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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.

Fluorogenic RNA aptamers such as Mango are powerful tools for RNA imaging. An ultrabright RNA-activated fluorophore with improved photophysical performance has now been developed using a structure-informed, fragment-based screening approach. This system was studied using high-resolution crystallography and applied to image RNA in cells.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

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

Leishmania donovani is a protozoan parasite that can cause fatal infections in humans. Here the authors present a high resolution cryoEM structure of the L. donovani80S ribosome and compare it to its human counterpart to provide insight into the basis for drug selectivity towards this eukaryotic parasite.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

GWAS have identified more than 500 genetic loci associated with blood lipid levels. Here, the authors report a genome-wide analysis of interactions between genetic markers and physical activity, and find that physical activity modifies the effects of four genetic loci on HDL or LDL cholesterol.

Together with an accompanying paper presenting a transcriptomic atlas of the mouse lemur, interrogation of the atlas provides a rich body of data to support the use of the organism as a model for primate biology and health.

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.

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.

Intestinal cell types are organized into distinct neighbourhoods and communities within the healthy human intestine, with distinct immunological niches.

Studies using mouse and non-human primate models identify the innate immune regulator STING—acting via type I interferons—as a key regulator of nociception, suggesting new targets for the treatment of chronic pain.

Application of an electrical field to Geobacter sulfurreducens biofilms stimulates production of OmcZ nanowires, which undergo a pH-induced conformational switch that causes increased stiffness and conductivity due to enhanced heme group π-stacking.

A meta-analysis of genome-wide association study data from 77,418 individuals of East Asian ancestry with type 2 diabetes identifies novel variants associated with increased risk of type 2 diabetes.

Protein targets that are affected by ROS and underly impaired inotropic effects in the heart are largely unknown. Here, the authors identify the γ-subunit of IDH3 as a redox switch linking oxidative stress to impaired metabolism and heart function.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

Since 1987, immortalized cells from the ovary of a Chinese hamster have been the workhorse for producing recombinant therapeutics, including monoclonal antibodies, blood factors, hormones, growth factors and enzymes. Xu et al. provide the genome sequence of the ancestral CHO-K1 cell line, which should aid in the optimization of current production cell lines.

Split-FISH leverages a split-probe design to achieve enhanced specificity in multiplexed fluorescence in situ hybridization. Split-FISH reduces background and false positives, enabling transcriptome profiling in uncleared tissues.

Endocrinologists have traditionally focused on studying one hormone or organ system at a time. Here the authors use transcriptomic data from the mouse lemur to globally characterize primate hormonal signaling, describing hormone sources and targets, identifying conserved and primate specific regulation, and elucidating principles of the network.

Single-cell genome sequencing can provide detailed insights into the composition of single genomes that are not readily apparent when studying bulk cell populations. This Review discusses the considerable technical challenges of amplifying and interrogating genomes from single cells, emerging innovative solutions and various applications in microbiology and human disease, in particular in cancer.

A complex of suPAR and high-risk variants of APOL1 acting on integrin signaling in the kidney contributes to APOL1-associated chronic kidney disease.

Fernando Rivadeneira and colleagues in the Genetic Factors for Osteoporosis Consortium report a large-scale meta-analysis identifying new loci associated with bone mineral density (BMD) and risk of fracture. Thirty-two new loci are found to be associated with BMD, and 6 loci confer higher risk for low-trauma bone fracture.

An adversarial domain translation framework is presented for scalable integration of single-cell atlases across samples, technical platforms, data modalities and species.

The transcriptome changes driving the conversion of fibroblasts to neurons at the single-cell level are reported, revealing that early neuronal reprogramming steps are homogenous, driven by the proneural pioneer factor Ascl1; the expression of myogenic genes then has a dampening effect on efficiency, which needs to be counteracted by the neuronal factors Myt1l and Brn2 for more efficient reprogramming.

Interstitial cells of Cajal (ICC) were first described in the gastrointestinal tract, however ICC-like cells (ICC-LC) can also be found in the lower urinary tract (LUT), where they act as electrical pacemakers and as intermediary cells involved in the modulation of neurotransmission to adjacent smooth muscle cells. In this Review, Drumm et al. discuss the physiological functions of ICC-LC, focussing on their role as pacemakers, and consider how the study of their intracellular Ca²⁺dynamics will provide a better understanding of the role of ICC-LC in LUT excitability.

A multi-pronged activation approach applied to 54 actinobacterial strains doubles accessible metabolite space and enables discovery of gram-negative bioactivity, offering insights to harness nature’s chemical potential. The approach enhances or triggers natural product production across all 54 native actinobacterial strains, doubling total metabolite production and enabling the discovery of a new tetramic acid analog with gram-negative bioactivity. Insights from this large-scale study could lead to a more streamlined approach to unlock the full potential of nature’s chemical resources.

A risk haplotype for type 2 diabetes is identified with four amino acid substitutions in SLC16A11, which is present at ∼50% frequency in Native American samples and ∼10% in east Asian samples, but is rare in European and African samples; SLC16A11 may alter hepatic lipid metabolism, causing an increase in triacylglycerol levels.