Search

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

Eroglu et al. report that epicardial progenitor cells expressing the tight junction protein CLDN6 give rise to cardiomyocytes to contribute to cardiac muscle regeneration following heart injury in salamanders.

DNA 5-hydroxymethylcytosine (5hmC) modification is associated with gene transcription and used as a mark of mammalian development. Here the authors report a comprehensive 5hmC tissue map and analysis of 5hmC genomic distributions in 19 human tissues derived from 10 organ systems, thus providing insights into the role of 5hmC in tissue-specific development.

Dissolved organic matter becomes highly labile in dark anoxic groundwater environments, suggesting that groundwater extraction and subterranean groundwater discharge could be significant sources of greenhouse gases to the atmosphere.

Somatic mutations accumulate with age; however, the role they have in cardiac aging is unclear. Here Choudhury et al. describe the somatic mutation landscape of human heart muscle cells by single-cell whole-genome sequencing and report mutational signatures indicative of increased oxidative DNA damage and failed repair.

Analysis of 14,106 tumor genomes highlights recurrent mutations in mitochondrial ribosomal RNA encoded within the mitochondrial genome. Mutations occur at hotspot positions and are under strong purifying selection in the germline.

Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.

Fibroblast-like synoviocytes are important mediators of joint pathology in rheumatoid arthritis (RA). Here the authors show that Lasp1 is epigenetically regulated and highly expressed by these cells in RA and its deletion can limit joint pathology in a mouse model of inflammatory arthritis.

HIV reservoir dynamics are still incompletely understood. Here, the authors use barcoded HIV in a humanized mouse model to show that cell clones linked to viremia are likely eliminated, while proliferated cell clones contribute to viremia, are likely more resistant to elimination and might fuel viral persistence.

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.

Plant hypocotyl elongation response to light and temperature. Here the authors show that shade combined with warm temperature synergistically enhances the hypocotyl growth response via the PIF7 transcription factor, auxin, and as yet unknown factor.

A deep learning model trained on raw pixel data in hundreds of thousands of echocardiographic videos for the prediction of one-year all-cause mortality outperforms clinical scores and improves predictions by cardiologists.

Association analyses in over 1 million individuals identify 535 new loci influencing blood pressure traits. The results provide new insights into blood pressure regulation and highlight shared genetic architecture between blood pressure and lifestyle exposures.

Subglacial lakes and jökulhlaups (glacier outburst floods) are common in volcanic and glaciated environments, and can pose potential threats to communities living downstream. Here, the authors find that seismic tremor signals during subglacial floods can be used to locate and track the speed and size of the flood before it arrives at the river system, and improves previous methods of early glacial flood warning by a factor of 5.

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

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

Single-cell transcriptomic analysis of mouse hypothalamus and behavioural experiments show that specific hypothalamic networks regulate conflicting feeding versus parenting behaviours of female mice.

A highly potent and selective small-molecule catalytic inhibitor of the protein lysine methyltransferase NSD2 shows therapeutic efficacy in preclinical models of KRAS-driven pancreatic cancer and lung cancer.

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.

Hoang et al. developed a deep-learning framework called ENLIGHT–DeepPT that predicts therapy response based on imputed transcriptomics and shows predictive power across patient cohorts and cancer types.

A large empirical assessment of sequence-resolved structural variants from 14,891 genomes across diverse global populations in the Genome Aggregation Database (gnomAD) provides a reference map for disease-association studies, population genetics, and diagnostic screening.

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 bacterial ubiquitin ligase NleL evades host defence mechanisms both by inhibiting pyroptosis and by preventing infected intestinal epithelial cells from being extruded into the lumen and expelled in the faeces.

This study uncovered genetic associations with environmental sensitivity in psychiatric and neurodevelopmental traits in an international collaboration using data from more than 21,000 monozygotic twins—the largest genetic study of monozygotic twin differences to date.

DNA as a high density storage medium is receiving increasing attention, but long term physical storage is an unsolved problem. Here the authors show that up to 1 TB of data stored as dehydrated DNA spots on a glass cartridge can be retrieved in a spot of water using digital microfluidics with minimal data loss and contamination.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

Observation-based modelling suggests that recent acceleration of Earth’s north magnetic pole towards Siberia can be linked to elongation of a lobe of negative magnetic flux at the core–mantle boundary beneath Canada.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

N-Myc fuels neuroendocrine prostate cancer. Here, the authors describe how targeting HSP70, a major N-Myc partner, coordinates with STUB1 to facilitate the degradation of N-Myc. This process slows neuroendocrine prostate cancer growth, improves the efficacy of Aurora Kinase A inhibitors, and reduces neuroendocrine pathway activity.

Study shows PTSD predisposition shares distinct genes and genomic regions with several cardiovascular conditions. Here the findings reveal neuronal, immune, and metabolic pathways, and repurposed drug targets that further the understanding of the comorbidity.

Predicting declines in commercially harvested species is crucial to avoid overexploitation. An analysis of historical whaling records identifies early warning signals in body size and abundance data 40 years before the collapse of whale stocks.

An integrated transcriptome, genome, methylome and proteome analysis of over 200 lung adenocarcinomas reveals high rates of somatic mutations, 18 statistically significantly mutated genes including RIT1 and MGA, splicing changes, and alterations in MAPK and PI(3)K pathway activity.

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.

Magma movement is thought to trigger volcanic tremor. However, analysis of seismic data suggests that tremor prior to the Bárðarbunga eruption in Iceland instead marked the crust cracking open, whereas subsequent magma flow was seismically silent.

Over one hundred loci have been identified to be associated with the familial risk of prostate cancer but the functional effects are poorly understood. Here the authors use single-nucleotide variant and epigentic data to show an underlying genetic architecture marked by histone modification.

Combining enzymes from different pathways in nature could enable de novo peptide design, but determining enzyme-specificity rules is non-trivial. Here a biophysical model combining enzymes sourced from bacterial ribosomally synthesized and post-translationally modified peptide (RiPP) gene clusters was generated to formalize enzyme-specificity rules and create peptide scaffolds with defined post-translational modifications.

Coherent patterns in the initial growth of extratropical peatlands throughout the Southern Hemisphere during the last glacial track changes in the latitudinal position of the southern westerly winds, according to an analysis of basal peat radiocarbon ages.

Toxoplasma gondii evolved two ISWI remodellers, TgSNF2h and TgSNF2L. TgSNF2h forms a complex that insulates active genes, regulates MORC-driven sexual commitment and ensures precise gene expression, safeguarding the parasite’s developmental program.

Electrochemical properties of organic mixed ionic–electronic conductors depend on their microstructure in operational ionic environments. The microstructure of a model organic mixed ionic–electronic conductor across multiple length scales in both dry and hydrated states, as well as its evolution on hydration, is revealed using cryogenic four-dimensional scanning transmission electron microscopy.

The intricate regulation of cell death pathways remains to be understood. Here the authors identify that PTPN23 functions as a cell death checkpoint to restrain apoptosis, necroptosis and pyroptosis via regulating the endosomal sorting of death receptors and Toll-like receptors.

Majzner and colleagues show that engineering T cells with a membrane-tethered version of the signaling adaptor molecule SLP-76 alongside a chimeric antigen receptor (CAR) enhances CAR T cell activity against low-antigen-density tumors.

Timothy Frayling, Joel Hirschhorn, Peter Visscher and colleagues report a meta-analysis of genome-wide association studies for adult height in 253,288 individuals. They identify 697 variants in 423 loci significantly associated with adult height and find that these variants cluster in pathways involved in growth and together explain one-fifth of the heritability for this trait.

Electrically and mechanically tunable molecular junctions show large image-charge effects.

Data collected from more than 2,000 taxa provide an unparalleled opportunity to quantify how extreme wildfires affect biodiversity, revealing that the largest effects on plants and animals were in areas with frequent or recent past fires and within extensively burnt areas.