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Glioblastoma is characterised by high levels of intratumoural heterogeneity and plasticity, hindering treatment. Here, the authors develop an analytical framework, scFOCAL, to predict the sensitivity of glioblastoma cell subpopulations to therapies based on reversal of disease transcriptional signatures to identify synergistic therapeutic combinations.

DNA double-strand breaks endanger genome stability. Here, the authors present cryo-EM structures showing how Ku70/80 and DNA-PK bind DNA ends on nucleosomes, offering a mechanistic model for break recognition within chromatin.

Elevated levels of IL-33 induce the production of autoantibodies through an unknown mechanism. Here, the authors show that IL-33 disrupts splenic architecture and germinal center organization, causing an expansion of antibody-secreting plasmablasts and plasma cells. In multiple mouse models of inflammation, administration of IL-33 exacerbates the pathology, increasing the production of autoantibodies, whereas IL-33 blockade reverses autoantibody production in a model of lung inflammation.

Pulmonary type 2 inflammation is associated with type 2 innate lymphoid cells. Here the authors use the Collaborative Cross mouse panel to show that ILC2 abundance during type 2 lung inflammation is different across the panel and identify free-fatty acid receptor 3 (Ffar3) as a gene responsible and show cytokine and ILC2 functional changes.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

De novo structural variants are an important cause of rare disorders but remain poorly understood. Here, the authors analyse over 12,000 families and reveal the prevalence, diversity, and clinical impact of complex de novo structural variants.

A machine-learning-based computational approach to probe pathway coessentiality reveals that complex II of the electron transport chain regulates de novo purine synthesis, and can be targeted to treat acute myeloid leukaemia.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

This research developed and compared firearm-specific and method-agnostic machine-learning models using data from 800,579 Army veterans, revealing that model choice and intervention thresholds impact predictive accuracy and fairness, guiding tailored suicide prevention efforts.

How the complex interplay between multiple nutrients within the microenvironment dictates potential sites of metastatic cancer growth is explored.

Most active particles studied to date lack the ability to undergo controlled shape transformations and control over their propulsion in response to environmental stimuli. Here, the authors present a class of active particles made from stimuli-responsive materials that exhibit fully reversible shape-dependent propulsion.

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.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

The authors demonstrate dual-probe multi-messenger imaging of high-energy-density plasmas based on laser-wakefield-accelerated electrons. This enables spatiotemporally resolved simultaneous probing of plasma hydrodynamics and electromagnetic field evolution with both x-ray and electron beams.

How chemotherapeutic nucleoside 6-thio-2’-deoxyguanosine (6-thiodG) targets telomerase to inhibit telomere maintenance in cancer cells and tumors was unclear. Here, the authors show that telomere length and telomerase status determine 6-thio-dG sensitivity and uncover the molecular mechanism by which 6-thio-dG selectively inhibits telomerase synthesis of telomeric DNA.

A new version of nanorate DNA sequencing, with an error rate lower than five errors per billion base pairs and compatible with whole-exome and targeted capture, enables epidemiological-scale studies of somatic mutation and selection and the generation of high-resolution selection maps across coding and non-coding sites for many genes.

Surgical menopause occurs in premenopausal women who undergo radical cystectomy with bilateral oophorectomy to treat bladder cancer. This Review discusses the pathophysiology of surgical menopause in these patients and highlights current strategies to mitigate associated symptoms and long-term health risks.

Kraft, Murphy, Jones et al. identify extrachromosomal DNA (ecDNA)-interacting elements (EIEs) enriched for transposable elements within ecDNA in colorectal cancer cells. They show that EIE 14 integrated within ecDNA acts as an enhancer to promote cancer fitness.

Ischemic heart disease causes irreversible damage due to poor cardiomyocyte renewal. Here, the authors show that PKM2 modRNA therapy in pigs drives cardiomyocyte proliferation, minimizes fibrosis, restores cardiac function and prevents heart failure after injury.

Functional interrogation of the intracellular checkpoint CISH sheds light on its superior role in boosting anti-tumor T cell responses compared to other emerging targets across diverse cancer types.

Reported detections of gases in exoplanet atmospheres, including claims of biosignatures on K2-18 b, disappear when broader models are tested, revealing that such detections often reflect modelling limits rather than real signals.

The [1,2]-Wittig rearrangement of allylic ethers is traditionally considered to proceed via formation and recombination of radical pairs. Now it has been shown that an alternative reaction cascade, involving initial enantioselective [2,3]-rearrangement followed by base-promoted anionic fragmentation–recombination that proceeds with high enantiospecificity, allows a catalytic enantioselective [1,2]-Wittig process.

Metal–ligand cooperative catalysis involves both the metal and the ligand moieties present in a complex interacting with substrates. Cooperative catalysis is central to the mechanisms of hydrogenases, lactate racemase and alcohol dehydrogenase. This Perspective describes these enzymes, as well as the small-molecule mimics inspired by these elaborate natural catalysts.

The relation between magnetooptical activity and chirality has previously been confused. Chiral polymer films are presented with state-of-the-art Verdet constants, revealing the role of chirality, and a strategy to enhance the magnetooptical B term.

England’s adoption of Brazil’s community health worker model highlights the transformative potential of reverse innovation in addressing health inequities and strengthening primary care.

Pre-existing chronic diseases can delay or accelerate cancer diagnosis. Here the authors report that the duration of analgesic treatment as well as history of anxiety or depression can impact risk of advance stage lung and colon cancer in patients.

An exploratory analysis of the phase 3 ECOSPOR III trial shows that a higher dosage of the oral microbiome therapeutic VOWST led to enhanced pharmacokinetics, increased species engraftment and altered microbiome and metabolite profiles, providing mechanistic insights into how it may prevent Clostridioides difficile infection recurrence.

The authors find that TDP-43 loss of function—the pathology defining the neurodegenerative conditions ALS and FTD—induces novel mRNA polyadenylation events, which have different effects, including an increase in RNA stability, leading to higher protein levels.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Here, the authors examine the mechanisms behind cheatgrass’s successful invasion of North American ecosystems. Their genetic analyses and common garden experiments demonstrate that multiple introductions and migrations facilitated cheatgrass local adaptation.

It is unclear which aspects of experience shape sleep’s contributions to learning. Here, by combining neural recordings in rats with reinforcement learning, the authors show that reward-prediction signals support sleep-dependent learning over multiple days.

Here, the authors show that brain dynamics mature from childhood to adulthood with increased hierarchical propagation and reduced visual-somatomotor dynamics. Top-down hierarchical flow strengthens throughout this developmental period.

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.

Understanding the mechanisms underlying the survival of drug tolerant persister cells following chemotherapy remains elusive. Here, multi-omics analysis and experimental approaches show that the germ-cell-specific H3K4 methyltransferase PRDM9 promotes metabolic rewiring in glioblastoma stem cells.

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.

How DNA Polymerase Epsilon accomplishes continuous leading strand synthesis during DNA replication is not understood. Here, the authors describe a two tiers mechanism required to sustain Pol Epsilon processivity: CHTF18-dependent loading of PCNA at leading strand and dsDNA binding by its POLE3-POLE4 subunits.

An approach combining BONCAT, stable isotope probing and metaproteomics showcases the hidden metabolic interconnectivity of microorganisms within an anaerobic digestion community.

Phosphorus locked in ancient marine carbonates shows that ocean phosphorus rose and fell with atmospheric oxygen during the Great Oxidation Event, Earth’s first major oxygenation. Models suggest brief nutrient pulses could have accelerated oxygen production

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

Emerging materials between molecules and materials demand new modeling approaches. Here, the authors present a localized active space approach that enables accurate and efficient band structure calculations to capture long-range charge and energy transfer in correlated materials.

Access to green space has been a critical, and contentious, issue for neighbourhood inequality and health outcomes. This Analysis looks at how the COVID-19 pandemic interacts with availability of nature for urban residents.

Variants in NOS1AP can cause monogenic nephrotic syndrome. Here, the authors show that disrupting the intergenic NOS1AP splice isoform that is more prevalent in podocytes leads to monogenic kidney disease responsive to RAAS inhibition.

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.

Human and rodent supragranular pyramidal neurons differ in HCN channel-related properties. Comparison across primates reveals robust HCN1 expression and HCN channel-dependent physiology, with cell type dependent differences in macaques versus humans.

The discovery of an unusual protist named Solarion arienae, which has a mitochondrial genome with some intriguing features, provides insight into the early radiation of eukaryotic groups.

A key component of quantum error correction is the decoding algorithm, which needs to be accurate but also with a computational overhead that doesn’t lead to backlogs and allows fast logical clock rates. Here, the authors show an FPGA-driven decoder featuring a coarse-grained parallel architecture and on-the-fly error model updates, allowing both high accuracy and real-time operation.