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At present, there are no countermeasures against the GI genogroup of noroviruses. The authors characterize a protective human antibody that broadly recognizes this genogroup.

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.

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.

An analysis of data from 522 population-based studies encompassing 82 global regions and spanning more than a century (1920–2024) shows spatiotemporal transitions across epidemiologic stages 1 to 3 of inflammatory bowel disease, and models stage 4 progression.

The authors construct a time-calibrated phylogeny spanning >90% of spiny-rayed fishes to explore patterns of body shape disparity within acanthomorphs. They find a trend of steady accumulation of lineages from the Cenozoic, with an increase in morphological disparity following the Cretaceous–Palaeogene event, facilitating the radiation of diverse morphotypes that characterize acanthomorphs’ widespread ecological success today.

Glacier shrinkage intensifies phosphorus limitation but alleviates carbon limitation in glacier-fed streams, according to analyses of resource stoichiometry and microbial metabolism in glacier-fed streams from mountain regions.

Cancer genetics has benefited from the advent of next generation sequencing, yet a comparison of sequencing and analysis techniques is lacking. Here, the authors sequence a normal-tumour pair and perform data analysis at multiple institutes and highlight some of the pitfalls associated with the different methods.

Combination of epidemiology, preclinical models and ultradeep DNA profiling of clinical cohorts unpicks the inflammatory mechanism by which air pollution promotes lung cancer

Microplastics have spread across the globe and reached even the most remote locations, but an understanding of their origins remains largely elusive. Here the authors quantify and characterise microplastics across the North Pole, finding that synthetic fibers like polyester are dominant and likely sourced from the Atlantic Ocean.

The Clostridium difficile virulence factors TcdA and TcdB contain a glucosyltransferase domain (GTD), which has both glucohydrolase (GH) and glucosyltransferase (GT) activities. Here, the authors characterize the transition state features of the TcdA and TcdB GH reactions by measuring kinetic isotope effects and they identify two transition state analogues, isofagomine and noeuromycin that inhibit TcdA and TcdB. They also present the crystal structures of TcdB-GTD bound to these inhibitors and the reaction product UDP.

Understanding how SARS-CoV-2 gains initial entry into the human body is a key step towards the development of prophylaxes and therapeutics for COVID-19. Here, the authors show that ACE2, the receptor for SARS-CoV-2, is abundantly expressed in the motile cilia of the human nasal and respiratory tract and is not affected by the use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers.

Izar and colleagues demonstrate that loss of Pip4k2c in melanoma cells promotes liver metastatic tropism driven by PI3K-AKT pathway activation in the insulin-rich liver milieu, which can be abrogated by inhibition of SGLT2 or a ketogenic diet.

Phenotypic screens in organoids and primary cells are scaled up using perturbation pooling.

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

Genomic studies often lack representation from diverse populations, limiting equitable insights. Here, the authors show that the BIG Initiative captures extensive genetic diversity and reveals ancestry-linked health disparities in a community-based Mid-South cohort.

Engineered live bacteria could represent a new class of therapeutic treatment for human disease. Here, the authors use a human gut-on-a-chip microfluidics system to characterize an engineered live bacterial therapeutic, designed for the treatment of phenylketonuria, and to construct mathematical models that predict therapeutic strain function in non-human primates.

A system to express neoantigens in tumor cells and mice circumvents central T cell tolerance.

Spatial molecular imaging analysis of human pancreatic adenocarcinomas describes multicellular neighborhoods in the tumor microenvironment. Ligand–receptor analysis using optimal transport-based SCOTIA identifies interleukin-6 as a mediator of chemoresistance.

Excessive complement C3 causes synaptic stripping and neurodegeneration. Here, the authors used the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis and single-cell RNA sequencing to show that C3 expression defines disease-associated reactive glia. C3 deletion abrogated these pro-inflammatory glia and protected neurons.

This Consensus Statement presents the standards for technical reporting in environmental and host-associated microbiome studies (STREAMS) guidelines.

Multivalent nanobodies against SARS-CoV-2 from mice engineered to produce camelid nanobodies recognize conserved epitopes that are inaccessible to human antibodies and show promise as a strategy for dealing with viral escape mutations.

The histone methyltransferase DOT1L and the chromatin reader BRD4 together facilitate transcription of genes critical to the molecular pathogenesis of MLL leukemia.

De novo assemblies of 43 Y chromosomes spanning 182,900 years of human evolution reveal considerable diversity in the size and structure of the human Y chromosome.

Interferon-ε is a tumour suppressor expressed in the epithelial cell of origin of ovarian cancer, which it restricts by direct action on tumour cells and especially by activation of anti-tumour immunity.

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.

Lynch, Brenner and colleagues find that tissue-resident γδ T cells reside in adipose tissues in both mice and humans. These cells play essential roles in regulating thermogenesis and supporting age-dependent increases in adipose-tissue regulatory T cell populations.

Leveraging metabarcoding and metagenomics, a survey of bacteria in the benthic microbiome across 152 glacier-fed streams (GFSs) provides a global reference for future climate-change microbiology studies on the vanishing GFS ecosystem.

Genotype and exome sequencing of 150,000 participants and whole-genome sequencing of 9,950 selected individuals recruited into the Mexico City Prospective Study constitute a valuable, publicly available resource of non-European sequencing data.

 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. 

A newly developed genetically engineered mouse model enables the analysis of specific antigen presentation in vivo, providing insights into the tumour immunopeptidome and cancer progression.

Transcriptomic and chromatin accessibility analyses of naive and transplanted colon cancer organoids in a mouse model reveal a key role for the transcription factor SOX17 in establishing a permissive immune environment for tumour cells.

Clinically significant genetic variation in Asian populations is under-characterized. Here, the authors show the diversity in prevalence and spectrum of human disease and pharmacogenetic variants in a multi-ethnic Asian population.

A dataset of coding variation, derived from exome sequencing of nearly one million individuals from a range of ancestries, provides insight into rare variants and could accelerate the discovery of disease-associated genes and advance precision medicine efforts.

A large, open dataset containing parallel recordings from six visual cortical and two thalamic areas of the mouse brain is presented, from which the relative timing of activity in response to visual stimuli and behaviour is used to construct a hierarchy scheme that corresponds to anatomical connectivity data.

Here, Schwartz, Bravo, and Ahsan et al. show how multi-subunit fusion proteins are arranged around a crRNA in a type III CRISPR-Cas effector to cleave target RNA. Structures and molecular dynamics of this complex show three distinct active sites that can be used for programmable RNA cleavage.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

Active emulsions and liquid crystalline shells offer a unique framework for exploring topological matter due to their complex morphologies and dynamic properties. Here the authors report how activity generates diverse nonequilibrium states, from defect-free motile states to complex topologically active configurations, providing insights into controlled flow and topology in active systems.

The balance between precipitation and evaporation in the Caribbean region during the Common Era can be estimated through analyses of sedimentary foraminiferal assemblages that record submarine groundwater discharge.

Mouse models of lung and colorectal cancer with sporadic DNA mismatch repair deficiency clarify that the intratumor heterogeneity and clonal architecture rather than tumor mutational burden are powerful determinants of immunotherapy response.

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.

Whole-genome sequence data for 108 individuals representing 28 language groups across Australia and five language groups for Papua New Guinea suggests that Aboriginal Australians and Papuans diverged from Eurasian populations approximately 60–100 thousand years ago, following a single out-of-Africa dispersal and subsequent admixture with archaic populations.