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Bone marrow adipose tissue (BMAT) comprises over 10% of total fat mass but its systemic metabolic role is unclear. Here, the authors show that BMAT glucose uptake is not insulin or cold responsive; however, BMAT basal glucose uptake is higher than in white adipose tissue or skeletal muscle, underscoring BMAT’s potential to influence systemic glucose homeostasis.

Shen et al. show that FMRP promotes mitochondrial fusion through HTT. FMRP loss caused fragmented mitochondria and oxidative stress in immature neurons, and enhancing mitochondrial fusion rescued neuronal and behavioral deficits in Fmr1-mutant mice.

Identifying the mechanisms that regulate hair cell regeneration may contribute to developing treatments for hearing loss in humans (pages 1136–1139).

Social learning is a crucial human ability. Here, the authors examined children in 7 cultures and show that children’s reliance on social information and their preference to follow the majority vary across societies. However, the ontogeny of majority preference follows the same, U-shaped pattern across all societies.

In severe autism, deleterious variants at conserved residues are enriched in patients arising from female-enriched multiplex families, enhancing the detection of key autism genes in modest numbers of cases.

Mixed lineage kinase domain-like (MLKL) is the terminal protein in the pro-inflammatory necroptotic cell death program. Here the authors show that MLKL trafficking and plasma membrane accumulation are crucial necroptosis checkpoints, and that accumulation of phosphorylated MLKL at intercellular junctions promotes necroptosis.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

A genomic constraint map for the human genome constructed using data from 76,156 human genomes from the Genome Aggregation Database shows that non-coding constrained regions are enriched for regulatory elements and variants associated with complex diseases and traits.

The enteric nervous system (ENS) plays a key role in regulating gut motility and homeostasis yet it remains a challenging system to record from. Here, the authors develop a novel abdominal window permitting simultaneous optical and electrical recording of mouse ENS system activity over prolonged time periods.

Genome-wide analyses identify common variants associated with 11 distinct neuropathology endophenotypes, providing insights into the mechanisms underlying the genetic risk of Alzheimer’s disease and related dementias.

Stem cells of the liver, colon and small intestine gradually accumulate mutations throughout life at a similar rate even though cancer incidence varies greatly among these tissues.

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.

HNF1B is overexpressed in the clear cell subtype and epigenetically silenced in the serous subtype of ovarian cancer. Pearce and colleagues now show that genetic variants in HNF1B are differentially associated with risks of developing these two cancer subtypes, possibly through an epigenetic mechanism.

In a mouse model of the 5q- subtype of myelodysplastic syndrome, haploinsufficiency of the ribosomal protein gene Rps14 leads to anemia through a mechanism involving innate immune signaling and the Tlr4 ligand S100A8, which induces a p53-dependent block to erythroid differentiation.

Wenzel et al. detect radio signatures of two forms of cyanopyrene, a small molecular sheet of carbon, which can be used as indicators of the abundance of pyrene. Their findings suggest that small polycyclic aromatic hydrocarbons must be formed in or transported to the cold interstellar medium.

Lipochitooligosaccharide (LCO) perception by legumes is required to establish symbiotic relationships with nitrogen fixing bacteria. Here the authors show that nutrient starvation can activate LCO perception in cereals to promote symbiotic association with arbuscular mycorrhizal fungi.

A strategy for inferring phase for rare variant pairs is applied to exome sequencing data for 125,748 individuals from the Genome Aggregation Database (gnomAD). This resource will aid interpretation of rare co-occurring variants in the context of recessive disease.

The relationship between cellular histogenesis and molecular phenotypes for the EWSR1- ATF1 fusion in clear cell sarcoma (CCS) requires further characterization. Here, the authors investigate the EWSR1-ATF1 gene regulation networks in CCS cell lines, primary tumors, and mesenchymal stem cells.

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.

A study shows that clonal haematopoiesis of indeterminate potential is associated with an increased risk of chronic liver disease specifically through the promotion of liver inflammation and injury.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

Whole-genome sequencing and phenotype data sharing are introduced in a national health system to streamline diagnosis and to discover coding and non-coding variants that cause rare diseases.

Genome-wide association studies have identified regions which confer risk of high-grade serous epithelial ovarian cancer. Here the authors use expression quantitative train locus analysis to identify candidate genes and functionally characterise them, identifying a role for HOXD9 in ovarian cancer.

In a study of children with high genetic risk aged 2 years or older, a risk score integrating pancreatic islet autoantibodies, genetic factors and family history is highly predictive of type 1 diabetes in the subsequent 8 years.

Cellulose is produced in plants by cellulose synthase complexes (CSCs) that are assembled in the endomembrane system and then trafficked to the plasma membrane. Here Zhang et al. show that the Golgi-localized STELLO1 and 2 proteins are required for the proper assembly and distribution of CSCs in plant cells.

Better analytical methods are needed to extract biological meaning from genome-wide association studies (GWAS) of psychiatric disorders. Here the authors take GWAS data from over 60,000 subjects, including patients with schizophrenia, bipolar disorder and major depression, and identify common etiological pathways shared amongst them.

The functional role of synaptotagmin-17 (syt-17) has remained unanswered. In this study, authors demonstrate that syt-17 exists in two distinct pools in hippocampal neurons (Golgi complex and early endosomes), where it served two completely independent functions: controlling neurite outgrowth and synaptic physiology

The strength of the global meridional overturning circulation in the stratosphere is uncertain. An analysis of satellite data, reanalyses and model simulations reveals a strength of 6.3–7.6 × 10⁹ kg s⁻¹, but no convergence at higher altitudes.

The genomic characterisation of nasopharyngeal carcinoma (NPC) remains crucial. Here, the authors perform whole-genome sequencing for 70 NPCs with EBV gene expression, report the somatic alterations and EBV-mediated effects converging on NF-κB activation and immune escape and identify targetable homozygous MTAP deletions.

Page et al., use wearable biosensors to monitor vital sign trends in patients with Lassa fever in Sierra Leone. Tachycardia and reduced heart rate variability associate with poor outcomes, though technical limitations hinder broader implementation.

Small-cell lung cancer (SCLC) is an aggressive disease with limited therapeutic options. Here the authors perform an immunogenomic analysis of limited-stage SCLC, revealing a homogeneous mutational landscape, but limited T-cell infiltration and a cold and heterogeneous T cell repertoire.

Michael Talkowski and colleagues analyze balanced chromosomal abnormalities in 273 individuals by whole-genome sequencing. Their findings suggest that sequence-level resolution improves prediction of clinical outcomes for balanced rearrangements and provides insight into pathogenic mechanisms such as altered gene regulation due to changes in chromosome topology.

Investigation of variation in three cohorts has identified multiple genetic signals associated with the pregnancy-specific liver disorder, intrahepatic cholestasis of pregnancy, giving insight into the disease which can cause preterm birth and stillbirth.

In hepatocellular carcinoma driven by non-alcoholic steatohepatitis, aberrant T cell activation and impaired immune surveillance seem to make hepatocellular carcinoma less responsive to anti-PD1 or anti-PDL1 immunotherapy.

Label-free imaging of the endogenous pigment lipofuscin at near-infrared and shortwave-infrared wavelengths enables the longitudinal monitoring of liver injury in mice and in biopsied human livers.

Single-nucleus and spatial, whole-transcriptome profiling of 43 pancreatic adenocarcinomas provides a refined molecular and cellular classification, highlighting a new neoadjuvant treatment-associated neural-like progenitor tumor cell state.

This Review outlines the screening, enrolment and recruitment challenges in the TEDDY (The Environmental Determinants of Diabetes in the Young) study. The key findings related to the first primary end point are discussed, and future directions of study are highlighted.

The delivery route and dose of the BCG vaccine profoundly alters the protective outcome after Mycobacterium tuberculosis challenge in non-human primates.

Characterization of ten temperate mycobacteriophages reveals at least five distinct prophage-expressed viral defence systems that interfere with infection by either closely related or unrelated lytic and temperate phages.