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Smoking remains a leading cause of preventable death and disease. Here, the authors explore the link between smoking and DNA methylation using arrays and next generation sequencing, and develop mCigarette, an epigenetic biomarker of smoking.

The highly conserved striatin-interacting phosphatase and kinase (STRIPAK) multimeric complex regulates the Hippo signaling pathway through phosphatase activity. A recent structure of the core STRIPAK hub reveals how striatins tetramerize to serve as a scaffolding platform for the assembly of an intricate architecture, which is distinct from that of all other protein phosphatase 2A (PP2A) complexes.

An image analysis framework makes use of rotation-invariant autoencoders and point clouds for morphology-appropriate representation learning to better understand the organization of complex subcellular structures.

Efficient sunlight-to-fuel conversion requires materials that produce long-lived charges, but increasing carrier lifetimes in visible-light-active photocatalysts has proven difficult. Now it has been shown that rapid charge deactivation via metal-centred states prevents long lifetimes and limits photocatalytic performance. These insights bridge solid-state and molecular photochemistry, informing strategies for improved photocatalyst design.

A distinct population of CD4 T cells resides in specific regions of the steady-state brain, and these T cells are programmed in the periphery by the microbiome to coordinate adaptive behaviour.

Swanton and colleagues present a clonal expression signature, ORACLE, which, in combination with clinicopathological and molecular risk factors, can predict survival of patients with lung adenocarcinoma, and they prospectively validate its prognostic value.

Sexually selected traits primarily drive reproductive success, but their secondary functions are less well studied. Here, the authors show that antler retention among male elk involves a trade-off between predator deterrence and reproductive success in the next breeding season.

A luminescence cascade system achieves 500-fold higher intensity and 8-fold longer signal persistence than conventional bioluminescence assays, enabling reliable and effective use of bioluminescence for point-of-care diagnostics.

Future bioinspired locomotion systems need design’s agility and adaptiveness. Here, the authors report a musculoskeletal leg design which leverages multi-layered electrohydraulic actuators to achieve highly energy-efficient and versatile motion.

Nunes and colleagues analyze supply chain constraints and climate consequences of new tailpipe emissions standards in the US. They find that the standards promote electric vehicle adoption and would reduce emissions significantly, but adoption may be constrained by critical mineral supplies.

Analyses of multiregional tumour samples from 421 patients with non-small cell lung cancer prospectively enrolled to the TRACERx study reveal determinants of tumour evolution and relationships between intratumour heterogeneity and clinical outcome.

Somatic mutations are identified from circulating cell-free DNA using a single-molecule-based lowpass whole-genome sequencing method. The regional distribution of mutations can identify a tumor-specific mutational profile in patients with cancer and can be used to monitor patients through treatment.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

Betaglycan is a co-receptor for selective TGF-β family ligands. Here, the authors solve its structure in complex with TGF-β and the signaling receptors, which explains its ligand selectivity and reveals its mechanism in potentiating TGF-β signaling.

Crabeater seals feed predominantly on Antarctic krill. Combining seal tracks and diving behaviour with environmental variables allows the future foraging habitat, and therefore krill distribution, to be predicted, suggesting a shift offshore and south along the western Antarctic Peninsula.

Genome-wide association analyses identify new risk loci for heart failure and its subtypes, extending understanding of the underlying biological pathways and disease mechanisms.

Using HDX-MS, X-ray crystallography, cryo-EM, and MD simulations, the authors examined the conformational dynamics of GAD65 in its apo- and holo- states and its interaction with the autoimmune polyendocrine syndrome type 2-associated autoantibody b96.11.

Cross-ancestry genome-wide association analyses in individuals of European and East Asian ancestry identify 11 new risk loci for intracranial aneurysms and highlight a polygenic architecture explaining a substantial fraction of disease heritability.

Cell shape provides a structural signature for the classification and investigation of the jamming of bronchial epithelial layers in asthma.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

By linking data from a 40-year birth cohort study with multiple administrative databases, the authors show that 20% of the population accounts for close to 80% of economic burden. Strikingly, this group can be predicted with high accuracy from as early as 3 years old.

Predictive electrocatalyst design is challenged by uncontrollable precatalyst reconstruction during operation. Here, informed by operando spectroscopies, activation protocols are developed to stabilize surfaces and improve catalyst reliability.

A method, RARE-seq, for sensitive detection of cell-free RNAs in blood is demonstrated to have diverse clinical applications including diagnosing and characterizing human cancers, and tracking response to RNA therapeutics.

Double Asteroid Redirection Test (DART) mission’s impact on asteroid Dimorphos has led to various impact related features. Here, the authors show that those features result naturally from the dynamical interaction of the ejecta with the binary system and solar radiation pressure.

A barcode-based approach applied to UK Biobank and an Icelandic cohort identifies drivers of clonal hematopoiesis (CH) and finds associations between CH and multiple diseases. Genome-wide association analyses identify 25 loci associated with CH susceptibility.

Cardiovascular and metabolic risk factors (CVM) impact brain structure and increase dementia risk. Here, the authors developed and validated machine learning models to measure the neuroanatomical changes in people with cardiovascular and metabolic diseases that are cognitively unimpaired.

The Dog Aging Project is an open-data, community science study to identify genetic, environmental and lifestyle factors associated with canine healthy lifespan, generating knowledge that could readily translate to human ageing.

Wolf behavioural, spatial, and serological data over 26 years show that wolf territory overlap with areas of high cougar density is a significant predictor of T. gondii infection. Further, infection increases the likelihood that wolves make high-risk decisions such as dispersing and becoming a pack leader.

Analyses of the TRACERx study unveil the relationship between tissue morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk of lung adenocarcinomas.

Oxygen contained within cosmic spherules is sourced from the atmosphere, making micrometeorites a possible archive for past atmospheric conditions. Here, Packet al. compare the isotopic composition of oxygen in cosmic spherules from Antarctica with that of the troposphere, and validate the value of this archive.

A multi-ancestry genome-wide gene–smoking interaction study identifies 13 new loci associated with serum lipids.

Spatial multi-omics methodologies are essential for capturing the molecular heterogeneity of complex biological systems. In this study, the authors introduce a multi-omics imaging workflow capable of mapping metabolite-protein interactions with spatial specificity, enabling pathway-level resolution across distinct placental tissue microenvironments.

BMI contributes to various diseases, but it was unclear whether the risk was mediated by BMI itself. Here, the authors demonstrate that BMI mediates most of this risk, and suggest an upper bound on disease risk that can be mitigated by lowering BMI.

Remyelination can restore neural function. Here, the authors characterize the drivers and limits of endogenous remyelination and explore a therapy that rescued remyelination deficits and accelerated neuronal functional recovery, although complete remyelination was not required.

DNA from tumour cells can be detected in the blood of cancer patients. Here, the authors show that cell free DNA fragmentation patterns can identify lung cancer patients and when this information is further interrogated it can be used to predict lung cancer histological subtype.

The ability of BCG vaccination to prevent pulmonary tuberculosis could be improved by targeting mucosal immunity within the lung. Here the authors compare latent Mtb-infected donors with intradermal or oral BCG vaccine recipients to show distinct systemic and pulmonary immune responses are induced by differing routes of natural infection or vaccination.

An initial draft of the human pangenome is presented and made publicly available by the Human Pangenome Reference Consortium; the draft contains 94 de novo haplotype assemblies from 47 ancestrally diverse individuals.

The spectrally narrow photoluminescence lines occurring in transition metal dichalcogenides (TMD) heterostructures at low temperature have been attributed to interlayer excitons (IXs) localized by the moiré potential between the TMD layers. Here, the authors show that these lines are present even when the moiré potential is suppressed by inserting an hBN spacer between the TMD layers.

Understanding the oxygen reduction reaction at fuel cell cathodes requires information on adsorbed oxygenated species. Sanchez Casalongue et al. report in situidentification of oxygenated intermediates at cathodes and establish a correlation between the cathode potential and the surface speciation.