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Aberrant oncogene expression can cause replication stress leading to chromosomal breaks. Here the authors map the chromosomal break loci induced by two different oncogenes and by a replication inhibitor, and show that each treatment induces a unique pattern of breaks in the same cell type.

A new model merges behavioural science and machine learning to predict choice under risk and uncertainty. Tested on multiple large datasets, it outperforms top psychological and AI models, enabling accurate, interpretable forecasts of human decisions.

Through in vivo tracking of tumor-specific CD8⁺ T cells in response to immunotherapy in mice, Barboy et al. characterize the tumor response to anti-PD-1 therapy and optimize a combination treatment with anti-4-1BB agonist.

Here the m¹A modification is discovered in messenger RNA and mapped at the transcriptome-wide level; the modification is conserved, dynamic, accumulates in structured regions around translation initiation sites upstream of the first splice site, and correlates with higher protein expression.

A high-resolution, global atlas of mortality of children under five years of age between 2000 and 2017 highlights subnational geographical inequalities in the distribution, rates and absolute counts of child deaths by age.

In Caenorhabditis tropicalis, selective expression of genetic alleles from one parent but not the other can arise from maternally inherited small transcripts acting via the PIWI-interacting RNA host defence pathway.

Aneuploidy and chromosomal truncations are frequent outcomes of CRISPR–Cas9 editing in human T cells.

Madrer et al. identify a Parkinson’s disease–specific increase in transfer RNA (tRNA) fragments in human blood, cerebrospinal fluid and postmortem brain tissue, demonstrating the ability of blood-based tRNA fragment quantification to distinguish between pre-symptomatic patients and healthy controls.

Single-cell analyses in a reporter mouse model and human tissues identify a rare cell subset that produces erythropoietin in vivo, opening potential new avenues for research in erythropoiesis and oxygen homeostasis.

QTL mapping in multicellular animals usually requires generation, maintenance, and phenotyping large panels of recombinant individuals. Here, the authors develop ceX-QTL mapping, a method for fast genetic mapping via bulk selection on millions of unique recombinant C. elegans individuals.

The medial prefrontal cortex (mPFC) orchestrates multifaceted light-sensitive cognitive and emotional processes. Here, Zangen et al. show mPFC neuronal encoding of environmental light intensity, and propose a pathway that may drive this encoding.

Adenosine deaminase acting on RNA 1 (ADAR1) edits adenosine to inosine. Here the authors, using parallel analysis of RNA secondary structure sequencing, provide evidence that ADAR1 induces sequence-context-dependent RNA secondary structures changes, often leading to stabilization of the RNA duplex.

A human binary protein interactome map that includes around 53,000 protein–protein interactions involving more than 8,000 proteins provides a reference for the study of human cellular function in health and disease.

Fine-scale geospatial mapping of overweight and wasting (two components of the double burden of malnutrition) in 105 LMICs shows that overweight has increased from 5.2% in 2000 to 6.0% in children under 5 in 2017. Although overall wasting decreased over the same period, most countries are not on track to meet the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025.

The lineage-specific receptor CSF1R controls macrophage development and homeostasis. Here the authors show that deletion of a conserved Csf1r enhancer (FIRE) selectively depletes brain microglia and resident macrophages in the epidermis, kidney, heart and peritoneum of otherwise healthy mice.

Enterococcus strains harbour a plasmid-encoded defence against reuterin, a toxin produced by Limosilactobacillus reuteri, mediating a mutualistic metabolic interaction between these two gut microbiota members.

Colorectal tumors with mutated KRAS and APC require the amino acid transporter SLC7A5 to drive tumorigenesis. Mechanistically, SLC7A5 drives transcriptional and metabolic reprogramming by maintaining intracellular amino acid levels, leading to enhanced protein synthesis.

How synaptic plasticity affects neural coding reliability is not well understood. Here, the authors find that reducing neurotransmitter release probability triggers a homeostatic compensation to maintain neural coding and behavioral reliability.

Mitochondria are maternally inherited, but the mechanisms underlying paternal mitochondrial elimination remain unclear. Here, the authors show that Drosophila eggs rapidly degrade paternal mitochondria after fertilization by triggering an innate immunity pathway commonly employed against invading microbes.

Affinity tagging, mass spectroscopy and a tailor-made scoring system are used to identify 497 high-confidence interactions between human proteins and human immunodeficiency virus proteins.

PIC-seq characterizes cellular crosstalk by sorting and sequencing physically interacting cells.

Omar et al. test six leading large language models with 300 doctor-designed clinical vignettes containing a single fake lab value, sign or disease. They show that the models repeat or elaborate on the planted error in up to 83 % of cases with a simple mitigation prompt halving the rate but not eliminating the risk.

Here, using the K18-hACE2 transgenic mice model, the authors report the in vivo efficacy of a fully human neutralizing antibody against SARS-CoV-2 and show that when administered before or up to 3 days post infection, treated mice do not exhibit disease symptoms while 80% of control animals succumb to the infection.

DestVI models continuous cell states in spatial transcriptomics data.

Single-cell analyses reveal cDC1 as conserved immunological drivers of non-alcoholic steatohepatitis in mice and humans

Assembly and analysis of the Schmidtea mediterranea genome indicate that this planarian’s chromosome 1 may be evolving into a sex chromosome.

Amit and colleagues report that the specific interaction of a CD4⁺PD-1⁺CXCL13⁺ T-cell subset with antigen-presenting cells reprograms the tumor microenvironment and response to immune checkpoint inhibitors in non-small cell lung cancer.

Deep-Z uses deep learning to go from a two-dimensional snapshot to three-dimensional fluorescence images. The method improves imaging speed while reducing light dose, and was shown to be useful for accurate structural and functional imaging of neurons in Caenorhabditis elegans.

In Alzheimer's disease, PD-1 immune checkpoint blockade reduces pathology and improves memory in mice with established disease.

Deletions on chromososme 5q are associated with myelodysplastic lesions. The genes responsible have largely remained elusive. But use of an RNA interference-based approach that can identify haploinsufficient tumour suppressor genes identifies RPS14, which regulates ribosomal RNA processing as a candidate tumour suppressor gene responsible for this so-called 5q⁻ syndrome.

Carbonyl sulphide is taken up by plants, and could potentially serve as a powerful proxy for photosynthetic carbon dioxide uptake. Field measurements in Israel suggest that carbonyl sulphide fluxes provide an independent constraint on indirect estimates of ecosystem photosynthesis.

The persistence of leukemic stem cells (LSCs) is known to limit the success of imatinib in patients with chronic myeloid leukaemia (CML). Here, the authors identify a reliance of these persisting LSCs on pyruvate carboxylase mediated pyruvate anaplerosis for survival after imatinib and demonstrate the therapeutic efficacy of targeting this using an inhibitor of mitochondrial pyruvate carrier.

Here, Noy-Porat, Makdasi et al. report the isolation of a panel of neutralizing mAbs selected against SARS-CoV-2 receptor-binding domain (RBD) from a phage display library constructed based on patient samples collected in the acute phase of the disease, which show efficient neutralizing activities against authentic virus in vitro.

In this study, the authors show that host microbiota play a key role in modulating microglia homeostasis. Germ-free mice or mice with only limited microbiota complexity displayed defects in microglial cell proportions and maturation, leading to impaired innate immune responses. The authors find that short-chain fatty acid signaling regulates these effects in vivo.

Co-ChIP, a method for measuring the genome-wide co-occurrence of histone marks, sheds light on the complexity of the histone code.

Macrophages serve important functions in defense and tissue homeostasis. Jung and colleagues demonstrate that a resident population of macrophages controls the innervation of brown adipose tissue and thereby regulates energy use.

Single cell dissection of plasma cell heterogeneity in myeloma patients reveals new insights into disease that may inform early diagnosis and clinical management.

Rothová et al. deconstruct endodermal cell fate trajectories through single-cell transcriptomics and identify the central intermediate population transdifferentiating from an extra-embryonic to an embryonic identity.

Single-cell whole-genome sequencing shows that 'foreground' cell-to-cell structural variation and alterations in copy number are associated with genomic diversity and evolution in triple-negative breast and high-grade serous ovarian cancers.

Yofe et al. demonstrate that FcγR engagement early after anti-CTLA-4 blockade induces a rapid remodeling of innate immunity and activation of type I interferon signaling, which are crucial for successful anti-CTLA-4 therapy.