Volume 515

  • No. 7528 27 November 2014

    A tumour cell (left) interacts with three T cells and a tumour-infiltrating immune cell. This issue of Nature features five papers reflecting the current intense interest in the targeting of immune checkpoints as cancer therapy, and detailed work on identifying patients likely to respond this therapeutic strategy. Specifically, blockade of the transmembrane protein PD-L1 or its cell-surface receptor PD-1, upregulated in many different cancers, has shown promise in preclinical experiments and now in clinical trials. Powles et al. report on a clinical phase 1 study in metastatic urothelial bladder cancer treated with the anti-PD-L1 antibody MPDL3280A (page 558), and Tumeh et al. (page 568) and Herbst et al. (page 563) examine how PD-L1/PD-1 blockade enhances therapeutic responses in metastatic melanoma and lung cancer, respectively. Yadav et al. (page 572) and Gubin et al. (page 577) demonstrate the role of mutant tumour antigens in forming ligands for T-cell responses activated by PD-L1/PD-1 inhibition. Cover: Allison Bruce

    Nature Outlook


  • No. 7527 20 November 2014

    The mouse is the premier model organism in biomedical research. To gain greater insights into the shared and species-specific transcriptional and cellular regulatory programs, the Mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications and replication domains throughout the mouse genome in diverse cell and tissue types. These finding are compared with the corresponding human data to confirm substantial conservation in the newly annotated potential functional sequences, and to reveal pronounced divergence of other sequences involved in transcriptional regulation, chromatin state and higher order chromatin organization. The data and their analyses provide a valuable resource for research into mammalian biology and mechanisms of human diseases. This issue of Nature includes four further Mouse ENCODE papers and in News & Views, Piero Carninci considers how the mouse ENCODE datasets will contribute to our understanding of human biology and biomedicine. Cover: Kelly Krause/ Nature

    Nature Outlook


  • No. 7526 13 November 2014

    Clinical depression is the most common major mental health disorder and by some measures, it is responsible for a greater burden of disability than any other cause. In this special issue, Nature asks why the burden is so great, how science is helping, where today’s research is headed and what the future may hold.

  • No. 7525 6 November 2014

    A simulation of a high-efficiency plasma wakefield accelerator. An electron beam with a two-bunch structure is travelling through plasma from top-left to bottom-right. Particle colliders that operate at the high-energy frontier using electric fields generated by radio waves are approaching the limits of feasibility in terms of size and cost, but there are other acceleration techniques that could make such less expensive and more compact devices. The plasma wakefield accelerator, in which an electron bunch is accelerated by making it ‘surf� on a plasma wave excited by another electron bunch, promises an energy gain in the gigaelectron-volt regime over just a few centimetres � an energy gain that requires hundreds of metres using traditional accelerators. Previously, this technique had only been used to accelerate a very small number of electrons at a time. Now, researchers working at FACET, the Facility for Advanced Accelerator Experimental Tests at SLAC National Accelerator Laboratory, USA, have achieved acceleration of about half a billion electrons at once with an unprecedented efficiency for a plasma accelerator. This achievement could be a milestone in the development of affordable and compact accelerators for applications ranging from high energy physics to medical and industrial applications. Cover: Weiming An & Frank Tsung, University of California Los Angeles, using QuickPIC simulation and VisIT visualization software