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Evidence for balancing selection acting on loci that control complex traits is limited. Here, the authors show evidence for past selection on chemical profile in a perennial wildflower by two ecological drivers, herbivory and drought, consistent with balancing selection on this trait.

Pelagibacter simultaneously produces the biogenic gases methanethiol and dimethyl sulfide from dimethylsulfoniopropionate, regulated by a kinetic switch that balances DMSP allocation between each pathway depending on cellular sulfur demands.

Mapping the nature of multiprotein nanostructures in cellular contexts remains challenging. Here, Kang and Schroeder et al. report multiplexed expansion revealing, a technique which expands proteins away from each other, for nanoscale localisation and antibody visualisation of >20 proteins in the same specimen.

Cocaine addiction is accompanied by dysfunction in neural circuits related to reward, but it is unclear how these adaptations occur. Here, authors identify granulocyte-colony stimulating factor as a potent mediator of cocaine-induced adaptations, and show that it can alter the motivation for cocaine.

The prognosis of cancer patients with lymph node (LN) metastasis is worse than those without. Here, the authors report that while histone deacetylase 11 (HDAC11) inhibition suppresses tumor growth within the LN, it also promotes cancer cell migration out of the LN to form distant metastasis, and therefore suggest caution with HDAC inhibitors.

Joshi et al. show that γ-protocadherins suppress the anti-inflammatory KLF2 and KLF4 pathway and that targeting them is a viable therapeutic strategy to protect against atherosclerosis.

Parhizkar et al. show that lemborexant, an orexin receptor antagonist, protects against neurodegeneration in male tau transgenic mice by preventing tau protein build-up and inflammation, highlighting its potential for preventing neurodegeneration.

CD56, a splicing variant of NCAM, marks human NK cell differentiation stages. Here the authors show that developing human NK cells form CD56-enriched synapses with stromal cells, and CD56 is critical to promote motility of NK cells that increases with their maturation.

Targeting TBK1 is an effective strategy to overcome resistance to cancer immunotherapy.

Hundreds of RNAs and proteins are imaged in fixed tissue at subcellular resolution.

Single-cell and single-nucleus RNA sequencing are used to construct a cellular atlas of the human heart that will aid further research into cardiac physiology and disease.

Bayati et al. discovered that sequential treatment of iPSC-derived dopaminergic neurons with α-synuclein fibrils and proinflammatory cytokines leads to the formation of Lewy body–like inclusions, through the downregulation of lysosomal proteins.

The genetically encoded GEVAL sensors allow ratiometric imaging of the spatiotemporal dynamics of cellular GTP levels in living cells.

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.

Here the authors connect inherited Apolipoprotein E genotype with the risk of developing Alzheimer’s disease by demonstrating how, in an isoform- and lipidation-specific way, apoE modulates the aggregation, clearance and toxicity of Amyloid-beta.

Isolates of authentic SARS-CoV-2 variants BA.1 and BA.2 exhibit similar infectivity and pathogenicity and show susceptibility to neutralizing therapeutic antibodies and antiviral compounds in mouse and hamster models.

Elevated IL-33 levels have been correlated with metastasis and poor prognosis. Here the authors show in mouse tumour xenograft models that PDGF-BB produced by tumour cells induces IL-33 via Sox7 in tumour pericytes, and IL-33 promotes metastasis through its effects on tumour-associated macrophages.

Alcohol is thought to lead to neuroadaptive changes, although the underlying molecular mechanisms are unclear. Here, the authors find ethanol treatment alters GABA_B-receptor expression via fragile-X mental retardation protein in mice, leading to antidepressant-like behaviours.

Previously, authors have identified GW461484A (GW) as an inhibitor of the kinase Yck2 in the fungal pathogen Candida albicans. Here, they report the synthesis of GW analogs with improved pharmacological properties and activity in mouse models of systemic candidiasis.

In the developing heart, blood flow transmits mechanical signals to progenitor cells that ultimately leads to valve formation. Here, the authors identify the origin of the valve progenitor cells and fibronectin1bas a transcriptional target of the mechanotransduced signals responsible for valve formation.

Vascularization remains a significant challenge in organoid technology. Here, the authors develop a microfluidic platform that enhances organoid growth, function and maturation, by establishing functional perfusable vascular networks.

Coordinated neuronal activity may mediate memory in hippocampal CA1. Here, the authors use an array of machine-learning classifiers to reveal how higher-order population dynamics and learning-induced spine plasticity are disrupted in amnestic mice.

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.

A strategy for inferring phase for rare variant pairs is applied to exome sequencing data for 125,748 individuals from the Genome Aggregation Database (gnomAD). This resource will aid interpretation of rare co-occurring variants in the context of recessive disease.

Using single-molecule microscopy, Jeon et al. study the dynamics of interactions between Spt–Ada–Gcn5 acetyltransferase and transcription activators on both chromatinized and nonchromatinized DNA templates.

The ANK3 gene, encoding the scaffolding protein AnkyrinG, is linked to risk for bipolar disorder through its neuronal functions. Here, the authors show that loss of oligodendroglial AnkyrinG may also contribute to bipolar-like behaviors in mice.

Synthetic Notch (SynNotch) receptors can be used to endow cells with custom sense-and-respond capabilities. Here, the authors introduce a fluorescein-binding SynNotch as a versatile tool for controlling gene expression responses to diverse stimuli via ligands based on fluorescein-conjugates.

The thymus harbors a complex constitutively active inflammatory network with innate-like T cells representing one of its central nodes. Here, the authors show that these cells can induce tolerance to inflammation-associated self-antigens, a class of molecules that otherwise largely mirrors the spatial and temporal distribution of pathogen-derived antigens.

Amino acids availability is normally a limitation for protein synthesis and can determine cancer progression and therapy response. Here, the authors show that MYC-associated cancer has a dependency on tryptophan not because of translation regulation, but Indole 3-Pyruvate synthesis.

[¹⁸F]OXD-2314 is a brain penetrant positron emission tomography radiotracer with high affinity for tau aggregates in Alzheimer’s disease (AD) and non-AD tauopathies based on in vitro and in vivo studies, and is suitable for first-in-human use.

In an aqueous quinone-mediated system, both pH swing and nucleophilicity swing mechanisms contribute to CO₂ capture, but traditional measurement methods report only the combined contributions, without quantifying their relative contributions. Here the authors introduce thermodynamic and kinetic analyses coupled with two in situ experimental techniques to quantify the contributions of these mechanisms.

A platform for mRNA lipid nanoparticle delivery to the placenta to treat pre-eclampsia is shown to improve fetal and maternal health in mice and has potential clinical applications in obstetric disorders and women’s health.

When brain metastases form, the blood–brain barrier morphs into the blood–tumor barrier (BTB), surrounded by neuroinflammatory response. Here, the authors show that S1P3 is upregulated in neuroinflammatory response in highly BTB permeable lesions, and modulation of S1P3 could impact BTB permeability.

Perivascular and leptomeningeal macrophages, collectively termed here parenchymal border macrophages, are shown to regulate flow dynamics of cerebrospinal fluid, implicating this cell population as new therapeutic targets in neurological diseases such as Alzheimer’s.

The endometrium is activated by the pregnancy hormones estrogen and progesterone to facilitate embryo implantation, and errors in endometrial responsiveness can lead to reduced fertility or endometriosis. Here they show that GREB1 interacts with hormone receptors in the endometrium, leading to normal or pathological consequences depending on the hormones involved.

Feeding-relevant vagal signaling occurs between the gastrointestinal tract and the brain, but it is unclear if this pathway influences cognitive processes. This study shows that endogenous gastrointestinal derived vagal sensory signaling promotes hippocampal-dependent memory function via a multi-order brainstem–septal pathway.

Temperature is known to influence plant disease development. Here Huot et al. show that elevated temperature can enhance Pseudomonas syringae effector delivery into plant cells and suppress SA biosynthesis while also finding a temperature-sensitive branch of the SA signaling pathway in Arabidopsis.

Drug dependence shifts the balance in action selection away from goal-directed to habitual responding. Here, the authors report that chronic passive exposure to alcohol leads to suppression of orbitofrontal cortex inputs to dorsomedial striatum resulting in downregulation of goal-directed behavior.

Addiction-related behaviors are believed to result from drug-evoked synaptic changes, but their causality is unclear. The authors show that bidirectional optogenetic modifications of synaptic strength distinctly alter alcohol-seeking behavior.

How the immune system responds to epithelial cancers beyond neoantigen-driven adaptive immunity is poorly understood. Kansler et al. reveal an innate immune surveillance response mediated by cytotoxic ILC1 sensing of cancer cell-expressed IL-15.

This protocol describes how to undertake high spatial and temporal Ca²⁺ imaging of ex vivo multicellular myocardial strips that include the endocardial surface, allowing the study of the Ca²⁺ signaling that underpins cardiomyocyte contraction.

Developmental and epileptic encephalopathies are devastating neurological disorders. Here, the authors establish a cohort of patients with variants in the gene DENND5A and use human stem cells to discover a disease mechanism involving altered cell division.

The use of clean energy sources is essential for the humankind. Here, authors show new experiments carried out with Deuterium-Tritium fusion reactions. Results show that energy production by such reactions can be more efficient than expected, confirming fusion as an alternative to fossil fuels.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

Treatment failure following chimaeric antigen receptor (CAR) T cell therapy is common yet incompletely understood. In this study, the authors demonstrate that deletion of the mitochondrial negative regulator, MCJ, in CAR T cells promotes target cell killing ex vivo and augments their efficacy in an in vivo B cell leukaemia model.