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A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

Sexual dimorphism in genetic vulnerability to schizophrenia, systemic lupus erythematosus and Sjögren’s syndrome is linked to differential protein abundance from alleles of complement component 4.

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.

Replenishing key extracellular matrix (ECM) proteins facilitate wound healing through unclear mechanisms. Here the authors report that injury-triggered Agrin, an ECM proteoglycan, tunes a mechanocompetent niche by engaging MMP-12, thereby enforcing efficient skin wound healing.

This paper describes molecular subtypes of cervical cancers, including squamous cell carcinoma and adenocarcinoma clusters defined by HPV status and molecular features, and distinct molecular pathways that are activated in cervical carcinomas caused by different somatic alterations and HPV types.

The chemotherapeutic efficacy of prodrug is limited by its cancer-targeting ability. Here this group reports an engineered commensal Lactobacillus plantarum strain with anticancer prodrugs loading on the surface for nasopharyngeal carcinoma cell-targeting and growth inhibition.

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.

A case–control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.

Glaucoma is the most common cause of irreversible blindness worldwide. Here, the authors carry out a large meta-analysis of genetic data from individuals of European and Asian ancestry and identify 10 new loci associated with vertical cup-disc ratio, a key factor in the clinical assessment of patients with glaucoma.

Post-fast refeeding increases intestinal stem cell function and tumour formation by augmenting protein synthesis via polyamine metabolism.

Genome-wide association analyses of post-traumatic stress disorder and its symptom subdomains in individuals of European and African ancestry provide insights into its relationship with anxiety and depressive disorders and identify potential candidates for drug repositioning.

Demyelination leads to nerve damage and inflammation. Here, the authors show multisensory gamma stimulation’s potential to mitigate demyelination and neuroinflammation, suggesting that this might be a therapeutic strategy for demyelinating diseases.

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.

Although the common genetic variants contributing to blood lipid levels have been studied, the contribution of rare variants is less understood. Here, the authors perform a rare coding and noncoding variant association study of blood lipid levels using whole genome sequencing data.

An initial draft of the human pangenome is presented and made publicly available by the Human Pangenome Reference Consortium; the draft contains 94 de novo haplotype assemblies from 47 ancestrally diverse individuals.

In the standard Si transistor gate stack, replacing conventional dielectric HfO₂ with an ultrathin ferroelectric–antiferroelectric HfO₂–ZrO₂ heterostructure exhibiting the negative capacitance effect demonstrates ultrahigh capacitance without degradation in leakage and mobility, promising for ferroelectric integration into advanced logic technology.

Using a make-on-demand library that contains hundreds-of-millions of molecules, structure-based docking was used to identify compounds that, after synthesis and testing, are shown to interact with AmpC β-lactamase and the D₄ dopamine receptor with high affinity.

2D Weyl semimetals are spin-polarized analogues of graphene that promise access to various topological properties of matter. Here, the authors evidence spin-polarized Weyl cones, Weyl nodes, and Fermi strings in monolayer bismuthene.

Per- and polyfluoroalkyl substances (PFAS) are persistent and bioaccumulative pollutants in soil. Here, the authors developed a rapid electrothermal mineralization method that can efficiently mineralize PFAS while maintaining soil properties.

The EMDataResource Ligand Model Challenge aimed at assessing the reliability and reproducibility of modeling ligands bound to protein and protein–nucleic acid complexes in cryo-EM maps determined at near-atomic resolution. This analysis presents the results and recommends best practices for assessing cryo-EM structures of liganded macromolecules.

Prokineticin-2 (PK2) is a secreted protein involved in a number of physiological functions. Here, the authors find that PK2 expression increases in surviving DA neurons from Parkinson's disease patients, and show it protects against dopaminergic degeneration in PD mouse models.

Quantitative mass spectrometry enables the proteome-wide assessment of biomolecular binding affinities. While previous approaches mainly focused on protein–small molecule interactions, the authors here present a method to probe protein–DNA and protein–nucleosome binding affinities at proteome scale.

Lenardo and colleagues identify a new human genetic disease, GISELL, whereby ceramide lipid homeostasis is disrupted, thereby altering T cell longevity. Deficiency of GTPase of the immunity-associated protein 5 (GIMAP5) in patients leads to cellular senescence, immunodeficiency and early mortality.

A spinal cord neuroprosthesis targeting leg motor neurons in real time improves walking and reduces freezing of gait in non-human primate models and in one individual with advanced Parkinson’s disease.

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

Slowly evolving cnidarians are useful models to study genome architecture. This study shows that sea anemones have a high degree of chromosomal macrosynteny, but poor microsynteny conservation. This is correlated with a small genome size and short distances of cis-regulatory elements to genes.

Which combination of current genome sequencing and assembly approaches results in high-quality, complete diploid genome assemblies is determined.

Naked mole-rats are hypoxia-tolerant mammals, and during hypoxia their body temperature decreases via unknown mechanisms. Here the authors report that the hypoxia-induced body temperature decrease in naked mole rats occurs through decreased brown adipose tissue thermogenesis via decreases in a key thermogenic mitochondrial protein: UCP1.

An approach for the design of protein pores is demonstrated by the computational design and subsequent experimental expression of both an ion-selective and a large transmembrane pore.

Inflammation of brain endothelial cells is seen in neurodegenerative conditions and in aging. Here the authors examine the role of astrocytes in blood brain barrier function using an iPSC-derived cell co-culture model.

Oxygen in shallow shelf waters rose linearly with atmospheric oxygen in the Neoproterozoic era, potentially driving the first radiation of marine animals, but widespread ocean oxygenation came later, according to reconstructions of oxygen levels and marine productivity.

The inhibition of bacterial glycosyltransferase has the potential to be an effective therapeutic target against drug resistance bacteria. Here, the authors present a novel class of inhibitor compounds based on a monosaccharide scaffold, which are able to eliminate bacterial infections in mice.

Systemic inflammation is recognized as a central pathobiologic feature in heart failure with preserved ejection fraction (HFpEF). Here, the authors report 70 pro- and anti-inflammatory eicosanoid and eicosanoid-related metabolites associated with HFpEF status.

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.

Asymmetric inheritance of organelles, proteins and RNAs occurs during stem cell division. Here the authors show the strength of pairing of homologous Stat92E loci, a stem cell-specific gene, changes immediately after the asymmetric division due to asymmetric inheritance of new histones to one of the daughter cells and is important for turning off gene expression in this cell as it differentiates.

Crystal structures of the σ₂ receptor are determined and used to perform a docking screen of nearly 500 million molecules, identifying σ₂-selective ligands and providing insight into the role of σ₂ in neuropathic pain.

The role of impaired lung function in lung cancer etiology is complex due to the relation of cigarette smoking to both conditions. Here, supported by Mendelian randomization analysis the authors find a link between pulmonary function impairment and lung cancer risk beyond smoking, implicating immune-related pathways

Stratified medicine promises to tailor treatment for individual patients, however it remains a major challenge to leverage genetic risk data to aid patient stratification. Here the authors introduce an approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue-specific gene expression levels, and highlight its ability to identify biologically meaningful and clinically actionable patient subgroups, supporting the notion of different patient ‘biotypes’ characterized by partially distinct disease mechanisms.

The One Thousand Plant Transcriptomes Initiative provides a robust phylogenomic framework for examining green plant evolution that comprises the transcriptomes and genomes of diverse species of green plants.

The Cancer Genome Atlas Network describe their multifaceted analyses of primary breast cancers, shedding light on breast cancer heterogeneity; although only three genes (TP53, PIK3CA and GATA3) are mutated at a frequency greater than 10% across all breast cancers, numerous subtype-associated and novel mutations were identified.

This preprint further characterizes a superantigen motif identified in SARS-CoV-2 spike protein and evaluates a monoclonal antibody targeting this region that can neutralize live virus.

Chemical imaging, including infrared spectroscopic microscopy with molecular sensitivity, is useful for label-free biomedical analyses, but is limited by slow speed and poor image quality. Here, the authors design a fast mid-infrared microscope with low noise and high spatial resolution for high-throughput imaging of whole slides.

Protected areas across mega-diverse Southeast Asia are associated with elevated vertebrate biodiversity inside their boundaries and in surrounding areas.

Observations are reported of HClO₃ and HClO₄ in the atmosphere and their widespread occurrence over the pan-Arctic during spring, providing further insights into atmospheric chlorine cycling in the polar environment.