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Weaver and colleagues show that TGFβ-induced collagen deposition and metabolic reprogramming of the breast cancer microenvironment by tumor-associated macrophages restrict the antitumor activity of CD8⁺ T cells in female breast cancer.

Crystal structures of the ABC transporter MsbA in complex with two selective small-molecule antagonists reveal an unprecedented allosteric mechanism of inhibition.

The US COVID-19 Scenario Modeling Hub produced medium to long term projections based on different epidemic scenarios. In this study, the authors evaluate 14 rounds of projections by comparing them to the epidemic trajectories that occurred, and discuss lessons learned for future similar projects.

A dataset of 16 plant traits sampled from 2,461 individual trees from 74 tropical forest sites around the world is used to show a strong link between climate and plant functional diversity and redundancy, with drier tropical forests likely being less able to respond to declines in water availability.

Although progress in the coverage of routine measles vaccination in children in low- and middle-income countries was made during 2000–2019, many countries remain far from the goal of 80% coverage in all districts by 2019.

This study presents the first annual update of the indicator framework developed by the Food Systems Countdown Initiative, published in Nature Food in 2023. Almost half of all indicators show some desirable trends. Governance and resilience indicators were revealed as the most connected across themes, constituting entry points for transformative change.

An extinction-risk assessment of reptiles shows that at least 21.1% of species are threatened by factors such as agriculture, logging, urban development and invasive species, and that efforts to protect birds, mammals and amphibians probably also benefit many reptiles.

Most confirmed susceptibility variants for epithelial ovarian cancer lie in non-protein-coding sequences. Here Permuth-Wey and colleagues investigate variants in 3′ untranslated regions (UTRs) and uncover a new susceptibility locus.

A longitudinal evolutionary analysis of 126 lung cancer patients with metastatic disease reveals the timing of metastatic divergence, modes of dissemination and the genomic events subject to selection during the metastatic transition.

An integrated analysis of de novo and inherited coding variants in 42,607 individuals with autism spectrum disorder identifies 60 risk genes of which five have not previously been associated with neurodevelopmental disorders.

In this study, Kagan et al. highlight the relevance of adequate cardiolipin homeostasis by offering mechanistic insight into the pathogenesis of Barth syndrome. The study shows how altered accumulation of mono-lyso-cardiolipin, one of the derivatives of the mitochondrial lipid cardiolipin, forms an anomalous peroxidase complex with cytochrome c, thus leading to increased oxidation of polyunsaturated phospholipids.

Roland et al. report the results of a randomized, non-comparative phase 2 trial of neoadjuvant nivolumab or a combination of nivolumab and ipilimumab in patients with resectable retroperitoneal dedifferentiated liposarcoma and extremity/truncal undifferentiated pleomorphic sarcoma.

Mathematical modelling of 15 years of data from South Africa reveals the spread and vaccine-driven changes in fitness and antimicrobial resistance of Streptococcus pneumoniae.

Analyses of expression profiles from whole blood of 31,684 individuals identify cis-expression quantitative trait loci (eQTL) effects for 88% of genes and trans-eQTL effects for 37% of trait-associated variants.

Post-translationally modified histones are recognized by effector proteins which contain specific binding modules; for example, the bromodomain-containing BET proteins bind acetylated lysine residues during gene activation. Here a synthetic small molecule is described that interferes with the binding of certain BET family members to acetylated histones. The compound inhibits activation of pro-inflammatory genes in macrophages and has activity in a mouse model of inflammatory disease.

Here, the authors functionally characterize a complex genetic variant relevant in prostate cancer that regulates IRX4 expression through epigenetic activation. This work highlights the significance of non-single nucleotide polymorphism causal variants in explaining disease risk.

Chromodomain Helicase DNA-binding (CHD) proteins have been implicated in neurodevelopmental processes. Here, the authors identify missense variants in CHD3 that disturb its chromatin remodeling activities and cause a neurodevelopmental disorder with macrocephaly and speech and language impairment.

Patient-derived xenografts are important tools for cancer drug development. Here, the authors develop models from 22 non-small cell lung cancer patients. They show genomic differences between models created from different spatial regions of tumours and a bottleneck on model establishment.

Comparison of non-invasive [¹¹C]metomidate PET-CT with adrenal vein sampling for predicting biochemical remission of primary aldosteronism showed non-superiority, suggesting that the non-invasive method is suitable for the diagnosis of unilateral primary aldosteronism.

Measurements of subclonal expansion of ctDNA in the plasma before surgery may enable the prediction of future metastatic subclones, offering the possibility for early intervention in patients with non-small-cell lung cancer.

You’re unique just like everyone else. But when does such individuality appear? Laskowski et al. find that clonal fish show unique behavioral patterns on their first day of life, and these patterns predict their behavior up to at least 10 weeks later.

By modelling the radio, optical, UV and X-ray data of the unusually bright cosmological explosion AT 2022cmc, Pasham et al. argue for the presence of a highly collimated jet moving at ≳99.99% the speed of light.

Analyses of the TRACERx study unveil the relationship between tissue morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk of lung adenocarcinomas.

Results of the TRACERx study shed new light into the association between body composition and body weight with survival in individuals with non-small cell lung cancer, and delineate potential biological processes and mediators contributing to the development of cancer-associated cachexia.

Simon Gayther and colleagues report 3 new risk variants for mucinous ovarian carcinoma (MOC) on the basis of an analysis of 1,644 MOC cases and 21,693 controls. They confirm an eQTL association between the HOXD9 promoter and risk SNPs at 2q31.1 using chromosome conformation capture analysis and show that HOXD9 overexpression associates with neoplastic transformation.

Analyses of multiregional tumour samples from 421 patients with non-small cell lung cancer prospectively enrolled to the TRACERx study reveal determinants of tumour evolution and relationships between intratumour heterogeneity and clinical outcome.

Sias et al. show that dopamine projections to the basolateral amygdala drive the reward learning that supports the predictions and inferences needed for adaptive decision-making.

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.

Computational and machine-learning approaches that integrate genomic and transcriptomic variation from paired primary and metastatic non-small cell lung cancer samples from the TRACERx cohort reveal the role of transcriptional events in tumour evolution.

Here, the authors design a multiplex serology platform to quantitatively measure antibodies against 20 infectious agents in UK Biobank participants and confirm associations of antibody responses with sociodemographic characteristics, HLA genetic variants, and disease outcomes.

A combination of genomic and clinical features improves predictions of response to immune checkpoint blockade.

The authors present palaeoclimatic data in the form of stable isotope records from equid teeth spanning 12,500 years of human occupation at the site of Ilsenhöhle in Ranis, Germany, including the earliest occupation of the site by Homo sapiens ~45,000 years ago.

Patricia Munroe, Christopher Newton-Cheh, Andrew Morris and colleagues perform association studies in over 340,000 individuals of European ancestry and identify 66 loci, of which 17 are novel, involved in blood pressure regulation. The risk SNPs are enriched for cis-regulatory elements, particularly in vascular endothelial cells.

Stig Bojesen, Georgia Chenevix-Trench, Alison Dunning and colleagues report common variants at the TERT-CLPTM1L locus associated with mean telomere length measured in whole blood. They also identify associations at this locus to breast or ovarian cancer susceptibility and report functional studies in breast and ovarian cancer tissue and cell lines.

Small, lightweight LED implants and a radio-frequency transducer as a power source enable wireless optogenetic stimulation in the brain, spinal cord and peripheral nervous system of behaving mice.

Inflammation of brain endothelial cells is seen in neurodegenerative conditions and in aging. Here the authors examine the role of astrocytes in blood brain barrier function using an iPSC-derived cell co-culture model.

Inhibitors of PI3 kinase are in development for the treatment of cancer. But whether these compounds will work as single agents remains to be seen. Engelman et al. now show that a PI3K-mTOR inhibitor is effective in a mouse model of lung cancer induced by a mutant PIK3CA but has no effect on Kras-induced tumors. Combining the PI3K-mTOR inhibitor with a MEK inhibitor induced regression of mouse Kras tumors, suggesting that such combinations may be beneficial in human tumors (pages 1315–1316).

There is an unmet clinical need for simple, accessible biomarkers to select patients who are more likely to respond to immune checkpoint therapy. Here the authors show that a lower neutrophil-to-lymphocyte ratio is associated with better overall and progressive-free survival, as well as higher rate of response, in a multi-cancer cohort of patients treated with immune checkpoint inhibitors.

JWST observations of GRB 221009A reveal the associated supernova, confirming that the GRB resulted from the collapse of a rapidly rotating massive star. The lack of r-process emission suggests that these extreme events are not key sources of the heaviest elements.

Defective ribonucleotide excision repair causes ID4, an indel cancer signature characterized by deletions of 2–5 base pairs.

Tham and Bernardo et al. show that cardiomyocyte-specific knockout of estrogen receptor alpha induces increased adiposity and tissue metabolic alterations specifically in female mice, likely in part due to changes in the proteomic content of the heart-derived extracellular vesicles.

Stromal cell recruitment, activation and crosstalk with cancer cells is poorly understood. Here, the authors demonstrate that cancer cell-derived Hedgehog ligand  triggers stromal remodeling that in turn induces a cancer-stem-cell like, drug-resistant phenotype of nearby cancer cells while treatment with smoothened inhibitors reverses these phenotypes.

Using zooarchaeology, palaeoproteomics, ancient sediment DNA and stable isotope analyses, the authors characterize the ecology of the Homo sapiens individuals associated with the ‘transitional’ Lincombian–Ranisian–Jerzmanowician technocomplex at Ilsenhöhle in Ranis.

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

Fluorine nuclear magnetic resonance spectroscopy of the stimulatory heterotrimeric G protein reveals a conformational landscape shaped by interactions with nucleotides, the lipid bilayer and a G-protein-coupled receptor.

In tumours aberrant epigenetic modifications can alter the transcriptional state. Here, the authors identify a common tumour-specific shift to transcriptional repression associated with DNA methylation and chromatin dysregulation at the transcription start site.

Multiwavelength observations of a galactic nucleus exhibit quasi-periodic X-ray eruptions (QPEs) that repeat every 22 days, a timescale intermediate between those of other QPEs and so-called repeating nuclear transients. The eruptions are likely to be driven by the interaction between an orbiting body and a central massive black hole.