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Skin prick testing for allergy diagnosis is limited by variability due to differences in test setting and operator expertise. Here, the authors develop and validate an AI-assisted readout method for reading allergy skin test results, and find that integrating AI enhances standardization throughout the skin prick testing process.

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.

High contiguity human genomes can be assembled de novo in 6 h using nanopore long-read sequences and the Shasta toolkit.

Using sequencing and haplotype-resolved assembly of 65 diverse human genomes, complex regions including the major histocompatibility complex and centromeres are analysed.

Head and neck squamous cell carcinoma (HNSCC) frequency and risk factors vary considerably across regions and ancestries. Here, the authors conduct a multi-ancestry genome-wide association study and fine mapping study of HNSCC subsites in cohorts from multiple continents, finding susceptibility and protective loci, gene-environment interactions, and gene variants related to immune response.

Myocardial contractile force and intracardiac hemodynamic shear stress coordinate the initiation of trabeculation in heart development. Here, the authors report that radially aligned myocardial strain activates snai1b⁺/Notch⁻ cardiomyocytes, initiating delamination for trabeculation.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

Complete sequences of chromosomes telomere-to-telomere from chimpanzee, bonobo, gorilla, Bornean orangutan, Sumatran orangutan and siamang provide a comprehensive and valuable resource for future evolutionary comparisons.

Fenton et al. show that FMRP granules dock at the mitochondrial midzone in a Rab7-dependent manner in axons and dendrites, where they promote local MFF synthesis and fission at the mitochondrial midzone.

The early events preceding the development of morphological abnormalities represent a key gap in the understanding of cancer. Here, the authors employ an oncogenic tagging strategy to define the contributions of HIF1A and HIF2A to the cell-type specific early events in VHL-associated oncogenesis and support therapeutic targeting of HIF2A early in VHL-associated cancers.

Here the authors reveal how an incoherent feedforward C/EBPα–Notch circuit times lung cell fate, guiding alveolar development, repair after injury, and shifts between protective and reparative states.

A fresh approach to protein design that incorporates excited intermediate states enables precise control over the lifetime of protein interactions, with potential applications in cell-signalling modulation and in biosensors and synthetic circuits.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.

Landsat satellite images reveal coherent interannual beach narrowing and widening across California in response to changes in central North Pacific wave power, with no 1985-2021 statewide mean shoreline loss. Low wave power (beach widening) correlates poorly with the El Niño climate index.

Stem cell repair of injured monkey spinal cords restores hand function in 53% of trials.

mRNA vaccines targeting SARS-CoV-2 also sensitize tumours to immune checkpoint inhibitors.

The SWEET project is a multicenter, randomized, controlled trial that shows that long-term consumption of sweeteners and sweetness enhancers improves body weight control and elicits beneficial gut microbiota changes in adults with overweight or obesity.

Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.

Circular RNAs offer advantages for mRNA therapies but are challenging to produce. Here, the authors develop a chemical method to generate circular RNAs with internal cap structures, enabling cap-dependent translation, chemical modification, and enhanced stability.

Barbosa, Stein et al. show that rather than operating independently, PFC persistent activity and ‘activity-silent’ mechanisms interact dynamically to produce serial effects in working memory, consistent with attractor models with synaptic plasticity.

Fifty years of plankton and water samples show that the proportion of carbon, nitrogen and phosphorus in the ocean now substantially differs from the Redfield ratio, probably reflecting a reduction in phosphorus limitation.

Whole-genome sequencing and phenotype data sharing are introduced in a national health system to streamline diagnosis and to discover coding and non-coding variants that cause rare diseases.

The largest harmonized proteomic dataset of plasma, serum and cerebrospinal fluid samples across major neurodegenerative diseases reveals both disease-specific and transdiagnostic proteomic signatures, including a robust plasma profile associated with the APOEε4 genotype.

Femtosecond photoexcitation drives a coherent twist–untwist motion of the moiré superlattice in 2° and 57° twisted WSe₂/MoSe₂ heterobilayers.

Results for the final phase of the 1000 Genomes Project are presented including whole-genome sequencing, targeted exome sequencing, and genotyping on high-density SNP arrays for 2,504 individuals across 26 populations, providing a global reference data set to support biomedical genetics.

Profiling of a combinatorial library of post-translationally modified histone H3–based peptides reveals that Thr3 phosphorylation, Arg2 methylation and Thr6 phosphorylation can modulate recognition of Lys4 methylation status by PHD fingers. Additionally, Thr6 phosphorylation, a previously undescribed modification, is shown to exist in native histones.

iExoKras^G12D are engineered exosomes for the delivery of siRNA targeting KRAS^G12D. Here the authors describe the results of a phase I trial of iExoKrasG12D in patients with metastatic pancreatic cancer, reporting safety and clinical activity, as well as immunological correlates informing on tumor immune microenvironment reprograming and future combination with immune checkpoint inhibitors.’

BamA is the catalytic core of the BAM complex, which inserts proteins into bacterial outer membranes. Here, the authors show that hinge flexibility between BamA’s β-barrel and POTRA domains is vital, demonstrating how evolution has fine-tuned the BamA sequence and structure for function.

Elephant endotheliotropic herpesvirus (EEHV) haemorrhagic disease is a major threat for juvenile Asian elephants. This study reports a proof-of-concept trial that evaluates the safety and immunogenicity of a vaccine against EEHV.

This study reveals how cardiolipin governs mitochondrial morphology by modulating the activity of human OPA1 and how its replacement by monolyso-cardiolipin, as observed in Barth syndrome, impacts mitochondrial membrane-shaping mechanisms.

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.

Plant hypocotyl elongation response to light and temperature. Here the authors show that shade combined with warm temperature synergistically enhances the hypocotyl growth response via the PIF7 transcription factor, auxin, and as yet unknown factor.

Nonninger et al. identify the TFEB–TGFβ signaling axis as a regulator of stem cell resilience that protects against a senescence-like state during the adult diapause in Caenorhabditis elegans, a mechanism conserved in vertebrate aging and mammalian cancer.

The automated detection of transient phenomena in the sky has developed rapidly in recent years, driven by robotic telescopes such as the Zwicky Transient Facility and the Asteroid Terrestrial-impact Last Alert System. Here the authors summarize the state of the art and look ahead to more discoveries during the Legacy Survey of Space and Time era.

Through in vivo tracking of tumor-specific CD8⁺ T cells in response to immunotherapy in mice, Barboy et al. characterize the tumor response to anti-PD-1 therapy and optimize a combination treatment with anti-4-1BB agonist.

Comparison between structures of human, mouse and rat P2X7 receptors define ortholog-specific pharmacology and facilitated structure-based drug design of UB-MBX-46, an antagonist that selectively inhibits the human P2X7 receptor with sub-nanomolar potency.

This pilot trial showed that perioperative treatment with the isocitrate dehydrogenase (IDH) inhibitor safusidenib of patients with low-grade IDH-mutant glioma, with craniotomy and lumbar puncture before and after treatment, is feasible and safe and enabled in-depth translational investigation of safusidenib treatment-induced changes in the tumor, including electrophysiological effects.

A structure of monolayer and bilayer graphene with a small twist between them shows correlated insulating states that can be tuned by changing the twist angle or applying an electric field.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Quantum mechanics allows to generate nearly ideal random strings from initially weak random sources, important for security of data systems, but this remains elusive in practice. Here the authors propose a realistic, error-tolerant and secure protocol for randomness amplification of arbitrary bits.

Atlantic hurricane activity has increased since 1995. It is widely thought that rising Atlantic sea surface temperatures have played a role in this increase, but the magnitude of this contribution is not known. The contribution for storms that formed in the tropical North Atlantic, Caribbean Sea and Gulf of Mexico is quantified using a statistical model based on two environmental variables: local sea surface temperature and an atmospheric wind field. It is found that local sea surface warming was responsible for roughly 40 per cent of the increase in hurricane activity between 1996 and 2005.

Electrochemical properties of organic mixed ionic–electronic conductors depend on their microstructure in operational ionic environments. The microstructure of a model organic mixed ionic–electronic conductor across multiple length scales in both dry and hydrated states, as well as its evolution on hydration, is revealed using cryogenic four-dimensional scanning transmission electron microscopy.

Sznajder et al. identified a molecular link between autism and myotonic dystrophy, showing that a tandem repeat mutation in a single gene can disrupt splicing of multiple autism-related genes during brain development, leading to autism-like traits.