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Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

Alterations in the tumour suppressor genes STK11 and/or KEAP1 can identify patients with advanced non-small-cell lung cancer who are likely to benefit from combinations of PD-(L)1 and CTLA4 immune checkpoint inhibitors added to chemotherapy.

Fitness landscapes largely shape the dynamics of evolution, but it is unclear how they shift upon ecological diversification. By engineering genome-wide knockout libraries of a nascent bacterial community, Ascensao et al. show how ecological and epistatic patterns combine to shape adaptive landscapes.

The pathogenic bacterium Pseudomonas aeruginosa can be found in vacuoles and cytoplasm within infected cells. Here, Schator et al. show that extracellular bacteria use a type-III secretion system to induce Ca²⁺ influx into host cells and promote vacuole escape of intracellular bacteria and in vivo dissemination.

Wolves in Asia are remarkably diverse, inhabiting some of the world's hottest deserts to the high plains of the Tibetan plateau. However, they remain understudied and poorly understood. Here, we sequenced whole genomes of wolves in Asia to assess their evolutionary history and genetic diversity.

A sunlight-activated chemical spray increases wheat yield in field trials across rainfall conditions.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

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.

Twin and adoption studies suggest that 30 to 60% of the variance in many personality traits is due to inherited factors. However, there is little knowledge of the number or identity of the responsible genes, how they differ between individuals, or how their gene products interact with the developing brain and with environmental and experiential factors to generate the complex blend of attitudes and actions that comprise human temperament¹. In the accompanying paper, Ebstein et al.² have found a population association between a long allele of polymorphic exon III repeat sequence of the D4 dopamine receptor gene (DADR) and the normal personality trait of Novelty Seeking. The possibility of a causal relationship between DADR and Novelty Seeking is further supported by studies showing that the number of exon III repeats can affect the binding of ligands to the receptor^3,4; that DADR is expressed in lim-bic areas involved in cognition and emotion^5,6; that dopamine mediates exploratory behaviour in experimental animals^7–12; that the rewarding effects of amphetamines and cocaine are related to dopamine release¹³; and that Novelty Seeking is low in dopamine-deficient patients with Parkinson's disease¹⁴. We investigated the relationship between DADR exon III sequence variants and personality test scores in a population of 315 mostly male siblings, other family members and individuals from the United States. The association between long alleles of exon III and personality traits related to Novelty Seeking was confirmed. Moreover, family studies showed that this association is the result of genetic transmission rather than of population stratification.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

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.

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.

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.

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.

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.

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.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

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

This study reveals neuronal targets of Lac-Phe in the hypothalamus that mediate its suppression of food intake.

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.

Crossing the blood–brain barrier in primates is a major obstacle to gene delivery in the brain. Here an adeno-associated virus variant (AAV.CAP-Mac) is identified and demonstrated for crossing the blood–brain barrier and delivering gene sequences to the brain of different non-human primates species.

Glaciers on the west Antarctic Peninsula flowed on average 12% faster during the summer compared with winter due to a mix of oceanic and atmospheric influences, according to an analysis of remote sensing data from 2014 to 2021.

N-Hydroxysuccinimide (NHS)-ester derivatives are one of the most widely used acylating agents. In this work, the authors report that ring-opening reaction of the succinimide to afford N-succinamide derivatives is a present, sometimes dominant, side-reaction of thio-NHS esters, and show that the extent of side reaction is lysine nucleophile- and therefore site-dependent with both side-reaction and desired reaction occurring within the same protein substrate.

Osteosarcomas (OS) are aggressive bone tumors which have no actionable recurrent driver mutations. Here the authors identify aberrant expression of EZHIP in a subset of OS patients as an oncogenic driver, which exhibits vulnerability to epigenetic therapies.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

Disulfide-based dimerization of modified identical and heterologous nanobody scaffolds enables higher-order assembly for high-resolution cryo-electron microscopy structure determination that is widely applicable to small protein targets.

Cyanobacteria are shown to produce alkanes that sustain communities of pentadecane-degrading bacteria, and possibly archaea, as part of an alkane cycle in the ocean.

Glutamatergic and GABAergic (γ-aminobutyric acid-producing) cortical neuronal activity drives proliferation of small lung cell cancer via paracrine interactions and through synapses formed with tumour cells.

Metabolic liver disease is highly prevalent in subjects with obesity and involves inflammation, insulin resistance, and fibrosis, leading to cirrhosis. Here, the authors show the IFNγ-IL12 axis in regulating intercellular crosstalk in the liver and playing a major role in the pathogenesis of metabolic liver disease.

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.

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.

PdCO is a switchable optogenetic tool for inhibiting synaptic transmission in neuronal terminals in vivo, as demonstrated in a variety of contexts mainly in the mouse.

Following the observation that higher circulating levels of metabolites derived from niacin—an essential micronutrient that is fortified in cereals—are associated with a higher risk for cardiovascular events, genetic and preclinical studies established links among niacin-derived metabolites, soluble vascular adhesion molecule 1 levels and leukocyte adhesion to the vascular endothelium.

Despite the importance of osteoclast secretory lysosomes in bone digestion, the proteins that regulate them remain ill defined. Here, the authors identify Slc37a2 as a secretory lysosome sugar transporter that is required for maintenance of skeletal bone mass.

The study advances the use of serological surveys to guide trachoma elimination program decisions and provides a way to set thresholds for whether or not to continue an intervention program.

Jung et al. show that shelter experience boosts dopamine release in the nucleus accumbens, generating a goal-location memory. Reactivating a neuronal ensemble developed from shelter experience enables memory-guided navigation to the goal during escape.

A radical-based method for functionalizing native sugars shows a way to remove typical protecting-group manipulations.

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.

In an updated report on 70 laboratory-confirmed highly pathogenic avian influenza A H5N1 cases in the USA between March 2024 and May 2025, the absence of human-to-human transmission to date was confirmed, with no known mutations of resistance to neuroaminidase inhibitors.

Here, combining X-ray crystallography, cryo-electron tomography and animal studies, the authors show that the monoclonal antibody against Ebola virus glycoprotein (GP1,2) 3A6 exerts protection via binds to a conformation of GP1,2 that is lifted from the virion membrane, providing insights into the mechanism of action with implications for the design of anti-Ebola therapeutics.