Translational research articles within Nature

Featured

  • 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

  • News & Views |

    Disorders caused by single genes, such as fragile X syndrome, share symptoms with the genetically complex autism spectrum disorders. It emerges that effective drugs for the former may lead to therapies for the latter.

    • Evdokia Anagnostou

  • News & Views |

    Drug candidates that are related to a common metabolite called adenosine inhibit inflammation and reduce bone destruction in artificial joints. The finding suggests a potential approach to increasing the durability of prosthetic implants.

    • Joel Linden

  • News & Views |

    The protein Sema3A both restrains bone degradation and stimulates bone building in mice, suggesting a potential therapy for conditions such as osteoporosis. See Article p.69

    • Mone Zaidi
    •  & Jameel Iqbal

  • Career Brief |

    Venture-capital funding in the United Kingdom represents a boost for translational research.

  • Article |

    Semaphorin 3A (Sema3A) is shown to function as a protector of bone, by synchronously inhibiting osteoclastic bone resorption and promoting osteoblastic bone formation.

    • Mikihito Hayashi
    • , Tomoki Nakashima
    •  & Hiroshi Takayanagi

  • Career Brief |

    Tenure-track posts will focus on translational cancer research.

  • News |

    Mission of newly formed NCATS is to dramatically speed up production of drugs and other therapies, but sceptics question agency’s ability to deliver.

    • Meredith Wadman

  • Outlook |

    The United States publishes more biomedical research papers than ever before, yet drug development is stagnating. Several new initiatives aim to turn this knowledge into new remedies.

    • Amy Maxmen

  • News & Views |

    Heart failure is characterized by weakened contractions of heart muscle. A drug that directly activates the key force-generating molecule in this muscle may be a valuable tool to strengthen the failing heart.

    • Donald M. Bers
    •  & Samantha P. Harris

  • News & Views |

    New clinical trials report the efficacy of two mechanism-based therapies for treating human pancreatic neuroendocrine tumours. Studies in mouse models have contributed to these success stories, and continue to do so.

    • David Tuveson
    •  & Douglas Hanahan

  • News |

    Translational-science centre remains on the fast track, despite concerns about upheaval.

    • Meredith Wadman

  • Editorial |

    An increasing number of biomedical researchers are testing their ideas on people. The early-phase clinical-trial results are a promising sign of greater cooperation between scientists and clinicians.

  • Career Brief |

    The UK Wellcome Trust launches new PhD studentships in several fields.

  • Opinion |

    Translational-research programmes supported by flexible, long-term, large-scale grants are needed to turn advances in basic science into successful vaccines to halt the AIDS epidemic, says Wayne C. Koff.

    • Wayne C. Koff

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