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K11/K48 branched ubiquitin chains regulate protein degradation and cell cycle progression. Here, the authors report the structural basis of how such a branched ubiquitin chain is recognized by the human 26S proteasome, revealing a multivalent binding mode that underlies selective recognition.

Khawaja et al. show sex-specific differences in neuronal-activity regulation by chaperone-mediated autophagy and that loss of chaperone-mediated autophagy leads to defective neuronal physiology and increased seizure susceptibility, linking chaperone-mediated autophagy to neuronal excitability.

Computational models can help to explain the dynamics of cellular infection with pathogens. Here the authors use computational models to assess the single cell infection parameters of human macrophage infection with Legionella pneumophila and the effects on immunometabolism at a single cell and population level.

A gene therapy method using AAV can help deliver HIV-fighting antibodies long-term, but the body often rejects them. Here the authors show that a short course of the drug rapamycin helps prevent host anti-drug antibody responses, showing successful antibody delivery in mice and monkeys.

Vertical transmission is thought to favour beneficial host–microbe interactions, but these may also be context dependent. Here Bruijning et al. show with a model that variable environments can select for bet-hedging by hosts via imperfect vertical transmission of microbes.

In vitro propagation of the pathogenic bacterium Coxiella burnetii, the causative agent of Q fever, leads to attenuated virulence and lipopolysaccharide (LPS) truncation. Here, Long et al. show that a strain considered to be avirulent (NMII) can be recovered from infected animals, and these isolates display increased virulence and an elongated LPS due to reversion of a 3-bp mutation in a gene.

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.

Research on sustainable diets has primarily focused on human and planetary health, neglecting workers in food value chains. This study quantifies the risk of forced labour embedded in five different diets in the USA, underscoring the need to integrate such risk in sustainable diet transition efforts.

The BabyScreen+ study offered genomic screening to 1,000 newborns in Australia, and showed that the approach is feasible and positively received by families, leading to molecular diagnoses in 1.6% of babies.

Genomic deletions in poxviruses are not well understood, the authors found large deletions in >2% of Mpox virus genomes during routine surveillance, highlighting their role in poxvirus evolution and potential impact on diagnostics and therapeutics.

Using a new analytical method for tracking gamma band events in mouse visual cortex, flexible encoding of visual information according to behavioural context is shown.

Context counts, and not just for social and economic aspects of urban life. This study finds that, for 16 cities in the United Kingdom, the landcover of the rural surroundings is a better predictor of ticks and environmental Lyme disease hazard than the landcover within the cities themselves.

BPTF is known to regulate chromatin accessibility and self-renewal in mammary epithelial stem cells. Here, the authors discover that BPTF inhibition delays tumor formation, re-activates ERα expression, increases sensitivity to tamoxifen treatment, and inhibits metastatic development.

Using data from the CoVPN 3008 study, the authors show that the neutralizing antibody correlate of risk holds in people living with HIV. However, the nAb correlate was weaker and shorter-lived in a vaccine-immunity versus hybrid-immunity population.

Polymer thin films that emit and absorb circularly polarised light are promising in achieving important technological advances, but the origin of the large chiroptical effects in such films has remained elusive. Here the authors demonstrate that in non-aligned polymer thin films, large chiroptical effects are caused by magneto-electric coupling, not structural chirality as previously assumed.

Cellular senescence is an underlying mechanism of aging. Among older Americans, higher expression of genes linked to cellular senescence is seen in women and those with class II obesity, and is associated with worse health outcomes.

Here, the authors provide molecular insight into the remarkable ability of Tardigrades to withstand high levels of radiation by demonstrating that their Dsup protein interacts with multiple surfaces of the nucleosome to protect the genome from oxidative DNA damage.

Aggregating similar single cells into metacells is a common heuristic for sparse data, but risks mixing dissimilar cells. Here, authors present mcRigor, which detects and filters heterogeneous metacells, optimizes metacell partitioning, and improves reliability in single-cell omics studies.

HippoMaps provides an open-source resource for studying the human hippocampus at different scales and with different modalities such as histology, fMRI, structural MRI and EEG.

How age affect the immune response to malaria is not fully understood. Here, the authors characterise the transcriptome and serum inflammatory cytokines in children and adults in response to malaria, showing that there is an increase of inflammatory chemokine and cellular responses in adults compared to children.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

Researchers use a chimeric approach to reveal the first near-atomic resolution structures the yellow fever virion, showing key differences between vaccine and virulent strains that affect how antibodies recognise and neutralise the virus.

This study incorporates local ancestry into the Genome Aggregation Database (gnomAD) to improve allele frequency estimates for admixed populations, enhancing variant interpretation and enabling more accurate and equitable genomic research and clinical care.

Resolution of G4s has been suggested to be required for efficient DNA replication. Here, the authors show that the nuclease DNA2 and the DNA repair complex MutSα (MSH2-MSH6) are required to remove G4 stabilized by environmental compounds to allow efficient telomere replication.

Cancer evolutionary dynamics are quantitatively inferred using a method, EVOFLUx, applied to fluctuating DNA methylation.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Dietary cysteine enhances intestinal stem cell-mediated intestinal repair following injury by promoting CD8 T cell-regenerative immune responses.

Political ecology aims to understand how politics and power influence both social and ecological dynamics. Conservation biologists and political ecologists tackle many of the same pressing environmental problems, but from quite different perspectives. In this Viewpoint, five political ecologists discuss their views on how the field can understand and tackle the biodiversity crisis.

Head and neck squamous cell carcinoma (HNSCC) frequency and risk factors vary considerably across regions and ancestries. Here, the authors conduct a multi-ancestry genome-wide association study and fine mapping study of HNSCC subsites in cohorts from multiple continents, finding susceptibility and protective loci, gene-environment interactions, and gene variants related to immune response.

Lee et al. use an aggregation-prone CLN4 mutant that causes lysosomal damage in neurons and show that in non-neurons, the ubiquitin ligase CHIP prevents CLN4-dependent lysotoxicity via microautophagy.

An understanding of the molecular mechanisms promoting the generation of immunoregulatory and tumour-promoting monocytes and macrophages is key to breaking the cycle of tumour myelopoiesis and developing more effective myeloid-targeting therapies.

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.

The authors develop and characterise a selective Greatwall inhibitor, C-604, and show that its cytotoxicity stems from PP2A-B55α hyperactivation. They identify B55α and Greatwall levels as biomarkers of responses to Greatwall-targeted therapy.

An analysis of popular media finds that, based on internet searches, documentary films can increase short-term interest in plant-based diets.

Border and colleagues present FUSION, an open-source, web-based platform designed to integrate spatial omics with histological context. FUSION enables intuitive, interactive exploration of cellular and tissue-level features across diverse organs and assay types.

In this Stage 2 Registered Report, Buchanan et al. show evidence confirming the phenomenon of semantic priming across speakers of 19 diverse languages.

Mutual paracrine regulation of the cytokines GREM1 and SPP1 mediate mesenchymal and epithelial cell fate in pancreatic cancer.

Neuroimmune communication in Alzheimer’s disease (AD) is poorly understood. Here, the authors show that CD103–CD8+ resident memory T cells induce neurotoxicity and neuroinflammation in AD via the granzyme K–PAR-1 axis.

Yücel et al. examine how skin and hair characteristics impact functional near-infrared spectroscopy (fNIRS) signal quality and provide recommendations for inclusive use of fNIRS.

Cells use clathrin-mediated endocytosis to internalize biomolecular cargo. The authors demonstrate that the Epsin1 protein ensures uptake of ubiquitylated cargo through ubiquitin-dependent regulation of the stability of endocytic protein networks.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

DNA2 suppresses recombination-restarted replication and checkpoint activation at stalled forks, and its loss triggers recombination-dependent synthesis, checkpoint signalling and cell-cycle exit, highlighting its essential role in proliferation and growth failure in primordial dwarfism.

Maine et al., report post-hoc modeling of a secondary outcome of a Phase 1 clinical trial that assessed the long-term immunogenicity of a next-generation self-replicating RNA vaccine, RBI-4000 for rabies. The durability of immune responses from RBI-4000 is equal to or superior to a commercial vaccine using statistical decay modeling.

Wastewater surveillance for disease outbreaks currently requires lab testing which causes delays. Here, authors develop ultra-sensitive quantum sensors enabling 2-hour near-source pathogen detection from raw wastewater with high sensitivity and specificity, creating a portable “lab-in-a-suitcase” system.

This Bayesian statistical method uses timeseries microbiome data to infer interaction modules and is tested using a faecal transplant experiment in mice.

Comparison between structures of human, mouse and rat P2X7 receptors define ortholog-specific pharmacology and facilitated structure-based drug design of UB-MBX-46, an antagonist that selectively inhibits the human P2X7 receptor with sub-nanomolar potency.

Micro-C provides insights into genome organization in Plasmodium falciparum and defines the machinery used to spatially coordinate antigenic variation and stage-specific genes that are crucial for infection.

A horizon scan of international respondents identifies and discusses ten developing challenges in Antarctic conservation, revealing an increased emphasis on challenges related to governance, geopolitics and economics compared to a similar scan from 2012.

The ability to sequence oligonucleotides which consist entirely of artificial bases will facilitate their ongoing development and use. Here authors demonstrate de novo nanopore sequencing of DNA oligomers composed of “P” “Z” “S” and “B” bases with high sequencing accuracy.