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Human RIF1 protein protects cells from DNA replication stress, through mechanisms that remain uncertain. Here the authors demonstrate that the RIF1-Long isoform interacts with BRCA1 upon extended replication stress, enabling RAD51-dependent repair of broken replication forks.

PetaKit5D offers versatile processing workflows for light sheet microscopy data including performant image input/output, geometric transformations, deconvolution and stitching. The software is efficient and scalable to petabyte-size datasets.

Social disconnection across socioeconomic lines is explained by both differences in exposure to people with high socioeconomic status and friending bias—the tendency for people to befriend peers with similar socioeconomic status even conditional on exposure.

Ancient DNA reveals how the explosive expansion of Yamnaya steppe pastoralists began with a small community north of the Black Sea speaking ancestral Indo-European, and detects genetic links with Anatolian speakers, stemming from a common Indo-Anatolian homeland in the North Caucasus–lower Volga region.

Whole-genome sequencing analysis of 81 prehistoric individuals reveals how the genetic makeup of people from the North Pontic region was influenced by waves of migration during the Eneolithic period and Early Bronze Age.

N⁶-methyladenosine (m⁶A) modification of mRNA regulates gene expression in eukaryotes. Here, Zeng et al. show that m⁶A modification of mRNAs contributes to protection against the pathogen Helicobacter pylori by downregulating a host protein that acts as receptor for the pathogen.

Complete sequences of chromosomes telomere-to-telomere from chimpanzee, bonobo, gorilla, Bornean orangutan, Sumatran orangutan and siamang provide a comprehensive and valuable resource for future evolutionary comparisons.

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.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.

The authors report a co-occurrence of the U2AF1 S34F splicing factor mutation and ROS1 translocations in lung adenocarcinomas and profile effects of S34F on transcriptome-wide RNA binding. They further show that U2AF1 S34F enhances invasive potential and alters splicing of ROS1 fusion transcripts

InducTn-seq, a method for inducible mutagenesis followed by transposon insertion site sequencing, enables temporal control of transposition to bypass population bottlenecks and enable the quantification of gene fitness during in vivo Citrobacter rodentium infection.

Characterization of clinical isolates of the cryptic fungal pathogen Aspergillus latus revealed traits that distinguish it from other species. Steenwyck et al show that A. latus originated via allodiploid hybridization with both parental subgenomes actively expressed.

Pradhan et el report that neuromodulatory systems linked to stress and satiety are recruited to induce sickness behaviours during chronic infection of Caenorhabditis elegans with Pseudomonas aeruginosa.

A genome-wide study by the Long COVID Host Genetics Initiative identifies an association between the FOXP4 locus and long COVID, implicating altered lung function in its pathophysiology.

Comprehensive analyses of 178 lung squamous cell carcinomas by The Cancer Genome Atlas project show that the tumour type is characterized by complex genomic alterations, with statistically recurrent mutations in 11 genes, including TP53 in nearly all samples; a potential therapeutic target is identified in most of the samples studied.

Infection by Plasmodium falciparum can manifest as diverse symptoms and outcomes with different treatment requirements. Here the authors use metabolomics, proteomics and transcriptomics data from 79 children to identify potential omics signatures that correlate with different extent and nature of inflammation to provide insights into the development of future treatments.

In this study the authors show that monotonous basaltic volcanoes can host a range of melts in their sub-volcanic systems, extending to rhyolitic compositions. The study implies that volcanoes which have produced monotonous basaltic lavas on long timescales could transition to more explosive, silica-rich eruptions in the future.

The authors in this work introduce RosettaVS, an AI-accelerated open-source drug discovery platform. They apply this tool to multi-billion compound libraries, where it was able to identify compounds that bind important targets KLHDC2 and Na_V1.7.

Multi-ancestry genome-wide analyses identify 95 loci associated with post-traumatic stress disorder and implicate candidate genes, pathways and neurobiological systems underlying its pathophysiology.

Levantine Phoenicians made little genetic contribution to Punic settlements in the central and western Mediterranean between the sixth and second centuries bce; instead, the Punic people derived most of their ancestry from a genetic profile similar to that of Sicily and the Aegean, with notable contributions from North Africa as well.

A de novo-designed protein that precisely assembles a chlorophyll dimer has been developed. The design matches the conformation of the native ‘special pair’ of chlorophylls that functions as the primary electron donor in natural photosynthetic reaction centers. In the designed protein, excitonically coupled chlorophylls participate in energy transfer. The proteins were also redesigned to assemble into 24-chlorophyll nanocages.

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.

AAV vectors are a promising gene delivery vehicle but have a limited DNA packaging capacity. Here, the authors identify cellular restriction factors whose temporary inhibition significantly enhances transduction efficiency of oversized transgenes split into dual AAV vectors.

The use of NMR spectroscopy and development of a cellular BRET KRAS engagement assay revealed that noncovalent ligands can access the switch-II pocket of KRAS hotspot mutants.

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.

A rare case of asymptomatic dominantly inherited Alzheimer’s reveals confined tau pathology and unique proteomic features, highlighting potential resilience mechanisms decades beyond expected onset.

MatterGen is a model that generates stable, diverse inorganic materials across the periodic table and can further be fine-tuned to steer the generation towards a broad range of property constraints.

A finger-based brain–computer interface was developed for a person with tetraplegia to allow him to fly a virtual quadcopter, an innovation that can lead to improved social connectedness, recreation and a sense of enablement.

 A transcriptomic cell-type atlas of the whole adult mouse brain with ~5,300 clusters built from single-cell and spatial transcriptomic datasets with more than eight million cells reveals remarkable cell type diversity across the brain and unique cell type characteristics of different brain regions. 

Biomolecular condensates compartmentalize molecules without membranes. Understanding condensate composition is important given that their function relies on the selective exclusion or enrichment of molecules. Now, investigating small-molecule partitioning reveals variations across compounds, yet correlations indicate physical similarities between disparate condensates. Machine learning accurately predicts partitioning on the basis of physicochemical features, demonstrating the role of a hydrophobic environment in driving enrichment and exclusion.

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.

The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.

Analysis of 97,691 high-coverage human blood DNA-derived whole-genome sequences enabled simultaneous identification of germline and somatic mutations that predispose individuals to clonal expansion of haematopoietic stem cells, indicating that both inherited and acquired mutations are linked to age-related cancers and coronary heart disease.

Tracing barcoded clones of Klebsiella pneumoniae during pneumonia with bacteremia, Holmes and colleagues identify two modes of dissemination, with high or low bacterial burdens, and define the host and bacterial factors that influence this process.

Engineered kill-switch-encoding Mycobacterium tuberculosis infects, elicits immune responses and is cleared from immunocompetent and immunocompromised mice, providing a model of controlled tuberculosis infection.

The cGAS-STING pathway senses cytosolic DNA to activate interferon responses, but has also been implicated in autophagy induction. Here the authors show that, during herpes simplex virus infection, cGAS-induced autophagy is mediated by TBK1-induced TRIM23 phosphorylation and downstream signaling events to assist in antiviral immunity.

The Vertebrate Genome Project has used an optimized pipeline to generate high-quality genome assemblies for sixteen species (representing all major vertebrate classes), which have led to new biological insights.

Satellite-based mapping of vegetation shows that photosynthetic life occupies a total area of 44.2 km² across Antarctica.

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.

Mutations in the Wnt co-receptor, LRP5, lead to skeletal diseases in humans. Matthew Warman and his colleagues have now developed mutant mice with tissue-specific alterations of Lrp5 expression and found that these mice phenocopy the human skeletal diseases. They also found that Lrp5 acts locally to affect bone homeostasis. Their data suggest that increasing LRP5 signaling in mature bone cells may be a strategy to treat osteoporosis.