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A combined analysis of SARS-CoV-2 viral load and whole-genome sequences from COVID-19 patients, including some who were previously vaccinated, reveals that vaccine breakthrough infections are more commonly associated with antibody-resistant SARS-CoV-2 variants than infections in unvaccinated individuals, and that symptomatic breakthrough infections may be as efficient in spreading COVID-19 as unvaccinated infections.

Spatial transcriptomic studies and lineage tracing reveal that, after brain injury, transient profibrotic fibroblasts develop from existing brain fibroblasts, infiltrate lesions, regulate the local immune response and lead to beneficial scar tissue formation.

Creative experiences such as dance, music, drawing, and strategy video games might preserve brain health. The authors show that regular practice or short training in these activities is linked to brains that look younger and work more efficiently.

Brain age gaps (BAGs) highlight deviations from healthy brain aging, yet their biophysical underpinnings in aging and dementia are not well understood. Here, the authors use EEG connectivity and generative modeling across diverse populations to reveal that BAGs are influenced by geography, income, sex and education, with implications for understanding accelerated aging and dementia.

The social exposome—lifelong social and economic adversity—can shape brain health and dementia risk. Here, the authors show that an adverse social exposome is linked to poorer clinical, cognitive, and brain changes in Latin American older adults.

Enfortumab vedotin (EV) is the current standard treatment for advanced bladder cancer, but resistance typically develops within a year, highlighting the need for new therapies. This study demonstrates that NECTIN4-targeting CAR T cells are effective against bladder cancer, including EV-resistant cells, and their potency can be further enhanced by using rosiglitazone to boost NECTIN4 expression.

SARS-CoV-2 seroprevalence surveys provide estimates of the extent of prior infection in a population. In this nationally representative survey from Mexico, the authors estimate seroprevalence after the first epidemic wave at ~25%, with variation by region, age, socioeconomic status, and education level.

Gonzalez-Hurtado, Leveau and colleagues characterize adipose resident tissue macrophages across lifespan in mice, finding that nerve-associated macrophages, which mitigate inflammation and control lipolysis and catecholamine resistance, are lost during aging.

In vivo imaging reveals that vertebrate cells use RB pathway-dependent, cell-autonomous size control to trigger G1/S at a fixed size. Extrinsic cues alter growth rates but not the size threshold for S phase entry.

A global research network monitoring the Amazon for 30 years reports in this study that tree size increased by 3% each decade.

In-cell NMR reveals the molecular details of NDM-1 degradation, an enzyme linked to antibiotic resistance, and sheds light on protein quality control in the periplasm of live bacteria at an atomic level.

Analyses of the exposomes of populations across 40 countries found global disparities in healthy aging attributed to diverse biological, socioeconomic and political factors, with accelerated aging seen in populations from Egypt, South Africa, and Latin American and Caribbean regions.

Mondal et al. report that autophagy inhibition promotes p63 activation and metastasis in breast cancer. This process depends on NBR1, which forms cytoplasmic p62/SQSTM1 condensates that sequester the ITCH ubiquitin ligase and prevents p63 degradation.

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.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

PDGrapher uses large datasets of genetic and chemical interventions to find genetic targets that shift a gene expression phenotype from a diseased to a normal state.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

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.

Mass cytometry can be used to scale up multiplexed serology testing, as shown for the simultaneous detection of antibody levels against multiple SARS-CoV-2 proteins in hundreds of serum samples.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

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.

Studies of male genitalia show patterns of divergent evolution, whereas females have been less well studied. Using experimental evolution and quantitative genetic analysis, Simmons and Garcia-Gonzalez show that sexual selection drives the coevolution of female and male genital morphology in the dung beetleOnthophagus taurus.

Highly accurate antibody tests for SARS-CoV-2 are needed for surveillance in low-prevalence populations. Here, the authors find seroprevalence of less than 1% in two San Francisco Bay Area populations at the beginning of April, and that seroreactivity is generally predictive of in vitro neutralising activity.

Genome-wide association studies (GWAS) have revealed gene variants associated with breast cancer, but their association with breast cancer development in Latinas is not clear. Here, the authors carry out a GWAS of breast cancer in Latinas and identify a significant protective variant of Indigenous American origin in the 6q25 region.

Imidazole propionate produced by gut microbiota is associated with atherosclerosis in mouse models and in humans, and causes the development of atherosclerosis through activation of the imidazoline-1 receptor in myeloid cells.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

Here, the authors perform transcriptional profiling on tracheal aspirates of adults requiring mechanical ventilation for SARS-CoV2-induced acute respiratory distress syndrome (ARDS) and identify a dysregulated host response predicted to predicted to be potentially modulated by dexamethasone.

Conditional deletion of the transcriptional co-activator Brd4 in infiltrating Cx3cr1⁺ mouse macrophages ameliorates heart failure and substantially reduces fibroblast activation.

Chen et al. show that subtypes of immune cells in prenatal human brain promote angiogenesis in the germinal matrix. Conversely, in preterm infants, proinflammatory immune cells disrupt angiogenesis and promote germinal matrix hemorrhage.

Structural studies of certain Tn and STn antigen-targeting antibodies reveal that their V_H and V_L domains recognize the glycan antigen and the adjacent peptide region, respectively, enabling a V_H domain-focused and V_L domain-varying phage display library to generate antibodies targeting diverse glycopeptide epitopes.

LaccID, an engineered laccase, enables hydrogen-peroxide-free proximity labeling and electron microscopy (EM) in mammalian cells. Notably, LaccID is selectively active at the cell surface, enabling the mapping of the dynamic T cell–tumor surfaceome and its use as a genetically encodable EM tag, expanding the toolkit for cell-based imaging and proteomics.

A synthetic receptor platform that enables mammalian cells to respond to soluble factors allows specific signalling networks to be precisely controlled, with a variety of therapeutic applications.

Overexpression of c-MYC regulates tumor metabolism in pancreatic ductal adenocarcinoma (PDAC). Here the authors identify ELOVL6, a fatty acid elongase regulated by c-MYC, as a potential therapeutic target of PDAC.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.