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A 580,000-year cave record from southern Nevada reveals how temperature, ice sheets, and summer insolation influenced the southwest United States’ unique climate history over the last six glacial-interglacial cycles.

This study reports the development and preclinical evaluation of a humanized citrullinated histone H3 (CitH3) monoclonal antibody that mitigates inflammation, restores macrophage function, and protects against sepsis-induced pulmonary injury.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

Here, the authors characterize the epigenetic status of hybrid ecDNA in HPVOPC, identifying HPV oncogenes E6/E7 in hybrid ecDNA are flanked by somatic DNA enhancers with strong cis-interaction. It can be targeted with ecDNA disrupting therapeutics.

A stalagmite hydroclimate record (Tamaulipas, Mexico) from 62.5 to 5.1 ka showed (1) Atlantic and Pacific temperatures impacted precipitation changes and (2) there were dry conditions during Heinrich Stadials, possibly because moisture shifted south.

Cellular cargo transported along actin filaments is faced with a directional choice at an intersection. Here the authors show that myosin Va-bound cargo prefers to go straight through the intersection, and propose a model to explain this by a tug-of-war between motors on the lipid cargo that engage the actin tracks.

Multi-inflammatory syndrome in children (MIS-C) can be associated with SARS-CoV-2 infection but can also be similar to other inflammatory syndromes. Here the authors characterise the plasma proteome phenotype in MIS-C and compare to other SARS-CoV-2 related syndromes and find disproportionately high IFN-γ responses in MIS-C patients.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Here, the authors perform transcriptional profiling on tracheal aspirates of adults requiring mechanical ventilation for SARS-CoV2-induced acute respiratory distress syndrome (ARDS) and identify a dysregulated host response predicted to predicted to be potentially modulated by dexamethasone.

Over the twentieth century, droughts in southwestern North America have been linked to sea surface temperature variability in the North Pacific Ocean. Speleothem data from southern California suggest that links between the North Pacific and drought were less pronounced during the past millennium.

The Somatic Mosaicism across Human Tissues Network aims to create a reference catalogue of somatic mosaicism across different tissues and cells within individuals.

The molecular basis underlying infection infection-mediated lung pathology is not fully revealed. Here the authors report that SPARCL1 expressed in pulmonary capillary endothelial cells contributes to immune pathology in mouse model via pro-inflammatory macrophage induction, while circulating SPARCL1 levels corelate with COVID-19 lethality.

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.

After two decades of sustained growth, cancer diagnostics patents peaked in 2020 and have since stabilized, with a broad set of public and private players driving innovation.

Climate change is exposing marine species to unsuitable temperatures while also creating new thermal opportunities of varying persistence. Here, the authors examine how the interplay between these processes varies over time, demonstrating the potential of thermal opportunities to drive marine biodiversity changes, especially in the near and mid-term.

Here the authors conduct a multi-ancestry meta-analysis of telomere length, used diverse approaches to identify genes underlying association signals, and experimentally validated POP5 and KBTBD6 as regulators of telomere length in human cells.

Acute respiratory distress in macaques and baboons recapitulates COVID-19 disease progression in humans, making them suitable as models to test vaccines and therapies.

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.

The impacts of extreme weather and climate can be amplified by physical interactions among events and across a complex set of societal factors. This Perspective discusses the concept and challenge of connected extreme events, exploring research approaches and decision-making strategies.

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.

Using a globally coordinated strategic conservation framework to plan an increase in ocean protection through marine protected areas can yield benefits for biodiversity, food provisioning and carbon storage.

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.

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.

A spatial and temporal compilation of geochemical data documents a stepwise transgression of toxic euxinic waters into shallow oceans that drove a series of Late Devonian extinction events.

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.

Analysis of 97,691 high-coverage human blood DNA-derived whole-genome sequences enabled simultaneous identification of germline and somatic mutations that predispose individuals to clonal expansion of haematopoietic stem cells, indicating that both inherited and acquired mutations are linked to age-related cancers and coronary heart disease.

In Africa, COVID-19 has created a perfect storm of reduced funding, restrictions on the operations of conservation agencies, and elevated human threats to nature. This Perspective discusses solutions to move beyond this immediate crisis.

We evaluated the use of chimeric antigen receptor-modified T cells targeting GD2 (GD2-CART) for H3K27M⁺ diffuse midline glioma (DMG), finding that intravenous administration of GD2-CART, followed by intracranial infusions, induced tumour regressions and neurological improvements in patients with H3K27M-mutant pontine or spinal DMG.

The risk of developing cancer increases with age. Here, the authors address the contribution of age-dependent accumulation of senescent cells within the tumour stroma compartment and show that senescent cells increase the infiltration of myeloid-derived suppressor cells that inhibit cytotoxic T-cells, thus facilitating tumour outgrowth.

Transcriptomic and proteomic profiling of blood samples from individuals with COVID-19 reveals immune cell and hematopoietic progenitor cell alterations that are differentially associated with disease severity.

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.

This Review summarizes the latest evidence indicating that platelet and endothelial dysfunction are essential components of COVID-19 pathology, describes the potential mechanisms underlying the contribution of cardiovascular risk factors to the most severe outcomes in COVID-19, and highlights the roles of coagulopathy, thrombocytopathy and endotheliopathy in COVID-19 pathogenesis.

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.

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

Anticancer immunotherapy through checkpoint blockade enables the patient to mount active antitumour responses and can dramatically improve survival. In this Review, Mahoney, Rennert and Freeman examine targets for next-generation immunomodulators and discuss how these may be integrated in rational combination therapies with existing and upcoming immune-targeted drugs.

The paleo water table in the southwestern United States records global climatic shifts such as variations in the Northern Hemisphere summer insolation, shown by U-series and U-Th geochronology on calcite deposits in Nevada, USA.

COVID-19-associated AKI (COVID-19 AKI) is associated with high mortality and is an independent risk factor for all-cause in-hospital death in patients with COVID-19. This Consensus Statement from the Acute Disease Quality Initiative provides recommendations for the diagnosis, prevention and management of COVID-19 AKI and for areas of future research, with the aim of improving understanding of the underlying processes and outcomes for patients with COVID-19 AKI.

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.

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.

Both rare and common variants contribute to the aetiology of complex traits such as type 2 diabetes (T2D). Here, the authors examine the effect of coding variation on glycaemic traits and T2D, and identify low-frequency variation in GLP1Rsignificantly associated with these traits.