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Newly developed mouse models that enable cell-specific analyses of proteostasis dynamics across the lifespan of the mice reveal key aspects of neuronal proteostasis with ageing.

The tolerogenic activity of type 1 conventional dendritic cells (cDC1s) is determined by EPOR, which is preferentially expressed in cDC1s and induces antigen-specific FOXP3-expressing regulatory T cells.

One of three back-to-back papers to show dosage of BACH2 can modulate T cell differentiation and function and how we might apply this to enhance chimeric antigen receptor T cell therapies for cancer.

Itaconate is an airway metabolite released by phagocytes in response to infection. Here, the authors show that itaconate acts as a signal to simulate the adaptation of Pseudomonas aeruginosa to the lung by modifying RpoN through S-itaconation.

There are limited vaccines available for Ebola virus and none for broad protection from filoviruses. Here, the authors rationally design vaccines using nanoparticles and stabilized Ebola virus and other filovirus glycoproteins, characterize antibody epitopes and profile lymph node and antibody responses in mice.

In an arm of an ongoing multicenter phase 2 trial testing different therapies in patients with genetically profiled grade 2 or 3 meningiomas, treatment with an oral CDK4/6 inhibitor met the primary endpoint for progression-free survival at 6 months in patients with CDK or NF2 alterations.

Variation in SARS-CoV-2 viruses results in newly emergent virus lineages. Here, the authors characterize the BNT162b2 mRNA vaccines, adapted to two SARS-CoV-2 lineages, JN.1 and KP.2, measure responses elicited by these vaccines against contemporary and older SARS-CoV-2 variants in naive and antigen experienced animal models and describe the biophysical and structural properties of the spike proteins expressed by these vaccines.

Neural networks fundamentally dictate function. Here, the authors show thirteen uniquely connected neuron populations within the anterior thalamic nuclei, suggesting multiple parallel subnetworks support its emotional and cognitive functions.

Lowry et al. use embryonic motor neuron selector transcription factors to partially rejuvenate the gene expression profile of mature neurons, making them more resistant to an ALS model without compromising their normal function.

The enzyme ABHD18 is shown to have a key role in cardiolipin metabolism in mitochondria, offering a potential route for a small-molecule treatment of the rare genetic disease Barth syndrome.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

The mechanisms that determine whether fibrosis occurs during chronic skin inflammation are poorly understood. Here, the authors show that chronic inflammatory skin diseases characterized by skin fibrosis share activation of EGFR-STAT1 signaling in pathologic fibroblasts as a disease defining signaling mechanism.

Due to limited therapeutic options, patients with Ewing sarcoma typically receive intensive chemotherapy which limits quality of life and often resistance develops. Here, the authors identify a chemotherapy-induced JAK-STAT-GAS6-TAM kinase signaling cascade in Ewing sarcoma and therapeutically target this axis with TAM kinase inhibition.

Using different mouse models of Polycystic Kidney Disease, this research demonstrated that deletion of the Aurora Kinase A gene was able to prevent cyst initiation and growth, identifying it as a central regulator of pathogenesis in this condition.

α/β-hydrolase domain-containing protein 11 (ABHD11) is a mitochondrial hydrolase, and its expression in CD4 + T-cells has been linked to remission status in rheumatoid arthritis. Here the authors report that pharmacological inhibition of ABHD11 modulates T-cell effector function via increased 24,25-epoxycholesterol biosynthesis and subsequent liver X receptor activation.

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).

Chemotherapy-induced cardiotoxicity (CIC) is an adverse condition associated with several DNA damaging chemotherapeutics. Here, the authors discover that tumour ZNF281-mediated increase of purinergic signalling factors inosine and hypoxanthine promotes RBFOX1 degradation in cardiomyocytes, increasing the risk for developing CIC.

Antibodies against SARS-CoV-2 provide protection against infection, but the virus has evolved to evade them. Here, the authors characterize a human antibody with incomplete neutralization of SARS-CoV-2 variants and engineer it to enhance potency and expand coverage to all tested variants by increasing conformational flexibility.

The dorsal peduncular area of the mouse brain functions as a network hub that integrates diverse cortical and thalamic inputs to regulate neuroendocrine and autonomic responses.

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.

Using two-photon (2P) optogenetics and computational modeling, the authors find that neither space-based nor feature-based rules are sufficient to describe cell–cell interactions within the primary visual cortex (V1). Instead, models must include interactions between these cardinal axes.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

Z. Liu, Y. Liu and Z. Yu et al. discovered a subtype of valve interstitial cells underneath the valve endothelial cells sensing unidirectional flow. These cells express high levels of APOE, which is responsible for JAG1–NOTCH2-mediated fetal elastogenesis.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

Lipoprotein uptake dependent on sulfated glycosaminoglycans linked to cell-surface proteoglycans is a key determinant of ferroptosis sensitivity in cancer.

Allelic losses occurring in cancer cells have been suggested as potential targets for therapy. Here, the authors show how recurring loss of heterozygosity of a drug metabolic gene in colorectal cancers can be exploited using a low molecular weight compound.

Mesoscale connectomic mapping of the cortico–basal ganglia–thalamic network reveals key architectural and information processing features.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Single-cell transcriptome profiling of mouse embryos and newborn pups is combined with previously published data to construct a tree of cell-type relationships tracing development from zygote to birth.

A study finds that a protease called granzyme K can activate the entire complement cascade, explaining how it can drive destructive inflammation in inflammatory diseases such as rheumatoid arthritis.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

Cregg et al. find that a specific population of brainstem neurons act to control left–right turning of locomotor movements in mammals through distinct axial- and limb-based mechanisms. This turning pathway is the dominant system for natural directional movements.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

This study reveals how the pathogen Staphylococcus aureus adapts to the lung microenvironment, rich in host metabolites fumarate and itaconate, by using a key enzyme, FumC, to support its metabolic fitness, survival, and persistence.