Translational research

  • Article |

    Whole-transcriptome sequencing of a subset of 75 non-small-cell lung cancer specimens in a multi-institutional genome screening study identified a fusion of the CLIP1 and LTK genes with transformational potential due to constitutive LTK kinase activity.

    • Hiroki Izumi
    • , Shingo Matsumoto
    •  & Koichi Goto
  • Article |

    Alanine-scanning mutagenesis is used to identify the PF4 epitope that is recognized by anti-PF4 antibodies in patients with vaccine-induced immune thrombotic thrombocytopaenia, revealing that the epitope corresponds to the heparin-binding site on PF4.

    • Angela Huynh
    • , John G. Kelton
    •  & Ishac Nazy
  • Article |

    Aggressive cerebral cavernous malformations (CCMs) are found to grow through a three-hit cancer-like mechanism, involving gain of function of a gene that promotes vascular growth, and loss of function of genes that suppress it.

    • Aileen A. Ren
    • , Daniel A. Snellings
    •  & Mark L. Kahn
  • Article |

    A range of techniques are used to investigate the molecular landscape of chronic kidney disease, and the results suggest that distinct populations of pericytes and fibroblasts are the main source of myofibroblasts in kidney fibrosis.

    • Christoph Kuppe
    • , Mahmoud M. Ibrahim
    •  & Rafael Kramann
  • Article |

    Respiratory syncytial virus enters cells by binding to cell-surface IGFR1, which activates PKCζ and induces trafficking of the NCL coreceptor to the RSV particles at the cell surface.

    • Cameron D. Griffiths
    • , Leanne M. Bilawchuk
    •  & David J. Marchant
  • Article |

    SARS-CoV-2 modulates central cellular pathways, such as translation, splicing, carbon metabolism, proteostasis and nucleic acid metabolism, in human cells; these pathways can be inhibited by small-molecule inhibitors to prevent viral replication in the cells.

    • Denisa Bojkova
    • , Kevin Klann
    •  & Christian Münch
  • Article |

    In mouse models of pulmonary metastasis, adjuvant epigenetic therapy targeting myeloid-derived suppressor cells disrupts the premetastatic microenvironment after resection of primary tumours and inhibits the dissemination of residual tumour cells.

    • Zhihao Lu
    • , Jianling Zou
    •  & Malcolm V. Brock
  • Article |

    In patients with alcoholic hepatitis, cytolysin-positive Enterococcus faecalis strains are correlated with liver disease severity and increased mortality, and in mouse models these strains can be specifically targeted by bacteriophages.

    • Yi Duan
    • , Cristina Llorente
    •  & Bernd Schnabl
  • Article |

    A field trial succeeded in eliminating populations of the mosquito Aedes albopictus through inundative mass release of incompatible Wolbachia-infected males, which were also irradiated to sterilize any accidentally-released females, and so prevent population replacement.

    • Xiaoying Zheng
    • , Dongjing Zhang
    •  & Zhiyong Xi
  • Letter |

    Patient data from six clinical trials are used to compare the genomic landscapes of breast cancer metastases with those of primary tumours, revealing an increase in mutational burden and clonal diversity.

    • François Bertucci
    • , Charlotte K. Y. Ng
    •  & Fabrice André
  • Letter |

    α1,3-galactosyltransferase-knockout pig hearts that express human CD46 and human thrombomodulin require non-ischaemic preservation with continuous perfusion and post-transplantation growth control to ensure long-term orthotopic function of the xenograft in baboons.

    • Matthias Längin
    • , Tanja Mayr
    •  & Jan-Michael Abicht
  • Article |

    A PI3KCA inhibitor reverses symptoms in a mouse model of PROS/CLOVES syndrome, which results from gain-of-function mutations in PI3KCA, and produces improvements in patients with PROS/CLOVES syndrome.

    • Quitterie Venot
    • , Thomas Blanc
    •  & Guillaume Canaud
  • Article |

    Normothermic machine perfusion of the liver improved early graft function, demonstrated by reduced peak serum aspartate transaminase levels and early allograft dysfunction rates, and improved organ utilization and preservation times, although no differences were seen in graft or patient survival.

    • David Nasralla
    • , Constantin C. Coussios
    •  & Peter J. Friend
  • Article
    | Open Access

    Analyses of genomes from 914 children, adolescents, and young adults provide a comprehensive resource of genomic alterations across a spectrum of common childhood cancers.

    • Susanne N. Gröbner
    • , Barbara C. Worst
    •  & Stefan M. Pfister
  • Letter |

    Using optical mapping and 3D ultrasound, the dynamics and interactions between electrical and mechanical phase singularities were analysed by simultaneously measuring the membrane potential, intracellular calcium concentration and mechanical contractions of the heart during normal rhythm and fibrillation.

    • J. Christoph
    • , M. Chebbok
    •  & S. Luther
  • Article |

    Disulfiram is metabolized into copper–diethyldithiocarbamate, which binds to NPL4 and induces its aggregation in cells, leading to blockade of the p97–NPL4–UFD1 pathway and induction of a complex cellular phenotype that results in cell death.

    • Zdenek Skrott
    • , Martin Mistrik
    •  & Jiri Bartek
  • Letter |

    Mouse models of breast carcinoma and other solid tumours show that selective cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors not only induce tumour cell cycle arrest but also promote anti-tumour immunity.

    • Shom Goel
    • , Molly J. DeCristo
    •  & Jean J. Zhao
  • Letter |

    Introducing chimeric antigen receptors into the endogenous T-cell receptor locus reduces tonic signalling, averts accelerated T-cell differentiation and delays T-cell exhaustion, leading to enhanced function and anti-tumour efficacy compared to random integrations.

    • Justin Eyquem
    • , Jorge Mansilla-Soto
    •  & Michel Sadelain
  • Letter |

    PI3Kδ controls the expression of the recombinogenic enzyme AID; excessive AID activity caused by PI3Kδ inhibition can induce genomic instability in leukaemia and lymphoma cells, as well as in patients with chronic lymphocytic leukaemia treated with PI3Kδ inhibitors.

    • Mara Compagno
    • , Qi Wang
    •  & Roberto Chiarle
  • Letter |

    Preclinical evaluation and optimization of mitochondrial replacement therapy reveals that a modified form of pronuclear transfer is likely to give rise to normal pregnancies with a reduced risk of mitochondrial DNA disease, but may need further modification to eradicate the disease in all cases.

    • Louise A. Hyslop
    • , Paul Blakeley
    •  & Mary Herbert
  • Letter |

    Exploring the genetic basis of congenital cataracts in two families identifies a molecule, lanosterol, which prevents intracellular protein aggregation of various cataract-causing mutant crystallins, and which can reduce cataract severity and increase lens transparency in vivo in dogs.

    • Ling Zhao
    • , Xiang-Jun Chen
    •  & Kang Zhang
  • Article |

    Lenalidomide, a derivative of thalidomide, is an effective drug for myelodysplastic syndrome; lenalidomide binds the CRL4CRBN E3 ubiquitin ligase and promotes degradation of casein kinase 1a, on which the malignant cells rely for survival.

    • Jan Krönke
    • , Emma C. Fink
    •  & Benjamin L. Ebert
  • Brief Communications Arising |

    • Trevor J. Pugh
    • , Shantanu Banerji
    •  & Matthew Meyerson
  • Letter |

    A large ex vivo screen of approved and investigational anti-cancer drugs in primary cells derived from CML and ALL patients identifies axitinib, a VEGFR inhibitor approved for the treatment of kidney cancer, as a potent inhibitor of BCR–ABL1(T315I) with unique binding interactions that overcome the gatekeeper resistance mutation, highlighting the potential of repurposing existing drugs for additional cancer types.

    • Tea Pemovska
    • , Eric Johnson
    •  & Krister Wennerberg
  • Letter |

    A study of genome evolution in a metastatic breast cancer bearing an activating PIK3CA mutation, following treatment with the PI(3)Kα inhibitor BYL719, shows that all metastatic lesions, when compared to the pre-treatment tumour, had lost a copy of PTEN; parallel genetic evolution of separate sites with different PTEN genomic alterations had led to a convergent PTEN-null phenotype resistant to PI(3)Kα inhibition.

    • Dejan Juric
    • , Pau Castel
    •  & Maurizio Scaltriti
  • Letter |

    Nicotinamide N-methyltransferase (NNMT) expression is increased in white adipose tissue and liver of obese and diabetic mice, Nnmt knockdown protects against diet-induced obesity by altering the availability of adipose S-adenosylmethionine and NAD+, rendering Nnmt a novel target for treating obesity and type 2 diabetes.

    • Daniel Kraus
    • , Qin Yang
    •  & Barbara B. Kahn
  • Letter |

    The airway mucin Muc5b (but not Muc5ac) is required for mucociliary clearance, defence against bacterial infection in the airways and middle ear, and maintenance of immune homeostasis in the lungs; Muc5b deficiency causes accumulation of apoptotic macrophages, impairment of phagocytosis and reduced production of interleukin-23, leading to infection and inflammation.

    • Michelle G. Roy
    • , Alessandra Livraghi-Butrico
    •  & Christopher M. Evans
  • Letter |

    Training with a multitasking video game is shown to improve cognitive control abilities that decline with age, revealing the plasticity of the ageing brain; these behavioural improvements were accompanied by underlying neural changes that predicted the training-induced boost in sustained attention and enhanced multitasking performance 6 months later.

    • J. A. Anguera
    • , J. Boccanfuso
    •  & A. Gazzaley