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This study examines the history of North Atlantic deep-water masses, as recorded in marine sediments. Major lithological changes and increased rate of deposition reveal that stronger deep-ocean circulation initiated 3.6 million years ago.

Barcia Durán, Dayasagar, et al. map the expression of immune checkpoints in human atherosclerosis and examine the influence of lipid-lowering treatments and type 2 diabetes to understand how immune checkpoint inhibitors worsen cardiovascular risk in survivors of cancer.

mRNA vaccines have been successfully developed, but a better understanding of in vivo distribution of the encoded antigen may aid further improvements. Here the authors use PET imaging and demonstrate transient expression of the vaccine antigen in the injection site and draining lymph nodes in mice and non-human primates.

Myocardial infarction accelerates atherosclerosis through activation of the sympathetic nervous system, and the consequent release of haematopoietic stem and progenitor cells.

Examining drivers of the latitudinal biodiversity gradient in a global database of local tree species richness, the authors show that co-limitation by multiple environmental and anthropogenic factors causes steeper increases in richness with latitude in tropical versus temperate and boreal zones.

In this study, the authors provide a global overview of SARS-CoV-2 genome sequencing, and estimate the proportion of cases sequenced and time to genome upload. They identify disparities and highlight the need to strengthen surveillance in lower and middle income countries.

Here, Dzanibe et al show that in utero HIV/ARV exposure sequentially disrupts infant immunologic trajectories, beginning with NK cells that predict vaccine antibody responses and followed by delayed T cell memory maturation linked to skewed TCR clonality.

Multisystem inflammatory syndrome in children (MIS-C) onsets in COVID-19 patients with manifestations similar to Kawasaki disease (KD). Here the author probe the peripheral blood transcriptome of MIS-C patients to find signatures related to natural killer (NK) cell activation and CD8+ T cell exhaustion that are shared with KD patients.

FGF19 increase in post-bariatric hypoglycaemia is mediated by bile acid dysregulation, and can be countered by inhibiting bile acid transport.

Cretaceous amber from the Ecuadorian Napo region provides exceptional evidence of a resinous forest ecosystem and diverse arthropod fauna in equatorial Gondwana, as revealed by integrated analyses of amber geochemistry and bioinclusions, palynology, and associated macrofloras.

An IgE antibody recognising Folate Receptor-alpha has been tested in clinical trials for ovarian cancer and preclinical studies show macrophage involvement in the anti-tumoural functions of IgE. Here the authors demonstrate that IgE induces proinflammatory activation of ovarian cancer patient macrophages, which reverses their immunosuppressive induction of Treg cells and promotes CD8⁺ T cell function.

An activator of DNA polymerase γ restores function to disease-causing mutant variants and demonstrates a potential route to treatments for inherited mitochondrial disorders involving POLG mutations.

A reconstruction of the genomic history of japonica and indica rice over 9,000 yr with geographic, environmental, archaeobotanical and paleoclimate data.

Here, the authors perform a genome-wide association study to identify 157 significant testosterone genetic variants in male veterans, of which 8 are ancestry-specific. Men with higher testosterone genetic scores have lower odds of diabetes, hyperlipidemia, gout, and cardiac disorders.

Wang et al. show the recruitment of the lipid channel protein VPS13C and formation of VPS13C-dependent contacts between endoplasmic reticulum and lysosomes after lysosomal damage.

The highly biodiverse Brazilian Atlantic Forest has a long history of deforestation and only a small portion of the original forest remains. This study examines the spatial and temporal patterns of this deforestation to understand the effectiveness of current laws at curbing forest loss.

pH alterations are a hallmark of many pathologies including cancer and kidney disease. Here the authors describe [1,5- 13 C2]Z-OMPD as a probe for hyperpolarized 13C-MRI with good pH sensitivity and hyperpolarization properties which combined with tailored MRI protocols allow sub-minute imaging of pH, renal perfusion and filtration simultaneously.

Epigenetic editing of PCSK9 in the liver, designed to induce DNA methylation and silence gene expression, achieved long-lasting reductions in LDL cholesterol levels in both transgenic mice expressing the human PCSK9 gene and cynomolgus monkeys.

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.

What is the state of trust in scientists around the world? To answer this question, the authors surveyed 71,922 respondents in 68 countries and found that trust in scientists is moderately high.

Klaus Bønnelykke and colleagues identify a common variant in CDHR3 associated with early childhood asthma with severe exacerbations. CDHR3 encodes a cell adhesion protein expressed at high levels in airway epithelium, suggesting a role for altered epithelial integrity in asthma pathogenesis.

Wood density is an important plant trait. Data from 1.1 million forest inventory plots and 10,703 tree species show a latitudinal gradient in wood density, with temperature and soil moisture explaining variation at the global scale and disturbance also having a role at the local level.

B cell germinal centres achieve a balance between clonal expansion and sequence diversification by suppressing somatic hypermutation during proliferative clonal bursts.

Even in the absence of external perturbations, waterfalls can gradually form from planar bedrock riverbeds as a result of unstable interactions between flow hydraulics, sediment transport and bedrock erosion.

Inferring evolutionary processes from biogeographic patterns is challenging. Here, the authors present a new method to examine spatial patterns of biodiversity and show that biogeographic patterns of Malagasy amphibians and reptiles are influenced by a combination of diversification processes.

The development of asthma following eczema is known as the atopic march. Here the authors conduct a GWAS on affected children and identify two novel loci associated with the disease phenotype.

It is unclear how mimetic radiations, the evolution of a species to resemble different model species, contribute to speciation. Here, the authors show patterns of mating behaviour and genetic divergence, suggesting that mimetic divergence has promoted incipient speciation in a group of Peruvian poison frogs.

Deep reinforcement learning (RL) has been successful in many fields but has not been used to directly improve behaviours by interfacing with living nervous systems. Li et al. present a framework that integrates deep RL agents with the nervous system of the nematode Caenorhabditis elegans. Their study shows that trained agents can assist animals in biologically relevant tasks and can be studied after training to map out effective neural policies.

T cell-specific antigens are discovered at high throughput without killing target cells.

The mechanisms of pathological astrocyte responses during multiple sclerosis remain unclear. Kadowaki et al. found in MS mouse models that CLEC16A suppresses astrocyte pathogenic activities related to mitochondria by boosting mitophagy.

Ji et al. identify an idiopathic generalised epilepsy network that links heterogeneously distributed brain abnormalities to a common brain network and deep brain stimulation sites which reduce generalised seizures.

Through circuit dissection in juvenile, adolescent and adult mice, Klune, Goodpaster and colleagues reveal multiple developmental switches in mPFC–NAc and mPFC–BLA pathways that underlie developmental transitions in threat avoidance behavior.

How cells adapt to glucose starvation is still elusive. Here, Levy et al. show that the mTOR substrate 4EBP1 protects human, mouse, and yeast cells from glucose starvation and is exploited by cancer cells to promote tumorigenesis.

The hydroxyl radical is a key oxidant in the Earth’s atmosphere. The inclusion in an atmospheric chemistry model of a detailed mechanism of isoprene oxidation, involving the buffering of hydroxyl radical concentrations, improves agreement between model simulations of hydroxyl radical levels and observations.

Alison Abbott visits an exhibition charting the artistic and scientific interests of painter and collector Gabriel von Max.

LKB1-mut has been shown as a major genetic driver of primary resistance to immune checkpoint inhibitors. Here this group reports the identification of the LKB1-IAP-JAK dynamic complex as a molecular determinant for immune response of LKB1-mut lung cancer cells.

Nasal anti-CD3 therapy shows promise for treating traumatic brain injury by reducing neuroinflammation and aiding recovery in mice. It induces interleukin-10-producing regulatory T cells that enhance microglial phagocytic activity and reduce chronic inflammation, potentially aiding brain repair.

Variations in expression of the gene ORMDL3 were found to be associated with development of childhood asthma, suggesting this gene should be examined in more patient groups.

Bipolar disorder (BD) is a severe mood disorder, which has been shown to have a large genetic component. Here the authors identify two previously unreported BD risk loci and provide further insights into the biological mechanisms underlying BD development.

Human brain organoids are plagued by heterogeneity and poor reproducibility, critical parameters for reliable disease modeling and drug testing. Here, the authors report on Hi-Q organoids which solve these limitations and can be cryopreserved in large quantities.

A class of cationic—amidine-based degradable—lipids can now be readily synthesized through a tandem multi-component amine–thiol–acrylate conjugation reaction. Mechanistic studies provided key insights, from which the observed lead lipid enabled mRNA delivery to multiple organs, highlighting the potential for developing mRNA vaccines and therapeutics to treat various diseases.