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Decoding the content of extracellular vesicles (EVs) is key to understanding cell communication. Nikonorova et al. used targeted proximity labeling to uncover polycystin EV cargo and cargo-loading mechanisms in C. elegans.

In an analysis of long-term safety events in 783 patients treated with T cell therapy in 38 trials, 2.3% of patients developed second primary malignancies, and vector integration analyses revealed no pathological insertions.

Measuring rhythm priors in 39 participant groups from 15 countries, the authors find that properties of rhythm representations are common across cultures, while variation from place to place related to local musical traditions exists.

Serino et al. studied the sense of agency for actions generated via a brain–machine interface. They show that primary motor cortex encodes not only motor and sensory signals, but also subjective agency signals, enabling improved brain–machine interface proficiency.

During embryogenesis, the cytoplasmic protein Myomarker (MYMK) mediates muscle fibre formation by fusion of myoblasts. Here, the authors identify autosomal recessive mutations in MYMK that cause Carey-Fineman-Ziter syndrome in humans, and model the disease variants in zebrafish.

Osteoarthritis is a chronic, heritable disease with no available treatment. Here, the authors show that a validated, rapid-throughput joint phenotyping pipeline detects osteoarthritis in the mouse knee following surgical provocation, in aging and after single gene deletion or point mutation.

A multidimensional feature-based approach reveals subtle, task-dependent interactions between brain regions and networks, providing a sensitive method to study the neural basis of flexible behaviour.

Basal cell adenoma (BCA) and basal cell adenocarcinoma (BCAC) of the salivary gland are rare tumours. Here the authors report that BCA and BCAC patients possess distinct genomic profiles despite histopathological similarities, and identify a recurrent FBXW11 missense mutation (p.F517S) which leads to accumulation of β-catenin in BCA and higher expression of Wnt/β-catenin targets.

The role of stem/progenitor cell populations in mammary gland morphogenesis is not well understood. Here, the authors show that a transcriptional repressor, Blimp1, is expressed in a rare luminal stem cell population, which contribute to duct formation, and survive multiple rounds of pregnancy and involution.

Type 2 diabetes (T2D) is prevalent in populations worldwide, however, mostly studied in European and mixed-ancestry populations. Here, the authors perform a genome-wide association study for T2D in over 5,000 sub-Saharan Africans and identify a locus, ZRANB3, that is specific for this population.

Answer ALS is a resource of patient-derived iPS cell lines, multi-omic data derived from iPS neurons and longitudinal clinical and smartphone data from over 1,000 patients with ALS. This serves as a foundation to identify distinct disease subgroups.

Structural studies of the CRISPR-associated transposon comprising Cas12k, TnsC, TnsB and TniQ from Scytonema hofmannii using cryo-electron microscopy reveal insights into the architecture and mechanism of RNA-guided DNA transposition.

Genome-wide association analysis of gout and urate identifies 148 new loci, implicating biological pathways and prioritizing candidate genes involved in inflammatory processes.

Cytosolic coat proteins capture secretory cargo and sculpt membrane carriers for intracellular transport, such as COPII which mediates Endoplasmic Reticulum to Golgi trafficking of thousands of cargoes. Here authors visualise the complete, membrane-assembled COPII coat by cryo-electron tomography and subtomogram averaging, revealing the full network of interactions within and between coat layers.

The authors selectively modify chromatin in a specific gene in vivo to examine the link between chromatin dynamics and drug- and stress-evoked responses. They report that histone methylation or acetylation at the FosB locus in nucleus accumbens is sufficient to control drug- and stress-evoked transcriptional and behavioral responses.

Neurofibromatosis type 1 (NF1) is a genetic disorder caused by mutations in neurofibromin and associated with disruptions in physiology and behavior. Here the authors show that neurofibromin regulates metabolic homeostasis via a discrete brain circuit in a Drosophila model of NF1.

Here the authors dissect the contribution of IL-21 signaling to immune checkpoint-responding CD8⁺ T cells from mouse models and patients being treated for advanced melanoma.

Nationwide genomic biobank in Mexico unravels demographic history and complex trait architecture from 6,057 individuals.

Population-based association analyses of rare genetic variants with complex traits are limited by the availability of data from sufficiently large cohorts. Here, Cirulli et al. report gene-based collapsing analysis of exomes from 49,960 participants of the UK Biobank and 21,866 participants of the Healthy Nevada Project over a total of 4377 traits.

Duan et al. find that the membrane skeleton protein spectrin is required for myoblast fusion in Drosophila, accumulating in a mechanosensitive manner in the receiving partner during cell–cell fusion to modulate adhesion and protrusion events.

This study identifies molecular pathogenesis in the kidney of myotonic dystrophy type 1 (DM1). The authors reveal downregulated metabolism genes in urinary extracellular vesicles (EVs) and kidney tissue, with elevated urine metabolites, suggesting urinary EVs as indicators of renal and metabolic disturbance.

In cancer, the impact on cellular fitness of copy-number gains affecting collaterally-amplified genes remains poorly understood compared to oncogenes. Here, the authors integrate genomic data from tumours and cell lines and identify a class of ‘Amplification-Related Gain Of Sensitivity’ (ARGOS) genes, with potential therapeutic applications.

Gene duplication and subsequent paralogue diversification are major obstacles to genotype-to-phenotype predictability.

In this study, the authors show that they can induce the direct conversion of fibroblasts into nociceptor neurons via the expression of only five key transcription factors. They further confirm that these induced neurons are bona fide nociceptors by demonstrating that their expression profiles resemble that of their endogenous counterparts and show that they are responsive to common nociceptor agonists.

Minichromosome maintenance protein 10 (MCM10) is critical for eukaryotic DNA replication. Here, by modelling MCM10 variants in human cell lines, the authors reveal a mechanism of MCM10-associated disease, finding that loss of MCM10 function constrains telomerase activity.

BMI1, a core element of the polycomb repressive complex 1, is suggested to have oncogenic activity in a variety of cancers. Here, the authors report the structure of BMI1 bound to the protein PHC2, identify BMI1 homo-oligomerization interfaces, and analyse the role of BMI1 protein-protein interactions in PRC1 function.

Genetic surveillance of Plasmodium falciparum has been ongoing in the Greater Mekong Subregion since 2017. Here, the authors report data until 2022, and demonstrate changes in drug resistance profiles of circulating strains coinciding with changes in frontline therapy policies.

Zhang et al. show that dynamin forms a helical structure with actin and, upon disruption, enhances branched actin polymerization, constituting a dynamic cycle to regulate actin cytoskeleton mechanical strength.

In this study the authors identify a possible link between the gene FAM222A and brain atrophy. The protein it encodes is found to accumulate in plaques seen in Alzheimer’s disease, and functional analysis suggests it interacts with amyloid-beta.

Evan Eichler and colleagues report an expanded copy number variation (CNV) morbidity map of developmental delay, with additional resequencing of candidate genes in regions implicated by large CNVs. They identify several new disease-associated CNVs and show how their combined approach facilitates discovery of new developmental syndromes and disease genes.

Proximity ferroelectricity is reported in wurtzite heterostructures, which enables polarization reversal in wurtzites without the chemical or structural disorder that accompanies elemental substitution.

The interconversion of the two spin isomers of formaldehyd has been studied in the gas phase but has never been observed experimentally in the condensed phase. Here the authors report the encapsulation of formaldehyde inside C60 cages and observe spin-isomer conversion of the formaldehyde guest molecules in the cryogenic solid state.

The mechanisms of PARP inhibitor (PARPi) resistance are poorly understood. Here the authors employ a CRISPR mutagenesis approach to identify PARP1 mutants causing PARPi resistance and find that PARP1 mutations are tolerated in BRCA1 mutated cells, suggesting alternative resistance mechanisms.

The lipid kinase phosphatidylinositol-4-OH kinase (PI(4)K) is identified as a target of the imidazopyrazines, a new antimalarial compound class that can inhibit several Plasmodium species at each stage of the parasite life cycle; the imidazopyrazines exert their inhibitory action by interacting with the ATP-binding pocket of PI(4)K.

In this study the authors utilise Hi-C, ATACseq, and RNA-seq data from 12 diagnosis/relapse matched leukemia specimens to reveal 3D genome organization as a critical factor in reshaping the transcriptional output of leukemia cells under the selective pressures of therapy.

Ramachandran et al. identify a previously unappreciated function for transcriptional repressor B cell lymphoma 6 (BCL6) in muscle proteostasis and strength, and provide mechanistic insight into the molecular underpinnings of this function.

Understanding mechanisms of PLpro substrate selectivity offers new ways to decouple substrate activities and will inform new therapeutic strategies. Here, the authors use multi-disciplinary approaches to uncover how PLpro from SARS-CoV-2 can discriminate between different substrates.

Most studies of the genetics of the metabolome have been done in individuals of European descent. Here, the authors integrate genomics and metabolomics in Black individuals, highlighting the value of whole genome sequencing in diverse populations and linking circulating metabolites to human disease.

Developmentally regulated expression of the transcriptional repressor Prdm1 (Blimp1) in the early mammalian embryo controls global epigenetic changes required for specification of primordial germ cells. A new study demonstrates that a close family member, Prdm14, similarly activated in response to Bmp and Smad signals, also has an essential role during establishment of the germ cell lineage.

Although continuous monitoring of tissue oxygenation is critically important after tissue/organ graft procedures, current technologies have key limitations. Here, the authors develop a miniaturized, minimally invasive, self-anchoring optical probe and demonstrate continuous monitoring of oxygenation in porcine flap and organ models.

Here the authors identify TNIP1 as a risk factor for a fatal neurodegenerative disorder and discover specific genetic loci associated with the three main subtypes of this disorder. The findings highlight distinct disease mechanisms, emphasizing the roles of immunity and the notch signaling pathway.