell carcinoma, depicts the evolutionary trajectories of tumors in patients and highlights the opportunity for early intervention.
  • Cancer-Germline Antigen Expression Discriminates Clinical Outcome to CTLA-4 Blockade

    • Sachet A. Shukla,
    • Pavan Bachireddy,
    • Bastian Schilling,
    • Christina Galonska,
    • Qian Zhan,
    • Clyde Bango,
    • Rupert Langer,
    • Patrick C. Lee,
    • Daniel Gusenleitner,
    • Derin B. Keskin,
    • Mehrtash Babadi,
    • Arman Mohammad,
    • Andreas Gnirke,
    • Kendell Clement,
    • Zachary J. Cartun,
    • Eliezer M. Van Allen,
    • Diana Miao,
    • Ying Huang,
    • Alexandra Snyder,
    • Taha Merghoub,
    • Jedd D. Wolchok,
    • Levi A. Garraway,
    • Alexander Meissner,
    • Jeffrey S. Weber,
    • Nir Hacohen,
    • Donna Neuberg,
    • Patrick R. Potts,
    • George F. Murphy,
    • Christine G. Lian,
    • Dirk Schadendorf,
    • F. Stephen Hodi,
    • Catherine J. Wu
    Increased expression of a subcluster of MAGE-A cancer-germline antigens predicts resistance specific to CTLA-4, but not PD-1, blockade, and its association with autophagy suppression implicates the role of autophagy in regulating primary resistance to anti-CTLA-4 therapy in melanoma patients.
  • Tumor-Induced Generation of Splenic Erythroblast-like Ter-Cells Promotes Tumor Progression

    • Yanmei Han,
    • Qiuyan Liu,
    • Jin Hou,
    • Yan Gu,
    • Yi Zhang,
    • Zhubo Chen,
    • Jia Fan,
    • Weiping Zhou,
    • Shuangjian Qiu,
    • Yonghong Zhang,
    • Tao Dong,
    • Ning Li,
    • Zhengping Jiang,
    • Ha Zhu,
    • Qian Zhang,
    • Yuanwu Ma,
    • Lianfeng Zhang,
    • Qingqing Wang,
    • Yizhi Yu,
    • Nan Li,
    • Xuetao Cao
    A population of immune cells in the erythroid lineage are induced in a mouse model of hepatocellular carcinoma, which promotes tumor progression through artemin production.
  • An Integrated Genome-wide CRISPRa Approach to Functionalize lncRNAs in Drug Resistance

    • Assaf C. Bester,
    • Jonathan D. Lee,
    • Alejandro Chavez,
    • Yu-Ru Lee,
    • Daphna Nachmani,
    • Suhani Vora,
    • Joshua Victor,
    • Martin Sauvageau,
    • Emanuele Monteleone,
    • John L. Rinn,
    • Paolo Provero,
    • George M. Church,
    • John G. Clohessy,
    • Pier Paolo Pandolfi
    A CRISPR activation screen identifies both coding and noncoding pathways involved in resistance to chemotherapy.
  • Transcriptome Engineering with RNA-Targeting Type VI-D CRISPR Effectors

    • Silvana Konermann,
    • Peter Lotfy,
    • Nicholas J. Brideau,
    • Jennifer Oki,
    • Maxim N. Shokhirev,
    • Patrick D. Hsu
    A new family of RNA-targeting CRISPR-Cas systems allows specific modulation of splicing events to reduce pathological tau isoforms in a neuronal model of frontotemporal dementia.
  • Nuclear-Import Receptors Reverse Aberrant Phase Transitions of RNA-Binding Proteins with Prion-like Domains

    • Lin Guo,
    • Hong Joo Kim,
    • Hejia Wang,
    • John Monaghan,
    • Fernande Freyermuth,
    • Julie C. Sung,
    • Kevin O’Donovan,
    • Charlotte M. Fare,
    • Zamia Diaz,
    • Nikita Singh,
    • Zi Chao Zhang,
    • Maura Coughlin,
    • Elizabeth A. Sweeny,
    • Morgan E. DeSantis,
    • Meredith E. Jackrel,
    • Christopher B. Rodell,
    • Jason A. Burdick,
    • Oliver D. King,
    • Aaron D. Gitler,
    • Clotilde Lagier-Tourenne,
    • Udai Bhan Pandey,
    • Yuh Min Chook,
    • J. Paul Taylor,
    • James Shorter
    Nuclear-import receptors can reverse phase separation and aggregation of proteins with prion-like domains, including FUS and TDP-43, to mitigate neurodegeneration in vivo.
  • Nuclear Import Receptor Inhibits Phase Separation of FUS through Binding to Multiple Sites

    • Takuya Yoshizawa,
    • Rustam Ali,
    • Jenny Jiou,
    • Ho Yee Joyce Fung,
    • Kathleen A. Burke,
    • Seung Joong Kim,
    • Yuan Lin,
    • William B. Peeples,
    • Daniel Saltzberg,
    • Michael Soniat,
    • Jordan M. Baumhardt,
    • Rudolf Oldenbourg,
    • Andrej Sali,
    • Nicolas L. Fawzi,
    • Michael K. Rosen,
    • Yuh Min Chook
    Distributed, energetically weak interactions between a karyopherin and the FUS nuclear localization signal disrupt FUS phase separation.
  • Phase Separation of FUS Is Suppressed by Its Nuclear Import Receptor and Arginine Methylation

    • Mario Hofweber,
    • Saskia Hutten,
    • Benjamin Bourgeois,
    • Emil Spreitzer,
    • Annika Niedner-Boblenz,
    • Martina Schifferer,
    • Marc-David Ruepp,
    • Mikael Simons,
    • Dierk Niessing,
    • Tobias Madl,
    • Dorothee Dormann
    Phase separation of FUS is regulated by both arginine methylation and binding to the nuclear import receptor Transportin/Karyopherin-β2, and this control can be compromised in the neurodegenerative diseases FTD and ALS.
  • FUS Phase Separation Is Modulated by a Molecular Chaperone and Methylation of Arginine Cation-π Interactions

    • Seema Qamar,
    • GuoZhen Wang,
    • Suzanne J. Randle,
    • Francesco Simone Ruggeri,
    • Juan A. Varela,
    • Julie Qiaojin Lin,
    • Emma C. Phillips,
    • Akinori Miyashita,
    • Declan Williams,
    • Florian Ströhl,
    • William Meadows,
    • Rodylyn Ferry,
    • Victoria J. Dardov,
    • Gian G. Tartaglia,
    • Lindsay A. Farrer,
    • Gabriele S. Kaminski Schierle,
    • Clemens F. Kaminski,
    • Christine E. Holt,
    • Paul E. Fraser,
    • Gerold Schmitt-Ulms,
    • David Klenerman,
    • Tuomas Knowles,
    • Michele Vendruscolo,
    • Peter St George-Hyslop
    Phase transition of the RNA-binding protein FUS is mediated by cation-π interactions between C-terminal arginines and N-terminal tyrosines and is modulated by arginine methlylation.
  • Structural Basis for Teneurin Function in Circuit-Wiring: A Toxin Motif at the Synapse

    • Jingxian Li,
    • Moran Shalev-Benami,
    • Richard Sando,
    • Xian Jiang,
    • Amanuel Kibrom,
    • Jie Wang,
    • Katherine Leon,
    • Christopher Katanski,
    • Olha Nazarko,
    • Yue C. Lu,
    • Thomas C. Südhof,
    • Georgios Skiniotis,
    • Demet Araç
    An adhesion protein with an unexpected, toxin-like fold shows how alternative splicing can regulate synaptic connections.
  • Evolutionary Convergence of Pathway-Specific Enzyme Expression Stoichiometry

    • Jean-Benoît Lalanne,
    • James C. Taggart,
    • Monica S. Guo,
    • Lydia Herzel,
    • Ariel Schieler,
    • Gene-Wei Li
    Enzymatic pathways have exquisitely preferred protein expression stoichiometry that is conserved across broad evolutionary lineages despite many opportunities to diverge due to changes in sequence and regulation.
  • GPR68 Senses Flow and Is Essential for Vascular Physiology

    • Jie Xu,
    • Jayanti Mathur,
    • Emilie Vessières,
    • Scott Hammack,
    • Keiko Nonomura,
    • Julie Favre,
    • Linda Grimaud,
    • Matt Petrus,
    • Allain Francisco,
    • Jingyuan Li,
    • Van Lee,
    • Fu-li Xiang,
    • James K. Mainquist,
    • Stuart M. Cahalan,
    • Anthony P. Orth,
    • John R. Walker,
    • Shang Ma,
    • Viktor Lukacs,
    • Laura Bordone,
    • Michael Bandell,
    • Bryan Laffitte,
    • Yan Xu,
    • Shu Chien,
    • Daniel Henrion,
    • Ardem Patapoutian
    A GPCR is a critical sensor for fluid shear stress in blood vessels.
  • Expanding Actin Rings Zipper the Mouse Embryo for Blastocyst Formation

    • Jennifer Zenker,
    • Melanie D. White,
    • Maxime Gasnier,
    • Yanina D. Alvarez,
    • Hui Yi Grace Lim,
    • Stephanie Bissiere,
    • Maté Biro,
    • Nicolas Plachta
    Expanding actin rings zipper the mouse embryo to seal it and allow formation of the blastocyst cavity.

Resource

  • In Silico Labeling: Predicting Fluorescent Labels in Unlabeled Images

    • Eric M. Christiansen,
    • Samuel J. Yang,
    • D. Michael Ando,
    • Ashkan Javaherian,
    • Gaia Skibinski,
    • Scott Lipnick,
    • Elliot Mount,
    • Alison O’Neil,
    • Kevan Shah,
    • Alicia K. Lee,
    • Piyush Goyal,
    • William Fedus,
    • Ryan Poplin,
    • Andre Esteva,
    • Marc Berndl,
    • Lee L. Rubin,
    • Philip Nelson,
    • Steven Finkbeiner
    In silico labeling, a machine-learning approach, reliably infers fluorescent measurements from transmitted-light images of unlabeled fixed or live biological samples.

Retraction

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