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MYCN amplification is common in neuroblastomas. Here the authors analyse the MYCN amplicon structure and its epigenetic regulation by integrating short- and longread genomic and epigenomic data and find two classes of MYCN amplicons in neuroblastomas, one driven by local enhancers and the other by hijacking of distal regulatory elements.

The bicyclic azetidines, a class of potent, well-tolerated antimalarial compounds that is active against multiple stages of the Plasmodium life-cycle, has been discovered following screens against libraries of compounds reminiscent of natural products.

The authors pooled resources to identify best practices and develop a new standardized protocol for estimating functional connectivity in rats with magnetic resonance imaging.

During somatic cell reprogramming, the cell transits through intermediate states. Here, the authors perform an in-depth quantitative proteomic analysis of the reprogramming of mouse embryonic fibroblasts to induced pluripotent stem cells and observe two waves of proteome reorganisation.

Meta-analysis of genome-wide association studies for cognitive ability identifies 190 new loci and implicates 939 new genes related to neurogenesis, neuron differentiation and synaptic structure.

Contrary to the view that urbanization is a major driver of the global rise in obesity, the global increase in body-mass index is shown to be mostly due to increases in the body-mass indexes of rural populations.

Transmission spectroscopy observations from the James Webb Space Telescope show the detection of carbon dioxide in the atmosphere of the gas giant exoplanet WASP-39b.

The homeobox NKX2 family of transcriptional factors has been shown to regulate fundamental developmental processes. Here, the authors show that NKX2-3 is a bona fideoncogenic driver in marginal-zone B-cell lymphoma and that it promotes lymphomagenesis by shaping lymphocyte dynamics and promoting BCR signalling.

Debate continues over how best to classify cortical interneurons. Standardizing the nomenclature used to describe these cells might aid classification efforts. Here, a committee of interneuron researchers propose a standardized set of terms to describe the morphological, molecular and physiological features of an interneuron.

Paul Thompson and colleagues report a genome-wide association study for hippocampal, intracranial and total brain volume. They identify a locus at 12q24 associated with hippocampal volume and a locus at 12q14 associated with intracranial volume.

Receptor activator of nuclear factor-κB (RANK)/RANK-ligand (RANKL) signaling regulates the tumor-immune crosstalk. Here the authors show that systemic RANKL inhibition promotes CD8 + T cell infiltration in patients with early breast cancer and that loss of RANK signaling in tumor cells drives a T cell-dependent anti-tumor response in preclinical models.

Quantum electrodynamics predicts a rare process in which light is scattered by light. The ATLAS Collaboration reports signs of this elusive effect in the collisions of ultra-relativistic lead ions.

The recovery of human genomic data from environmental DNA samples raises ethical questions regarding consent, privacy, surveillance and data ownership, which will need to be grappled with as the environmental DNA field moves forward.

A tunable photonic microwave filter is monolithically integrated in an InP chip. The filter includes all of the required elements — a laser, a modulator and a photodetector — and its response can be tuned by controlling the electric currents.

Although termites are major human pests, they have an important role in maintaining ecosystem function and biodiversity. Here, the authors sequence the genome and transcriptomes of a dampwood termite and highlight genes that may be involved in the mechanisms underlying insect social behaviour.

A meta-analysis of genome-wide association studies for neuroticism identifies novel loci, pathways and potential drug targets. Further analysis implicates specific brain regions and evaluates genetic overlap with other neuropsychiatric traits.

Using the GTEx data and others, a comprehensive analysis of adenosine-to-inosine RNA editing in mammals is presented; targets of the various ADAR enzymes are identified, as are several potential regulators of editing, such as AIMP2.

Here we describe an open collaborative effort termed the ‘Ruminant T2T Consortium’. It aims to generate complete diploid assemblies for many species of ruminants to examine chromosomal evolution in the context of natural selection and domestication.

The emergence of novel catalytic functions in ancient proteins likely played a role in the evolution of modern enzymes. Here, the authors use protein sequences from Precambrian beta-lactamases and demonstrate that a single hydrophobic-to-ionizable amino acid mutation can lead to substantial Kemp eliminase activity.

Experiments at the Joint European Torus tokamak show improved thermal ion confinement in the presence of highly energetic ions and Alfvénic instabilities in the plasma.

There is currently no disease-modifying treatment for Parkinson’s disease, a common neurodegenerative disorder. Here, the authors use genetic variation associated with gene and protein expression to find putative drug targets for Parkinson’s disease using Mendelian randomization of the druggable genome.

Power exhaust is one of the biggest challenges stopping fusion energy. This article shows experimental evidence for strategically shaping the power exhaust region as a solution to this challenge, utilising physics understanding to strike a balance between engineering complexity and power exhaust benefits, consistent with reduced models and simulations.

Three planets orbit the Sun-like star ν² Lupi. CHEOPS data show that all of them are transiting and show remarkable diversity. In particular, dry and gas-poor inner planet b has experienced extensive atmospheric loss, while planets c and d are water rich and have a small gaseous envelope of primordial origin.

Exhibiting low-energy (un)folding barriers and fast kinetics, ultrafast folding proteins are enticing models to study protein dynamics. The authors use single molecule force spectroscopy AFM to capture the compliant behaviour hallmarking the dynamics of ultrafast folding proteins under force.

The authors show that rare genetic variants contribute to large gene expression changes across diverse human tissues and provide an integrative method for interpretation of rare variants in individual genomes.

The interaction of water molecules with a protein results in a frictional force that influences protein conformational dynamics and folding, though the nature of the protein also influences the friction. Here, the authors use molecular simulations to examine the origin of this protein contribution.

The Raf-1 kinase is important for mitogenic MAPK signalling but also inhibits pro-apoptotic Hippo signalling. Kolch and colleagues have found that the Hippo kinase LATS1 phosphorylates Raf-1 in a feedback regulatory loop to inhibit both pathways, and demonstrate by experiments and modelling that competing protein interaction can form the basis for a switch-like transition between signalling pathways.

Mutations in the ATM tumor suppressor gene confer hypersensitivity to DNA-damaging chemotherapeutic agents. Here, the authors provide evidence that these hypersensitivities reflect a crucial role for ATM at damaged replication forks being to prevent toxic DNA end-joining leading to chromosome fusions and cell death.

Combined genomic and transcriptomic approaches identify the landscape of extrachromosomal circular DNA in neuroblastoma and reveal that extrachromosomal circular DNA is a major source of somatic rearrangements.

Precision oncology is important for patient treatment. Here the authors review the current applications of microfluidic systems to cancer precision medicine, and discuss the issues that must be addressed prior to getting these technologies into the clinic.

Malumbres and colleagues reveal that mitotic arrest is accompanied by reduced mitochondrial mass and oxidative respiration resulting in activation of AMPK and induction of glycolysis to promote cell survival.