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Cell
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Sep 14, 2012

Volume 150Issue 6p1085-1300
Open Archive
On the cover: The ability to learn and remember previously encountered pathogens is a hallmark of the vertebrate immune system. CD8+ T cells, called central memory cells (TCM), mediate much more rapid and vigorous immune responses against the viruses that they recognize compared to their uneducated precursors, the naive T cells (TN). In this issue, Sung et al. (pp. 1249–1263) compare, at the single-cell level, the response of TN and TCM to a subcutaneous viral challenge. The invading virions are rapidly transported to the draining lymph nodes, where they infect macrophages that line the periphery of these bean-shaped organs. The image shows a cross-section of a lymph node in which virus-infected macrophages are identified by their yellow-green color. Initially, both TN and TCM reside in the deep T cell area (the dark region in the center of the organ). TCM, unlike TN, expresses CXCR3, a chemokine receptor that enables TCM to sense distant viral infections and to migrate peripherally between the B cell follicles (red) and into the medulla (the blue-green region on the left). This chemokine-dependent redistribution of TCM provides rapid access to viral antigen, which is critical for expedient clearance of the virus and, thus, represents a key molecular feature of immunological memory. Oil on canvas painting by Meghan Perdue....
On the cover: The ability to learn and remember previously encountered pathogens is a hallmark of the vertebrate immune system. CD8+ T cells, called central memory cells (TCM), mediate much more rapid and vigorous immune responses against the viruses that they recognize compared to their uneducated precursors, the naive T cells (TN). In this issue, Sung et al. (pp. 1249–1263) compare, at the single-cell level, the response of TN and TCM to a subcutaneous viral challenge. The invading virions are rapidly transported to the draining lymph nodes, where they infect macrophages that line the periphery of these bean-shaped organs. The image shows a cross-section of a lymph node in which virus-infected macrophages are identified by their yellow-green color. Initially, both TN and TCM reside in the deep T cell area (the dark region in the center of the organ). TCM, unlike TN, expresses CXCR3, a chemokine receptor that enables TCM to sense distant viral infections and to migrate peripherally between the B cell follicles (red) and into the medulla (the blue-green region on the left). This chemokine-dependent redistribution of TCM provides rapid access to viral antigen, which is critical for expedient clearance of the virus and, thus, represents a key molecular feature of immunological memory. Oil on canvas painting by Meghan Perdue.

Leading Edge

In This Issue

BenchMarks

  • Behind the Movement

    • Dagmar Ringe,
    • Gregory A. Petsko
    This year, the Albert Lasker Basic Medical Research Award will be shared by Michael Sheetz, James Spudich, and Ronald Vale for discoveries concerning the biophysical actions of cytoskeletal motor-protein machines that move cargo within cells, contract muscles, and enable cell motility.
  • Liver Transplantation: From Inception to Clinical Practice

    • Silvia Vilarinho,
    • Richard P. Lifton
    The 2012 Lasker-DeBakey Clinical Medical Research Award will be conferred on Thomas Starzl of the University of Pittsburgh School of Medicine in Pittsburgh, Pennsylvania, USA and Roy Calne of the University of Cambridge in Cambridge, UK. They are recognized for pioneering the development of liver transplantation, an intervention that saves 20,000 lives world-wide each year.
  • Pure Genes, Pure Genius

    • Steven L. McKnight
    The 2012 Albert Lasker Special Achievement Award in Medical Science will be shared by Donald Brown and Tom Maniatis for their scientific work leading to the purification and study of single genes by physical and molecular biological methodologies. Brown and Maniatis are also recognized for their extraordinary commitment and generosity in promoting the careers of young scientists. The impact of these accomplishments has transformed biological and medical science over the past four decades.

Previews

  • Diabetic β Cells: To Be or Not To Be?

    • Sapna Puri,
    • Matthias Hebrok
    β cell dysfunction with subsequent apoptosis is considered a significant contributor to the development of type 2 diabetes. Emerging data from Talchai et al. suggest β cell dedifferentiation as an alternative mechanism of insulin insufficiency that might be more amenable to intervention in at least a subset of patients.
  • Building Bridges for Spinal Cord Repair

    • Phillip G. Popovich
    For nearly a century, neuroscientists have sought to restore neurological function across spinal cord lesions. Lu et al. now present significant progress toward this goal, showing in rats that transplanted neural stem cells establish a functional bridge across completely transected spinal cords.

Articles

  • Mapping the Hallmarks of Lung Adenocarcinoma with Massively Parallel Sequencing

    • Marcin Imielinski,
    • Alice H. Berger,
    • Peter S. Hammerman,
    • Bryan Hernandez,
    • Trevor J. Pugh,
    • Eran Hodis,
    • Jeonghee Cho,
    • James Suh,
    • Marzia Capelletti,
    • Andrey Sivachenko,
    • Carrie Sougnez,
    • Daniel Auclair,
    • Michael S. Lawrence,
    • Petar Stojanov,
    • Kristian Cibulskis,
    • Kyusam Choi,
    • Luc de Waal,
    • Tanaz Sharifnia,
    • Angela Brooks,
    • Heidi Greulich,
    • Shantanu Banerji,
    • Thomas Zander,
    • Danila Seidel,
    • Frauke Leenders,
    • Sascha Ansén,
    • Corinna Ludwig,
    • Walburga Engel-Riedel,
    • Erich Stoelben,
    • Jürgen Wolf,
    • Chandra Goparju,
    • Kristin Thompson,
    • Wendy Winckler,
    • David Kwiatkowski,
    • Bruce E. Johnson,
    • Pasi A. Jänne,
    • Vincent A. Miller,
    • William Pao,
    • William D. Travis,
    • Harvey I. Pass,
    • Stacey B. Gabriel,
    • Eric S. Lander,
    • Roman K. Thomas,
    • Levi A. Garraway,
    • Gad Getz,
    • Matthew Meyerson
    Whole-exome and whole-genome sequencing of 183 lung adenocarcinoma tumor/normal DNA pairs reveals new candidate genes as attractive targets for biological characterization and therapeutic targeting of lung cancer.
  • Genomic Landscape of Non-Small Cell Lung Cancer in Smokers and Never-Smokers

    • Ramaswamy Govindan,
    • Li Ding,
    • Malachi Griffith,
    • Janakiraman Subramanian,
    • Nathan D. Dees,
    • Krishna L. Kanchi,
    • Christopher A. Maher,
    • Robert Fulton,
    • Lucinda Fulton,
    • John Wallis,
    • Ken Chen,
    • Jason Walker,
    • Sandra McDonald,
    • Ron Bose,
    • David Ornitz,
    • Donghai Xiong,
    • Ming You,
    • David J. Dooling,
    • Mark Watson,
    • Elaine R. Mardis,
    • Richard K. Wilson
    Whole-genome sequencing of 17 lung cancer patients reveals that smokers with lung cancer show 10× the number of point mutations than patients who were never smokers. Alterations were identified in 54 genes for which targeted drugs are available.
  • Loss of 5-Hydroxymethylcytosine Is an Epigenetic Hallmark of Melanoma

    • Christine Guo Lian,
    • Yufei Xu,
    • Craig Ceol,
    • Feizhen Wu,
    • Allison Larson,
    • Karen Dresser,
    • Wenqi Xu,
    • Li Tan,
    • Yeguang Hu,
    • Qian Zhan,
    • Chung-wei Lee,
    • Di Hu,
    • Bill Q. Lian,
    • Sonja Kleffel,
    • Yijun Yang,
    • James Neiswender,
    • Abraham J. Khorasani,
    • Rui Fang,
    • Cecilia Lezcano,
    • Lyn M. Duncan,
    • Richard A. Scolyer,
    • John F. Thompson,
    • Hojabr Kakavand,
    • Yariv Houvras,
    • Leonard I. Zon,
    • Martin C. Mihm Jr.,
    • Ursula B. Kaiser,
    • Tobias Schatton,
    • Bruce A. Woda,
    • George F. Murphy,
    • Yujiang G. Shi
    Genome-wide mapping of 5-hmC reveals that loss of 5-hmC is an epigenetic hallmark of melanoma, with diagnostic and prognostic implications. Downregulation of IDH2 and TET family enzymes likely underlies 5-hmC loss in melanoma, and rebuilding the 5-hmC landscape suppresses melanoma growth in animal models.
  • Microprocessor, Setx, Xrn2, and Rrp6 Co-operate to Induce Premature Termination of Transcription by RNAPII

    • Alexandre Wagschal,
    • Emilie Rousset,
    • Poornima Basavarajaiah,
    • Xavier Contreras,
    • Alex Harwig,
    • Sabine Laurent-Chabalier,
    • Mirai Nakamura,
    • Xin Chen,
    • Ke Zhang,
    • Oussama Meziane,
    • Frédéric Boyer,
    • Hugues Parrinello,
    • Ben Berkhout,
    • Christophe Terzian,
    • Monsef Benkirane,
    • Rosemary Kiernan
    Microprocessor functions independently of RNAi to control transcriptional elongation of the HIV-1 RNA as well as cellular pre-mRNA transcripts.
  • Set3 HDAC Mediates Effects of Overlapping Noncoding Transcription on Gene Induction Kinetics

    • TaeSoo Kim,
    • Zhenyu Xu,
    • Sandra Clauder-Münster,
    • Lars M. Steinmetz,
    • Stephen Buratowski
    The Set3 histone deacetylase complex targets the promoters of yeast genes that are overlapped by noncoding transcripts, thus modulating their response to changing growth conditions. The ncRNAs recruit Set3 by promoting the deposition of histone methylation marks that are recognized by the deacetylase complex.
  • Transcription of Two Long Noncoding RNAs Mediates Mating-Type Control of Gametogenesis in Budding Yeast

    • Folkert J. van Werven,
    • Gregor Neuert,
    • Natalie Hendrick,
    • Aurélie Lardenois,
    • Stephen Buratowski,
    • Alexander van Oudenaarden,
    • Michael Primig,
    • Angelika Amon
    Transcription of two noncoding RNAs controls sporulation in yeast. One is a lncRNA transcribed in cis to a critical meiosis gene to generate a repressive chromatin environment; the second is an antisense transcript that blocks transcription of a second meiotic regulator.
  • RNF168 Ubiquitinates K13-15 on H2A/H2AX to Drive DNA Damage Signaling

    • Francesca Mattiroli,
    • Joseph H.A. Vissers,
    • Willem J. van Dijk,
    • Pauline Ikpa,
    • Elisabetta Citterio,
    • Wim Vermeulen,
    • Jurgen A. Marteijn,
    • Titia K. Sixma
    The RING domain of RNF168 recognizes H2A/H2AX at sites of double-strand DNA breaks. RNF168 ubiquitinates these histones at lysines 13–15 to enable the recruitment of downstream factors and drive DNA repair.
  • Ragulator Is a GEF for the Rag GTPases that Signal Amino Acid Levels to mTORC1

    • Liron Bar-Peled,
    • Lawrence D. Schweitzer,
    • Roberto Zoncu,
    • David M. Sabatini
    Identification of two additional subunits of the Ragulator complex reveals intrinsic GEF activity, explaining how Ragulator activates the Rag GTPases that, in turn, activate the mTORC1 pathway.
  • Single-Cell Expression Analyses during Cellular Reprogramming Reveal an Early Stochastic and a Late Hierarchic Phase

    • Yosef Buganim,
    • Dina A. Faddah,
    • Albert W. Cheng,
    • Elena Itskovich,
    • Styliani Markoulaki,
    • Kibibi Ganz,
    • Sandy L. Klemm,
    • Alexander van Oudenaarden,
    • Rudolf Jaenisch
    Jaenisch and colleagues use single-cell analyses to circumvent the challenges associated with studying the minority of cells in a population that reprogram to pluripotency, and they uncover mechanistic insights to the reprogramming process.
  • Pancreatic β Cell Dedifferentiation as a Mechanism of Diabetic β Cell Failure

    • Chutima Talchai,
    • Shouhong Xuan,
    • Hua V. Lin,
    • Lori Sussel,
    • Domenico Accili
    Challenging a prevalent view that pancreatic β cells undergo apoptosis in conditions that induce diabetes, this study shows that dedifferentiation is a major mechanism of β cell loss.
  • A Spatially-Organized Multicellular Innate Immune Response in Lymph Nodes Limits Systemic Pathogen Spread

    • Wolfgang Kastenmüller,
    • Parizad Torabi-Parizi,
    • Naeha Subramanian,
    • Tim Lämmermann,
    • Ronald N. Germain
    A network of diverse lymphoid cells are spatially prepositioned close to sentinel macrophages lining the lymph nodes where they can rapidly and efficiently receive cytokine signals from the pathogen-sensing phagocytes, thus blocking the dissemination of bacteria and viruses that attempt to hijack the lymphatic network.
  • Chemokine Guidance of Central Memory T Cells Is Critical for Antiviral Recall Responses in Lymph Nodes

    • Jung Hwan Sung,
    • Han Zhang,
    • E. Ashley Moseman,
    • David Alvarez,
    • Matteo Iannacone,
    • Sarah E. Henrickson,
    • Juan C. de la Torre,
    • Joanna R. Groom,
    • Andrew D. Luster,
    • Ulrich H. von Andrian
    Chemokines ensure that memory T cells in the lymph node gain rapid access to viral antigens by guiding them to sites of viral entry. This facilitated exposure is important for the development of immunological memory.
  • Long-Distance Growth and Connectivity of Neural Stem Cells after Severe Spinal Cord Injury

    • Paul Lu,
    • Yaozhi Wang,
    • Lori Graham,
    • Karla McHale,
    • Mingyong Gao,
    • Di Wu,
    • John Brock,
    • Armin Blesch,
    • Ephron S. Rosenzweig,
    • Leif A. Havton,
    • Binhai Zheng,
    • James M. Conner,
    • Martin Marsala,
    • Mark H. Tuszynski
    Following severe spinal cord injury in rats, functional outcomes can be improved by the engraftment of neural stem cells embedded in a matrix that contains a growth factor cocktail. The resulting neurons extend axons over long distances and form reciprocal synaptic connections with neurons from the host.

Resources

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