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Liposarcoma (LPS) is a rare cancer that can acquire resistance to chemotherapy. Here, the authors map super-enhancers in LPS, finding BET-protein dependent mechanisms that can be targeted by a BET protein degrader, which also can overcome acquired resistance to chemotherapy in LPS.

Transcriptomic and clinical data analyses from multiple cohorts of patients with cancer receiving immunotherapy find that PD-1 blockade potentiates tumor-specific IgG1 plasma cell responses that complement cellular immunity and contribute to clinical benefit.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

Climate limits where insects can live and which species can coexist. Using thermal tolerances of 653 moths on Asian mountains, this study shows warmer temperatures broaden thermal tolerance traits diversity; daily variation has little influence, and strong seasonality mildly weakens this pattern.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Rusca et al. propose the plural climate storylines framework to build on the narrative element of physical climate storylines with methods that emphasize power asymmetries, decoloniality, co-production and desired futures. The goal of pluralizing climate storylines is to promote just, equitable development interventions.

Early adversity may sensitize people to the effects of later stress, amplifying psychopathology risk. Here, the authors show this stress sensitization effect for adolescents who experienced prolonged institutional deprivation in childhood, but not those assigned to foster care intervention.

Motivated by the need for a non-living and versatile multiblock semi-crystalline polyolefin synthetic method, the authors report a method for producing previously inaccessible iPP-b-LLDPE linear multiblocks wherein the overall molecular weights, individual block lengths, and crystallinity can be controlled.

Provencio and colleagues reported the exploratory efficacy outcomes and safety results from the CheckMate 77T phase 3 trial in patients with stage III resectable non-small-cell lung cancer.

Wade and colleagues analyze data from the Bucharest Early Intervention Project to examine whether stress reactivity measured at age 12 may serve as a mechanism linking early institutional deprivation with psychopathology at age 16.

The authors summarize changes in circuits after spinal cord injury and current strategies to target these circuits in order to improve recovery, but also advocate for new concepts of reorganizing circuits informed by multi-omic single-cell atlases.

RNA base editing represents an exciting modality in precision genetic medicine. Here the authors develop short, metabolically stable RNA oligonucleotides (RESTORE 2.0) that enable precise and efficient RNA base editing, demonstrating successful in-vivo correction of a disease-causing human mutation.

Although climate action is undermined by political interests and institutional inertia, multiple safeguards are in place to prevent backsliding on progress so far, and positive feedbacks reinforce progress despite opposing forces. Key elements of climate action are irreversible and can be further strengthened by commitments, investments and positive narratives.

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.

Despite exhibiting ferroelectric features, SrTiO₃ fails to display long-range polar order at low temperatures due to quantum fluctuations. An ultrafast X-ray diffraction experiment now probes polar dynamics of this material at the nanometre scale.

Genomic analysis of 118 cervical tumors from Ugandan individuals identifies HPV-clade-specific differences in tumor DNA methylation, regulatory-region-associated histone marks, gene expression and pathway dysregulation.

Rutz and colleagues report STK40, a non-catalytic member of the Tribbles pseudokinase family, negatively regulates c-Jun activity during proliferative T cell responses and exhaustion.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

CAR T cell therapies have been developed to treat paediatric diffuse intrinsic pontine glioma (DIPG), however, clinical efficacy remains limited. Here, the authors report that engineering B7-H3-targeting CAR T cells to express the chemokine receptor CXCR3-A enhances their trafficking and efficacy in DIPG preclinical models.

Microbiome analyses of living trees show that a single tree can host approximately one trillion bacteria, with microbial communities distinctly partitioned between heartwood and sapwood and with minimal similarity to other tissues or ecosystem components.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Post-translational modifications on tau protein in the brain could distinguish primary tauopathies. Here, the authors assess insoluble and soluble tau extracted from post mortem human tauopathy brains and show 4R/3R tau isoform ratio in aggregates is associated with specific modifications on soluble tau protein.

This Consensus Statement presents the standards for technical reporting in environmental and host-associated microbiome studies (STREAMS) guidelines.

Machine-learning algorithms trained on 25,000 geolocated soil samples are used to create high-resolution global maps of mycorrhizal fungi, revealing that less than 10% of their biodiversity hotspots are in protected areas.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

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.

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.

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.

Velocimetry diagnostics such as photon Doppler velocimetry (PDV) are essential to the field of shock and high energy density physics. Here, the authors demonstrate a system that dramatically extends the velocity dynamic range of PDV into the regime of fusion experiments by harnessing a time lens.

Biotech is no longer the exclusive domain of Western economies. A group of experts from around the world discuss emerging trends and opportunities for biotech in territories outside the United States and Europe.

Commensal bacteria such as Lactobacillus rhamnosus can inhibit the pathogenicity of the fungus Candida albicans. Here, Alonso-Roman et al. investigate the interplay between C. albicans, L. rhamnosus and intestinal epithelial cells, showing that changes in the metabolic environment, induced by the bacteria, trigger adaptations in C. albicans that reduce fungal pathogenicity.

Bacterial transcription factor Rho (ρ) is a key regulator of transcription termination. Here, the authors show that Escherichia coli ρ forms inactive oligomers and filaments in the presence of stress-associated nucleotides (p)ppGpp and ADP.

Data collected from more than 2,000 taxa provide an unparalleled opportunity to quantify how extreme wildfires affect biodiversity, revealing that the largest effects on plants and animals were in areas with frequent or recent past fires and within extensively burnt areas.