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In this study, the authors describe SANA, a nitroalkene derivative of salicylate, as a potential activator of creatine-dependent energy expenditure and thermogenesis in adipose tissue. Preclinical and clinical data from this paper also suggest that SANA improves glucose homeostasis and promotes weight loss in mice and humans.

Inactivating PPP2R1A mutations correlate with better survival after immune checkpoint blockade in patients with ovarian clear cell carcinoma, suggesting that targeting the phosphatase 2A (PP2A) pathway may represent an effective startegy for improving responses to immunotherapy.

Functional roles of natural acetylcholine (ACh) dynamics are not fully understood. This study reveals dynamic changes in ACh release across the mouse striatum during learning and extinction, identifying how and where release dynamics shape brain plasticity to gate learning and promote extinction of cue-reward associations.

Here the authors show that PD-1 controls coinhibitory receptor expression by T_reg cells. The absence of PD-1 expression could induce CD30 expression, thereby enhancing T_reg function and tumor escape, suggesting that CD30 might be a therapeutic target in cases of anti-PD-1 resistance.

Metformin may serve as a non-toxic intervention to inhibit mitochondrial metabolism and slow DNMT3A-R882 clonal haematopoiesis expansion, thus delaying or averting progression to acute myeloid leukaemia.

The lipid transporter FATP2 reprograms neutrophils to polymorphonuclear myeloid-derived suppressor cells by mediating the uptake of arachidonic acid and promoting the synthesis of prostaglandin E₂.

In the eye, intraocular pressure (IOP) regulation is critical for proper vision. High IOP can result in glaucoma a blinding disease. Here the authors show that tyrosine kinase FYN controls IOP by phosphorylating VE-cadherin, a key component in cell junctions.

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.

Meet the first known Neanderthal family ever found. Plus, the bubonic plague left lingering scars on the human genome and scientists’ share their personal experiences of racism.

NASA has become the first US agency to pre-emptively fire career employees as part of a radical downsizing of the federal government. Plus, the activity of a certain gene variant is linked to obesity in Labrador retrievers.

Pathologically activated neutrophils, termed myeloid-derived suppressor cells, in the tumour microenvironment spontaneously undergo ferroptosis, which negatively regulates anti-tumour immunity through the release of oxygenated lipids, therefore limiting the activity of human and mouse T cells.

Omega-3 supplements seem to slow biological ageing. Plus, how scientific-integrity policies can help protect US scientists from political interference.

Hutchinson-Gilford Progeria Syndrome is characterized by premature aging with cardiovascular disease being the main cause of death. Here the authors show that inhibition of the NAT10 enzyme enhances cardiac function and fitness, and reduces age-related phenotypes in a mouse model of premature aging.

Ionic levels in neurons provide the potential energy for all neuronal communication. Here the. authors show a very large modulation of [Cl^-]_i neocortical pyramidal cells, from day to night, with marked effects on cortical excitability and processing.

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.

Here the authors show in female mice at mid-life that deletion of estrogen receptor β in astrocytes induced cognitive impairment, hippocampal atrophy, glial activation and synaptic loss. ERβ ligand treatment restored cognition and decreased neuropathology in these animals.

A tiny chip might have compromised Apple and Amazon, diamond-shaped graphs could prevent correlation-causation confusion and Europe’s ambition open-access plan is being sold stateside.

During the antigen-dependent phase of B cell development, clones expressing high-affinity B cell receptors are transferred from light zones to dark zones of germinal centers, while transforming their energy metabolism. Here authors show that in the light zones, the hypoxic microenvironment promotes growth arrest and apoptosis in B cells, while miR-155 protects the high-affinity clones via inducing a switch in energy utilization.

Intestinal regionalization is characterized by robust and resilient structural cell states and the intestine can adapt to environmental stress in a spatially controlled manner through crosstalk between immunity and structural cell homeostasis.

CERN will eject Russian scientists at the end of November, but keep a foot in the door with Moscow. Plus, how ‘deintensifying’ cancer treatment could help people and the planet.

Although thymic function declines with age, the thymus also has the ability to regenerate following injury. Here, the authors demonstrate that IL-33 and type-2 innate lymphoid cells trigger the expansion of eosinophils following radiation injury, which in turn produce IL-4 to stimulate the recovery of the thymus mesenchyme during thymus regeneration.

T cell responses can be generated to either pathogen infection or from priming with a vaccine. Here the authors compare T cell generation, phenotype and single cell transcriptome of participants vaccinated with a mpox vaccine or infected with the virus showing that the virus induced T cells showed more effective function and phenotype.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

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.

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.

The role of type I interferon signalling in the control of myeloid derived suppressor cells (MDSC) activity remains controversial. Here the authors show that downregulation of type I interferon receptor is observed in MDSC from cancer patients and tumor-bearing mice and is required for the activation of their immune suppressive properties.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

A spike in respiratory illnesses in children is the result of common winter infections — not a novel pathogen. Plus, how to stop waves in their tracks and why we might embrace the feeling of uncertainty.

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.

Neutrophils are linked to tumor progression. Gabrilovich and colleagues demonstrate that neutrophils have tumor-stage-dependent alterations in motility, function and metabolism: in early phases, they are highly motile with altered metabolism, whereas at later stages, they become highly suppressive.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Following years of development, electronic paper is now entering ebooks, mobile phones and signs, and, as Duncan Graham-Rowe reports, is starting to gain the market acceptance that it has long strived for.

A small molecule that restores the integrity of the intestinal barrier provides a novel therapeutic strategy for inflammatory bowel diseases.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

Regulatory T cell (T_reg) maintenance and function require IL-2, yet this cytokine is only present in low levels in vivo. In this study, the authors demonstrate that that T_reg use heparanase to access IL-2 bound to heparan sulfate proteoglycans in the extracellular matrix of inflamed brain tissue in mice.