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Brown adipose tissue (BAT) is key for metabolic balance. Here, the authors show that RAP250 deficiency enhances BAT activity. Under these conditions, BAT-derived neuritin-1 regulates thermogenesis and fat metabolism, showing therapeutic promise for obesity and metabolic disorders.

The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

Here the authors report that brown adipocyte-derived vaspin reduces heat-producing activity in brown fat by blocking adrenergic signals, helping to regulate energy expenditure and maintain metabolic balance.

ATF6α activation in human and preclinical models of hepatocellular carcinoma is significantly associated with an aggressive tumour phenotype characterized by reduced survival, glycolytic reprogramming and local immunosuppression.

Brown adipose tissue, known produce heat by metabolizing fat, is also secretes molecules capable of communicating with other organs. Here the authors show that brown adipose tissue secretes kininogen, a component of heat system regulation, that provides auto-regulatory inhibitory signaling in brown adipose tissue.

The lowest-frequency gravitational wave background may be shaped by supermassive black hole binaries that scatter nearby stars or dark matter. In this case, the NANOGrav 15-year dataset favours dense galactic centres with 10⁶ solar masses per cubic parsec.

HIV-1 integrase forms an RNA-binding module on the luminal side of the mature capsid lattice.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

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.

In a phase 1b/2 trial, an off-the-shelf vaccine using gorilla adenoviral and modified vaccinia Ankara vectors with over 200 mutated peptides known to be present in persons with mismatch-repair-deficient tumors is safe and elicits neoantigen-specific T cells in individuals with Lynch syndrome.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

The transcription factor ATF4 and its effector lipocalin 2 (LCN2) have a key role in immune evasion and tumour progression, and targeting the ATF4–LCN2 axis might provide a way to treat several types of solid tumour by increasing anti-cancer immunity.

Spatiotemporal insight into photoactivation of the prototypical B₁₂ photoreceptor CarH is revealed across nine orders of magnitude in time, identifying a transient adduct that distinguishes it from thermally activated B₁₂ enzymes.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Laurila et al. extend findings from rodents to humans by demonstrating, in a clinical trial, that the gut hormone secretin, which is secreted in response to a meal, induces thermogenesis and satiation in healthy males.

Alström syndrome (AöS) is a rare genetic disorder characterized by metabolic problems. Here, the authors show that in AöS models, defects in cilia and autophagy lead to ACBP accumulation, which drives obesity. An anti-ACBP antibody reduces weight gain and metabolic dysfunction, highlighting ACBP as a therapeutic target for this ciliopathy.

Moral-Sanz, Fernández-Carrasco and colleagues identify senolytic properties of sea anemone-derived pore-forming toxins, with selectivity mediated by senescence-associated lipid profiles. An optimized senotoxin improves the efficacy of chemotherapy in mouse models.

Brown adipose tissue (BAT) burns, rather than stores, energy and has thus been explored as a way to combat obesity. Aaron Cypess and his colleagues isolate neck fat from adult humans and show that BAT exists in this region, define its anatomical localization in the neck relative to white adipose tissue and demonstrate that it is functional.

This study reveals diverse soil nematode community patterns across Atacama habitats, including dunes, high elevation mountains and fog oases. Latitude, rainfall and elevation were found to be associated with diversity and reproductive modes.

Ageing of the immune system is now realized to drive systemic ageing, and there is interest in targeting immune ageing in order to promote healthy ageing. Here, the authors detail how ageing affects different immune cell populations and discuss strategies to rejuvenate the immune system in order to extend healthspan.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Non-nutritive sensory components of high-fat diet, such as bacon flavour, are sufficient to impair metabolic health in offspring in mice.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

Benito-Martínez, Salavessa and colleagues show that keratin intermediate filaments and microtubules control the three-dimensional perinuclear position of melanin-containing organelles, shielding the DNA from photodamage.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

Despite extensive structural studies elucidating how antigens are anchored to antigen-presenting molecules and presented to T cells, little is known about the display mechanism of the lipid-antigen-presenting molecule CD1c. Here, by combining structural immunology, lipidomics, and biophysical analysis, the authors reveal that the CD1c binding cleft accommodates two different lipids, one of them with a bulky headgroup positioned sideways for display to T cells, rather than upwards, different from the conventional upright antigen-presentation mode

In vivo experiments and clinical cohort analyses show that hypoxia-inducible factor 2 (HIF2)-induced parathyroid hormone-related protein (PTHrP) expression contributes to cachexia in the context of renal cell carcinoma (RCC). The pathway can be targeted by HIF2 inhibitors, including belzutifan, which may reduce cachexia in patients with RCC.

The authors propose a Generalized Latent Equilibrium framework for fully local credit assignment in physical, dynamical neuronal networks such as the brain. By exploiting dendritic structure and prospective coding in cortical neurons, it enables an online approximation of backpropagation through space and time.

H5N1 avian influenza viruses caused an outbreak in dairy cattle. We show that the potential for avian viruses to replicate in cow cells varies across H5N1 evolution, suggesting that the risk of spillover into mammals differs between variants.

This multicenter study demonstrates use of dried and capillary blood as a minimally invasive, scalable approach for Alzheimer’s biomarker testing in research, with potential as a widely scalable population-based research approach, especially in resource-limited settings.

The metastatic potential of patients following breast cancer neoadjuvant therapy is highly variable. Here, the authors demonstrated the predictive and prognostic value of ctDNA in 723 patients with high-risk early-stage breast cancer using serial analysis.

G49, a dual glucagon/glucagon-like peptide-1 receptor agonist, triggers an inter-organ crosstalk between adipose tissue, pancreas and liver, leading to brown fat activation with the final outcomes of increased energy expenditure and body weight loss.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

CRISPR gene targeting in multicellular organisms results in genetic mosaics, limiting knockout efficiency. Here, the authors develop an improved system using Cas12a with multiple guides per gene, and demonstrate high accuracy and superior knockout efficiency in fruit flies.

Intermittent fasting is investigated as an alternative to caloric restriction as a treatment modality for weight loss and improvement of cardiometabolic risk factors. Here the authors report the secondary and exploratory outcomes of a randomized controlled cross-over trial showing that six months of intermittent fasting reduced body weight and improved lipid profiles, which associated with altered GLP−1–related enteroendocrine signaling and B-cell pathways based on colon transcriptomics and plasma metabolimics.

It is unclear how cell compartmentalization emerged in prebiotic conditions. Now it is shown that a temperature gradient in a confined space can bring the core components of a cell together.

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.

Riparian vegetation reduced gulf turbidity up to 800 meters offshore, overlapping coral reefs and seagrasses, while pasture and gravel roads increased turbidity, according to a scalable framework using remote sensing and causal inference methods.

Pathogenic variants in UNC13A underlie a novel neurodevelopmental syndrome, with three subtypes defined by distinct genotypes with varying clinical and functional impacts characterized in cellular and animal models.

Yücel et al. examine how skin and hair characteristics impact functional near-infrared spectroscopy (fNIRS) signal quality and provide recommendations for inclusive use of fNIRS.

Metal halide perovskites feature crystalline-like electronic band structures and liquid-like physical properties that allow chemical manipulation of the structure with low energy input. Here, the authors leverage the low formation energy of 2D metal halide perovskites to demonstrate films that reversibly switch between multiple colors using tunable quantum well thickness.

Kinematic measurements of the Perseus galaxy cluster reveal two drivers of gas motions: a small-scale driver in the inner core associated with black-hole feedback and a large-scale driver in the outer core powered by mergers.

Eggplants are important vegetables worldwide. Here, the authors report 40 genome assemblies of Solanum melongena, its progenitor S. insanum and the allied species S. incanum to construct two pangenomes, and identify loci associated with multiple traits via pangenome-wide association analysis.

Activity-dependent oligodendroglial plasticity contributes to neuronal functions. Here the authors show that adaptive oligodendrocyte progenitor cell responses are disrupted in neurofibromatosis 1, impairing oligodendroglial dynamics and resulting in motor learning deficits in Nf1-deficient and Nf1-mutant mice.

In this study, the authors generated iPSC lines from more than 100 sporadic ALS cases, which recapitulated key disease phenotypes and enabled large-scale drug screening, identifying a promising combination therapy of baricitinib, memantine and riluzole.