| | Ageing: Tools to eliminate senescent cells
Ageing and many diseases are partly driven by the accumulation of damaged cells that no longer divide. It emerges that these senescent cells can be eradicated in mice using a drug that interferes with the activity of the protein FOXO4. | Cancer: Tumours build their niche
It emerges that tumour cells can give rise to non-dividing cells that form part of the supporting microenvironment known as the niche. These niche cells secrete proteins that drive tumour growth and progression. | Selectivity determinants of GPCR–G-protein binding
The identification of the positions and patterns of amino acids that form the selectivity determinants for the entire human G-protein and G-protein-coupled receptor signalling system. | Endothelial TLR4 and the microbiome drive cerebral cavernous malformations
Lipopolysaccharide derived from gut bacteria can accelerate the formation of cerebral cavernous malformations by activating TLR4 on endothelial cells, and polymorphisms that increase expression of the genes encoding TLR4 or its co-receptor CD14 are associated with higher CCM lesion burden in humans. | Discovery of nitrate–CPK–NLP signalling in central nutrient–growth networks
In response to nitrate, Ca2+-sensor protein kinases (CPKs) act as master regulators to coordinate downstream signalling responses that are essential for shoot growth and root establishment in Arabidopsis. | Predictive compound accumulation rules yield a broad-spectrum antibiotic
The authors use computational modelling and a set of chemically synthesized compounds to define the physicochemical properties required for small-molecule accumulation in Gram-negative bacteria. | | Common genetic variation drives molecular heterogeneity in human iPSCs | Continental crust formation on early Earth controlled by intrusive magmatism
Modelling of two modes of continental crust formation suggests that before plate tectonics began operating, the Archean early Earth’s tectonic regime was governed by intrusive magmatism. | Intratumoural heterogeneity generated by Notch signalling promotes small-cell lung cancer
In a mouse model of small-cell lung cancer and in human tumours, activation of the Notch pathway can lead to a cell fate switch of neuroendocrine cells to less proliferative non-neuroendocrine cells, generating intratumoural heterogeneity. | A rhodopsin in the brain functions in circadian photoentrainment in Drosophila
The Drosophila rhodopsin Rh7 works with cryptochrome to mediate circadian light entrainment by pacemaker neurons. | A Wnt-producing niche drives proliferative potential and progression in lung adenocarcinoma
A subset of Kras and p53 mutant cancer cells acts as a Wnt-producing niche for another cancer cell subset, and porcupine inhibition disrupts Wnt secretion in this niche, thereby suppressing proliferative potential and leading to therapeutic benefit. | TRAF2 and OTUD7B govern a ubiquitin-dependent switch that regulates mTORC2 signalling
Ubiquitination of the GβL subunit, a component of both mTORC1 and mTORC2, acts as a regulatory switching mechanism to balance levels of mTORC1 and mTORC2; the failure of this mechanism in some cancers leads to elevated mTORC2 formation and tumorigenesis. | Whole-brain serial-section electron microscopy in larval zebrafish
A complete larval zebrafish brain is examined and its myelinated axons reconstructed using serial-section electron microscopy, revealing remarkable symmetry and providing a valuable resource. | | Corrigendum: The genome of Chenopodium quinoa | | Corrigendum: Earth’s first stable continents did not form by subduction | | | | 
npj Climate and Atmospheric Science: open for submissions
An open access, online-only journal providing researchers, policy makers and the public with the latest research on weather and climate, publishing high-quality papers that focus on topics including climate dynamics, climate variability, weather and climate prediction, climate change, weather extremes, atmospheric composition including aerosols, the hydrological cycle and atmosphere-ocean interactions. | | | | | | | | | | | Asia’s glaciers are a regionally important buffer against drought
Glaciers in the high mountains of Asia provide a uniquely drought-resilient source of water, supplying summer meltwater sufficient for the basic needs of 136 million people.
Hamish D. Pritchard | Visualization and targeting of LGR5+ human colon cancer stem cells
LGR5+ cells in human colorectal cancer tissue xenografted into mice act as cancer stem cells, and differentiated cancer cells can revert to cancer stem cells and express LGR5 after ablation of existing LGR5+ cells.
Mariko Shimokawa, Yuki Ohta, Shingo Nishikori et al. | Whole-genome landscapes of major melanoma subtypes
The first large, high-coverage whole-genome sequencing study of melanomas from cutaneous, acral and mucosal sites.
Nicholas K. Hayward, James S. Wilmott, Nicola Waddell et al. | Maintenance of persistent activity in a frontal thalamocortical loop
Thalamic neurons show selective persistent activity that predicts movement direction, and their photoinhibition decreases activity in the anterior lateral motor cortex, and vice versa, suggesting that persistent activity requires reciprocal excitation in a thalamocortical loop.
Zengcai V. Guo, Hidehiko K. Inagaki, Kayvon Daie et al. | Protein–phospholipid interplay revealed with crystals of a calcium pump
Solvent contrast modulation reveals how the lipid bilayer actively participates in the conformational switches of Ca2+-ATPase through the actions of tryptophan, arginine and lysine residues, which function as membrane floats and anchors.
Yoshiyuki Norimatsu, Kazuya Hasegawa, Nobutaka Shimizu et al. | | Multi-phase volcanic resurfacing at Loki Patera on Io
Interferometric telescope observations of the Jovian moon Io reveal that the floor of the Loki Patera volcano has been resurfaced in two waves, with different starting times and velocities.
K. de Kleer, M. Skrutskie, J. Leisenring et al. | Preparation and coherent manipulation of pure quantum states of a single molecular ion
By exploiting a co-trapped Ca+ ion, a single CaH+ ion is prepared in pure quantum states, which are coherently manipulated, using a protocol that could easily be extended to other molecular ion species.
Chin-wen Chou, Christoph Kurz, David B. Hume et al. | The effect of illumination on the formation of metal halide perovskite films
Films of metal halide perovskite are used as the absorber material in solar cells, and light irradiation during their formation is shown to affect their crystallization, morphology and photovoltaic performance.
Amita Ummadisingu, Ludmilla Steier, Ji-Youn Seo et al. | Decarboxylative alkenylation
Starting with alkyl carboxylic acids, a simple olefin synthesis using any substitution pattern or geometry, based on amide-bond synthesis with nickel- or iron-based catalysis, is described.
Jacob T. Edwards, Rohan R. Merchant, Kyle S. McClymont et al. | Thalamic amplification of cortical connectivity sustains attentional control
The mediodorsal nucleus of the thalamus amplifies the functional connectivity of the prefrontal cortex, thereby sustaining cortical representations of rule sets without relaying categorical information.
L. Ian Schmitt, Ralf D. Wimmer, Miho Nakajima et al. | FGF-dependent metabolic control of vascular development
Fibroblast growth factor receptor (FGFR) signalling is a crucial regulator of endothelial metabolism and vascular development.
Pengchun Yu, Kerstin Wilhelm, Alexandre Dubrac et al. | Human pluripotent stem cells recurrently acquire and expand dominant negative P53 mutations
The authors surveyed whole-exome and RNA-sequencing data from 252 unique pluripotent stem cell lines, some of which are in the pipeline for clinical use, and found that approximately 5% of cell lines had acquired mutations in the TP53 gene that allow mutant cells to rapidly outcompete non-mutant cells, but do not prevent differentiation.
Florian T. Merkle, Sulagna Ghosh, Nolan Kamitaki et al. | Surrogate Wnt agonists that phenocopy canonical Wnt and β-catenin signalling
The authors describe water-soluble surrogate Wnt agonists, with specificity towards some frizzled (FZD) receptors, which can maintain human intestinal organoid cultures and have effects on the mouse liver in vivo.
Claudia Y. Janda, Luke T. Dang, Changjiang You et al. | Non-equivalence of Wnt and R-spondin ligands during Lgr5+ intestinal stem-cell self-renewal
R-spondin and Wnt ligand families act non-redundantly and cooperatively within the same molecular pathway in the intestinal stem-cell niche to maintain stem-cell competency and drive stem-cell expansion.
Kelley S. Yan, Claudia Y. Janda, Junlei Chang et al. | Dominant protection from HLA-linked autoimmunity by antigen-specific regulatory T cells
The molecular mechanism of Goodpasture disease is modelled to mechanistically determine how a human leukocyte antigen (HLA) allele can exert its dominant protective effect in autoimmune disease.
Joshua D. Ooi, Jan Petersen, Yu H. Tan et al. | Core Mediator structure at 3.4 Å extends model of transcription initiation complex
The 3.4 Å crystal structure of the 15-subunit core Mediator complex in yeast.
Kayo Nozawa, Thomas R. Schneider, Patrick Cramer | | | | |
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