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Serum urate concentration can be studied in large datasets to find genetic and epigenetic loci that may be related to cardiometabolic traits. Here the authors identify and replicate 100 urate-associated CpGs, which provide insights into urate GWAS loci and shared CpGs of urate and cardiometabolic traits.

The number of individuals in a given space influences animal interactions and network dynamics. Here the authors identify general rules underlying density dependence in animal networks and reveal some fundamental differences between spatial and social dynamics.

Genome-wide association studies (GWAS) have become a key tool to discover genetic markers for complex traits; however, environmental factors that interact with genes are rarely considered. Here, the authors conduct a GWAS of obesity traits, and find that smoking may alter genetic susceptibilities.

Understanding gene expression patterns that underlie developmental programs can inform engineering efforts for new or optimized forms. Here, the authors engineer a four-state history-dependent integrase-based recorder of gene expression in Arabidopsis and show its application in two developmental programs.

Comparisons within the human pangenome establish that homologous regions on short arms of heterologous human acrocentric chromosomes actively recombine, leading to the high rate of Robertsonian translocation breakpoints in these regions.

How ocean acidification will impact coastal biogenic habitats is unclear. This study predicts that indirect effects on habitat-forming organisms, combined with direct effects on biodiversity, will cause changes in structural complexity and extent of these habitats.

Together with a companion paper, the generation of a transcriptomic atlas for the mouse lemur and analyses of example cell types establish this animal as a molecularly tractable primate model organism.

The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke.

In a large pragmatic cluster-randomized trial involving 74 clinical units in 2 health systems in the United States, a real-time alert system assisting clinical care teams in identifying patients at risk of deterioration decreased mortality risk by 35.6%, with positive effects also on length of stay.

We present the complete 62,460,029-base-pair sequence of a human Y chromosome from the HG002 genome (T2T-Y) that corrects multiple errors in GRCh38-Y and adds over 30 million base pairs of sequence to the reference.

Nonninger et al. identify the TFEB–TGFβ signaling axis as a regulator of stem cell resilience that protects against a senescence-like state during the adult diapause in Caenorhabditis elegans, a mechanism conserved in vertebrate aging and mammalian cancer.

Cell type labelling in single-cell datasets remains a major bottleneck. Here, the authors present AnnDictionary, an open-source toolkit that enables atlas-scale analysis and provides the first benchmark of LLMs for de novo cell type annotation from marker genes, showing high accuracy at low cost.

Analysis of whole-genome sequences of 25,465 individuals of European ancestry shows that rare variants contribute substantially to the heritability of height and body mass index.

Erik Ingelsson and colleagues report a large-scale genome-wide meta-analysis for associations to the extremes of anthropometric traits, including body mass index, height, waist-to-hip ratio and clinical obesity. They identify four loci newly associated with height and seven loci newly associated with clinical obesity and find overlap in the genetic structure and distribution of variants identified for these extremes of the trait distributions and for the general population.

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.

Data from over 700,000 individuals reveal the identity of 83 sequence variants that affect human height, implicating new candidate genes and pathways as being involved in growth.

Malonyl-CoA (M-CoA) is essential for polyketide biosynthesis, but its limited availability constrains production. Here the authors engineer and evolve an orthogonal M-CoA pathway in Escherichia coli to improve M-CoA metabolism, increasing M-CoA levels and polyketide yields.

In a phase 1 trial, treatment of individuals with mixed hyperlipidemia with a monoclonal antibody targeting the angiopoietin-like protein 3/8 complex resulted in dose-dependent reductions in the levels of triglycerides and low-density lipoprotein cholesterol, while increasing the levels of high-density lipoprotein.

The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.

Sequencing analyses of human prefrontal cortex from donors ranging in age from 0.4 to 104 years show that ageing correlates with an accumulation of somatic mutations in short housekeeping genes and a reduction in the expression of these genes.

The combination of neoadjuvant nivolumab, ipilimumab and chemotherapy showed promising efficacy in patients with resectable non-small cell lung cancer, with higher tumor immune cell infiltration and tertiary lymphoid structures after treatment compared with neoadjuvant nivolumab plus chemotherapy.

Thicker oceanic crust forms from a hot mantle. Observations of unusually thick oceanic crust that formed 170 million years ago in the Atlantic and Indian oceans suggest that the ancient supercontinent Pangaea helped insulate and warm the mantle.

A recent Nature article reports that mRNA vaccines against SARS-CoV-2 confer improved survival among patients with advanced-stage non-small-cell lung cancer or melanoma receiving immune-checkpoint inhibitors owing to activation of systemic immunity, potentiating antitumour responses. This retrospective proof-of-principle study indicates the potential for combined therapeutic interventions, although both the timing of vaccination as well as the nature of the elicited immune responses requires further investigation.

The Ly49 gene family mainly encodes inhibitory or activating surface receptors on natural killer cells. Here the authors show that in mice, inhibitory and activating Ly49 genes are regulated by two distinct sets of cis-regulatory elements, and that different Ly49 genes can be cross-regulated.

Phytoplankton productivity is high in the polar oceans. Lidar observations from 2006–2015 reveal that phytoplankton biomass was characterized by annual cycles influenced by sea-ice extent in the Antarctic and ecological processes in the Arctic.

Around 1 in 136 pregnancies is lost due to a pathogenic small sequence variant genotype in the fetus.

Gemin5 is a WD repeat protein that binds small nuclear RNAs (snRNAs) through a specific sequence in the context of the SMN complex, a function required for spliceosomal snRNP biogenesis. Reduced levels of SMN cause spinal muscular atrophy. A series of biochemical experiments now indicate that the WD repeat region of Gemin5 recognizes the snRNAs in a sequence-specific fashion, suggesting that WD repeats are capable of RNA binding.

The dorsal peduncular area of the mouse brain functions as a network hub that integrates diverse cortical and thalamic inputs to regulate neuroendocrine and autonomic responses.

RMC-7977, a compound that exhibits potent inhibition of the active states of mutant and wild-type KRAS, NRAS and HRAS variants has a strong anti-tumour effect on RAS-addicted tumours and is well tolerated in preclinical models.

RNA-guided CRISPR-associated transposases (CAST) are natural systems with broad potential in biotechnology. Here, the authors report compact type V-K CAST discovered from genome-resolved metagenomics and demonstrate targeted integration of a large transgene to a safe-harbor site in the human genome.

By regulating the level of accessible cholesterol on endothelial cells via OSBP/ORP-mediated transport, tetraspanin tunes the balance of Cdc42 and RhoA activities to affect vascular inflammation. Reducing accessible cholesterol by statin treatment or blocking its non-vesicular transport by OSBP/ORP inhibition can limit vascular inflammation.

A generative AI model, Orion, learns a robust and generalizable pattern of non-small cell lung cancer from cancer-specific circulating non-coding RNAs. Orion enhances the performance of liquid biopsy for early cancer detection and tumor subtyping.

Complementary transistors are critical for multistage circuits. Asymmetry of source/drain contacts enables creation of single-material, matched complementary organic amplifiers with long-term in vivo stability

Systematic analysis from the Global Burden of Disease study reported that, despite global improvements from 1990 to 2021, dietary iron deficiency-associated disease burden remains high in women, children and residents in low socio-demographic index countries.

Glioblastoma is resistant to immune-checkpoint inhibitors. In this study, the authors report the results of an expansion cohort (n = 25) of a randomized testing neoadjuvant plus adjuvant pembrolizumab versus adjuvant pembrolizumab alone in patients with recurrent glioblastoma with resectable tumors.

AQRNA-seq allows accurate quantification of small RNAs.