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Protecting the ocean from increasing threats requires the development of high-seas marine reserve networks. An approach that optimizes biodiversity, minimizes climate change exposure and reduces fisheries conflict enables low-regret climate-smart conservation areas to be identified.

Barton et al. show that persisting infection with either gammaherpesvirus 68 or murine cytomegalovirus protects mice against subsequent bacterial infection. The authors argue that the co-evolution of mouse and virus provides a survival benefit not only to the virus but also to the host.

Few studies have considered the effects of changes in climatic variability on disease incidence. Now research based on laboratory experiments and field data from Latin America shows that frog susceptibility to the pathogenic chytrid fungus is influenced by temperature variation and predictability through effects on host and parasite acclimation.

MNK2 was identified as the target of a small molecule named CID661578 that can stimulate pancreatic β-cell generation in zebrafish, pig and human organoids. CID661578 prevents MNK2 from binding to eIF4G in the translation initiation complex.

Torrano et al. use bioinformatics analyses to identify PGC1α as a transcriptional regulator of a metabolic program downstream of ERRα that opposes metastatic dissemination in prostate cancer.

Lymphocytes exit lymph nodes and return to the bloodstream through the efferent lymphatics. Cyster and colleagues show that lymphocytes exit into cortical sinuses by a pathway dependent on sphingosine 1-phosphate receptor type 1.

Species sharing a common enemy such as a parasitoid or predator can indirectly affect one another. Here, Frost et al. use quantitative food-web data from communities of caterpillar hosts to show experimentally that apparent competition is important in predicting food-web structure across habitats.

Neutralizing antibodies for respiratory syncytial virus (RSV) can reduce disease in hospitalized children, but current options show limited efficacy. Here, the authors isolate potent single-domain antibodies from llamas that recognize the prefusion conformation of RSV F and prevent RSV replication in mice.

The complex microenvironmental signalling pathways that govern haematopoietic stem cell (HSC) activity remain poorly defined. Here, the authors identify endothelial NF-κB signalling as regulating regenerative HSC function, accelerating haematopoietic recovery following myelosuppressive injury in mice.

The transduction of mechanical forces into signals that alter cardiac contractility is important for heart function. Here the authors show that integrin-linked kinase acts as a mechanosensor in cardiomyocytes, and affects cardiac contractility by regulating SERCA-2a and phospholamban.

In hypoxic conditions, cells depend on anaerobic respiration, which results in extracellular acidosis. Khacho et al.find that acidosis serves a protective function, enhancing mitochondrial respiratory capacity and sustaining ATP synthesis despite limited oxygen availability, by both promoting mitochondrial fusion and inhibiting fission.

Tissir et al. find that atypical cadherins Celsr2 and 3 and planar cell polarity signaling are required for the proper development and function of cilia in ependymal cells, and that their loss of function markedly impairs cerebrospinal fluid circulation.

The role of alternative splicing in pancreatic cancer (PDAC) development remains to be explored. Here, RBFOX2 is shown to regulate exon splicing events in transcripts encoding proteins involved in cytoskeletal remodelling programs and its downregulation promotes PDAC progression and liver metastasis.

Insulin can signal through phosphotidylinositol 3-kinase (PI3K) to increase cellular growth, which often results in increased protein translation and stress of the endoplasmic reticulum (ER). Umut Ozcan and his colleagues now find that insulin signaling leads to the disassociation of p85α and p85β, the heterodimeric regulatory subunits of PI3K, allowing them to interact with and increase the nuclear localization of a key transcription factor that resolves ER stress. Thus, in states of insulin resistance, such as in prediabetes, resolution of ER stress is hampered, further exacerbating the disease (pages 374–376 and 438–445).

Genomes and transcriptomes of five distinct lineages of African cichlids, a textbook example of adaptive radiation, have been sequenced and analysed to reveal that many types of molecular changes contributed to rapid evolution, and that standing variation accumulated during periods of relaxed selection may have primed subsequent diversification.

Breaking down the endothelial barrier is a hallmark of systemic inflammatory response syndrome. Here the authors show that palmitoylation, a post-translational modification of proteins, plays a critical role in altering endothelial function during inflammation, and suggest the targeting of palmitoyl acyltransferase DHHC21 as potential disease therapy.

Protein antigens, such as HIV envelope protein, require adjuvants for high immunogenicity. Here the authors show that a combined adjuvant approach with slow antigen delivery and potent ISCOMs adjuvant primes robust germinal center activity and humoral immunity in non-human primates. pSer-modified antigen shifts immunodominance to allow subdominant epitope-targeting of rare B cells.

Targeted protein degradation (TPD) is a key modality for drug discovery. Here the authors present the discovery and analysis of reversible DCAF1-PROTACs, which show efficacy in cellular environments resistant to VHL-PROTACs or with acquired resistance to CRBN-PROTACs.

In chickens, influenza A virus relies on host protein ANP32A. Here the authors use CRISPR/Cas9 to generate homozygous gene edited chickens containing two ANP32A amino acid substitutions that prevent viral polymerase interaction.

NLR proteins contribute to antiviral immune responses. Lemon and colleagues show that NLRX1 promotes antiviral responses in hepatocytes by competing with the kinase PKR for viral double-stranded RNA, which allows accumulation of the transcription factor IRF1 for early control of viral replication.

Juno’s global infrared mapping of Jupiter’s moon Io determined the distribution as well as the energy output of its volcanoes. Spatial differences emerge, with the equator more active than the polar zones and more heat flow at the north pole than at the south, indicative of an uneven lithosphere.

Regulatory T cells normally maintain high expression of the phosphatase PTEN. Turka and colleagues use conditional deletion of PTEN in regulatory T cells to show that it is critical for their function and stability.

A global analysis of antimicrobial resistance (AMR) across 27,155 genomes and 69 drugs reveals patterns in AMR gene transfer between species and identifies 142 AMR gene candidates, two of which were tested and confirmed as contributing to AMR.

Eran Segal and colleagues report that promoters driving expression of cellular respiration genes in aerobic yeast species encode relatively open chromatin, whereas promoters associated with the same genes in anaerobic yeast species encode relatively closed chromatin. These results suggest that phenotypic diversity may in part be influenced by changes in the DNA-encoded nucleosome organization of promoters.

Membrane technology using well-defined pore structure enables high ion purity and recovery but achieving uniform pore structure and effective pore area is challenging. Here the authors introduce dendrimers that self-assemble, facilitating the formation of polyamide nanofilms with well-defined effective pore ranges and uniform pore structures.

Cytoskeletal remodeling is known to facilitate mitophagy, but the mechanism is not fully understood. Here, the authors show that damaged mitochondria recruit a RhoA GTPase activating protein that promotes their capture and encasement by autophagosomes.

Chondroitin sulfate proteoglycans (CSPGs) secreted by astrocytes are known to inhibit OPC differentiation and remyelination. Here, the authors identify a novel CSPG synthesis inhibitor and find it can rescue OPC differentiation in vitroand accelerate remyelination in mice following focal demyelination.

A translational study demonstrates the role of myeloid inflammatory cells in driving disease progression and treatment resistance in prostate cancer and shows that these cells can be targeted therapeutically.

Mutations that dysregulate Notch1 and Ras/PI3K signalling are common in T-cell acute lymphoblastic leukaemia; here, treatment with a PI3K inhibitor is shown to induce drug resistance that is associated with downregulation of activated Notch1 signalling, suggesting that inhibition of both Notch1 and PI3K could promote drug resistance.

The components of the tumour microenvironment contribute to prostate cancer initiation and progression. Here the authors perform single-cell RNA sequencing and spatial transcriptomics analysis of prostate cancer stroma from mouse models at different stages of the disease and develop a gene signature to predict distant metastasis in patients.

The natural product nimbolide covalently reacts with a functional cysteine of the E3 ubiquitin ligase RNF114, resulting in impaired substrate recognition and degradation, enabling the use of nimbolide for targeted protein degradation.

The Bacillus cereus enterotoxin haemolysin BL induces pore formation and activation of the NLRP3 inflammasome, leading to enhanced lethality during infection.

Combining a large-scale manipulative field experiment with long-term genetic assays and modelling, the authors document evidence of ecological–evolutionary feedbacks between aphids and parasitoids through resistance conferred by heritable bacterial symbionts.

Cytotoxic T lymphocyte (CTL)-based immunotherapies can induce tumor regressions by targeting HLA class I-bound tumor-associated peptides. Here, the authors identified a peptide derived from Vestigial-like 1 (VGLL1) as a shared, potentially therapeutic CTL target expressed by multiple cancer types.

A pair of glucose-sensing neurons identified in the brain of Drosophila melanogaster regulates secretion of adipokinetic hormone and Drosophila insulin-like peptide 2, suggesting that these neurons have key roles in maintenance of glucose homeostasis.

The relationship between metabolomic and behavioral changes is not well understood. Here, the authors analyze metabolome changes in D. melanogaster heads and bodies during hunger and satiety, and develop the Flyscape tool to visualize the resulting metabolic networks and integrate them with other omics data.

Rare earth elements are used in electronics, but increase in demand could lead to low supply. Here the authors conduct experiments on the International Space Station and show microbes can extract rare elements from rocks at low gravity, a finding that could extend mining potential to other planets.

Necroptosis is a regulated form of inflammatory cell death driven by activated MLKL. Here, the authors identify a mutation in the brace region that confers constitutive activation, leading to lethal inflammation in homozygous mutant mice and providing insight into human mutations in this region.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) play critical roles in the biogenesis, localization and transport of RNA. Here authors investigate a role for hnRNPs in sterol metabolism in mice and provide insights into their role in selective promoter activation.

Pancreatic ductal adenocarcinoma is characterized by a highly immunosuppressive tumour microenvironment. Here, the authors show that specialized subsets of tumour-infiltrating dendritic cells induce distinct CD4⁺ T cell programs and specifically identify a CD103^–CD11b⁺ subset which induces tumor-promoting FoxP3^– Type-1 regulatory T cells.

Stress induces hair greying in mice through depletion of melanocyte stem cells, which is mediated by the activation of sympathetic nerves rather than through immune attack or adrenal stress hormones.

The blood circulation time is important to the biomedical application of nanomaterials. Here, the authors explore the effect of protein corona formation on the blood residency of nanomaterials and show circulation times are governed by the dynamic remodelling of protein opsonins in vivo.

A positron emission tomography imaging tracer is developed to image mitochondrial function in vivo, and application of this tracer to a mouse model of lung cancer identifies distinct functional mitochondrial heterogeneity between tumour cells.

Mutant RAS family members occur in a wide range of tumour types, and there is a great interest in identifying isoform-specific inhibitors. Here, the authors characterise two designed ankyrin repeat proteins (DARPins) that specifically inhibit the KRAS isoform by binding to the region around the KRAS-specific residue histidine 95 and show that they affect KRAS/effector interactions in different ways.

Oncolytic viruses promote an inflammatory response and elicit anti-tumor immunity. Here the authors show, unexpectedly, that the oncolytic virus, VSVIFNβ, induces type I interferon responses that, when combined with chimeric antigen receptor (CAR) T therapy, lead to the attrition of both CAR T and conventional T cells, thus dampening their anti-tumor activity.

The antimicrobial β-lactone obafluorin is produced by a Nonribosomal Peptide Synthetase (NRPS). Here the authors present the crystal structure of the obafluorin NRPS and develop a reconstitution assay that allows them to analyse product formation from obafluorin NRPS mutants and alternate substrates.