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Several computational tools have now been developed to identify copy number variations (CNVs) from scRNA-seq data. Here authors benchmark these methods, showing that performance is affected by dataset quality, CNV type and reference dataset, with methods including allelic information being more robust in large datasets.

Direct visualisation of heterogeneous cell populations in live animals has been challenging. Here, the authors optimize cell transplantation into optically clear immune-deficient zebrafish, and use intravital imaging to track and to assess functional diversity of individual cancer cells in vivo.

Somatic copy number alterations (CNAs) of parts of the genome can contribute to the development and progression of various cancers. Here, the authors present a statistical method to detect clonal and allele-specific CNAs from single-cell RNA-sequencing data with high robustness.

In a zebrafish model of human cutaneous and acral melanomas, CRKL amplification causes tumours to favour a fin location, indicating that tumour location is determined by both the driver oncogenes and the pre-existing positional identity gene program.

The hematopoiesis of patients with del(5q) Myelodysplastic Syndromes is composed of a mixture of cells with and without the deletion. Here, the authors show that del(5q) and non-del(5q) cells share similar transcriptional alterations, with del(5q) cells presenting additional lesions. Moreover, hematological response to lenalidomide is associated with the reversal of some transcriptional lesions in both del(5q) and non-del(5q) cells.

CD19-negative relapses are observed in patients with B-cell acute lymphoblastic leukemia (B-ALL) treated with anti-CD19 CAR-T cells. Here, by single-cell RNA sequencing of leukemic cells in a patient with B-ALL, the authors show that pre-existing CD19 negative leukemic subclones are present before CAR-T cell therapy and can account for the relapse.

Hybrid Unmixing offers enhanced imaging of multiplexed fluorescence labels, enabling longitudinal imaging of multiple fluorescent signals with reduced illumination intensities.

The alternative splicing factor Nova2 is best known for its pivotal function in the brain. Giampietro et al. reveal an important role for Nova2 in the regulation of alternative splicing of transcripts in the vascular endothelium that are crucial for the maintenance of endothelial cell polarity and vessel lumen formation in zebrafish.

The cell wall of the oral bacterium Streptococcus mutans carries SCC, a rhamnose-containing polysaccharide with glucose side-chain decorations. Here, the authors report the SCC structure and the synthesis mechanism, revealing how four glucosyltransferases work together to synthesize the side-chains.

WHaloCaMP is a chemigenetic calcium indicator that can be combined with different rhodamine dyes for multiplexed or FLIM imaging in vivo, as demonstrated for calcium imaging in neuronal cultures, brain slices, Drosophila, zebrafish larvae and the mouse brain.

BindCraft, an open-source, automated pipeline for de novo protein binder design with experimental success rates of 10–100%, leverages AlphaFold2 weights to generate binders with nanomolar affinity without the need for high-throughput screening.

Metastatic prostate cancer can be difficult to biopsy and characterise. Here, the authors use cell-free DNA methylation analysis to illustrate changes in hypermethylation in metastatic disease.

HACE1 is an E3 ligase that promotes degradation of the GTPase Rac1. Here Daugaard et al. show that HACE1 inhibits the activity of Rac1-dependent NADPH oxidase complexes, which reduces the production of cellular reactive oxygen species and cell cycle progression.

The process by which actinic keratosis differentiates to malignant invasive cutaneous squamous cell carcinoma is unclear. Here, the authors use RNA-seq to illustrate a disease continuum between the two states, and use in vivo models to confirm the role of Tgfbr2, Trp53, and Notch1 in this process.

Two studies by Sugden et al. and Jin et al. show that endoglin regulates endothelial cell migration through VEGFR2 signalling and controls blood vessel diameter in response to blood flow.

Methods to directly label active neurons are still lacking. Here the authors develop CaMPARI2, a photoconvertible fluorescent protein sensor for neuronal activity with improved brightness and calcium binding kinetics, as well as an antibody to amplify the activated sensor signal in fixed samples.

InfraRed-mediated Image Restoration (IR²) uses deep learning to combine the benefits of deep-tissue imaging with NIR probes and the convenience of imaging with GFP for improved time-lapse imaging of embryogenesis.

The NLRP3 inflammasome is involved in IL-1 production and pyroptosis. Pelegrín et al. demonstrate that it is also released extracellularly as a functional proinflammatory particle.

Statistically unbiased prediction utilizing spatiotemporal information in imaging data (SUPPORT) is a self-supervised deep learning approach to accurately denoise voltage and calcium imaging data while preserving true dynamic signals.

Melanocytes above the haematopoietic niche protect haematopoietic stem cells from ultraviolet-light-induced DNA damage in aquatic vertebrates throughout evolution; this niche moved to the bone marrow during the transition to terrestrial life.

The cell wall of the bacterial pathogen Group A Streptococcus is decorated with a polysaccharide termed GAC, which is a target for vaccine development. Here, Rush et al. characterize the linkage between GAC and peptidoglycan, and identify a protein that deacetylates the linkage and thus protects the pathogen against host cationic antimicrobial proteins.

Gain-of-function mutations in NLRP3 result in Cryopyrin-Associated Periodic Syndrome in human patients. Here authors show that although these NLRP3 variants are constitutively active, they preserve their responsiveness to external pro-inflammatory stimuli, and they interfere with the immune-metabolic inflammatory pathways in monocytes.

Schwab, Rao et al. report that Zeb1 mediates enhanced ferroptosis sensitivity in cancer cells after EMT activation, associated with altered expression of selected lipogenic enzymes and an subsequent increase in the PUFA:MUFA ratio.

Combined patch clamp recording, biocytin staining and single-cell RNA-sequencing of human neurocortical neurons shows an expansion of glutamatergic neuron types relative to mouse that characterizes the greater complexity of the human neocortex.

Examination of demographic age trajectories for species from a wide range of taxonomic groups shows that these species have very diverse life-history patterns; mortality and reproduction vary greatly with age for both long- and short-lived species, and the relationships between ageing, mortality and reproduction are clearly complex.

The development of Sulfopin, a highly selective and potent, covalent Pin1 inhibitor that phenocopies Pin1 knockout and regresses tumors in murine and zebrafish models of neuroblastoma as well as in a pancreatic cancer mouse model.

Here, the authors present the upstream pathway that controls the activation of the NLRP3 inflammasome during bacteraemia. The CNF1 toxin from Escherichia coli activates the Rho GTPase Rac2 and its activity is sensed by NLRP3, which is activated by a signalling cascade involving p21-activated kinases 1 and 2.

Genomic and cell-free DNA sequencing clarify the clinical diagnosis and inform treatment initiation in a cohort of 356 patients with vascular anomalies.

Unconventional oil and gas production has increased drastically in the US, but its environmental impacts are not well known. Here, the authors show that these wells can be associated with elevated levels of airborne particle radioactivity in downwind locations.

Borealis, a newly discovered mud volcano in the Polar North Atlantic, expels warm Neogene sediments and methane fluids. It hosts unique habitats, with carbonate structures offering refuge and nursery grounds for marine life, highlighting conservation importance.

Components of the gut virome of 1-year-old children are associated with increased risk of development of asthma later in life, probably through direct interaction between phages and the host immune system.

Cerebrospinal fluid (CSF) is essential for brain development. Here, the authors use gold nanoparticle enhanced X-ray microtomography to map CSF distribution in post-natal rodents and describe particle size-dependent CSF pathways that transport CSF into the brain parenchyma of rodents.

This genome-wide association study identifies 162 genetic loci linked to income, shedding light on the complex interplay between genetics, income, education and health.

A study of zebrafish identifies an innate mechanism of blood vessel formation through the transdifferentiation of lymphatic endothelial cells, and provides in vivo evidence for a link between cell ontogeny and functionality in endothelial cells.

The affected cellular populations during Alzheimer’s disease progression remain understudied. Here the authors use a cohort of 84 donors, quantitative neuropathology and multimodal datasets from the BRAIN Initiative. Their pseudoprogression analysis revealed two disease phases.

Here, Swarte et al. use metagenomics to investigate the association between the gut microbiome and Health-Related Quality of Life (HRQoL) in kidney transplant recipients, showing evidence for the association of multiple taxonomic, metabolic and neuroactive pathways (gut brain modules) with lower HRQoL, together suggesting potential modifiable gut microbial factors to improve HRQoL.

Action on climate change requires public support. A study of public opinion in the United States reveals substantial variation across the nation.