Medical research

  • Article
    | Open Access

    Predictive models that relate brain activity to phenotype reliably fail when applied to subgroups of participants who do not fit stereotypical profiles, showing that the utility of a one-size-fits-all modelling approach is limited.

    • Abigail S. Greene
    • , Xilin Shen
    •  & R. Todd Constable
  • Article
    | Open Access

    Sequencing of individual human lymphocyte clones shows that they are highly prone to mutations, with higher burdens in memory cells than in naive cells arising from mutational processes associated with differentiation and tissue residency.

    • Heather E. Machado
    • , Emily Mitchell
    •  & Peter J. Campbell
  • Article |

    OrganEx—an extracorporeal pulsatile-perfusion system with cytoprotective perfusate for porcine whole-body settings—preserved tissue integrity, decreased cell death and restored selected molecular and cellular processes across multiple vital organs after 1 h of warm ischaemia in pigs.

    • David Andrijevic
    • , Zvonimir Vrselja
    •  & Nenad Sestan
  • Article
    | Open Access

    Mild cold exposure activates a substantial amount of brown adipose tissue (BAT) in a patient with cancer, reducing tumour-associated glucose uptake, and activation of BAT in mice inhibits the growth of tumours by decreasing blood glucose and impeding glycolysis-based metabolism in cancer cells.

    • Takahiro Seki
    • , Yunlong Yang
    •  & Yihai Cao
  • Article
    | Open Access

    To measure selection on variants, whole-genome sequencing of approximately 150,000 individuals from the UK Biobank is used to rank sequence variants by their level of depletion.

    • Bjarni V. Halldorsson
    • , Hannes P. Eggertsson
    •  & Kari Stefansson
  • Article |

    Treatment with neoadjuvant BRAF/MEK-targeted therapy results in higher rates of major pathological response in female compared with male patients with melanoma, and pharmacological inhibition of androgen receptor signalling improved the responses of male and female mice to BRAF/MEK-targeted therapy.

    • Christopher P. Vellano
    • , Michael G. White
    •  & Jennifer A. Wargo
  • Article |

    Organoids originating from human multipotent ocular surface epithelial stem cells are similar to native lacrimal glands and undergo functional maturation when transplanted adjacent to the eyes of recipient rats, developing lumina and producing tear-film proteins.

    • Ryuhei Hayashi
    • , Toru Okubo
    •  & Kohji Nishida
  • Article
    | Open Access

    Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

    • Athanasios Kousathanas
    • , Erola Pairo-Castineira
    •  & J. Kenneth Baillie
  • Article
    | Open Access

    A phase I dose-escalation trial of GD2-CAR T cells in children and young adults with diffuse midline gliomas to assess the feasibility of manufacturing, safety and tolerability, and to preliminarily assess efficacy.

    • Robbie G. Majzner
    • , Sneha Ramakrishna
    •  & Michelle Monje
  • Perspective |

    The Dog Aging Project is an open-data, community science study to identify genetic, environmental and lifestyle factors associated with canine healthy lifespan, generating knowledge that could readily translate to human ageing.

    • Kate E. Creevy
    • , Joshua M. Akey
    •  & Benjamin S. Wilfond
  • Article
    | Open Access

    A single dose of a small-molecule HIV capsid inhibitor provides long-term protection from repeated simian–human immunodeficiency virus challenges in macaques and might serve as a novel strategy for HIV prevention in humans.

    • Samuel J. Vidal
    • , Elena Bekerman
    •  & Dan H. Barouch
  • 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
    | Open Access

    Whole-exome sequencing analysis of 454,787 individuals in the UK Biobank is used to examine the association of protein-coding variants with nearly 4,000 health-related traits, identifying 564 distinct genes with significant trait associations.

    • Joshua D. Backman
    • , Alexander H. Li
    •  & Manuel A. R. Ferreira
  • Article
    | Open Access

    A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

    • Harald S. Vöhringer
    • , Theo Sanderson
    •  & Moritz Gerstung
  • Article |

    Whole-genome sequencing analysis of somatic mutations in liver samples from patients with chronic liver disease identifies driver mutations in metabolism-related genes such as FOXO1, and shows that these variants frequently exhibit convergent evolution.

    • Stanley W. K. Ng
    • , Foad J. Rouhani
    •  & Peter J. Campbell
  • Article |

    The viral lineage responsible for the February 2021 outbreak of Ebola virus disease in Guinea is nested within a clade that predominantly consists of genomes sampled during the 2013–2016 epidemic, suggesting that the virus might have re-emerged after a long period of latency within a previously infected individual.

    • Alpha Kabinet Keita
    • , Fara R. Koundouno
    •  & N’. Faly Magassouba
  • 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 |

    A robust, cost-effective technique based on whole-exome sequencing data can be used to characterize immune infiltrates, relate the extent of these infiltrates to somatic changes in tumours, and enables prediction of tumour responses to immune checkpoint inhibition therapy.

    • Robert Bentham
    • , Kevin Litchfield
    •  & Nicholas McGranahan
  • 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 |

    Two malaria vaccines comprising Plasmodium falciparum sporozoites and treatment with either pyrimethamine or chloroquine induced durable protective responses against both the African vaccine strain and a heterologous South American strain of P. falciparum.

    • Agnes Mwakingwe-Omari
    • , Sara A. Healy
    •  & Patrick E. Duffy
  • 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 |

    Statistical analysis of COVID-19 transmission among users of a smartphone-based digital contact-tracing app suggests that such apps can be an effective measure for reducing disease spread.

    • Chris Wymant
    • , Luca Ferretti
    •  & Christophe Fraser
  • 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
  • Perspective
    | Open Access

    This Perspective discusses how the Somatic Cell Genome Editing Consortium aims to accelerate the implementation of safe and effective genome-editing therapies in the clinic.

    • Krishanu Saha
    • , Erik J. Sontheimer
    •  & Jiangbing Zhou
  • Article |

    Phylogenies of human placental cells based on whole-genome sequencing of bulk samples and microdissections reveal extensive mutagenesis in placental tissue, and suggest that mosaicism is a typical part of normal placental development.

    • Tim H. H. Coorens
    • , Thomas R. W. Oliver
    •  & Sam Behjati
  • Article |

    The 501Y.V2 variant of SARS-CoV-2 in South Africa became dominant over other variants within weeks of its emergence, suggesting that this variant is linked to increased transmissibility or immune escape.

    • Houriiyah Tegally
    • , Eduan Wilkinson
    •  & Tulio de Oliveira
  • Article |

    In a rat model of short bowel syndrome, transplantation of small intestinal organoids into the colon partially restores intestinal function and improves survival—a proof of principle that organoid transplantation might have therapeutic benefit.

    • Shinya Sugimoto
    • , Eiji Kobayashi
    •  & Toshiro Sato
  • Article
    | Open Access

    The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.

    • Daniel Taliun
    • , Daniel N. Harris
    •  & Gonçalo R. Abecasis
  • Article |

    Single-stranded, DNA-damage-associated small RNAs generated by a BRCA1–RNA-interference complex promote PALB2–RAD52-mediated DNA repair at transcriptional termination pause sites that contain R-loops and are rich in single-stranded DNA breaks in both quiescent and proliferating cells.

    • Elodie Hatchi
    • , Liana Goehring
    •  & David M. Livingston