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Analyses of samples from patients with acute myeloid leukaemia reveal that drug response is associated with mutational status and gene expression; the generated dataset provides a basis for future clinical and functional studies of this disease.

DNA methylation and H3K9 dimethylation are two linked epigenetic marks of silenced chromatin in plants that depend on the activity of CMT3/2 and SUVH4/5/6. Here the authors identify AGDP1 as an H3K9me2-binding protein required for heterochromatic non-CG DNA methylation, H3K9 dimethylation, and transcriptional silencing.

Mapping of the clonal structure of bone marrow cells in patients with acute myeloid leukemia treated with the IDH2 inhibitor enasidenib reveals heterogeneity in the cellular differentiation response and in mechanisms of relapse.

High-grade serous ovarian carcinoma is often associated with TP53 mutation and chromosomal instability (CIN). Here, the authors generate ex vivo cultures from biopsies and ascites of patients and perform characterization to evaluate CIN mechanisms and compare drug sensitivity with patient responses.

Growth hormone (GH) is a major modulator of physical growth and metabolism that is under tight regulatory control. Here the authors describe the signaling profile of GPR101, an orphan receptor that enhances GH secretion principally via constitutively activated Gs-PKA and Gq/11-PKC pathways.

Designing high radiation efficiency antennas for portable transmitters in low frequency communication systems remains a challenge. Here, the authors report on using piezoelectricity to more efficiently radiate while achieving a bandwidth eighty three times higher than the passive Bode-Fano limit.

Despite the identification of genetic risk loci for late-onset Alzheimer’s disease (LOAD), the genetic architecture and prediction remains unclear. Here, the authors use genetic risk scores for prediction of LOAD across three datasets and show evidence suggesting oligogenic variant architecture for this disease.

There is evidence that disordered proteins play a role in the mineralization process. Here, the authors report on the development of elastin-like recombinant protein membranes using disordered-ordered interplay to investigate and guide mineralization.

High-entropy metallic glasses are an unexplored class of nanomaterials and are difficult to prepare. Here, the authors present an electrosynthetic method to design these materials with up to eight tunable metallic components and show multifunctional electrocatalytic water splitting capabilities.

Rebecca Fitzgerald and colleagues report whole-genome sequence analyses of 23 paired samples of Barrett's esophagus and esophageal adenocarcinoma. Their analyses of the clonal architecture of these lesions shows that copy number increases and heterogeneity persists during development of esophageal adenocarcinoma.

Loss of Nestin sensitizes non-small cell lung carcinoma (NSCLC) to oxidative stress. Here, the authors report a feedback loop between Nestin and Nrf2 wherein Nestin competes with Nrf2 for Keap1 binding, preventing Nrf2 degradation, and show the Nestin–Keap1–Nrf2 axis to regulate redox homeostasis in NSCLC.

The CRISPR–Cas9-mediated generation of germline-transmissible mutations of SHANK3 in cynomolgus macaques (Macaca fascicularis) forms the basis of a non-human-primate model of autism spectrum disorder and Phelan–McDermid syndrome.

Circulating tumour DNA profiling in early-stage non-small-cell lung cancer can be used to track single-nucleotide variants in plasma to predict lung cancer relapse and identify tumour subclones involved in the metastatic process.

An artificial-intelligence program called AlphaGo Zero has mastered the game of Go without any human data or guidance. A computer scientist and two members of the American Go Association discuss the implications. See Article p.354

Land-based mitigation for meeting the Paris climate target must consider the carbon cycle impacts of land-use change. Here the authors show that when bioenergy crops replace high carbon content ecosystems, forest-based mitigation could be more effective for CO₂ removal than bioenergy crops with carbon capture and storage.

Universities are ramping up their war on waste, but shifting deep-rooted mindsets remains a challenge.

Recent evidence has blurred the line between comets and asteroids, although until now neither ice nor organic material had been detected on the surface of an asteroid. Here, the spectroscopic detection of water ice and organic material on the asteroid 24 Themis is reported. Water ice thus seems to be more common on asteroids than previously thought, and may be widespread in asteroidal interiors at smaller heliocentric distances than expected.

Cellulose nanocrystals (CNCs) spontaneously organize into a helical arrangement but flexible CNC elastomer composite materials with this structure were so far not realized. Here the authors demonstrate the fabrication of a CNC based elastomer composite and its application as a photonic strain sensor.

Maintaining the intestinal barrier function requires a balance of multiple signalling pathways. Here the authors show that A20, an anti-inflammatory and anti-apoptotic protein, and Atg1611, an autophagy regulator, cross-regulate their respective protein levels and function to serve compensatory and redundant roles in fine-tuning gut barrier homeostasis.

Long a staple of science fiction, laser weapons are edging closer to the battlefield — thanks to optical fibres.

Nine experts give their opinion on the 'known unknowns' in malaria research.

Tissues-specific gene expression requires coordinated cis-regulatory elements. Here the authors use dCas9-based enhancer targeting to remodel local epigenetic landscapes and activate or inactive transcription.

Van Loo and colleagues report that loss of the Zeb2 regulator of epithelial-to-mesenchymal transition from the intestinal epithelium leads to inflammation, increased intestinal permeability and colorectal cancer development, which is enhanced by the resident intestinal microbiome.

Diffuse Gastric Cancer (DGC) is increasingly being considered separate to intestinal type gastric cancer; several fusions events have been reported as drivers of the disease but few of those have been subsequently validated. Here the authors perform RNA-seq on early-onset DGC patients who had not been treated with chemotherapy or radiation and identify a previously unknown fusion.

When knowledge is uncertain, experts should avoid pressures to simplify their advice. Render decision-makers accountable for decisions, says Andy Stirling.

Deforestation by the ancient Maya led to a destabilization of organic carbon preserved in the underlying soils and reduced the magnitude of the soil carbon sink in this region.

A polished and reinforced thinned-skull procedure is used to create a large, chronically stable window in the skull that allows repeated imaging of cortical structures as well as optically guided physiological manipulation. It is proposed as an alternative to the craniotomy and current thinned-skull methods.

Lipid droplets (LDs) and peroxisomes are both generated by budding off the endoplasmic reticulum (ER). Here, the authors show that the yeast protein Pex30 marks ER subdomains where both LD and peroxisome biogenesis occurs, and identify MCTP2 as the putative mammalian Pex30 ortholog.

The vanadium redox flow battery is promising for commercial applications, but is hampered by high-cost electrolytes that are typically prepared via electrolysis. Here the authors demonstrate cost-effective chemical production of a high-quality vanadium electrolyte using platinum nanoparticles as a catalyst.

The Greenland Ice Sheet is the largest land ice contributor to sea level rise and understanding the long-term glacier response to external forcing is key to improved projections. Here the authors show Greenland’s three largest outlet glaciers will likely exceed current worst-case scenario

Random mutagenesis can uncover novel genes involved in phenotypic traits. Here the authors perform a large-scale phenotypic screen on over 100 mouse strains generated by ENU mutagenesis to identify mice with age-related diseases, which they attribute to specific mutations revealed by whole-genome sequencing.

Chandarlapaty and colleagues use longitudinal ctDNA samples to identify genomic alterations in PTEN and ESR1 associated with resistance in a phase I/II trial of a PI3K inhibitor and aromatase inhibition for hormone receptor–positive metastatic breast cancer.

The spatial location of proteins within a cell is a key element of protein function. Here the authors describe hyperLOPIT—a proteomics workflow that allows the simultaneous assignment of thousands of proteins to subcellular niches with high resolution—and apply it to mouse pluripotent stem cells.

1000 Genomes imputation can increase the power of genome-wide association studies to detect genetic variants associated with human traits and diseases. Here, the authors develop a method to integrate and analyse low-coverage sequence data and SNP array data, and show that it improves imputation performance.

Lanthanide-doped nanocrystals can be used to upconvert infrared radiation into visible light, and are thought to be promising for a range of photonic and biological imaging applications. It is now shown that the upconversion efficiency can be improved by appropriately clustering the lanthanide ions on different structural sublattices.

Coronal mass ejections from the Sun play an important role in space weather, yet a full understanding of their behaviour remains elusive. Towards this aim, Möstl et al. present a suite of observations showing that an ejection was channelled away from its source region, explaining incorrect forecasts.

The PI3K/Akt/mTOR pathway has been previously implicated in fibrosis and a pan-PI3K/mTOR inhibitor is currently under clinical evaluation for the treatment of IPF. Here the authors show that the mTORC1/4E-BP1 axis is critical for TGF-β1-induced fibrogenesis in in vitro and ex vivo models and that canonical PI3K/Akt signalling is dispensable.

The carbon balance in Southeast Asia is highly uncertain. Here, the authors show that land use changes and occurrence of strong El Niño control decadal shifts in the carbon balance of this region.

This study presents a new use of a widely used metric known as the global warming potential (GWP) to compare the impact of cumulative climate pollutants such as CO₂ versus short-lived climate pollutants, such as methane and black carbon.

Gao, Nowak-Imialek, Chen et al. generate porcine and human stem cells that possess expanded developmental potency for both embryonic and extra-embryonic cell lineages.

The high spatial resolution of secondary ion mass spectrometry and the high resolving power of the Orbitrap mass spectrometer are combined in a single imaging platform, the 3D OrbiSIMS. The instrument's capabilities for resolving lipids and neurotransmitters in the brain with subcellular spatial resolution, and a drug in a single cell in three dimensions is demonstrated.

Epigenetic changes associated with post-natal differentiation have been characterized. Here the authors generate epigenomic and transcriptional profiles from primary human breast cells, providing insights into the transcriptional and epigenetic events that define post-natal cell differentiation in vivo.