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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.

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.

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.

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.

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.

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.

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.

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.

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.’

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.

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.

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.

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.

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

Silane, which is a precursor to the sandy surfaces of rocky planets and dusty clouds on gas giants, is seen directly in another world—a low-metallicity brown dwarf in which oxidation is slow and gas mixing is fast.

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.

Experimental tests and computational simulations of a scaled-down specimen of a real steel truss bridge identify and characterize the latent resistance mechanisms following critical failures, demonstrating how loads supported by failed components can be redistributed and enable structure resilience.

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.

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.

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.

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.

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.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

Here the authors show that MUSHER lncRNA enhances Arabidopsis seed dormancy by integrating the ABA and DOG1 pathways. Chromatin retention of MUSHER and all other lncRNAs tested is mediated by U1 snRNP.

Current catalysts for water-splitting electrolyzers are scarce and unstable under acidic conditions. Here, the authors report that cobalt oxyhydroxide works across all pH levels, delivering stable industrial-scale current for 400 h while its redox behavior adapts with acidity.

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.

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.

Meta-analyses in up to 1.3 million individuals identify 87 rare-variant associations with blood pressure traits. On average, rare variants exhibit effects ~8 times larger than the mean effects of common variants and implicate candidate causal genes at associated regions.

Magnetic splitting in an antiferromagnetic state of cubic NdBi gives rise to Fermi arcs with bands that have opposing curvature.

Typical quantum error correcting codes assign fixed roles to the underlying physical qubits. Now the performance benefits of alternative, dynamic error correction schemes have been demonstrated on a superconducting quantum processor.

Transposable elements in somatic cells become increasingly mobile during ageing. Here, the authors show that in the nematode Caenorhabditis elegans, downregulation of transposable elements extends lifespan, and that their increases with age are coupled with progressively growing N⁶-adenine methylation in these genetic loci.

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.

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.

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.

The Late Miocene terrestrial climate in eastern North Greenland displayed elevated temperatures at moderate atmospheric CO₂ levels and was highly variable, reflecting the shifting orbital and ocean circulation forcings in the Arctic as the world cooled, according to proxy records from speleothems.

Engineering stabilized proteins is essential for industrial and pharmaceutical biotechnologies. Here, authors present Stability Oracle, a Graph-Transformer framework trained on protein masked microenvironments to predict protein thermodynamic stability, using less training data while achieving improved generalization.

Scientists find that spongin, a key biomaterial in sponges, contains the same collagens as mammals and that these biocomposites contain brominated crosslinks. Now, the question: “Maybe we are all sponge to some degree?” is no longer so absurd.

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

An analysis of the impact of logging intensity on biodiversity in tropical forests in Sabah, Malaysia, identifies a threshold of tree biomass removal below which logged forests still have conservation value.

Experimental measurements of high-order out-of-time-order correlators on a superconducting quantum processor show that these correlators remain highly sensitive to the quantum many-body dynamics in quantum computers at long timescales.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

The third variable (V3) loop on the HIV-1 Env glycoprotein is required for viral entry. Here, the authors applied DARPin technology to produce broadly neutralizing inhibitors targeting a region of V3 that becomes accessible after binding to the CD4 receptor.

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.

Sialoglycan receptor binding promotes the D2 domain up conformation in the HKU1 coronavirus spike protein. Here the authors show that this conformational change is driven fundamentally by the full structuring of the canonical embecovirus binding site.

cryoDRGN-ET is a generative neural network method for heterogeneous reconstruction of cryo-ET subtomograms. Using subtomogram tilt-series images, it can capture states diverse in both composition and conformation.

Ellis and colleagues show that combination of EZH2 inhibition and anti-PD-1 can increase antitumor immune responses in typically ‘immune cold’ prostate cancer, by increasing EZH2-regulated dsRNA–STING–ISG response signaling.