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Mangrove ecosystems are facing severe climate threats. However, this study shows that strategically expanding protected areas to include the most climate-resilient sites can safeguard biodiversity and ecosystem services for the future, and this can be achieved with only a modest increase in protected area.

Pathogenic variants in UNC13A underlie a novel neurodevelopmental syndrome, with three subtypes defined by distinct genotypes with varying clinical and functional impacts characterized in cellular and animal models.

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.

Single-cell transcriptomic analyses of Plasmodium falciparum and Anopheles gambiae reveal key developmental stages, processes and factors in parasite–mosquito interactions and identify potential targets for blocking malaria transmission.

A population of highly interconnected cells in glioblastoma makes these tumours resistant to general damage but vulnerable to targeted disruption of this small fraction of cells and their rhythmic Ca²⁺ oscillations.

T cells undergo age-related changes that impair their organismal functions. Here Soto-Heredero et al. show that regulatory T cells characterized by the expression of KLRG1 accumulate with age in both mice and humans and exhibit features including mitochondrial decline and an inflammatory phenotype.

Plasma extracellular vesicles contain quantifiable amounts of TDP-43 and full-length tau, allowing the accurate assessment of pathology in frontotemporal dementia, frontotemporal dementia spectrum disorders and amyotrophic lateral sclerosis.

Whilst the ChAdOx1 nCoV-19 (AZD1222) vaccine has demonstrated efficacy against symptomatic disease, variants of concern (VOCs) with spike protein substitutions have led researchers to explore updating vaccines from ancestral spike protein. Authors use a Syrian hamster model to evaluate a vaccine encoding the spike protein of Beta VOC and assess efficacy against VOCs.

Using pancreatic organoids and genetic mouse models, Antonucci et al. show that cellular stress activates an NRF2–EZH2 epigenetic axis leading to metabolic reprogramming and subsequent malignant transformation of KRAS-mutant benign lesions.

How astrocytes influence neuronal plasticity remains unclear, as they are typically considered as modulators of core mechanisms driven by neuronal components. Here, authors show that Long-term depression (LTD) induction in the hippocampus triggers calcium signaling in the astrocyte and enhances SNARE-dependent astrocytic glutamate release, which is then responsible for the activation of postsynaptic NMDA receptors and synaptic depression.

Authors utilise a murine model of infection to provide mechanistic insight into how antimicrobial therapy may be a predisposing risk factor for hospital-acquired pneumonia. They show that antibiotic-induced microbiota perturbations compromise inflammatory monocytes and thereby impair antibacterial defence.

Albumin selectively inhibits Mucorales growth through the release of bound free fatty acids.

Oligodendrocyte progenitor cells (OPCs) contribute to developmental synapse elimination in animal models. Here, the authors use a human brain organoid model to demonstrate that that uptake of synapses in a subset of human OPCs depends on growth arrest-specific gene 6 (GAS6)-AXL signaling.

The role of interferon-γ (IFNγ) in anti-viral immunity has been unclear. Here the authors show that bacterial-induced or intranasally administered IFNγ effectively restricts SARS-CoV-2 infection in mice through effects on non-hematopoietic cells.

Petroni et al. report that the infiltration of IL-17A-secreting γδ T cells in the tumor microenvironment coupled with the accumulation of immunosuppressive macrophages is associated with resistance to CDK4/CDK6 inhibition in HR⁺HER2⁻ breast cancer.

The distribution and organisation of matrix molecules in the tumour stroma help shape solid tumour progression. Here they perform temporal proteomic profiling of the matrisome during breast cancer progression and show that collagen XII secreted from CAFs provides a pro-invasive microenvironment.

Here the authors show efficacy of a low-dose, unmodified, bivalent mRNA vaccine against SARS-CoV-2 variants in two female rodent models and find that combination of mRNA encoding Beta and Delta Spike sequences induces broadly neutralizing antibodies and robust T-cell responses.

The involvement of nuclear pore proteins in cellular mechanosensing and metastasis is unclear. Here the authors identify that nuclear pore protein NUP210 promotes metastasis through the interaction with mechanotransducer LINC complex protein and chromatin to regulate mechanosensitive genes.

Neuromuscular junctions (NMJs) are denervated in amyotrophic lateral sclerosis (ALS) through unknown mechanisms. Here, the authors show immune cells infiltrating muscle of ALS patients and mouse models, driven by CCL2-CCR2, which can be blocked to protect NMJs.

SARS-CoV-2 infection is milder in children, but direct comparison with adults is rare. Here the authors show that immune responses are higher in children, retained for 12 months or longer and can neutralize Alpha, Beta and Delta variants.

Heterologous vaccination regimens for COVID-19 could be useful for example if there is a shortage of one vaccine type. Here, Spencer et al. show that heterologous vaccination with a self-amplifying RNA vaccine and an adenoviral vectored vaccine performs at least as well as the homologous vaccinations in mice.

Necroptosis has immunogenic cell death properties. Here, the authors show that the intra-tumor delivery of mRNA that codes for the necroptosis effector MLKL triggers neo-epitope-specific anti-tumor T cell responses and inhibits primary tumor growth and lung metastasis.

Whole-genome sequencing and mutational signature analysis of 265 head and neck cancer samples collected from eight different countries provide insight into the vital contribution of tobacco smoke in disease etiology.

Radiation therapy (RT) has been shown to improve responses to immunotherapy in preclinical cancer models, but deep responses in patients are still rare. Here the authors provide immunological insights into the response to RT and CTLA4 inhibition in tumor bearing mice and show that agonistic CD40 therapy improves response to the combination of RT and immune checkpoint inhibition.

Understanding the effect of vaccination on emerging SARS-CoV-2 variants of concern is of increasing importance. Here, James et al. report that two doses of vaccination with the Pfizer-BioNTech vaccine induce more robust immune responses to the B.1.1.7 and B.1.351 SARS-CoV-2 lineages than does natural infection.

While current COVID-19 vaccines provide certain protection, more effective vaccination strategies are still desirable. Here the authors show, using mouse vaccination models, that priming with a systemic mRNA and boosting with an intranasal adenoviral vector vaccine induces comprehensive T cell and mucosal immunity.

A new class of drugs, hexahydroquinolines, inhibits host haemoglobin endocytosis by Plasmodium falciparum and displays both therapeutic and transmission-blocking activities.

Several exposures are required for protection from clinical malaria in endemic areas. Using the controlled human malaria infection model, Ferrer et al. here show that two exposures to Plasmodium falciparum infected mosquitoes induce partial preerythrocyte immunity in previously malaria naïve individuals. Immunity correlates positively with both anti-circumsporozoite protein antibody and CD69 + CD8 + T cell levels.

The loss of nicotinamide adenine dinucleotide is reported to be associated with muscle mitochondrial dysfunction in murine cancer models. Here the authors show that niacin supplementation improves mitochondrial metabolism and reduces muscle wasting in mouse models of cachexia.

Epstein–Barr virus infection generates a neuroinvasive B cell subset, which recruits activated T cells to the central nervous system, promoting multiple sclerosis.

Serological analysis and infection outcomes of participants in the multi-center, prospectively enrolled OCTAVE cohort, comprising 2,686 participants with immune-suppressive diseases who recieved two COVID-19 vaccines, reveals specific clinical phenotypes that might benefit from specific COVID-19 therapeutic strategies.

Midbrain ventral tegmental neurons project to prefrontal cortex (PFC) and modulate cognition. The authors discovered a mesocortical circuit that provides glutamatergic excitation of interneurons and inhibits pyramidal neurons in the PFC. Moreover, they identified the subset of dopaminergic progenitors that generates these mesocortical neurons. Loss of these progenitors results in the loss of the inhibitory circuit and increased perseverative behavior.

Many developing tissues require Par-driven polarization, but its role in mammalian tissue maintenance is unclear. Here, the authors show that in mouse epidermis, Par3 governs tissue homeostasis not via orientation of cell division but by coupling cell mechanics with mitotic accuracy and genome integrity.

In this study, the authors show that spontaneous calcium spiking activity in thalamocortical neurons modulates the rate of axonal growth during development via regulation of Robo1 transcription.

LINE-1 retrotransposons are a type of mobile DNA element normally repressed in the body. Here the authors show that LINE-1 sequences can jump in mouse parvalbumin interneurons and also promote the transcription of key parvalbumin interneuron genes.

Stathmin-2 is lost in amyotrophic lateral sclerosis. Here the authors show that stathmin-2 has an essential role in the maintenance of axon structure, with its loss from adult motor neurons resulting in axonal collapse and muscle denervation.

In this study, the authors evaluated the protective capacity of a mucosal, live-attenuated SARS-CoV-2 vaccine and show that it induces systemic and mucosal humoral immunity, protects from clinical disease symptoms, and prevents virus transmission in hamsters more efficiently than an intramuscular mRNA vaccine.

Demystifying the spawning strategies of fish can help us understand their evolutionary drivers and better inform fisheries management. This study reveals the spawning strategies of pelagic fish, showing that the benefits of co-located spawning across time and space outweigh the potential drawbacks.

Recurrent somatic mutations altering residues in the transmembrane domain of CADM1 are identified in aldosterone-producing adenomas. Follow-up studies implicate a role of gap junction communication in regulating aldosterone production.

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).