| | Cancer: Precision T-cell therapy targets tumours
The T cells of the immune system can destroy tumours, but their activation can be inefficient. Vaccines that exploit tumour mutations elicit robust T-cell responses to tumours, with potential clinical benefits. | Neurodegeneration: Taming tangled tau
The protein tau forms abnormal filamentous aggregates called tangles in the brains of people with neurodegeneration. Structures of two such filaments offer pathways to a deeper understanding of Alzheimer's disease. | Cancer: Keeping it real to kill glioblastoma
The results of in vitro and in vivo screens to identify genes that are essential for the survival of a type of brain cancer show almost no overlap, underlining the need for caution when interpreting in vitro studies. | Cryo-EM structures of tau filaments from Alzheimer’s disease
High-resolution structures of tau filaments shed light on the ultrastructure of neurofibrillary lesions in Alzheimer’s disease. | An immunogenic personal neoantigen vaccine for patients with melanoma
The results of a phase I trial assessing a personal neoantigen multi-peptide vaccine in patients with melanoma, showing feasibility, safety, and immunogenicity. | Transcription elongation factors represent in vivo cancer dependencies in glioblastoma
Web An in vivo RNA interference screening strategy in glioblastoma enabled the identification of a host of epigenetic targets required for glioblastoma cell survival that were not identified by parallel standard screening in cell culture, including the transcription pause–release factor JMJD6, and could be a powerful tool to uncover new therapeutic targets in cancer. | Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer
The authors report the first-in-human application of personalized neo-antigen RNA vaccines in patients with melanoma. | Dependency of a therapy-resistant state of cancer cells on a lipid peroxidase pathway
Therapy-resistant cancer cell states identified across diverse contexts are selectively vulnerable to ferroptotic cell death induced by inhibition of lipid peroxidase pathways converging on GPX4. | Pre-oral gut contributes to facial structures in non-teleost fishes
In contrast to the prevailing belief that the gut begins with the mouth and continues backwards from there, this work shows that substantial areas of the faces of ray-finned fishes originate from the pre-oral gut or endoderm. | Nutrient sensing modulates malaria parasite virulence
Malaria parasites use a sensing mechanism to moderate their growth in response to the nutrient content of their host. | Crystal structures of agonist-bound human cannabinoid receptor CB1
Crystal structures of the human cannabinoid receptor 1 (CB1) bound to the agonists AM11542 and AM841 reveal notable structural rearrangements upon receptor activation, and this flexibility may be a common feature among other G-protein-coupled receptors. | | Erratum: Structure of the Cpf1 endonuclease R-loop complex after target DNA cleavage | | | Brief Communications Arising | | | | | | 
npj Materials Degradation is a new open access journal that is now open for submissions. The journal publishes the finest content describing basic and applied research discoveries in the area of corrosion (degradation) and protection of materials.
| | | | | | | | | | | West Antarctic Ice Sheet retreat driven by Holocene warm water incursions
During the early Holocene epoch—and since the 1940s—variations in Southern Hemisphere westerly winds controlled the upwelling of Circumpolar Deep Water and seemingly ice-sheet retreat in West Antarctica.
Claus-Dieter Hillenbrand, James A. Smith, David A. Hodell et al. | Climate change drives expansion of Antarctic ice-free habitat
Permanently ice-free areas, home to almost all of Antarctica’s biodiversity, are projected, in the worst case, to expand by over 17,000 km2 as a result of climate change by the end of this century, with potentially deleterious consequences for the continent’s biodiversity.
Jasmine R. Lee, Ben Raymond, Thomas J. Bracegirdle et al. | Recurrent and functional regulatory mutations in breast cancer
High-depth sequencing of targeted regions in primary breast cancer identifies mutated promoter elements with recurrent mutations at specific and/or nearby bases, suggesting selection of certain non-coding events.
Esther Rheinbay, Prasanna Parasuraman, Jonna Grimsby et al. | Cell-cycle dynamics of chromosomal organization at single-cell resolution
Single-cell Hi-C analysis in thousands of mouse embryonic stem cells shows that chromosomal compartments, topological-associated domains and long-range loops all have distinct cell-cycle dynamics.
Takashi Nagano, Yaniv Lubling, Csilla Várnai et al. | Single-molecule analysis of ligand efficacy in β2AR–G-protein activation
Single-molecule FRET imaging provides insights into the allosteric link between the ligand-binding and G-protein nucleotide-binding pockets of the β2 adrenergic receptor (β2AR) and improved understanding of the G-protein activation mechanism.
G. Glenn Gregorio, Matthieu Masureel, Daniel Hilger et al. | | Selective sp3 C–H alkylation via polarity-match-based cross-coupling
Using a triple catalytic approach, a selective sp3 C–H alkylation is demonstrated that is applicable in late-stage functionalization of pharmaceutical compounds.
Chip Le, Yufan Liang, Ryan W. Evans et al. | Electron cryo-microscopy structure of the mechanotransduction channel NOMPC
Single-particle electron cryo-microscopy analysis of the mechanotransduction channel NOMPC reveals that it contains a bundle of four helical spring-shaped ankyrin repeat domains that undergo motion, potentially allowing mechanical movement of the cytoskeleton to be coupled to the opening of the channel.
Peng Jin, David Bulkley, Yanmeng Guo et al. | Three-dimensional integration of nanotechnologies for computing and data storage on a single chip
Multiple nanotechnologies are integrated on a single chip to realize a three-dimensional integrated circuit architecture that combines computing and data storage—a potentially transformative advance in computing.
Max M. Shulaker, Gage Hills, Rebecca S. Park et al. | Episodic kinematics in continental rifts modulated by changes in mantle melt fraction
GPS measurements are used to investigate the continental rift system of North Island, New Zealand, and to develop a model for short-term deformation involving flexing of an elastic upper crust caused by episodic changes in mantle viscosity and melt fraction.
Simon Lamb, James D. P. Moore, Euan Smith et al. | Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin
Chemotherapy drugs can cause pyroptotic cell death by activating caspase-3 to cleave gasdermin E, potentially contributing to their toxicity and adverse effects.
Yupeng Wang, Wenqing Gao, Xuyan Shi et al. | Tracing the origins of relapse in acute myeloid leukaemia to stem cells
Identification of the cell types from which relapse arises in acute myeloid leukaemia, by following leukaemia propagation from patient-derived leukaemia samples.
Liran I. Shlush, Amanda Mitchell, Lawrence Heisler et al. | mTORC1-dependent AMD1 regulation sustains polyamine metabolism in prostate cancer
mTOR complex 1 signalling regulates polyamine metabolism and thereby promotes tumorigenesis, through regulation of the stability of a key enzyme, AMD1.
Amaia Zabala-Letona, Amaia Arruabarrena-Aristorena, Natalia Martín-Martín et al. | Quantifiable predictive features define epitope-specific T cell receptor repertoires
The authors characterize epitope-specific T cell repertoires, identify shared and recognizable features of TCRs, and develop tools to classify antigen specificity on the basis of sequence analysis.
Pradyot Dash, Andrew J. Fiore-Gartland, Tomer Hertz et al. | Identifying specificity groups in the T cell receptor repertoire
The authors devise an algorithm that can cluster T cell receptor (TCR) sequences sharing the same specificity, predict the HLA restriction of these TCR clusters on the basis of subjects’ genotypes and help to identify specific peptide major histocompatibility complex ligands.
Jacob Glanville, Huang Huang, Allison Nau et al. | RNase III nucleases from diverse kingdoms serve as antiviral effectors
RNase III from all three domains of life elicits RNA-targeting antiviral activity that is independent of, and possibly predates, other known eukaryotic antiviral systems.
Lauren C. Aguado, Sonja Schmid, Jared May et al. | | | | |
