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Neural crest cells have been implicated in heart development, yet the mechanisms by which they act have remained elusive. Here, the authors show neural crest cells modulate Wnt signalling in cardiac progenitors, providing new insight into the mechanisms underpinning congenital heart defects.

The precise manipulation of unfunctionalized hydrocarbons remains a fundamental challenge in chemical synthesis and catalysis. Here an organocatalytic asymmetric hydroxylation of bicyclobutanes with alcohols is disclosed, enabling efficient access to tertiary cyclopropylcarbinyl ethers with high enantioselectivity (up to 98:2 e.r.).

Soil microbial populations bloom and then die-off in ecosystems with seasonal snowpack. This study showed that distinct taxa utilize different N sources for growth or energy during the microbial bloom and alter the fate of N after snowmelt.

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.

The authors use data on the entire Finnish population to develop a machine learning model for predicting COVID-19 vaccination uptake. Important predictors are proxies of socio-economic status, and those at high risk for COVID-19 consequences are less likely to get vaccinated.

Proteomic data from natural isolates of Saccharomyces cerevisiae provide insight into how these cells tolerate aneuploidy (an imbalance in the number of chromosomes), and reveal differences between lab-engineered aneuploids and diverse natural yeasts.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

MultiCell is a deep learning method to capture complex cell dynamics during multicellular development.

Growing demand for robust plasma and serum proteomics highlights the need for better standardization. Here, the authors introduce an open 211-peptide internal standard that enables consistent quantification, cross-platform alignment and clinical utility across serum and plasma studies.

Li and colleagues describe a monocyte-specific transcriptional state along with a persistent elevation of inflammatory markers specifically found in individuals with long COVID who had mild-to-moderate disease during acute SARS-CoV-2 infection.

Multi-ancestry genome-wide and transcriptome-wide association studies of aortic stenosis identify more than 200 independent risk loci and provide insights into its genetic architecture.

The study by Russo et al. demonstrates alterations in the presence of senescence hallmarks across cell types, inducers, and model systems. These findings spotlight TFAP4 as a key regulator of senescence phenotypes in aging and Parkinson’s Disease.

An allosteric site on the E3 ligase adapter cereblon can be targeted to modulate the efficacy of cereblon in targeted protein degradation applications.

Global mean surface warming has been slow over the past 15 years. An analysis of climate simulations suggests that the low warming rate can be explained by an unusual phase of El Niño/Southern Oscillation and solar and aerosol variability.

Candida auris can scavenge carbon dioxide from microenvironments through Nce103 to sustain fitness when colonizing human skin.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

How inflammation spreads from the skin to the joints in psoriatic disease is unclear. Here, the authors show that joint-resident fibroblasts can control differentiation of infiltrating skin-derived myeloid precursors that can become inflammatory macrophages.

The extracellular matrix protein laminin-α2 provides muscle fibers with essential structural support. Here, the authors show that muscle stem cells also secrete laminin-α2 to support their own proliferation during muscle regeneration.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

A hybrid machine learning and atomistic modelling strategy enables one-shot design of efficient enzymes to catalyse diverse biological and non-biological chemical transformations.

CGP and ASAF1 act at distinct stages of conoid complex biogenesis in T. gondii: CGP stabilises preconoidal rings post-replication, while ASAF1 directs early assembly and daughter cell formation.

Here the authors perform a trans expression quantitative trait locus meta-analysis study of over 3,700 people and link a USP18 variant to expression of 50 inflammation genes and lupus risk, highlighting how genetic regulation of immune responses drives autoimmune disease and informs new therapies.

Olfactory perception shows marked sexual dimorphism, yet its genetic basis remains underexplored. Here, the authors show sex-specific and shared genetic loci for odour identification, implicating olfactory receptor clusters and links to Alzheimer’s disease risk.

Cancer patients are at increased risk for severe bacterial infections due to immune dysfunction. Here, the authors show that chronic tumor-derived G-CSF drives NAMPT/NAD-dependent neutrophil dysfunction from the progenitor stage, and that targeting this pathway restores infection control.

CellSAM uses an object detector, CellFinder, to detect cells and prompt the Segment Anything Model (SAM) to generate segmentations. This universal model achieves human-level performance across a range of bioimaging data encompassing mammalian cells, yeast and bacteria.

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.

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.

The success of allogeneic hematopoietic stem cell transplantation for the treatment of haematological cancers is limited by the morbidity and mortality associated with graft-versus-host disease (GVHD). Here the authors show that the microbial metabolite desaminotyrosine contributes to graft-versus-leukemia responses while protecting against GVHD and promoting mTORC1 and STING-dependent intestinal regeneration.

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

Efficient lead optimization in drug discovery requires improving potency, synthetic accessibility, and physicochemical properties. Here, the authors utilize machine learning to screen large chemical spaces, demonstrating automated selection of optimized molecules to improve cycle times.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Weldy et al. show that smooth muscle expression of the RNA editing enzyme ADAR1 regulates activation of the double-stranded RNA sensor MDA5 in a novel mechanism of atherosclerosis.

This research quantifies hospital admissions in Shanghai for mental and behavioral disorders linked to humid heat, projecting a 68.2% increase by the 2090s under high greenhouse gas emissions and emphasizing the importance of mitigation strategies to reduce future morbidity burdens.

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.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

Regev, Casto et al. examine the temporal response patterns of neural populations in the language network and discover that these populations process information over different timescales.

Variants in NOS1AP can cause monogenic nephrotic syndrome. Here, the authors show that disrupting the intergenic NOS1AP splice isoform that is more prevalent in podocytes leads to monogenic kidney disease responsive to RAAS inhibition.

Reconfigurable arrays of up to 448 neutral atoms are used to implement and combine the key elements of a universal, fault-tolerant quantum processing architecture and experimentally explore their underlying working mechanisms.

Large genome-wide meta-analysis of clinically diagnosed late-onset Alzheimer’s disease (LOAD) from 94,437 individuals identifies new LOAD risk loci and implicates Aβ formation, tau protein binding, immune response and lipid metabolism.

Exome sequencing within a structured diagnostic process for rare diseases in Germany shows how facial image analysis and machine learning can guide variant prioritization and uncover many ultrarare diseases.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

Dahl et al. use neuromelanin-sensitive neuroimaging in a cohort of participants spanning ages 25 to 83 and report that ‘youth-like’ rostral locus coeruleus integrity is associated with better memory performance in the elderly.

Metabolites act as enzyme inhibitors, but their global impact on metabolism has scarcely been considered. Here, the authors generate a human genome-wide metabolite-enzyme inhibition network, and find that inhibition occurs largely due to limited structural diversity of metabolites, leading to a global constraint on metabolism which subcellular compartmentalization minimizes.

Timothy Frayling, Joel Hirschhorn, Peter Visscher and colleagues report a meta-analysis of genome-wide association studies for adult height in 253,288 individuals. They identify 697 variants in 423 loci significantly associated with adult height and find that these variants cluster in pathways involved in growth and together explain one-fifth of the heritability for this trait.