Experimental models of disease

  • Article |

    Virus-induced senescence is a central pathogenic feature in COVID-19, and senolytics, which promote apoptosis of senescent cells, can reduce disease severity in hamsters,mice, as well as humans infected with SARS-CoV-2.

    • Soyoung Lee
    • , Yong Yu
    •  & Clemens A. Schmitt
  • Article |

    Fibre snacks that target distinct features of the microbiomes of donors with obesity transplanted into gnotobiotic mice also lead to fibre-specific changes in the microbiome and physiology when used in controlled-diet human studies.

    • Omar Delannoy-Bruno
    • , Chandani Desai
    •  & Jeffrey I. Gordon
  • Article |

    Transgenic K18-hACE2 mice are a useful model of COVID-19 including anosmia; infection of these mice resulted in severe pneumonia and, in some cases, infection in the brain, which was prevented by convalescent plasma.

    • Jian Zheng
    • , Lok-Yin Roy Wong
    •  & Stanley Perlman
  • 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 |

    A system involving in vitro induction of presomitic mesoderm recapitulates oscillatory expression of core segmentation clock genes and travelling-wave-like gene expression, suggesting that this system can be used to study the human segmentation clock and provide insights into diseases associated with human axial skeletogenesis.

    • Mitsuhiro Matsuda
    • , Yoshihiro Yamanaka
    •  & Cantas Alev
  • Letter |

    In an inducible mouse model of pancreatic ductal adenocarcinoma, the signalling defect that underlies 90% of these tumours causes increased cell-surface expression of syndecan 1, leading to misregulation of macropinocytosis, and linking the defective signalling with nutrient-salvage pathways.

    • Wantong Yao
    • , Johnathon L. Rose
    •  & Giulio F. Draetta
  • Letter |

    The fragmentation of sleep in Apoe−/− mice induces monocytosis and accelerated atherosclerosis due to a reduction in hypocretin that otherwise restricts bone marrow CSF1 availability.

    • Cameron S. McAlpine
    • , Máté G. Kiss
    •  & Filip K. Swirski
  • Article |

    High salt intake changed the gut microbiome and increased TH17 cell numbers in mice, and reduced intestinal survival of Lactobacillus species, increased the number of TH17 cells and increased blood pressure in humans.

    • Nicola Wilck
    • , Mariana G. Matus
    •  & Dominik N. Müller
  • Article |

    Increasing expression of the autism-associated gene Ube3a, either alone or in combination with seizures, not only impairs sociability in mice but also reduces expression of the synaptic organizer Cbln1 in the ventral tegmental area, thus weakening glutamatergic transmission.

    • Vaishnav Krishnan
    • , David C. Stoppel
    •  & Matthew P. Anderson
  • Perspective |

    This work highlights the critical challenges in experimental design and interpretation due to important combinatorial effects of host and microbial genes, and calls for the development of minimal reporting requirements to improve the interpretation and reproducibility of experimental biology.

    • Thaddeus S. Stappenbeck
    •  & Herbert W. Virgin
  • Letter |

    Neutrophil ageing, which encourages inflammation and vaso-occlusion in a mouse model of sickle-cell disease, is shown to depend on the intestinal microbiota and activation of the TLR/Myd88 signalling pathways.

    • Dachuan Zhang
    • , Grace Chen
    •  & Paul S. Frenette
  • 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 |

    Failure of integrin-mediated cell-matrix attachment is sufficient to initiate dermal fibrosis and autoimmunity in mouse models of scleroderma; integrin-modulating therapies prevent the recruitment and activation of plasmacytoid dendritic cells that appear central to immunological dysregulation and maintenance of the pro-fibrotic synthetic programme.

    • Elizabeth E. Gerber
    • , Elena M. Gallo
    •  & Harry C. Dietz
  • Letter |

    The public health burden of dengue is unknown; here cartographic approaches are used to provide insight into the global, regional and national burden of dengue, with the finding that the global number of infections per year is around 390 million, more than three times the estimate of the World Health Organization.

    • Samir Bhatt
    • , Peter W. Gething
    •  & Simon I. Hay