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Brown adipose tissue (BAT) thermogenesis counteracts obesity and promotes metabolic health. The role of long non-coding RNAs (lncRNAs) in the regulation of this process is not well understood. Here the authors identify a maternally expressed lncRNA, H19, that increases BAT oxidative metabolism and energy expenditure.

The most frequent cause of familial Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are hexanucleotide repeat expansions in the non-coding region of the C9ORF72 gene that are translated into five dipeptide repeat (DPR) proteins. Here, the authors show that proline/arginine (PR) DPRs inhibit the prolyl isomerase PPIA and reveal the molecular mechanism of the impaired protein folding activity of PPIA by performing NMR measurements and determining a PR DPR bound PPIA crystal structure.

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.

Acquired resistance to immune checkpoint inhibitors limits therapeutic success in non-small-cell lung cancer, however, the underpinning immune parameters are largely unknown. Here authors distinguish resistance types based on immune cell infiltration, immune checkpoint molecule and cytokine expression level, using paired samples from patients in the sensitive and in the resistant disease phase.

Analyses of genomes from 914 children, adolescents, and young adults provide a comprehensive resource of genomic alterations across a spectrum of common childhood cancers.

The beetle Tribolium castaneum is a commonly used laboratory model, combining the ease of systematic RNAi experiments like those in Caenorhabditis elegans, with biology that is more representative of most insects than Drosophila melanogaster. A large consortium has sequenced and analysed the genome of the red flour beetle, creating a resource for biologists everywhere.

The climatic response to the 1257 Samalas eruption is unclear. Analyses of proxy data and medieval archives suggest that the eruption triggered some of the coldest summers of the past millennium, but only in some Northern Hemisphere regions.

α-ketoglutarate (αKG) is an intermediate in the tricarboxylic acid cycle that is required in the nucleus for genomic DNA demethylation by Tet3. Here, the authors show that the enzyme glutamate dehydrogenase, which converts glutamate to αKG, is redirected from the mitochondria to the nucleus.

In cancer, global DNA methylation loss and CpG island hypermethylation are commonly observed. Here, in breast cancer the authors find that hyper-variability of partially methylated domains is the prime source of DNA methylation variation and that these domains fuel CpG island hypermethylation.

The involvement of cAMP-dependent regulation of HCN4 in the chronotropic heart rate response is a matter of debate. Here the authors use a knockin mouse model expressing cAMP-insensitive HCN4 channels to discover an inhibitory nonfiring cell pool in the sinoatrial node and a tonic and mutual interaction between firing and nonfiring pacemaker cells that is controlled by cAMP-dependent regulation of HCN4, with implications in chronotropic heart rate responses.

Serotonin is released throughout the brain from diverse projections of neurons in the dorsal raphe nucleus. Here, the authors use optogenetics and fMRI mediated mapping of the mouse brain-wide serotonin network in response to acute stress and treatment with SSRI.

Lipid concentration in the serum is one of the most important risk factors for coronary artery disease and can be targeted for therapeutic intervention. A genome-wide association study in >100,000 individuals of European ancestry now finds 95 significantly associated loci that also affect lipid traits in non-European populations. Among associated loci are those involved in cholesterol metabolism, known targets of cholesterol-lowering drugs and those that contribute to normal variation in lipid traits and to extreme lipid phenotypes.

A genome-wide association study in ~3 million individuals identifies 3,952 independent variants associated with educational attainment. A polygenic index explains 12–16% of variance for this trait and contributes to risk prediction for ten diseases.

Systemic dissection of sexually dimorphic phenotypes in mice is lacking. Here, Karp and the International Mouse Phenotype Consortium show that approximately 10% of qualitative traits and 56% of quantitative traits in mice as measured in laboratory setting are sexually dimorphic.

Multiple GTP-binding proteins (GTPBPs) aid ribosome maturation. Here, authors pinpoint GTPBP8’s involvement in human mitoribosome maturation, demonstrating its specific binding to mitoribosomal large subunit RNA, which is necessary for ribosome assembly and protein synthesis.

The end of the green Sahara in the mid-Holocene was gradual, but punctuated by rapidly changing episodes of extreme drought and wetness, to which human societies were exposed and had to adapt to, as a lake record from southern Ethiopia suggests.

As demand for organ transplants exceeds availability there has been an unmet need to extend preservation of deceased donor kidneys. Here, the authors show that a cell-free nutrient-supplemented perfusate allows 4-day preservation of human kidneys using spatially resolved lipidomics and metabolomics.

Mark Caulfield, Paul Elliott and colleagues use data from the UK Biobank to perform genome-wide association analysis for blood pressure traits. They identify and validate 107 novel loci and highlight new biological pathways for potential therapeutic intervention for hypertension.

Many bacterial toxins and viruses deform membranes prior to entering cells via clathrin independent endocytosis. Here the authors show that multivalent lipid binding by globular particles can exceed a threshold adhesion energy required for membrane deformation and that this is sufficient for internalization.

Single-cell analysis reveals how anti-hypertensive drugs affect the risk of severe disease in patients with COVID-19 who have hypertension.

The authors show that post-transcriptional regulation of the cilia-driven leftward flow target dand5 is central to symmetry breakage in frog, fish and mouse and is mediated by a 139 nt Bicc1 responsive element in the dand5 3′UTR, and they present evidence that Pkd2 regulates this Bicc1/dand5 module.

In this work, the authors report NMR lipids Databank to promote decentralised sharing of biomolecular molecular dynamics (MD) simulation data with an overlay design. Programmatic access enables analyses of rare phenomena and advances the training of machine learning models.

Global challenges demand global solutions. Here, the authors show a distributed self-driving lab architecture in The World Avatar, linking robots in Cambridge and Singapore for asynchronous multi-objective reaction optimisation.

In this Review, Weingarth and colleagues discuss both recently discovered compounds and established envelope-targeting antibiotics, including compounds that target Gram-positive bacteria, more complex Gram-negative bacteria and mycobacterial pathogens, with a particular focus on their drug–target interactions.

JWST observations of CH₃⁺ in a protoplanetary disk in the Orion star-forming region are reported showing that gas-phase organic chemistry in the interstellar medium is activated by ultraviolet irradiation and the methyl cation.

Untargeted metabolomics demonstrate that apoptotic brown adipocytes release a specific pattern of metabolites with purine metabolites being highly enriched, and inosine is identified as a metabolite released during apoptosis regulating thermogenic fat and counteracting obesity.

A recently proposed structure of an N₂-bound Mo-nitrogenase has sparked considerable attention, although the direct evidence for N₂ binding and sulfur mobilization during turnover has remained elusive. Now, additional spectroscopic and kinetic measurements further support this state and provide evidence that belt-sulfur displacement is an essential aspect of the nitrogenase mechanism.

Stratified medicine promises to tailor treatment for individual patients, however it remains a major challenge to leverage genetic risk data to aid patient stratification. Here the authors introduce an approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue-specific gene expression levels, and highlight its ability to identify biologically meaningful and clinically actionable patient subgroups, supporting the notion of different patient ‘biotypes’ characterized by partially distinct disease mechanisms.

Mica is a naturally occurring 2D mineral that has been heavily studied in many diverse areas. Here authors present atomic force microscopy images to study the mica surface in ultra-high vacuum conditions; they unveil the distribution of its surface K⁺ ions and give insights into the distribution of subsurface Al³⁺ ions.

Extended exposure to breastfeeding in rodent pups protects them from diet-induced obesity in adulthood by increasing thermogenesis and energy expenditure. This is mediated by liver-derived FGF21 signalling to the lateral hypothalamic area.

Children are less likely to be infected with SARS-CoV-2 and develop less severe disease than adults, which makes estimation of infection rates challenging. Here, the authors conduct seroprevalence surveys of children in Germany, describe changes in prevalence over time, and identify risk factors for infection.

Analysis of genotyping-by-sequencing data for more than 20,000 barley accessions from a German genebank provides a framework for genomics-assisted genebank management and analysis of large germplasm collections for important crops.

The exact freshwater scenario that caused the 8.2 ka cold event is still debated. This study presents new evidence for a severe Labrador shelfwater freshening 8500 years ago that was caused by the Hudson Bay Ice Saddle collapse following a warming in subsurface waters.

Angiogenesis requires dynamic endothelial rearrangements and relative position changes within the vascular tubes. Here the authors show that a PI3K/NUAK1/MYPT1/MLCP pathway regulates actomyosin contractility in endothelial cells and cellular rearrangement during vascular patterning.

Chromatophores in cephalopod skin are known for fast changes in coloration due to light-scattering pigment granules. Here, authors demonstrate structural coloration facilitated by reflectin in sheath cells and offer insights into the interplay between structural and pigmentary coloration elements.

Panos Deloukas, Nilesh Samani and colleagues report a large-scale association analysis using the Metabochip array in 63,746 coronary artery disease cases and 130,681 controls. They identify 15 susceptibility loci, refine previous associations and use network analysis to highlight biological pathways.

Imaging changes in molecular geometries with sufficient temporal and spatial resolution to image nuclei is a critical challenge in the chemical sciences. Here the authors report gasphase Megaelectronvolt electron diffraction with 100 fs temporal resolution and subAngstrom spatial resolution.

Reengineering polyketide synthase encoding genes to produce analogues of natural products can be slow and low-yielding. Here the authors use accelerated evolution to recombine the gene cluster for rapid production of rapamycin-related products.

This meta-analysis of genome-wide association studies identifies four genetic loci associated with circulating leptin levels independent of adiposity. Examination in mouse adipose tissue explants provides functional support for the leptin-associated loci.

Phase-space optics is an indispensable tool for optical imaging and sensing. New optical hardware for light-field photography and pupil engineering for imaging with extended depth of field promote the use of phase-space representations as the primary object of optical signal processing.

Certain bacterial enzymes are packaged within protein chambers that provide a confined environment for their reactions to take place. Ban and colleagues now identify a family of proteins that form nanocompartments, similar to bacterial microcompartments such as the carboxysome, and show that the enzymes within are anchored by their C-terminal extensions to binding sites on the inner surface of the chamber.

Analysis of a large grassland biodiversity dataset shows that increases in local land-use intensity cause biotic homogenization at landscape scale across microbial, plant and animal groups, both above- and belowground, that is largely independent of changes in local diversity.

Emergence of Nagaoka polarons and kinetic magnetism is observed in a Hubbard system realized with strongly interacting fermions trapped in a triangular optical lattice.

Stable isotope-labelled amino acid incorporation into proteins reveals that genetically homogeneous yeast colonies contain metabolically distinct subpopulations that cross-feed each other and are phenotypically diverse.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Number of IL-9-expressing ILC2s are elevated in patients with inflammatory arthritis during remission, and these cells are critical in mice for the resolution of inflammatory arthritis via regulatory T cell induction. Delivery of DNA minicircles encoding IL-9 into inflamed joints ameliorates mouse experimental arthritis, suggesting possible therapeutic applications.