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Adjuvants are an important component of modern vaccines. Here, the authors employ a phenotypic screen of ~200k compounds and identify PVP-057, a TLR3 agonist with a simple scalable 3-step synthesis, as an adjuvant that induces durable humoral and cellular immunity to varicella-zoster virus (VZV) gE in mice.

Gene expression programs underlying memory are not well understood in Drosophila. Here, authors use mushroom body-specific RNA sequencing to characterize the transcriptional trace of long-term memory and key TFs that may regulate it.

Colorectal cancer is often diagnosed at later stages, leading to poor prognosis. Here, the authors utilise analysis of rectal mucus specimens using host and microbial analysis to detect cancer lesions.

Both environmental factors and genetic factors influence human immunity. Albert and colleagues leverage data from the Milieu Intérieur Consortium to comprehensively describe the effects of lifestyle, environment and genetics on human innate and adaptive immunity.

Sulfoquinovosyl diacylglycerols are produced by photosynthetic organisms and serve as sources of carbon and sulfur for bacteria. This work characterizes a sulfoquinovosidase, unveils a reservoir of organosulfur compounds in the ocean and elucidates their critical role in marine carbon cycling.

Clinical benefit or intestinal toxicity resulting from combined immune checkpoint blockade in patients with melanoma associates with prevalent commensal bacteria and can be decoupled by IL-1R inhibition.

This study reports that the gene SMPED1, located in a previously identified dichogamy-determining region in Alpinia species, controls the timing of sex-organ synchrony, improving our understanding of the evolutionary mechanisms of plant sexual diversity.

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

T cell immunity declines with thymic atrophy, but thymic cell grafts rescue T cell function.

Morley, Pomat and colleagues identify a homozygous mutation in COQ6 in an indigenous population of Papua New Guinea. This allele predisposes children to increased risk of acute lower respiratory infections in response to Streptococcus pneumoniae. This sensitivity is recapitulated in Coq6DY mice in the nonhematopoietic compartment.

Individuals with SYK gain-of-function variants develop immunodeficiency and systemic inflammation, which are recapitulated in a knock-in mouse model. Treatment of these mice with bone marrow transplantation or with a SYK inhibitor ameliorates disease symptoms, highlighting potential therapeutic strategies for patients with SYK mutations.

Metagenomic immunoglobulin sequencing (MIg-seq) uncovered patterns of IgA antibody binding of bacterial strains in the healthy human gut microbiome.

Majzner and colleagues show that engineering T cells with a membrane-tethered version of the signaling adaptor molecule SLP-76 alongside a chimeric antigen receptor (CAR) enhances CAR T cell activity against low-antigen-density tumors.

Epidemiological analyses coupled with immunological phenotyping suggest that humoral immunity induced by COVID-19 vaccines wanes more rapidly in individuals with severe obesity compared to individuals with a BMI within the normal range.

Endoplasmic reticulum (ER)-interorganelle membrane contact sites have emerged as key regulators of organelle dynamics. Here, the authors report that the ER-resident protein SNX19 mediates ER-endolysosome membrane contacts to maintain the perinuclear distribution of endolysosomes and restrict their motility.

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.

Trials in rhesus macaques show that a subunit vaccine against SARS-CoV-2, comprising the spike protein receptor-binding domain displayed on a nanoparticle protein scaffold, produces a robust protective response against the virus.

This study demonstrates the power of directed evolution to unlock latent functional potential in plant Rubisco. By identifying mutations that enhance CO₂ fixation and solubility, it advances avenues for improving crop photosynthesis and productivity.

Sexual dimorphism in genetic vulnerability to schizophrenia, systemic lupus erythematosus and Sjögren’s syndrome is linked to differential protein abundance from alleles of complement component 4.

Colorectal tumors with mutated KRAS and APC require the amino acid transporter SLC7A5 to drive tumorigenesis. Mechanistically, SLC7A5 drives transcriptional and metabolic reprogramming by maintaining intracellular amino acid levels, leading to enhanced protein synthesis.

Individuals over eighty years of age are less likely to mount a good immune response against SARS-CoV-2 (measured by neutralization titres) after the first dose of the BNT162b2 mRNA vaccine, but achieve good neutralization after the second dose.

The ChAdOx1 nCoV-19 vaccine against SARS-CoV-2 induces an immune response in rhesus macaques and leads to reduced SARS-CoV-2 viral loads in respiratory tissues and an absence of pneumonia, but not to a reduction in nasal virus shedding, compared with unvaccinated animals.

Installing algal pyrenoids or cyanobacterial carboxysomes into plants to enhance photosynthetic efficiency remains a formidable challenge. Here, the authors report the construction of CO₂-fixing nanocompartments by encapsulating Rubisco using encapsulin from Quasibacillus thermotolerans.

Schief and colleagues show that germline-targeting epitope scaffolds can elicit responses from rare broadly neutralizing antibody precursor B cells with predefined binding specificities and genetic features.

The advent of Acheulian stone-tool technologies 1.75 million years ago is likely to have coincided with changes in early human cognition. Using functional near-infrared spectroscopy neuroimaging, modern Acheulian toolmakers are shown to use the same brain network as is involved in playing the piano.

Highly pathogenic avian influenza is an increasing global concern but its distribution in remote regions is not known. Here, the authors conduct an environmental influenza surveillance study in remote, uninhabited regions of the Global South by sampling fresh bird guano.

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

Persistent DNA lesions can occur throughout the human lifespan and can remain in the genome of affected cells for several years and generate a substantial proportion of the mutational burden.

Durable clinical benefit observed in recurrent ovarian cancer patients treated with combination pembrolizumab, cyclophosphamide and bevacizumab are associated with increased T and B cell clusters, distinct microbial patterns, and altered metabolism.

ctDNA is a known poor prognostic factor for multiple cancer types, but variant-specificity is unknown. Here, the authors show variant-specific association of ctKRAS levels with survival in previously untreated metastatic pancreatic ductal adenocarcinoma patients in multiple cohorts.

Mucosal Associated Invariant T cells have been implicated in response to bacterial pathogens. Here the authors show that in human viral infections, these cells are activated by IL-18 in cooperation with other pro-inflammatory cytokines, producing interferon gamma and granzyme B.

During aging, the ability of skeletal muscle to repair itself declines, in part due to a decrease in muscle stem cells. Here, the authors report that muscle stem cells that accumulate mitochondrial damage fuse with existing muscle fibers in a manner that depends on the induction of Scinderin.

Stratified medicine promises to tailor treatment for individual patients, however it remains a major challenge to leverage genetic risk data to aid patient stratification. Here the authors introduce an approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue-specific gene expression levels, and highlight its ability to identify biologically meaningful and clinically actionable patient subgroups, supporting the notion of different patient ‘biotypes’ characterized by partially distinct disease mechanisms.

Combining expansion microscopy with super-resolution radial fluctuations captures the morphology of single proteins.

Monkeypox is caused by an emerging zoonotic virus. This study describes a detailed investigation into monkeypox outbreaks in chimpanzees through non-invasive environmental sampling, virus genomics, pathology, behavioural ecology and dietary metabarcoding.

Multiomic profiling of several cohorts of patients treated with immune checkpoint blockade highlights the presence and potential role of B cells and tertiary lymphoid structures in promoting therapy response.

Using metabolic dysfunction-associated steatohepatitis-driven hepatocellular carcinoma mouse models, an ATP citrate lyase inhibitor reduces tumour burden and enhances efficacy of current standards of care.

This study shows that a polymodal nociceptive sensory neuron in C. elegans detects both harsh body touch and noxious cold. Using calcium imaging and genetic tools, the researchers report that the same sensory neuron uses Degerin/Epithelial Na⁺ channel proteins MEC-10 and DEGT-1 for harsh touch detection and TRPA-1 channel for cold sensing.

A case–control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.

Here the authors uncovered CNOT3, a subunit of the CCR4-NOT complex, as an essential modulator of translation in leukemia. The work pointed to the potential of targeting the posttranscriptional circuitry via CNOT3 as a therapeutic vulnerability in acute myeloid leukemia.

Advances in omics provide a tool to understand mechanisms for plant–microbial interactions under stress. Here the authors apply genome-resolved metagenomics to investigate sorghum and its microbiome responses to drought, identifying an unexpected role of iron metabolism.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

Here, using metagenomic profiling in 180 individuals from the Democratic Republic of the Congo, the authors find associations between the gut microbiome and konzo, a neurodegenerative disease that mostly affects children and is caused by the consumption improperly processed cassava.

Age-associated B cells (ABC) have been shown to be associated with autoimmunity and ageing. Here the authors examine whether ABC are transcriptionally or functionally altered in participants with reduced immune cell function and show that, being transcriptionally similar, high pre-vaccine levels are associated with poor vaccine response.

Medulloblastomas are the most common malignant childhood brain tumours and are thought to arise from the cerebellum. There is substantial heterogeneity among medulloblastomas and some are thought to arise following aberrant Sonic Hedgehog pathway activation. It is now shown that a distinct subtype of medulloblastoma arises from the dorsal brainstem and is associated with altered WNT signalling. Distinct molecular and clinical profiles of the subtypes have implications for future treatment.

Emerging SARS-CoV-2 variants of concern were detected early and multiple cases of virus spread not captured by clinical genomic surveillance were identified using high-resolution wastewater and clinical sequencing.