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Analysis of 37 genomes together with more than 140 phenotypic traits links genomic features to ecological fitness and lifestyle diversity in Trichoderma fungi.

Growing demand for robust plasma and serum proteomics highlights the need for better standardization. Here, the authors introduce an open 211-peptide internal standard that enables consistent quantification, cross-platform alignment and clinical utility across serum and plasma studies.

Inventory data from more than 1 million trees across African, Amazonian and Southeast Asian tropical forests suggests that, despite their high diversity, just 1,053 species, representing a consistent ~2.2% of tropical tree species in each region, constitute half of Earth’s 800 billion tropical trees.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

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).

Limzerwala et al. show that FoxM1 insufficiency leads to chromosome segregation errors via RhoA modulation, causing tumor progression across different tissue types.

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.

Kavšek et al. reveal in this C. elegans study that the LIN-39 and DAF-16 transcription factors cooperate to regulate enhancer activity in VC neurons and ensure proper neuron maturation. This in turn is required for longevity under reduced IIS conditions, linking chromatin dynamics to lifespan extension.

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.

Improved vaccines and antivirals are needed for many enveloped viruses. Here, the authors identify sulfur-based small molecules that disrupt viral membrane properties, inhibiting fusion and entry, and safely inactivate influenza virus. The resulting inactivated influenza vaccine is protective in mice.

DNA from ancient wolves spanning 100,000 years sheds light on wolves’ evolutionary history and the genomic origin of dogs.

The low-density lipoprotein receptor family members LRP1, LRP4 and VLDLR are entry receptors for yellow fever virus.

Citizen science taps the efforts of non-experts. Here, authors describe Drugit, an extension of the crowdsourcing game Foldit, and its use in designing a non-peptide binder of Von Hippel Lindau E3 ligase for use with proteolysis targeting chimeras.

Genome-wide association analysis in over one million individuals of European ancestry identifies 2,103 independent genetic signals (including 113 new loci) associated with blood pressure traits.

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.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

Bacteria use diverse defence systems against phages, including a 164-residue prophage-encoded protein, Rip1, which senses conserved phage assembly rings to form membrane pores that block virion maturation and trigger premature host cell death.

Estimates from the Global Dietary Database indicated that 2.2 million new type 2 diabetes and 1.2 million new cardiovascular disease cases were attributable to sugar-sweetened beverages worldwide in 2020, with the highest burdens in sub-Saharan Africa, Latin America and the Caribbean.

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.

Jose Florez, Claudia Langenberg, Erik Ingelsson, Inga Prokopenko, Inês Barroso and colleagues perform large-scale association analyses using the Metabochip to gain further insights into the genetic architecture of glucose regulation. They identify 38 new loci influencing 1 or more glycemic traits and show that many of these loci also modify risk of type 2 diabetes.

A modularized open-source pipeline for invasive brain signal decoding bridges the gap between closed-loop neuromodulation and clinical brain–computer interface approaches in a large patient cohort.

In this Stage 2 Registered Report, Buchanan et al. show evidence confirming the phenomenon of semantic priming across speakers of 19 diverse languages.

Zeng et al. applied single-particle cryo-electron microscopy to native samples isolated from the human parasite Toxoplasma gondii, determining multiple structures of key components of the conoid, a cone-shaped organelle essential for host cell invasion.

Neutrophil-derived IL-1β has a role in preserving lipid stores during metabolic stress.

Genome-wide association meta-analyses of waist-to-hip ratio adjusted for body mass index in more than 224,000 individuals identify 49 loci, 33 of which are new and many showing significant sexual dimorphism with a stronger effect in women; pathway analyses implicate adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution.

This study identifies the proteins critical to fungal cellulosome assembly, characterizing the complex as evolutionarily chimeric — an independently evolved fungal complex co-opted catalytic activities from bacteria coexisting within the gut.

The study combines bulk, single-cell, and spatial transcriptomics of human carotid plaques. It identifies immune– stromal cell diversity, spatial macrophage gradients, smooth muscle cell heterogeneity, and morphology-defined plaque subtypes.

Ataxia telangiectasia and Rad3-related kinase (ATR) is a rational radiosensitization target. This trial evaluates the combination of the ATR inhibitor, ceralasertib, with palliative radiotherapy in 27 patients with advanced solid tumors.

Fillingim et al. show that biological and psychosocial factors jointly predict conditions associated with chronic pain.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

Brown et al. show that mouse islet progenitors with different transcriptomes produce distinct β-cell subtypes and maternal diet alter the subtype proportions. Similar β-cell subsets exist in humans, with a subset enriched in genes related to β cell function reduced in diabetes.

A large international panel of experts reach consensus on a new standard for reporting settings in psychedelic trials, identifying 30 key non-pharmacological factors to strengthen the rigor of psychedelic research.

Theory predicts that adaptive mutations can have indirect negative effects on fitness. This study demonstrates how ‘adaptation begets adaptation’: changes to the sociogenetic environment accompanying rapid adaptation in wild crickets provoked genome-wide compensatory adaptation.

A PICALM allele associated with increased risk of late-onset Alzheimer’s disease has a microglial-specific role in lipid droplet accumulation.

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.

Conditional cysteine restriction in mice causes substantial weight loss, exceeding that seen with essential amino acid restriction, by activating the integrated stress and oxidative stress responses, and by unexpectedly depleting coenzyme A, leading to metabolic inefficiency.

By assembling the genomes of 22 Fraxinus species and conducting comparisons including further species, the authors identify candidate loci for emerald ash borer resistance that have evolved convergently.

The conversational diagnostic artificial intelligence system AMIE (Articulate Medical Intelligence Explorer) has potential as a real-world tool for clinical history-taking and diagnostic dialogue, based on its performance in simulated consultations.

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.

Cecilia Lindgren and colleagues report results of a large-scale genome-wide association study for waist-to-hip ratio, a measure of body fat distribution. They identify 13 new loci associated with this trait, several of which show stronger effects in women than in men.

To investigate the link between the gut microbiome and ovarian health, here the authors transplant gut microbiota from estropausal female mice to young adult female mice. Microbial transplantation improves ovarian hormone profiles, follicle metrics and fertility-related outcomes, highlighting a causal role for the aging gut microbiome in regulating ovarian function.

Targeted proteomics enables robust hypothesis-driven research. Here, Yu et al. present a multiplexed approach for targeted pathway proteomics and apply it to quantify protein families across 480 fully genotyped Diversity Outbred mice, revealing impacts of genetic variation on protein expression and lipid metabolism.

Global leaf area has increased over the past four decades, raising hopes for its role in mitigating climate change through carbon uptake and cooling effects. This study shows that vegetation cover change, particularly tree cover gain in the Northern Hemisphere, plays a significant role in driving the greening trend.

Tetrahydrofuran can be unexpectedly cleaved by bimetallic sodium–magnesium and sodium–manganese bases. At least six bonds are broken in the one-pot reaction, but all fragments are separately captured to form crystalline compounds.

Exome sequencing of 851 trios from more than 2,500 individuals finds 187 genes with de novo mutations that contribute to meningomyelocele (spina bifida) and highlights critical pathways required for neural tube closure.