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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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

The inability of intrinsically photosensitive retinal ganglion cells to shift the circadian clock in the suprachiasmatic nucleus during daytime is caused by light-dependent depolarization block of these cells.

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.

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.

China’s carbon neutrality and clean-air policies cause global warming from reduced aerosols that nearly offsets cooling from reduced CO2 before 2060, with warming emerging afterwards, calling for early carbon neutrality and more mitigation strategies.

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.

Hiʻiaka is the largest moon of the distant dwarf planet Haumea. Here, the authors report the first multi-chord stellar occultations of Hiʻiaka, revealing its size, shape, and density, suggesting an origin from Haumea’s icy mantle.

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

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.

MAGPIE is a computational framework for co-registering spatially-resolved transcriptomics, metabolomics and tissue morphology for integrated downstream analysis. Case studies across lung, brain and breast reveal coordinated cross-modality molecular changes.

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.

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.

Ahmad et al. show that soluble histone H4 binds at histone genes and acts as a repressor of their expression. These findings suggest that histone H4 is a sensor of ongoing DNA replication. Ongoing chromatin assembly uses up soluble H4 and relieves histone gene repression; however, once DNA replication ceases, soluble H4 accumulates and represses the histone genes.

This study demonstrates the capability of deep learning protein design models in generating functionally validated β-strand pairing interfaces, expanding the structural diversity of de novo binding proteins and accessible target surfaces.

Grosjean et al. present a network-aware, self-supervised learning approach for screening neuronal activity dynamics. They demonstrate its applicability across a range of neural interventions.

The authors detail human antibodies that neutralize all three serotypes of poliovirus and mimic poliovirus receptor binding, accelerating antiviral development to further efforts to eradicate poliovirus.

Antibody response variability contributes to differential individual responses and disease outcomes. Here authors show that genetic variation to the IG kappa and IG lambda loci is an important determinant of antibody-mediated host responses in humans.

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.

mRNA vaccines targeting SARS-CoV-2 also sensitize tumours to immune checkpoint inhibitors.

Reanalysis of radiometric data from Cassini indicates that Titan does not contain a subsurface ocean, as strong tidal dissipation observed in its gravity field is not consistent with the presence of a liquid layer.

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.

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.

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 dynamics of antimicrobial-resistance plasmid transmission in hypervirulent Klebsiella pneumoniae are poorly understood. Here, Yong et al. show that anaerobic conditions favour the transfer of a distinct plasmid lineage, and the bacterial capsule poses only a modest barrier for plasmid transfer in the mouse gut.