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Probiotic Escherichia coli Nissle 1917 is engineered as an antitumour vaccination platform optimized for enhanced production and cytosolic delivery of neoepitope-containing peptide arrays to safely induce specific, effective and durable systemic antitumour immunity.

Fine-scale field analysis and modelling of the spatial dynamics of infection of Darwin’s frogs with Batrachochytrium dendrobatidis fungus identifies highly localized transmission dynamics that generate clustered epidemics and can drive collapse of local subpopulations.

A study in Drosophila has identified a neural circuit that selectively suppress movement-encoding proprioceptors during self-generated movements such as walking and grooming.

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 breast cancer, dormant cancer cells may develop into bone metastases. Here, the authors demonstrate that microenvironmental IL1β stimulates metastatic breast cancer cell colonisation in the bone via IL1β-NFKB/CREB-Wnt pathway activation and cancer stem cell colony formation

The slow release of pro-survival peptide analogues crosslinked to an injectable collagen–dendrimer biomaterial significantly prolongs the engraftment and survival of transplanted stem cells in mouse models of ischaemic injury.

FHL1A is a crucial host factor for alphavirus infection but its impact on pathogenesis is unclear. Here, the authors use a FHL1−/− knockout mouse model to show that the FHL1 splice variant impacts arthritis and myositis after chikungunya or o’nyong-nyong infections but not Ross River or mayaro virus infection.

Stem cell factor (SCF) is a cytokine with great potential for treating ischemia, stroke and heart attack, but therapies using SCF have been limited by acute allergic responses. The work describes a new therapeutic using transmembrane SCF delivered in lipid nanocarriers that is effective in treating ischemia without off-target effects.

Variants in the PSMC5 gene impair proteasome function and cellular homeostasis, altering brain development in children. This study reveals underlying molecular mechanisms contributing to this neurodevelopmental phenotype, and suggests therapeutic leads for neurodevelopmental proteasomopathies.

Acetylcholine–α9 nAChR signaling regulates thymic negative selection.

Polθ has been recently identified as a therapeutic target in cancer but specific inhibitors are currently unavailable. Here, the authors identify small molecule inhibitors of Polθ’s polymerase activity which elicit BRCA1/2 synthetic lethality, enhance the effect of PARP inhibitors and target PARP inhibitor resistance caused by 53BP1/Shieldin pathway defects.

Cytidine nucleotide triphosphate (CTP) is a key precursor involved in the metabolism of DNA, RNA and phospholipids. In this study, the authors examine the physiological consequences of CTP synthase (Ctps) 1 and 2 deletion in vivo and demonstrate that Ctps1 protects mice from fatal autoimmunity.

Perineural invasion and cancer-induced nerve injury of tumour-associated nerves are associated with poor response to anti-PD-1 therapy, which can be reversed by combining anti-PD-1 therapy with anti-inflammatory interventions.

Circulating monocytes contribute to the transition to pain chronicity but the molecular events that cause their deployment are still unclear. Using a mouse model of hyperalgesic priming, here the authors show that blood monocytes contribute to the emergence of chronic pain via a mechanism that requires a transient disruption of NAAA-regulated lipid signaling.

Spinal cord neural stem cells are generated from human pluripotent stem cells via a chemically defined, xeno-free method, and exhibit efficient and functional engraftment in rat spinal cord lesions.

The RIG-I like receptors sense RNA viruses and initiate antiviral immunity. Here the authors screen 375 definite ubiquitin ligases and propose UBR5 promotes RLR transcription by disengaging the TRIM28-imposed brake on the RLR promoters.

Chondroitinase injections into monkey spinal cords 4 weeks after hemisection injury increased corticospinal axon growth and corticospinal synapse formation and improved functional outcomes.

How genetic predisposition drives late-onset disease risk remains unclear. Here, the authors show that epigenetic predisposition via NR3C1-dependent early postnatal 3D gene regulation primes astrocytes for lifelong immune vulnerability.

Acinetobacter baumannii is a multi-drug-resistant pathogen of urgent international concern. Here, the authors develop a protein subunit vaccine which prevents A. baumannii catheter-associated urinary tract infections in mice by inhibiting Abp2D, a key adhesive virulence factor.

The authors identify a Cys→Ser transformation (C19S) in insulin leading to neoepitope presentation and CD4⁺ T cell autoreactivity in type 1 diabetes. Inflammation and oxidative stress enhanced C19S transformation in β cells and antigen-presenting cells, resulting in C19S-specific CD4⁺ T cells with an activated memory phenotype linked to disease progression.

Biodiversity is unevenly distributed across the tree of life, and theoretical work suggests that biological complexity may be influential in forming these patterns. Here, Brinkworth et al. have shown that bird clades with more complex appendicular skeletons tend to have lower extant species richness.

Ultrasound imaging with acoustic reporter genes has been limited to a single ‘tone’, restricting the types of experiments that can be achieved. This work introduces two acoustic reporter genes that enable multiplexed imaging in vitro and in mice.

Myeloid-specific mechanotransduction ablation downregulates pro-fibrotic fibroblast transcriptional profiles to reduce scar formation in human cells

Neutrophils secrete numerous immune effector molecules including cathelicidin which is associated with antimicrobial properties. Here the authors implicate neutrophil derived cathelicidin in modulation of CD4 T cell homoeostasis and the promotion of Th17 CD4 T cells.

A post eradication polio vaccine should be safe and easy to produce. Here, the authors characterize a recombinant virus-like particle polio vaccine with stabilized capsid proteins and show comparable immunogenicity to the current inactivated polio vaccine.

Using SCN2A haploinsufficiency as a proof-of-concept, upregulation of the existing functional gene copy through CRISPR activation was able to rescue neurological-associated phenotypes in Scn2a haploinsufficient mice and human neurons.

Mouse models show that myelin dysfunction and associated inflammation increase with age, which can promote amyloid-β deposition and therefore risk of developing Alzheimer’s disease.

Efficient repair of demyelinated CNS lesions involves the resolution of inflammation and induction of remyelination. Berghoff et al. show that sterol synthesis in microglia is key to both processes, which can be supported by squalene therapy.

Zhang et al. identify unimodal neural representations in the spinal cord of cutaneous mechanical and heat stimuli gated by a shared feed-forward local inhibitory neuron type and a neural transition during neuropathy, with increased excitatory drive.

Two drugs, miconazole and clobetasol, have functions that modulate differentiation of oligodendrocyte progenitor cells directly, enhance remyelination, and significantly reduce disease severity in mouse models of multiple sclerosis.

A computationally designed antigen based on the receptor binding domain of the spike protein of sarbecoviruses elicits broad humoral responses against severe acute respiratory syndrome viruses in mice, rabbits and guinea pigs.

Vaccine efficacy is enhanced by optimizing the design of polymeric particles for adjuvant and antigen delivery.

Distinct subsets of fibroblasts, which differ in their expression of thymus cell antigen 1 (THY1), are responsible for inflammation and tissue damage in mouse models of arthritis.

Mannino et al. provide a quantitative and ultrastructural timeline of nucleophagy in yeast with lattice light sheet microscopy and correlative light and electron tomography. They identify a role for dynamin-like protein 1 in outer nuclear membrane fission.