Preclinical research articles within Nature

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  • Article
    | Open Access

    During senescence, minority mitochondrial outer membrane permeabilization leads to the release of mtDNA into the cytosol through BAX and BAK macropores, in turn activating the cGAS–STING pathway, a major regulator of the senescence-associated secretory phenotype.

    • Stella Victorelli
    • , Hanna Salmonowicz
    •  & João F. Passos

  • Article
    | Open Access

    An orally bioavailable small-molecule active-site inhibitor of the phosphatases PTPN2 and PTPN1, ABBV-CLS-484, demonstrates immunotherapeutic efficacy in mouse models of cancer resistant to PD-1 blockade.

    • Christina K. Baumgartner
    • , Hakimeh Ebrahimi-Nik
    •  & Robert T. Manguso

  • Article |

    Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

    • William Hill
    • , Emilia L. Lim
    •  & Charles Swanton

  • Article
    | Open Access

    FXR regulates the levels of ACE2 in tissues of the respiratory and gastrointestinal systems that are affected by COVID-19, and inhibiting FXR with ursodeoxycholic acid downregulates ACE2 and reduces susceptibility to SARS-CoV-2 infection.

    • Teresa Brevini
    • , Mailis Maes
    •  & Fotios Sampaziotis

  • Article
    | Open Access

    Binding of the PD1-IL2v immunocytokine to PD-1 and IL-2Rβγ on the same cell leads to an alternative differentiation of stem-like CD8+ T cells into better effectors rather than exhausted T cells in models of both chronic infection and cancer.

    • Laura Codarri Deak
    • , Valeria Nicolini
    •  & Pablo Umaña

  • Article |

    Hydroxychloroquine did not confer protection against SARS-CoV-2 infection or reduce the viral load after infection in macaques; these findings do not support the use of hydroxychloroquine as an antiviral drug treatment of COVID-19 in humans.

    • Pauline Maisonnasse
    • , Jérémie Guedj
    •  & Roger Le Grand

  • Article |

    An artificial intelligence (AI) system performs as well as or better than radiologists at detecting breast cancer from mammograms, and using a combination of AI and human inputs could help to improve screening efficiency.

    • Scott Mayer McKinney
    • , Marcin Sieniek
    •  & Shravya Shetty

  • 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

  • Letter |

    The HIF-2 antagonist PT2399 is tested in mice bearing tumourgrafts derived from human renal cell cancers to demonstrate its efficacy, identify markers of sensitivity and characterize its effects.

    • Wenfang Chen
    • , Haley Hill
    •  & James Brugarolas

  • Letter |

    The authors report a new biomimetic nanodelivery platform in which polymeric nanoparticles enclosed in the plasma membrane of human platelets are used for disease-relevant targeting, and the therapeutic potential of the concept is demonstrated in animal models of coronary restenosis and systemic bacterial infection.

    • Che-Ming J. Hu
    • , Ronnie H. Fang
    •  & Liangfang Zhang

  • Article |

    Mutations that dysregulate Notch1 and Ras/PI3K signalling are common in T-cell acute lymphoblastic leukaemia; here, treatment with a PI3K inhibitor is shown to induce drug resistance that is associated with downregulation of activated Notch1 signalling, suggesting that inhibition of both Notch1 and PI3K could promote drug resistance.

    • Monique Dail
    • , Jason Wong
    •  & Kevin Shannon

  • Letter |

    Regeneration of the heart muscle after myocardial infarction with cardiomyocytes derived from human embryonic stem cells is demonstrated in non-human primates, with the grafts showing evidence of electromechanical coupling, although they were also associated with non-fatal arrhythmias.

    • James J. H. Chong
    • , Xiulan Yang
    •  & Charles E. Murry

  • Letter |

    PLX4032 is a selective inhibitor of the B-RAF protein that has shown promising results in an early clinical trial in melanoma patients with an activating mutation in B-RAF. Now the structure and function of this inhibitor are described. Translational data from a phase I trial show that clinical efficacy requires a substantial degree of inhibition of the ERK pathway downstream of B-RAF. The data also show that BRAF-mutant melanomas are highly dependent on B-RAF activity.

    • Gideon Bollag
    • , Peter Hirth
    •  & Keith Nolop

  • Article |

    African sleeping sickness, caused by Trypanosoma brucei species, is responsible for some 30,000 human deaths each year. Available treatments are limited by poor efficacy and safety profiles. However, a new molecular target for potential treatments has now been identified. The protein target is T. brucei N-myristoyltransferase. In further experiments, lead compounds have been discovered that inhibit this protein, kill trypanosomes in vitro and in vivo, and can cure trypanosomiasis in mice.

    • Julie A. Frearson
    • , Stephen Brand
    •  & Paul G. Wyatt

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