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A study of how sustainable fruit harvesting in Amazon peatlands can support livelihoods and aid efforts to mitigate climate change.

Oncogenic activation can generate replicative stress, leading to activation of ATR and Chk1. The hypothesis that these events could be exploited to selectively kill cancer cells is now demonstrated in vivo, using mouse models for cancer development. Myc-driven tumors are shown to be sensitive to ATR deficiency or inhibition of Chk1.

Phylogenomic analysis of 7,923 angiosperm species using a standardized set of 353 nuclear genes produced an angiosperm tree of life dated with 200 fossil calibrations, providing key insights into evolutionary relationships and diversification.

In this Viewpoint article, three scientists give their opinions on the generation and uses of patient-derived xenograft (PDX) models and the future of this field.

A Homo aff. erectus individual dated to 1.4 million to 1.1 million years ago found at Sima del Elefante (Sierra de Atapuerca, Spain) does not display the modern-human-like aspect of Homo antecessor found at the neighbouring Gran Dolina site (900,000–800,000 years ago).

Peinado and colleagues show that small extracellular vesicles and secreted NGFR cargo induce lymphangiogenesis and develop the lymph node pre-metastatic niche to promote melanoma metastasis, which could be targeted pre-clinically with NGFR inhibition.

RNA levels in post-mortem tissue can differ greatly from those before death. Studying the effect of post-mortem interval on the transcriptome in 36 human tissues, Ferreira et al. find that the response to death is largely tissue-specific and develop a model to predict time since death based on RNA data.

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.

Trees come in all shapes and size, but what drives this incredible variation in tree form remains poorly understood. Using a global dataset, the authors show that a combination of climate, competition, disturbance and evolutionary history shape the crown architecture of the world’s trees and thereby constrain the 3D structure of woody ecosystems.

An enduring paradox of urban economics is why cities support levels of enterprise, such as patents and inventions, higher than the countryside. Here Pentland et al. suggest that the density of social ties provides a greater flow of ideas, resulting in increased productivity and innovation.

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.

Group 2 Innate lymphoid cells (ILC2) are a source of type 2 cytokines, such as interleukin-5 (IL-5). Here Troch, Jakob et al. show a non-redundant role of ILC2-derived IL-5 required for the development and function of a subset of murine B cells.

Although the common genetic variants contributing to blood lipid levels have been studied, the contribution of rare variants is less understood. Here, the authors perform a rare coding and noncoding variant association study of blood lipid levels using whole genome sequencing data.

Tinker et al. identified the position and effects of major QTLs relative to a new fully annotated reference genome in five recombinant inbred line populations representing nine diverse oat (Avena sativa) varieties. They also characterized two major chromosome rearrangements that may impact breeding targets affected by QTL that are located in these regions.

Climate change is shifting species distribution globally. Here, the authors track four decades of changes in the thermal affinity of 1,817 marine species across European seas, showing that most communities have responded to ongoing ocean warming via increases of warm-water species or decreases of cold-water species.

A comprehensive analysis of models of brain metastasis and multiple cohorts of patient samples identifies a targetable molecular mechanism underlying the resistance to whole-brain radiotherapy that can inform patient selection for personalized radiotherapy.

The epigenetic factor Bmi1 regulates self-renewal of many adult stem cells, but its role in heart function is unknown. Here the authors show that Bmi1 prevents cardiac senescence by inhibiting the tumor suppressor protein p16^INK4ain adult mice, protecting them from dilated cardiomyopathy and heart failure.

Transcriptional profiling of Kras-driven early lesions—aimed at identifying founder events—reveals DDR1 as a therapeutic target relevant to adenocarcinoma.

Assembly of the hexaploid oat genome and its diploid and tetraploid relatives clarifies the evolutionary history of oat and allows mapping of genes for agronomic traits.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

Crop wild relatives’ genetic diversity is usually not considered in conservation planning. Here, the authors introduce an approach to identify conservation areas based on evolutionary and threat processes, by developing proxies of genetic differentiation, and including taxa’s habitat preferences.

Analysis of whole-genome sequences of 25,465 individuals of European ancestry shows that rare variants contribute substantially to the heritability of height and body mass index.

2D–2D heterostructures are typically held together by van der Waals interactions. Now, an on-device MoS₂–graphene heterostructure has been prepared that is covalently linked through a bifunctional molecule featuring a maleimide and a diazonium group. The electronic properties of the resulting heterostructure are shown to be dominated by the molecular interface.

The influence of X chromosome genetic variation on blood lipids and coronary heart disease (CHD) is not well understood. Here, the authors analyse X chromosome sequencing data across 65,322 multi-ancestry individuals, identifying associations of the Xq23 locus with lipid changes and reduced risk of CHD and diabetes mellitus.

Phase I trials have evolved from simple dose-finding studies to studies that provide therapeutic opportunities for patients where no standard therapy is available; however, various factors have hampered patient recruitment on phase I trials. The authors discuss how matching patients with specific genetic aberrations to specific therapies will improve drug attrition rates and improve patient outcomes.

Aß are extracellular deposits relevant in Alzheimer’s disease (AD). This study shows that Aß plaques are hubs of endothelial disassembly that induce non-productive angiogenesis. This process is aided by the microglia and unchained by reduced presenilin function, a trait of AD, in endothelial cells.

The exact function of glial cell line–derived neurotrophic factor (GDNF) in catecholaminergic cell survival in adulthood is unclear. Using a conditional GDNF-null mouse that suppresses GDNF expression in adulthood, Pascual et al. show that GDNF is an essential factor whose downregulation results in massive catecholaminergic neuronal death. Carlos Ibáñez discusses this paper in an accompanying News and Views.

The survival rates of patients with pancreatic cancer are low and have not improved significantly over the past three or four decades. Thus, effective treatments for this disease are an urgent unmet need. Novel treatment paradigms will probably be required, and many new therapeutic approaches are being tested in this setting. This Review outlines the state-of-the-art therapies for patients with pancreatic cancer, as well as the novel treatment strategies that are the focus of drug-development efforts.

A study shows that clonal haematopoiesis of indeterminate potential is associated with an increased risk of chronic liver disease specifically through the promotion of liver inflammation and injury.

STAARpipeline is a comprehensive framework for flexible and scalable rare-variant association analysis using whole-genome sequencing data and annotation information.

Monoclonal antibodies are being used to treat a variety of autoimmune disorders, including multiple sclerosis, neuromuscular diseases and rheumatoid arthritis, but neurological adverse effects have been reported in a substantial number of patients. Bosch et al. describe the characteristics, pathogenesis and outcomes of neurological disorders associated with monoclonal antibody therapy, and make recommendations regarding their management.

Most studies of the genetics of the metabolome have been done in individuals of European descent. Here, the authors integrate genomics and metabolomics in Black individuals, highlighting the value of whole genome sequencing in diverse populations and linking circulating metabolites to human disease.

Early stellarator designs suffered from high particle losses, an issue that can be addressed by optimization of the coils. Here the authors measure the magnetic field lines in the Wendelstein 7-X stellarator, confirming that the complicated design of the superconducting coils has been realized successfully.

Platelet aggregation is associated with myocardial infarction and stroke. Here, the authors have conducted a whole genome sequencing association study on platelet aggregation, discovering a locus in RGS18, where enhancer assays suggest an effect on activity of haematopoeitic lineage transcription factors.

Pooling participant-level genetic data into a single analysis can result in variance stratification, reducing statistical performance. Here, the authors develop variant-specific inflation factors to assess variance stratification and apply this to pooled individual-level data from whole genome sequencing.

The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.

As phase 1 of the Earth Microbiome Project, analysis of 16S ribosomal RNA sequences from more than 27,000 environmental samples delivers a global picture of the basic structure and drivers of microbial distribution.