Search

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

An analysis of data from the Sherlock-Lung study provides insight into the mutational processes that contribute to lung cancer in never smokers, and looks at the possible role of factors such as air pollution and passive smoking.

Inflammation induces changes in the extracellular matrix density and composition. Fowell and colleagues show that CD4⁺ effector T cells use integrin α_V for interstitial migration on fibronectin in inflamed tissues.

Alzheimer’s disease has been associated with increased structural brain aging. Here the authors describe a model that predicts brain aging from resting state functional connectivity data, and demonstrate this is accelerated in individuals with pre-clinical familial Alzheimer’s disease.

Patient and public involvement and engagement (PPIE), although well established in clinical settings, remains less well defined in laboratory-based settings, where infrastructure to support meaningful collaboration is limited. In this Comment, the authors propose a novel framework for embedding PPIE ambassadors into basic cancer research pipelines, outlining strategies to address power imbalances, enhance communication and facilitate knowledge translation.

This Review discusses multiomic approaches for the characterization and biological understanding of cellular senescence, including detailed case studies on skeletal muscle and adipose tissue that highlight current outstanding issues in the field.

The mechanism of macrophage cytotoxicity against cancer cells requires further illustration. By employing CRISPR screening in CAR-macrophage and cancer cell co-culture system, the authors identify depletion of ATG9A on cancer cells sensitizes them to macrophage-mediated killing, which can be synergic with CSF1R inhibition in cancer treatment.

Air surveillance offers a potential means of monitoring airborne pathogens without the need for individual sampling. Here, the authors perform continuous air sampling in 15 community settings in the US for 29 weeks and demonstrate its feasibility for routine detection of SARS-CoV-2 and other respiratory pathogens.

Atoms and molecules under extreme temperature and pressure can be investigated using dense plasmas achieved by laser-driven implosion. Here the authors report spectral change of copper in billions atmosphere pressure that can only be explained by a self-consistent approach.

Low-dimensional representations of functional brain anatomy relevant for dementia syndromes may exist. Here the authors propose a computational model of mental functions to catalogue this anatomy in Alzheimer’s and related dementias.

The quark structure of the f₀(980) hadron is still unknown after 50 years of its discovery. Here, the CMS Collaboration reports a measurement of the elliptic flow of the f₀(980) state in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of 8.16 TeV, providing strong evidence that the state is an ordinary meson.

Automated pathotyping of synovial tissue in arthritis is a major unmet need. Here, the authors develop and demonstrate the efficacy of an automated tissue and cellular pathotyping tool for inflammatory arthritis.

An online training module that synergistically targets two different mindsets can reduce stress levels in adolescents in the context of social-evaluative stressors—stressful experiences in which individuals fear that others are judging them negatively.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

By combining a chromatic focusing system with chirped laser pulses, the spatiotemporal distribution of the laser pulse is controlled in the focal region. The focal spot propagates over nearly 100 times its Rayleigh length at any velocity.

Deciding whether to perform pelvic lymph node dissection at the time of prostate cancer surgery could be assisted by using prostate-specific membrane antigen-PET imaging. In favourable intermediate-risk prostate cancer, this imaging technique could be used to identify patients who could forego pelvic lymph node dissection.

Paul Pharoah and colleagues report the results of a large genome-wide association study of ovarian cancer. They identify new susceptibility loci for different epithelial ovarian cancer histotypes and use integrated analyses of genes and regulatory features at each locus to predict candidate susceptibility genes, including OBFC1.

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.

Multiple comorbidities are associated with higher plasma P-tau181 and P-tau217 levels, and affects their normal reference ranges and cutpoints.

HNF1B is overexpressed in the clear cell subtype and epigenetically silenced in the serous subtype of ovarian cancer. Pearce and colleagues now show that genetic variants in HNF1B are differentially associated with risks of developing these two cancer subtypes, possibly through an epigenetic mechanism.

Border and colleagues present FUSION, an open-source, web-based platform designed to integrate spatial omics with histological context. FUSION enables intuitive, interactive exploration of cellular and tissue-level features across diverse organs and assay types.

A cluster-randomized controlled trial found that using an electronic system for symptom monitoring of patient-reported outcomes during treatment led to sustained improvements in emergency visits, quality of life and delayed deterioration of physical function in patients with metastatic cancer.

Bioenergetic capacity, the ability to maintain energy balance under stress, can be monitored using blood acylcarnitine profiles. Improving this capacity may slow Alzheimer’s disease progression.

In a phase 2 randomized control trial, intermittent senolytic therapy administered to postmenopausal women did not result in a reduction in the bone resorption marker, serum CTx, compared to control at 20 weeks.

Primary biliary cirrhosis is an autoimmune liver disease with poor therapeutic options. Here Cordell et al. a perform meta-analysis of European genome-wide association studies identifying six novel risk loci and a number of potential therapeutic pathways.

Chronic myelomonocytic leukaemia is classified as proliferative (pCMML) or dysplastic based on the white blood cell counts but biological differences are unclear. Here, the authors show genetic, transcriptomic and epigenomic differences between these two subtypes establishing that pCMML is RAS-pathway driven and that inhibiting RAS-driven PLK1 expression is a viable therapeutic target.

Humans are exposed to millions of chemicals but mass spectrometry (MS)-based targeted biomonitoring assays are usually limited to a few hundred known hazards. Here, the authors develop a workflow for MS-based untargeted exposome profiling of known and unidentified environmental chemicals.

Riboswitches contain an aptamer domain that recognizes a metabolite and an expression platform that regulates gene expression. Here the authors report the crystal structure of a preQ₁-sensing riboswitch from Carnobacterium antarcticus that shows two metabolites in a single binding pocket.

Choice-relevant computations across the medial prefrontal cortex differ only quantitatively between areas. Here the authors suggest these computations may be organized along a functional gradient.

Pulmonary large cell neuroendocrine carcinoma is an aggressive subtype of lung cancer. Here, the authors identify distinct subtypes based on genomic alterations and transcriptomic alterations.

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.

Prostate cancer (PrCa) involves a large heritable genetic component. Here, the authors perform multivariate fine-mapping of known PrCa GWAS loci, identifying variants enriched for biological function, explaining more familial relative risk, and with potential application in clinical risk profiling.

In a prospective study enrolling 1,222 patients from 22 emergency departments, a device using a machine-learning-based signature of blood mRNAs demonstrated clinically acceptable performance to diagnose bacterial and viral infections and to predict the all-cause need for critical care interventions within 7 days, with benchmark to established biomarkers and risk scores.

CRISPR-based genome editing therapeutics are entering the clinic, but in vitro and in vivo tools are needed to assess their safety and efficacy. The authors review complementary technologies to monitor the biological effects of genome editing across scales, including the direct measurement of editing outcomes in DNA, human microphysiological systems and non-invasive in vivo imaging.

Hundreds of genetic loci associated with age at menopause, combined with experimental evidence in mice, highlight mechanisms of reproductive ageing across the lifespan.

This study finds that sST2 is a disease-causing factor for Alzheimer’s disease. Higher sST2 levels impair microglial Aβ clearance in APOE4⁺ female individuals. A genetic variant, rs1921622, is associated with a reduction in sST2 level and protects against AD in APOE4⁺ female individuals.

Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.

Results from a comprehensive evaluation of the function of BRCA2 variants, particularly variants of uncertain significance, provide a useful resource to improve the clinical management of individuals who carry such genetic variants.