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Monomethylation of histone H4 lysine 20 (H4K20me1) contributes to DNA replication but the mechanism is not well understood. Here, the authors identify a conserved tandem Tudor ___domain of BAHCC1 as a H4K20me1-specific reader, which promotes the recruitment of MCM complex to chromatin for efficient DNA replication.

Filamin C is a key actin-binding protein involved in cardiomyopathies and musculoskeletal disorders. Here, Wang et al reveal that it interacts with the heat shock protein HSPB7 under biomechanical stress, forming a stable hetero-dimer which is regulated by phosphorylation.

Oxygen loss has been observed in the world’s oceans, due mainly to warming temperatures that reduce oxygen solubility and increase stratification. This study shows climate-induced salinity changes also impact oxygen patterns with effects either accelerating or counteracting warming-driven changes.

The seasonal vertical migration of copepods in polar oceans can be considered as a dispersal throughout the water column rather than a translocation to depth, according to field sampling of copepods that overwinter in the Central Arctic Ocean.

A novel antiviral targeting the SARS-CoV-2 PLpro protease shows strong efficacy in a mouse model, preventing lung pathology and reducing brain dysfunction. The study provides proof-of-principle that PLpro inhibition may be a viable strategy for preventing and treating long COVID.

Our annual survey highlights how immune-oncology and screens based on the application of cutting-edge omics technologies are providing a launchpad for a succession of startups interrogating biology across biomedicine.

The role of bile acid receptor TGR5 in feeding regulation remains elusive. Here, authors show that physiological and pharmacological activation of TGR5 in the nucleus of the solitary tract lowers feeding and enhances leptin signaling in rats.

Mechanistic understanding of cancer drug resistance is often fragmented. Here, the authors use the proteome-wide Cellular Thermal Shift Assay, revealing drug-induced resistance responses encompassing activation of translation synthesis and a protein ensemble labelled the Auxiliary DNA Damage Repair.

Latitudinal ecosystem boundaries in the global upper ocean may be driven by many factors. Here the authors investigate pole-to-pole eukaryotic phytoplankton metatranscriptomes, gene co-expression networks, and beta diversity, finding that geographic patterns are best explained by temperature gradients.

Clarke, Hawkinson and colleagues study the contribution of glycogen accumulation in the onset and progression of lung cancer.

A combination of palaeoclimate proxies and simulations shows that a common mechanism controls El Niño variation in cold and warm states, which supports expectations of more extreme El Niño occurrence in the future.

The role of IgG glycosylation in the immune response has been studied, but less is known about IgM glycosylation. Here the authors characterize glycosylation of SARS-CoV-2 spike specific IgM and show that it correlates with COVID-19 severity and affects complement deposition.

In myeloproliferative neoplasms, frameshift mutants of calreticulin turn into rogue cytokines by inducing constitutive activation of the Thrombopoietin Receptor (TpoR). Here, the authors define how mutant calreticulin acquires specificity for TpoR binding and triggers its constitutive activation.

Cells must respond to environmental changes. In three fungal species adapted to different temperatures, cellular responses are conserved yet tuned to each organism’s thermal niche, including the formation of adaptive biomolecular condensates.

Spatial metabolomics are used to describe the ___location and chemistry of small molecules involved in metabolic phenotypes. Here, Conroy et al. present a bioinformatic pipeline to analyze MALDI data and show that it can be used to identify actionable targets such as glycogen in fibrotic lungs of both human and mice.

Cryo-EM structures of human SERINC5 and its fly orthologue, along with extensive functional analyses, reveal the protein architecture and identify regions important for HIV-1 restriction.

A new discovery strategy, ‘reverse metabolomics’, facilitates high-throughput matching of mass spectrometry spectra in public untargeted metabolomics datasets, and a proof-of-concept experiment identified an association between microbial bile amidates and inflammatory bowel disease.

How brain networks organize and interact based on their hierarchical position remains poorly understood. Momi, Wang et al find that high-order brain networks show stronger responses to stimulation and greater dependence on recurrent feedback compared to low-order networks.

Relatively few techniques can quantitatively measure the effect of ligands on membrane protein stability. Here the authors demonstrate the use of ion-mobility mass spectrometry to accurately measure and quantify ligand-induced protein stabilization in the gas phase.

Iceberg-trajectory models along with multi-proxy evidence from sediment cores from the Indian Ocean show that northward shifts in Antarctic iceberg melt redistributed freshwater in the Southern Ocean during the Pleistocene.

In the study, the authors identify a protein excreted by the parasite Trichuris muris, p43, which can modulate IL-13 function, a key cytokine involved in host protection. These data suggest that p43 may be a novel therapeutic target for both whipworm infections and IL13 mediated pathologies.

Urbanization and climate-induced rainfall changes are enhancing flood risk, putting increased demand on urban hydrology management. This Review summarizes how perceptions and approaches in stormwater management are evolving, and emphasizes the need to transform stormwater from a hazard to a resource.

A new Lagerstätte from Montagne Noire, southern France, preserves a rare example of an Early Ordovician polar ecosystem.

Ecosystem services provided by coral reefs to coastal communities can depend on upstream land-use change activities such as forest restoration. This study assessed the social and ecological benefits provided by different watershed interventions designed at regional and national scales in Mesoamerica.

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).

Bile salt hydrolases encoded by the gut microbiome shape the bile acid pool, including microbial conjugated bile acids, which impact Clostridioides difficile infection in the murine gut.

Populations of river fish are threatened by pressures on land and water resources. Networks of reserves managed by Indigenous people at community level offer a way to conserve fish diversity and enhance yields of nearby fisheries.

A study aimed at revealing the role of small-scale fisheries in sustainable development shows they provide at least 40% of the global fishing catch and affect the livelihoods of 1 in 12 people in the world, among other important contributions.

The Arctic is changing faster than anywhere else on Earth. Interactions between clouds and aerosols play a role in these changes. We report how the quantities and origins of aerosols that affect cloud ice formation change over a full sea ice cycle

β-Aminobutyric acid (BABA) is a small-molecule activator of plant disease resistance. Binding of (R)-BABA to IBI1—an aspartyl-tRNA synthetase (AspRS)—primes noncanonical defense pathways, resulting in broad-spectrum disease resistance. Ligand binding also blocks AspRS activity, leading to accumulation of aspartic acid and uncharged tRNA, which activate a second plant stress response.

Serotonin regulates mood as well as intestinal homeostasis, but its role in lung immune homeostasis is less clear. Here, Renga et al. show that serotonin regulates immune and microbial metabolic functions in respiratory pneumonia, beyond its mood regulatory function, by modulating tryptophan metabolism in the cystic fibrosis lung.

Expansion of the chemical diversity of glycopeptide antibiotics (GPAs) to deal with the emergence and spread of GPA resistance is challenging. Here, the authors report a GPA synthetic biology platform in Streptomyces coelicolor for Type IV–V glycopeptide antibiotic production and discovery.

Lee et al. identify SHMT and one-carbon metabolism as a metabolic vulnerability conferred by LKB1 and KEAP1 loss in KRAS-mutant lung cancer.

Resistance to rifamycin antibiotics, which target bacterial RNA polymerases, is a growing problem. Here, the authors identify gene clusters from soil metagenomes encoding production of rifamycin analogues that are active against rifampicin-resistant bacteria through a distinct mechanism.

Pore-forming toxins act by forming oligomeric pores in lipid membranes. Here the authors report the crystal structure of the lysenin pore, providing insights into the assembly and function of the pore in addition to suggesting that its properties make lysenin potentially well-suited for nanopore sensing applications.

Most studies of the genetics of the metabolome have been done in individuals of European descent. Here, the authors integrate genomics and metabolomics in Black individuals, highlighting the value of whole genome sequencing in diverse populations and linking circulating metabolites to human disease.

In this study, the authors developed an ultra-long-acting injectable, biodegradable, and removable in-situ forming implant delivering cabotegravir (CAB ISFI). CAB ISFI was well tolerated and protected against multiple rectal SHIV challenges in female macaques.