Volume 16 Issue 2, February 2010

Volume 16 Issue 2

Neutrophil elastase degrades IRS-1 and speeds up lung tumor growth, according to a report by Steven Shapiro and his colleagues (pp 219–223). The cover shows a scanning electron micrograph of a small cancerous tumor filling an alveolus of the human lung. Credit: Moredun Scientific/Photo Researchers, Inc.

Editorial

  • Editorial |

    Everybody agrees that ensuring the integrity and accessibility of research data is crucial for scientific progress. Agreeing on the best way to do so is the hard part.

News

Correspondence

Book Review

News and Views

  • News & Views |

    Microbes in the gut can influence distant events, affecting the function of neutrophils in the circulation of mice ( pages 228–231 ). The findings should lead to new studies examining how intestinal microbes affect immunity.

    • Dana J Philpott
    •  & Stephen E Girardin
  • News & Views |

    Inflammatory cells can promote tumor cell proliferation, but the range of mechanisms has not been fully explored. A proteinase produced by neutrophils is now shown to enter tumor cells and promote their proliferation ( pages 219–223 ).

    • Barbara Fingleton
  • News & Views |

    One hazard of gene therapy is that the vector will insert into an inappropriate location, causing aberrant expression of genes that can lead to disease. A new study reveals how such events occurred in a recent gene therapy trial using a vector that has now fallen out of favor ( pages 198–204 ).

    • Cynthia E Dunbar
    •  & Andre Larochelle
  • News & Views |

    Researchers have long known that the peptide angiotensin II is central to blood pressure control—but there is yet more to learn. A new study shows how angiotensin II cooperates with the JAK2 kinase, better known for its role in cytokine signaling, to regulate blood vessel contraction and influence blood pressure ( pages 183–190 ).

    • Kenneth E Bernstein
    •  & Sebastien Fuchs
  • News & Views |

    The receptor for interleukin-7 is a susceptibility factor in multiple sclerosis, but its exact role in the disease has been unclear. New findings outline a function for interleukin-7 in the biology of T helper 17 cells, a subset of T cells recently identified as key players in autoimmune disorders ( pages 191–197 ).

    • Marc Veldhoen
    •  & Benedict Seddon

Community Corner

Between Bedside and Bench

  • Between Bedside and Bench |

    Muscle diseases can take many forms, from the progressive muscle degeneration of dystrophies to the childhood cancer rhabdomyosarcoma. In 'Bench to Bedside', Joel R. Chamberlain and Jeffrey S. Chamberlain discuss studies using antisense oligonucleotides to treat Duchenne muscular dystrophy and myotonic dystrophy. In 'Bedside to Bench', Simone Hettmer and Amy J. Wagers examine the implications of clinical studies describing a type of rhabdomyosarcoma that resembles acute leukemia. The findings dovetail with other studies suggesting that some of these cancers might originate outside of muscle tissue and highlight the need for a better understanding of the cells that give rise to this condition.

    • Joel R Chamberlain
    •  & Jeffrey S Chamberlain

Research Highlights

Articles

  • Article |

    In β-thalassemia, decreased β-globin synthesis leads to red blood cell loss, iron overload and anemia. Using a mouse model of this disease, Huihui Li et al. now describe a new approach for treating β-thalassemia: injection of the iron transporter transferrin. This therapy had many beneficial effects, including reversing splenomegaly and raising red blood cell counts.

    • Huihui Li
    • , Anne C Rybicki
    • , Sandra M Suzuka
    • , Leni von Bonsdorff
    • , William Breuer
    • , Charles B Hall
    • , Z Ioav Cabantchik
    • , Eric E Bouhassira
    • , Mary E Fabry
    •  & Yelena Z Ginzburg
  • Article |

    Angiotensin II contracts blood vessels and has been implicated as a causative factor in hypertension. Christophe Guilluy et al. now demonstrate that the guanine exchange factor Arghef1 is required for the hypertensive effects of angiotensin II in mice, and describe a new signaling pathway by which angiotensin II triggers Jak2-dependent activation of Arghef1 to cause smooth muscle cell contraction ( pages 165–166 ).

    • Christophe Guilluy
    • , Jérémy Brégeon
    • , Gilles Toumaniantz
    • , Malvyne Rolli-Derkinderen
    • , Kevin Retailleau
    • , Laurent Loufrani
    • , Daniel Henrion
    • , Elizabeth Scalbert
    • , Antoine Bril
    • , Raul M Torres
    • , Stephan Offermanns
    • , Pierre Pacaud
    •  & Gervaise Loirand
  • Article |

    Variation in the IL-7 receptor is associated with susceptibility to multiple sclerosis. Jingwu Zhang and his colleagues provide an explanation. They show that the cytokine IL-7 regulates the surival and proliferation of T helper type 17 cells—a cell type known to be involved in the pathogenesis of multiple sclerosis. The findings suggest that IL-7 antagonism could be useful in individuals with autoimmune diseases such as multiple sclerosis (pages 166–168).

    • Xuebin Liu
    • , Stewart Leung
    • , Chunxia Wang
    • , Zhu Tan
    • , Ji Wang
    • , Taylor B Guo
    • , Lei Fang
    • , Yonggang Zhao
    • , Bing Wan
    • , Xia Qin
    • , Limin Lu
    • , Runsheng Li
    • , Heng Pan
    • , Mingjuan Song
    • , Ailian Liu
    • , Jian Hong
    • , Hongtao Lu
    •  & Jingwu Z Zhang
  • Article |

    Transduced hematopoietic stem cells can benefit patients with X-linked chronic granulomatous disease (a genetic immunodeficiency), but it's not risk free. In two treated patients, insertional activation of MDS1EVI1, PRDM16 and SETBP1 markedly increased the number of transduced cells in the blood, leading to oligoclonal hematopoiesis, monosomy 7 and a myelodysplastic syndrome ( pages 163–165 ).

    • Stefan Stein
    • , Marion G Ott
    • , Stephan Schultze-Strasser
    • , Anna Jauch
    • , Barbara Burwinkel
    • , Andrea Kinner
    • , Manfred Schmidt
    • , Alwin Krämer
    • , Joachim Schwäble
    • , Hanno Glimm
    • , Ulrike Koehl
    • , Carolin Preiss
    • , Claudia Ball
    • , Hans Martin
    • , Gudrun Göhring
    • , Kerstin Schwarzwaelder
    • , Wolf-Karsten Hofmann
    • , Kadin Karakaya
    • , Sandrine Tchatchou
    • , Rongxi Yang
    • , Petra Reinecke
    • , Klaus Kühlcke
    • , Brigitte Schlegelberger
    • , Adrian J Thrasher
    • , Dieter Hoelzer
    • , Reinhard Seger
    • , Christof von Kalle
    •  & Manuel Grez
  • Article |

    The protein kinase mTOR is known to contribute to cancer development. However, existing drugs targeting mTOR, such as rapamycin, have not been very effective at inhibiting cancer cell survival and also have the unwanted side effect of immunosuppression. Studying preclinical models of leukemia driven by the BCR-ABL oncogene, Matthew Janes et al. now show that a new mTOR inhibitor—which unlike previous ones is an ATP competitive inhibitor that targets the active site of the enzyme—can overcome these drawbacks.

    • Matthew R Janes
    • , Jose J Limon
    • , Lomon So
    • , Jing Chen
    • , Raymond J Lim
    • , Melissa A Chavez
    • , Collin Vu
    • , Michael B Lilly
    • , Sharmila Mallya
    • , S Tiong Ong
    • , Marina Konopleva
    • , Michael B Martin
    • , Pingda Ren
    • , Yi Liu
    • , Christian Rommel
    •  & David A Fruman

Letters

  • Letter |

    Two amplified genes from chromosome 8q22—YWHAZ and LAPTM4B—are associated with metastatic breast cancer recurrence by promoting resistance to anthracyclines. YWHAZ codes for an antiapoptotic protein and LAPTM4B encodes a previously undescribed lysosomal protein.

    • Yang Li
    • , Lihua Zou
    • , Qiyuan Li
    • , Benjamin Haibe-Kains
    • , Ruiyang Tian
    • , Yan Li
    • , Christine Desmedt
    • , Christos Sotiriou
    • , Zoltan Szallasi
    • , J Dirk Iglehart
    • , Andrea L Richardson
    •  & Zhigang Charles Wang
  • Letter |

    Neutrophil elastase speeds up the progression of lung cancer by degrading insulin receptor substrate-1 and thereby phosphatidylinositol 3-kinase. This is the first description of a secreted proteinase gaining access to the inside of a cell to alter intracellular signaling ( pages 161–163 ).

    • A McGarry Houghton
    • , Danuta M Rzymkiewicz
    • , Hongbin Ji
    • , Alyssa D Gregory
    • , Eduardo E Egea
    • , Heather E Metz
    • , Donna B Stolz
    • , Stephanie R Land
    • , Luiz A Marconcini
    • , Corrine R Kliment
    • , Kimberly M Jenkins
    • , Keith A Beaulieu
    • , Majd Mouded
    • , Stuart J Frank
    • , Kwok K Wong
    •  & Steven D Shapiro
  • Letter |

    Smallpox was eradicated by vaccination with a related poxvirus, vaccinia virus, which was applied to superficially injured skin in a process called scarification. Recombinant poxvirus–based vaccines are attractive candidates for protecting against a number of different infections, but they are nowadays usually administered intramuscularly. Thomas Kupper and his colleagues now show that the traditional route of administration, scarification, enables poxvirus-based vaccines to mediate more potent immunity compared with the intramuscular route. In particular, scarification with the poxvirus vaccines induced the sort of immune responses that are required for protection of distant tissues, including the lung mucosa.

    • Luzheng Liu
    • , Qiong Zhong
    • , Tian Tian
    • , Krista Dubin
    • , Shruti K Athale
    •  & Thomas S Kupper
  • Letter |

    Jeffrey Weiser and his colleagues provide a mechanism for a beneficial effect from commensal bacteria that colonize the gut. They show that peptidoglycan from gut microbiota traverses the gut mucosa and boosts the systemic innate immune response by priming neutrophils in the bone marrow. Such priming requires the recognition of peptidoglycan by the intracellular receptor Nod-1 ( pages 160–161 ).

    • Thomas B Clarke
    • , Kimberly M Davis
    • , Elena S Lysenko
    • , Alice Y Zhou
    • , Yimin Yu
    •  & Jeffrey N Weiser

Technical Report

  • Technical Report |

    Colleen Delaney and colleagues have developed a new culture system for umbilical cord blood progenitors that improves myeloid engraftment in cord blood transplants using a Notch ligand–mediated ex vivo expansion strategy. The study demonstrates rapid hematopoietic engraftment in a NOD/SCID mouse model and a phase 1 myeloablative cord blood transplantation trial. The strategy could lead to better clinical outcomes as a result of reduced morbidity and mortality.

    • Colleen Delaney
    • , Shelly Heimfeld
    • , Carolyn Brashem-Stein
    • , Howard Voorhies
    • , Ronald L Manger
    •  & Irwin D Bernstein

Addendum

Corrigendum

Addendum

Erratum

Retraction