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Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

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 variability in clinical outcomes of SARS-CoV-2 infection is partly due to deficiencies in production or response to type I interferons (IFN). Here, the authors describe a FIP200-dependent lysosomal degradation pathway, independent of canonical autophagy and type I IFN, that restricts SARS-CoV-2 replication, offering insights into critical COVID-19 pneumonia mechanisms.

Active fluids, such as bacterial suspensions, exhibit chaotic flows at low Reynolds number - a phenomenon known as active turbulence. Here, the authors show a discontinuous transition from laminar to chaotic flows in unconfined active nematics.

How cells respond to replication-derived DNA damage that is carried over into mitosis is not well understood. Here, the authors show that CIP2A with TOPBP1 mediates the mitotic recruitment of the SLX4/MUS81/XPF nuclease complex to replication stress-induced DNA lesions to maintain genome integrity.

Zonal positioning in the liver determines whether the CTNNB1 oncogene can induce liver cancer.

Biosynthesis of all androgens from cholesterol first requires cytochrome P450 (CYP) 11A1 for generation of pregnanes and then CYP17A1 for biosynthesis of androgens, but CYP17A1 inhibition cannot completely inhibit androgen biosynthesis in prostate cancer. Here, the authors identify a role for CYP51A1 in the biosynthesis of androgens that completely bypasses the requirement for CYP17A1 and demonstrate that CYP51A1 is essential for the biosynthesis of ¹³C-testosterone from ¹³C-cholesterol in prostate cancer cells.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

The dense desmoplastic stroma and insufficient infiltrating T cells limit effective immunotherapy in pancreatic ductal adenocarcinoma (PDAC). The authors here administer an autologous dendritic cell (DC) vaccine (MesoPher) with an agonistic CD40-specific antibody (mitazalimab) to patients with metastatic PDAC after (m)FOLFIRINOX standard-of-care treatment and find MesoPher/mitazalimab combination therapy is safe and tolerable, accompanied with enhanced systemic and local immune responses.

TDP-43 dysfunction in ALS/FTD causes faulty splicing of the KCNQ2 ion channel, leading to toxic protein buildup, neuron hyperactivity and a potential new biomarker and treatment target using RNA-based therapies.

Convergent selection between crops can help to identify genetic variants with important roles in adaptation as a source of diversity for the improvement of cultivated species through the concept of inter-crop translational research for breeding.

Here, the authors report an exome-wide association study for multi-organ imaging traits by leveraging recent bioinformatic tools such as AlphaMissense. The identified signals elucidate the genetic effects from rare variants on human organs and their connections to complex diseases

Here the authors provide an explanation for 95% of examined predicted loss of function variants found in disease-associated haploinsufficient genes in the Genome Aggregation Database (gnomAD), underscoring the power of the presented analysis to minimize false assignments of disease risk.

Somatic mutations in blood cells (CHIP) are linked to diseases like heart disease, but the mechanisms are unclear. Here, the authors show that different CHIP driver genes alter unique sets of plasma proteins, some of which are validated in mouse models.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Researchers present GlycoGenius, an open-source tool that automates complex glycomics data analysis. It streamlines workflows, identifies known and previously unreported glycans, and enables faster, more accessible insights into glycobiology.

Serapio-García, Safdari and colleagues develop a method based on psychometric tests to measure and validate personality-like traits in LLMs. Large, instruction-tuned models give reliable personality measurement results, and specific personality profiles can be mimicked in downstream tasks.

Koala retroviruses are models of transposable element colonization of germlines. By mapping their integration sites in koala pedigrees, this study provides genetic risk scoring for breeding decisions and documents rates of acquisition and loss of retroviral integrations across generations.

MCL1 is an anti-apoptotic protein associated with cancer and therapy resistance. Here, the authors show that MCL1 regulates mTORC1 signalling and metabolism, explaining MCL1-inhibition reported cardiotoxicity, which can be mitigated by dietary leucine supplementation.

This multi-omic longitudinal analysis of the healthy human peripheral immune system constructs the Human Immune Health Atlas and assembles data on immune cell composition and state changes with age, including responses to cytomegalovirus infection and influenza vaccination.

The rapid expansion of agricultural irrigation raises concerns about exacerbating water scarcity, but land–atmosphere interactions are often overlooked. This study isolates irrigation impacts from other drivers using a multi-model framework to reveal that historical irrigation expansion substantially reduces net atmospheric water influx, intensifying drying trends and accelerating terrestrial water storage depletion, urging immediate mitigation strategies.

An effective CRISPR RNA occlusion strategy enhances mismatch detection when using Cas13.

Antimicrobial resistance genes that have been mobilized between bacterial species represent a subset of the naturally occurring resistome. Here, the authors compare the abundance, diversity and geographical patterns of acquired resistance genes with latent resistance genes in global sewage metagenomes.

u-Segment3D is a universal framework that translates and enhances 2D instance segmentations to a 3D consensus instance segmentation without training data. It performs well across diverse datasets, including cells with complex morphologies.

High-pressure-temperature experiments that explore the impact of carbon and silicon on the plastic deformation of hexagonal close-packed iron suggest depth-dependent elastic anisotropy in Earth’s inner core may originate from chemical stratification

Reliably probing rejuvenation and memory effects in spin glasses by means of simulations is difficult. Now, a state-of-the-art numerical study shows that at least three different length scales play a crucial role in aging dynamics of spin glasses.

The basic features of dopamine release sites are still largely unknown. Here, the authors determine the ultrastructure of fluorescent dopaminergic and glutamatergic synaptosomes in mouse striatum using cryo-correlative light and electron microscopy.

Sodium metal is of interest for high-energy-density batteries, but the lack of large-area ultrathin sodium metal foils hinders research. Here a metre-length, ultrathin (≤50 μm), mechanically strengthened sodium metal foil is fabricated by a roll-to-roll calendaring process with interfacial lubrication and functional modification.

Here the authors dissect the developmental and functional relationship between tumor-responsive cytotoxic T cells in the tumor versus the tumor-draining lymph nodes (tdLNs), finding that stem-like T_PEX cells dependent on MYB in the tdLNs are required for CD8⁺ T cell tumor infiltration and ICB responses.

Despite improving therapeutic options, the prognosis for patients with metastatic castration-resistance prostate cancer (mCRPC) remains poor. Here, the authors identify MCL1 copy number alterations as a prognostic and predictive biomarker, demonstrating its therapeutic potential as a drug target, either alone or in combination, in patients with mCRPC.

This study explores the genetic structure of hepatitis C virus outbreaks in rural U.S communities affected by the opioid crisis. Analysis of intra-host viral populations from 692 participants reveals hidden transmission networks.

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 International Brain Laboratory presents a brain-wide electrophysiological map obtained from pooling data from 12 laboratories that performed the same standardized perceptual decision-making task in mice.

The majority of incident HIV infections in Eastern and Southern Africa occur in the general population. Here, the authors harmonise data from eight open population-based cohort studies from six countries and describe individual and community-level risk factors for HIV acquisition.

Species’ traits and environmental conditions determine the abundance of tree species across the globe. Here, the authors find that dominant tree species are taller and have softer wood compared to rare species and that these trait differences are more strongly associated with temperature than water availability.

Parallel operation of two exchange-only qubits consisting of six quantum dots arranged linearly is shown to be achievable and maintains qubit control quality compared with sequential operation, with potential for use in scaled quantum computing.

Walmsley and colleagues report that systemic hypoxia induces persistent loss of histone H3K4me3 marks and epigenetic reprogramming in neutrophil progenitors, resulting in long-term impairment of subsequent neutrophil effector functions.

A re-assessment of the global carbon budget shows the natural land sink is substantially smaller than previously estimated, indicating emerging impacts of climate change on the evolution of the carbon sinks.

Polygenic risk scores can help identify individuals at higher risk of type 2 diabetes. Here, the authors characterise a multi-ancestry score across nearly 900,000 people, showing that its predictive value depends on demographic and clinical context and extends to related traits and complications.

A post hoc analysis of a multicentre, randomised trial showed that prediabetes remission is possible without total weight loss—providing weight is distributed to subcutaneous deposits as opposed to visceral ones.

Aging is a risk factor for neurodegenerative diseases associated with protein aggregation. Here the authors identify age-related hyperactivation of EPS8/RAC signaling in C. elegans as a driver of pathological protein aggregation, highlighting EPS8 and its regulators as potential therapeutic targets.

Combining high-resolution mapping of foliar and herbivore faecal sodium concentrations across Africa, the authors show that plant-derived sodium availability constrains megaherbivore densities at a continental scale.

Ubiquitin-conjugating enzymes (E2s), including UBE2D3, are important regulator of cellular function and fate. Here the authors report that IFN-y driven upregulation of UBE2D3 is associated with impaired antigen presentation in pancreatic cancer, also showing that its targeting enhances antitumor immunity.