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DNA methylation heterogeneity and dynamics hinder distinguishing early pathological changes from normal variation. Here, the authors identify stable sites whose disruption is linked to blood cancers, aging, and cardiovascular risk.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

This study shows that contrail avoidance can recover 9% of the global temperature budget by 2050. For every year of delay, the recoverable warming will diminish by 0.6%. This makes inaction (not fuel penalties) the most significant climate risk associated with avoidance.

KRAS is an oncogene that switches between a GDP-bound inactive state and a GTP-bound active state. Recently developed KRAS G12C inhibitors are specific to the GDP-bound inactive state. Here, the authors develop a class of covalent KRAS G12C inhibitors capable of targeting both states for the treatment of KRAS-driven cancer.

A follow-up analysis of a clinical trial that evaluated anti-PD-1 therapy in patients with cancer who are living with HIV provides mechanistic insights into transcriptomic, cellular and cytokine changes related to immune checkpoint inhibitor treatment and identifies a signature associated with clinical response.

Nitrogen isotope tree-ring chronologies show that rising atmospheric CO₂ has reduced nitrogen availability in boreal forests in Sweden, suggesting that elevated atmospheric CO₂ is causing oligotrophication in boreal forests.

How white matter develops along the length of major tracts in humans remains unknown. Here, the authors identify fundamental patterns of human white matter development along distinct axes that reflect brain organization.

From 2014–2017, marine heatwaves caused global mass coral bleaching, where the corals lose their symbiotic algae. The authors find, this event exceeded the severity of all prior global bleaching events in recorded history, with approximately half the world’s reefs bleaching and 15% experiencing substantial mortality.

Post-transcriptional regulation of mRNA translation was explored using Ribo-STAMP and single-cell RNA sequencing to reveal cell-type-specific and isoform-specific translation patterns across hippocampal neuronal and non-neuronal cell types, highlighting functional differences between CA1 and CA3.

Citizen science data are increasingly used in biodiversity monitoring. This study applies a digital twin approach to biodiversity monitoring using a large citizen science dataset on birds from Finland, demonstrating its potential for ecological forecasting.

In a randomized experiment in Chelsea, Massachusetts, USA, lower-income individuals who received cash transfers reduced calorie deficits and increased consumption of nutrient-dense, higher-cost foods. Their findings highlight the critical role that income support may have in a high-income country to reduce hunger.

Cryo-electron microscopy suggests a model in which microtubules, rather than adaptors in the cytoplasm, act as the primary platform for dynein–dynactin assembly, while LIS1 stabilizes low-microtubule-affinity intermediates near the pre-assembled complexes.

Estimates from the Global Burden of Disease study reveal declines in chronic respiratory disease mortality between 1990 and 2023—especially during the COVID-19 pandemic—but the burdens on people affected remain substantial.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

Insights into regulatory T cell biology are accelerating therapeutic innovation in cancer immunotherapy, autoimmune diseases and transplant rejection.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

A soft robotic probe enables continuous in utero monitoring of fetal physiological parameters, including heart rate, blood oxygen saturation, temperature and electrocardiogram data, during open or fetoscopic surgery to provide real-time information on fetal condition and distress.

Juno radio occultations precisely redefine Jupiter’s shape, measuring a polar diameter of 66,842 km and an equatorial diameter of 71,488 km, both smaller than long-used values, bringing models of the planet’s interior into better agreement with observations.

MedHELM, an extensible evaluation framework including a new taxonomy for classifying medical tasks and a benchmark of many datasets across these categories, enables the evaluation of large language models on real-world clinical tasks.

This study finds that native tree extinctions and alien naturalizations are pushing forests towards fast-growing, resource-demanding species. This global shift could affect carbon storage and ecosystem stability, highlighting the need to protect slow-growing trees.

Rising electricity and freshwater needs limit conventional hydrogen production. Here, the authors report a self-sufficient, electricity-free system that harvests atmospheric moisture to produce green hydrogen, offering a scalable and sustainable path to alleviate global green-hydrogen scarcity.

Nagarajan and colleagues overview the current challenges in microbiome analyses from human cancer samples and discuss the optimal practices for improving the standards of reporting the presence of microbiome species in human cancers.

The activity of the membrane-bound enzyme pMMO depends on copper but the location of the copper centers is still under debate. Here, the authors reconstitute pMMO in nanodiscs and use native top-down MS to localize its copper centers, providing insights into which sites are essential for activity.

A combination of biochemical, cell biological and electron microscopy analyses reveal a ‘nucleotide code’ that coordinates Lis1–dynein binding stoichiometry, which in turn governs Lis1’s ability to relieve dynein autoinhibition.

Five-year survival data and biomarker analysis of the PRADO extension cohort of the phase 2 OpACIN-neo trial, in which patients with high-risk stage III melanoma received neoadjuvant ipilimumab and nivolumab and underwent pathologic response-directed surgery and adjuvant therapy, show 71% event-free survival and 88% overall survival, with tumor mutational burden, IFNγ signature and PD-L1 expression associated with favorable outcomes.

The functions of the vast majority of brain-expressed spliced isoforms are unknown. Here the authors describe an isoform-resolution perturbation system coupled to a single cell transcriptomics read-out, and through this approach identify neuronal microexons that control autism-linked signatures underlying neuronal maturation and function

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.

Climate change can alter when and how animals grow, breed, and migrate, but it is unclear whether this allows populations to persist. This global study shows that shifts in seasonal timing are key to helping vertebrate species maintain population growth under global warming.

Scholl et al. show that PopZ forms filamentous condensates driven by its helical domain and inhibited by its disordered region. Phase-dependent conformations modulate client interactions and disruption of filamentation or condensation impairs cellular function and growth.

Human genetic loci that associate with composition of the oral microbiome are identified using saliva-derived DNA, where the same host genetics also shapes oral health and genetic variation in oral bacteria.

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.

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.

Understanding the organism-wide molecular effects of spaceflight becomes increasingly critical as space exploration accelerates. Here, the authors show that miRNAs mediate microgravity-induced adaptations via extracellular matrix, DNA damage and developmental pathways, as shown by small RNA profiling in 13 organs of mice during and after spaceflight.

Metabolite signatures were identified for subtypes of dietary carbohydrate, including added sugar, whole grain and refined grain, and showed different associations with type 2 diabetes, providing an objective measure of dietary risk.

This paper uses a multi-region model to show that single-region models used by thousands of companies to estimate CO2 emissions related to goods they purchase may drastically underestimate and misidentify the largest sources of upstream emissions.

Early life RSV infection contributes to risk of childhood asthma. Here, the authors develop a statistical model to predict age at first RSV infection in the United States based on birthdate, demographics, and RSV surveillance data which could be used to identify groups at risk of chronic respiratory sequalae like asthma.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

The hierarchy of DNA repair pathways at stalled replication forks is not fully understood. Here, the authors isolate two mutations in yeast RAD51 with defects in binding to duplex DNA and stalled replication forks, suggesting a role of Rad51 duplex DNA binding in fork stabilization and postreplication repair.

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

As Nature Aging celebrates its fifth anniversary, the journal asks some of the researchers who contributed to the journal early on to reflect on the past and the future of aging and age-related disease research, the impact of the field on human health now and in the future, and what challenges need to be addressed to ensure sustained progress.

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.

Authors report drug repurposing screens against O-GlcNAc cycling enzymes, finding kinase inhibitors that act as splicing modulators to disrupt O-GlcNAc homeostasis and downregulate OGT and OGA. These findings reveal splicing modulator chemotypes and approaches to disrupt O-GlcNAc homeostasis.

Here they combine in vivo imaging with proteomics to characterize a protein complex comprised of Ccdc78 and Ccdc33 that acts at the extreme distal tip of 9 + 2 motile cilia to control tip architecture, cilia length, and cilia beating.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.