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A martensitic alloy with a tensile strength exceeding 3 GPa and a fracture elongation of 5.13% is developed. These mechanical properties arise from interface complexes interacting with dense dislocation networks, which is a mechanism shown to be applicable to other compositions.

Fine-scale field analysis and modelling of the spatial dynamics of infection of Darwin’s frogs with Batrachochytrium dendrobatidis fungus identifies highly localized transmission dynamics that generate clustered epidemics and can drive collapse of local subpopulations.

The zebra finch robust nucleus of the arcopallium (RA) directs singing by providing descending projections to brainstem motor neurons. The authors show that electrophysiological characteristics of RA neurons rely on resurgent Na+ currents that emerge early during song development only in males.

An 18-gram haptic feedback ring can deliver powerful force sensations while detecting multi-directional touch inputs, potentially transforming the way we can interact with digital environments.

Therapeutic options for patients with renal medullary carcinoma (RMC) are limited. Here the authors report the results of a phase II clinical trial of anti-PD1 nivolumab plus anti-CTLA4 ipilimumab in RMC, associating the activation of a myeloid mimicry program in tumor cells to the rapid disease progression and hyper-progression observed in treated patients.

Kaiser et al. characterize the disordered extracellular N-terminus of a peptide-activated G protein-coupled receptor. They combine biophysical, biochemical, and computational methods to uncover its role in the activation of G protein and arrestin pathways.

It has been previously shown theoretically that the average path length of random walks inside a closed domain is invariant. Here the authors demonstrate that this invariance property can be used to predict the mean residence time of swimming bacteria exploring structured micro-environments.

Electrical excitability in neuroendocrine SCLC cells promotes tumour progression through action potential firing, increasing ATP demand and oxidative phosphorylation dependency, whereas non-neuroendocrine cells provide metabolic support, driving a tumour-autonomous cycle that enhances tumorigenesis and metastasis.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

Replica symmetry breaking describes identical copies of a randomly interacting system exhibiting different dynamics. Here, Pierangeli et al. observe this critical phenomenon in the optical wave propagation inside a disordered nonlinear waveguide.

Myocardial infarction accelerates atherosclerosis through activation of the sympathetic nervous system, and the consequent release of haematopoietic stem and progenitor cells.

Endothelial cells undergo rearrangements during angiogenic sprouting. Gerhardt and colleagues show that the flux in Notch signalling levels in individual cells of sprouting vessels results in differential dynamics of VE-cadherin at junctions to drive functional endothelial cell rearrangements during sprouting. They also find that differential VE-cadherin dynamics are affected in retinopathy and tumour vessels.

Nicastro, Brohée et al. find that the fatty acid synthesis intermediate malonyl-CoA inhibits mTORC1, showing mTORC1 senses the capacity of a cell to synthesise fatty acids and linking fatty acid generation with the overall biosynthetic output through mTORC1.

This study characterised the landscapes and changes of RNA m6A in brains of individuals with or without Alzheimer’s disease, and revealed roles of a promoter antisense RNA next to MAPT in neuronal gene regulation that promote neuronal survival.

BamA carries out the essential process of folding outer membrane β-barrels in Gram-negative bacteria and is a potential antibiotic target. Here, the authors discover macrocyclic peptide inhibitors that trap BamA in distinct structural conformations.

Albinism is a rare disorder often caused by high-effect rare variants in the TYR gene. Here, the authors study a large albinism cohort and find that a common variant in the TYR promoter contributes to albinism by modifying the penetrance of other common variants, demonstrating a complex genetic architecture.

We show that cytosolic inner mitochondrial membrane vesicles, devoid of outer mitochondrial membrane or mitochondrial matrix, are formed during resting state and directly herniate into lysosomes through pores formed by voltage-dependent anion channel 1 in the outer mitochondrial membrane, thereby allowing their selective removal.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

Structural and functional studies of the sodium leak channel, non-selective (NALCN) in complex with a distinct auxiliary subunit reveal the structural basis of the channel function and pharmacology and the functional impact of mutations that cause NALCN channelopathies.

MatterGen is a model that generates stable, diverse inorganic materials across the periodic table and can further be fine-tuned to steer the generation towards a broad range of property constraints.

Hofer et al. show that fasting promotes the synthesis of spermidine, which stimulates eIF5A hypusination to induce autophagy and increase lifespan in various species in a conserved manner.

A metalloenzyme capable of oxidatively cleaving cellulose, found in a microbial community specialized in lignocellulose degradation, could enable sustainable biofuel production.

Endocrine-disrupting chemicals can interfere with the normal function of the endocrine system leading to adverse health effects in humans. In this Review, the authors discuss how exposure to these chemicals might be major risk factors for prostate cancer, and they consider the various sources of endocrine-disrupting chemicals and their different modes of action.

Ambroziak, Nencini, Pohle and colleagues identify a slowly emerging plasticity mechanism in a discrete set of hypothalamic preoptic neurons that is triggered by long-term heat exposure and that drives thermal acclimation to promote heat tolerance in mice.

Climate change effects on animals are typically measured as decreases or increases in performance, compared to controls. Because both directions can have cascading effects at the ecosystem level, this study conducts a meta-analysis testing for deviations in biological responses using absolute rather than relative changes, showing that impacts on marine animals might have been largely underestimated.

Microscopic imaging techniques have a high spatio-temporal resolution but, in living animals, are hampered by cardiac and respiratory motion. This paper describes a microscopic setup that allows fluorescent confocal imaging of the beating mouse heart over a period of several hours.

How the brain controls pain perception remains elusive. Here, authors show that layers 5 and 6 of the somatosensory cortex suppress or enhance nociception through cell-type-specific cortical and corticothalamic interactions.

Adipogenesis is important for white adipose tissue function. Here the authors identify the transcription factor PATZ1 as a regulator of adipogenesis and adipocyte maintenance, and report that adipose-tissue specific loss of PATZ1 leads to reduced fat mass and larger adipocytes in mice.

A structure of the MRAS–SHOC2–PP1C complex supports a RAS-driven and multi-molecular model for RAF activation in which individual RAS–GTP molecules recruit RAF–14-3-3 and SHOC2–PP1C to activate the downstream pathway.

Here the authors show a mechanism by which mitochondrial electron transport and ROS contribute to the differentiation and function of regulatory B cells in the context of systemic lupus erythematosus.

Time-resolved serial crystallography at XFELs reveals ultrafast photochemical reactions, but high laser densities can cause photodamage to biological samples. Here, the authors study the early K-intermediate in bacteriorhodopsin at high power, showing overall conformation remains robust over a wide range.

During senescence, minority mitochondrial outer membrane permeabilization leads to the release of mtDNA into the cytosol through BAX and BAK macropores, in turn activating the cGAS–STING pathway, a major regulator of the senescence-associated secretory phenotype.

Single-cell multiome and spatial transcriptomic analysis reveals new disease markers in the hippocampus implicated in both early and late stage of a tauopathy model of Alzheimer’s Disease.

This study presents real-time observation of plasmon-driven hot carrier creation. Auger heating is operative in enhancing carrier energy beyond single-photon excitation. These findings open new avenues in plasmonic energy conversion and photocatalysis.

Clear experimental signatures of fractional statistics in topologically ordered phases have been lacking. Here, the authors predict detectable signatures of non-trivial mutual statistics of fractionalized excitations in gapped topological quantum spin liquids at finite temperature.

Analysing camera-trap data of 163 mammal species before and after the onset of COVID-19 lockdowns, the authors show that responses to human activity are dependent on the degree to which the landscape is modified by humans, with carnivores being especially sensitive.

Supervised deep learning models hold promise for the interpretation of histology images, but are limited by cost and quality of training datasets. Here, the authors develop a self-supervised deep learning method that can automatically discover features in cancer histology images that are associated with diagnosis, survival, and molecular phenotypes.

Rouge waves have been observed in a number of complex systems, but not in biological structures. Here, the authors report the observation of optical rouge waves manifesting in tumor-cell spheroids when illuminated by randomly modulated laser beams.