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The specifics of the pediatric immune response that gives rise to antibodies capable of neutralising diverse HIV-1 strains is not fully understood. Here the authors characterise the immune environment of Simian-HIV infected paediatric macaques and link to antibody neutralisation induction.

Mantle cell lymphoma (MCL) is a form of B-cell non-Hodgkin lymphoma with a high degree of genetic and clinical heterogeneity. Here, using a multi-omics approach, the authors investigate genetic alterations in association with the tumour microenvironment to identify potential therapeutic vulnerabilities.

The goal of the 1000 Genomes Project is to provide in-depth information on variation in human genome sequences. In the pilot phase reported here, different strategies for genome-wide sequencing, using high-throughput sequencing platforms, were developed and compared. The resulting data set includes more than 95% of the currently accessible variants found in any individual, and can be used to inform association and functional studies.

Here the authors use UK Biobank data to identify 251 genetic loci associated with serum triglycerides to HDL-cholesterol ratio, a surrogate marker for insulin resistance. Key genes, including PLA2G12A, PLA2G6, and TNFAIP8, offer potential therapeutic targets for metabolic diseases.

Dendritic cells are supplied antigens by other cells such as lymphatic endothelial cells (LEC) at late time points after immunization. Here the authors show antigen archiving is defined by a transcriptional program that can predict antigen archiving depending on the priming pathogen, and that boosting of immune responses increases the archiving.

Here, the authors provide molecular insight into the remarkable ability of Tardigrades to withstand high levels of radiation by demonstrating that their Dsup protein interacts with multiple surfaces of the nucleosome to protect the genome from oxidative DNA damage.

The pachycephalosaurian Zavacephale rinpoche, from the Early Cretaceous of Mongolia, provides crucial insights into the early evolution of dome-headed dinosaurs, including the development of the frontoparietal dome and decoupling of sociosexual and somatic maturity.

This study employs a functional genomic approach to identify a synthetic lethal interaction between CDS1 and CDS2 in uveal melanoma and other cancers, which may represent a potential therapeutic target.

In this work, the authors present E. coli PanSelect, a hybrid selection method for enriching E. coli from low-abundance microbiota, and apply it to stool samples from recurrent UTI sufferers, revealing distinct E. coli transcriptional profiles

A genome-wide association study meta-analysis combined with multiomics data of osteoarthritis identifies 700 effector genes as well as biological processes with a convergent involvement of multiple effector genes; 10% of these genes express the target of approved drugs.

Sequencing data from two large-scale studies show that most of the genetic variation influencing the risk of type 2 diabetes involves common alleles and is found in regions previously identified by genome-wide association studies, clarifying the genetic architecture of this disease.

Platelet aggregation is associated with myocardial infarction and stroke. Here, the authors have conducted a whole genome sequencing association study on platelet aggregation, discovering a locus in RGS18, where enhancer assays suggest an effect on activity of haematopoeitic lineage transcription factors.

In this work the authors demonstrate on-chip integration of Brillouin lasing operating at visible wavelengths, with engineered design for stable output. This technical and scientific advance will help develop integrated light sources for quantum computing or atomic and molecular spectroscopy.

Archaeopteryxcombined features of reptiles and birds, but the colour of its feathers has remained unclear. In this study, based on data from fossilized colour-imparting melanosomes, an isolated feather specimen fromArchaeopteryxis predicted to be black, providing clues to its plumage colour and function.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

Extrachromosomal DNA (ecDNA) congregates in clusters called ecDNA hubs that promote intermolecular interactions between gene-regulatory regions and thereby amplify the expression of oncogenes such as MYC in cancer cell lines.

A new reprogramming strategy used to produce human induced pluripotent stem cells from somatic cells results in epigenetic and functional profiles that are highly similar to those of human embryonic stem cells.

A metagenomic screen identifies retron reverse transcriptases for precise genome-editing applications.

Extrachromosomal DNA makes cancerous tumours resistant to treatment, but this research demonstrates that increasing transcription–replication conflict allows for targeted elimination of cancer cells containing extrachromosomal DNA, and thus sustained tumour regression in mice.

JWST data show that the exoplanet WASP-18b has thermally distinct regions of its dayside. The authors mapped the sizes of these regions, measured their temperatures and potentially identify water destruction in the hottest region.

In participants from a randomized controlled trial, doxy-PEP use over 6 months minimally affected the gut microbiome’s taxonomic composition but increased the abundance and active expression of tetracycline antibiotic resistance genes.

Deep learning methods in natural language processing generally become more effective with larger datasets and bigger networks. But it is not evident whether the same is true for more specialized domains such as cheminformatics. Frey and colleagues provide empirical explorations of chemistry models and find that neural-scaling laws hold true even for the largest tested models and datasets.

Molecular barcoding is used to show that progenitor cells in the human cortex can produce both excitatory neurons and inhibitory interneurons, with implications for our understanding of the evolution of the human brain.

The properties of materials can be drastically modified under extreme pressure. Here the authors investigate ramp-compressed sodium to 5 million atmospheres with in situ X-ray diffraction and optical reflectivity, revealing a complex temperature-driven polymorphism and suggesting the formation of a previously predicted electride phase.

Analysis of soundscape data from 139 globally distributed sites reveals that sounds of biological origin exhibit predictable rhythms depending on location and season, whereas sounds of anthropogenic origin are less predictable. Comparisons between paired urban–rural sites show that urban green spaces are noisier and dominated by sounds of technological origin.

The authors develop a computational method to design small DNA-binding proteins (DBPs) that target specific sequences. Designed DBPs show structural accuracy and function in both bacterial and mammalian cells for transcriptional regulation.

The transcription factor CREM is a pivotal regulator of NK cell function, making CREM a valuable target to increase the efficacy of anticancer immunotherapies based on this cell population and chimeric antigen receptors.

This study characterizes the three-dimensional (3D) genome architecture of 15 primary human cancer types from The Cancer Genome Atlas. The analyses identify different archetypes of enhancer usage and enhancer rewiring events due to different classes of mutations and structural variants.

The authors develop and characterise a selective Greatwall inhibitor, C-604, and show that its cytotoxicity stems from PP2A-B55α hyperactivation. They identify B55α and Greatwall levels as biomarkers of responses to Greatwall-targeted therapy.

Using sequencing and haplotype-resolved assembly of 65 diverse human genomes, complex regions including the major histocompatibility complex and centromeres are analysed.

An amphiphilic mimotope vaccine can be used in tandem with Food and Drug Administration (FDA)-approved CD19 CAR-T cell products.

Here, the authors establish a human in vitro model of neurodevelopment to investigate an allelic series of clinically relevant RING1 and RNF2 missense variants. The observations reveal that missense variants function according to a dominant-negative genetic mechanism.

Structural variants (SVs) in human genomes contribute diversity and diseases. Here, the authors use a multi-platform strategy to generate haplotype-resolved SVs for three human parent–child trios.

A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.

Groundwater resources are coming under increasing pressure leading to water quality loss. Here, the authors find that recent groundwater pumping has led to increasing arsenic concentrations in the San Joaquin Valley, California aquifers from arsenic residing in the pore water of clay strata released by overpumping.

This study introduces AdipoExpress, an eQTL meta-analysis of 2,344 subcutaneous adipose tissue samples, which triples the size of previous studies and expands the discovery of eQTLs colocalized with GWAS signals for cardiometabolic traits.

Tracking data from 17 marine predator species in the Southern Ocean are used to identify Areas of Ecological Significance, the protection of which could help to mitigate increasing pressures on Southern Ocean ecosystems.

Analyses of strain-resolved metagenomics with isolate sequencing data of skin samples from residents at nursing homes suggest that skin is a reservoir for Candida auris and other multidrug-resistant bacterial species.

A purpose-built implantable system based on biomimetic epidural electrical stimulation of the spinal cord reduces the severity of hypotensive complications in people with spinal cord injury and improves quality of life.

Bruton’s tyrosine kinase (BTK) is expressed in immune cells and microglia, where its role remains poorly understood. Here, the authors show that BTK modulates microglial neuroinflammatory pathways relevant to multiple sclerosis (MS) and report robust effects of BTK inhibition in human in vitro models and animal models of MS.

Neonatal antibiotic use is shown to reduce immune response to infant vaccines, accompanied by reduced abundance of Bifidobacteria in the gut microbiota, with experiments in mice indicating that probiotic therapy could be beneficial.

Experimental demonstration of quantum speedup that scales with the system size is the goal of near-term quantum computing. Here, the authors demonstrate such scaling advantage for a D-Wave quantum annealer over analogous classical algorithms in simulations of frustrated quantum magnets.

MetaSTAAR enables functionally informed rare variant association analysis in biobank-scale cohorts using an efficient, sparse matrix approach for summary statistic storage.

High productivity and associated carbon uptake, significant carbonate deposits and substantial global area extension render coralline algal beds as highly relevant contributors to the present and future oceanic carbon cycle

Dense calcium imaging combined with co-registered high-resolution electron microscopy reconstruction of the brain of the same mouse provide a functional connectomics map of tens of thousands of neurons of a region of the primary cortex and higher visual areas.

Ryan Emerson and colleagues report immunosequencing of the variable region of the TCRβ chain in 666 individuals with known cytomegalovirus (CMV) status. They show that CMV status and HLA genotype shape the T cell repertoire and demonstrate proof of principle that TCRβ sequencing can be used as a specific diagnostic of pathogen exposure.

Ancient sulfate mineral compositions reflect an increase in Earth’s oxidation state ~400 million years ago, likely including an increase in atmospheric oxygen levels and shift in mineral weathering pathways.