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The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

Enterololin is a narrow-spectrum antibiotic that selectively kills Enterobacteriaceae in vitro and in a mouse model of adherent-invasive Escherichia coli gut infection. AI-guided mechanism-of-action studies identified LolCDE as its molecular target.

Cryo-EM structures of the full-length Junin virus and Machupo virus spike glycoprotein complexes stabilized in the prefusion conformation. Analyses reveal features that regulate glycoprotein pH-dependent membrane fusion activity.

Emissions abatement efforts in the agriculture, forestry and land-use sector are vital to achieve climate change mitigation targets, but their effects on food security remain poorly understood. Using six global agroeconomic models, this study explores how afforestation, bioenergy and non-CO₂ emissions reductions could impact agricultural prices and the risk of hunger under different scenarios.

HEV-specific antiviral treatment is still lacking. Here, the authors functionally and structurally characterize broadly neutralizing antibodies isolated from HEV convalescent individuals and show that they have protective effects in human liver-chimeric mice infected with HEV.

Survival of competing microbial species pairs predicts competition outcome between a greater number of species: species that coexist with each other in pairs will survive, species that are excluded by any of the surviving species will go extinct.

A neural circuit in Drosophila reveals how the fly’s internal sense of heading rotates when it turns.

Dimethylsulfoniopropionate (DMSP) is an osmolyte produced by marine microbes that plays an important role in nutrient cycling and atmospheric chemistry. Here the authors go to the Mariana Trench—the deepest point in the ocean—and find bacteria are key DMSP producers, and that DMSP has a role in protection against high pressure.

Lipid particles loaded with RNA coding for tumour-unspecific antigens can enhance early responses of type-I interferons, mediating the success of immune checkpoint inhibitors as well as epitope spreading.

Cellular nuisance compounds are a burden in chemical biology and drug screening. Here the authors profile prototypical cytotoxic and nuisance compounds using the cell painting assay to systematically characterise cellular morphologies associated with compound-dependent cellular injury and nuisance activity.

The authors present an extensive profile of host transcriptional respones to a diverse group of pathogens and allergens. In doing so, they identify TH1, type I IFN, TH17, and TH2 responses, that underlie each immune response in both the blood and lung, which represents a global profile of host-pathogen immune responses.

The solid media portable cell killing assay uses metabolism-sensitive staining to illuminate the killing of antibiotic-tolerant bacteria under resource-depleted conditions, thereby enabling multiplex, genome-scale analyses for the identification of target strains.

Severe sepsis has a high mortality rate. Here, the authors provide genomic, transcriptomic, proteomic and metabolomic data across four sepsis-causing pathogens and identify a signature of global increase in fatty acid and lipid biosynthesis as well as cholesterol acquisition.

Parity induces an accumulation of CD8⁺ T cells, including cells with a tissue-resident-memory-like phenotype within human normal breast tissue, offering long-term protection against triple-negative breast cancer.

Actin-based structures in cells and tissues are built and maintained through a poorly understood balance between assembly and disassembly. Here, our findings provide insights into how factors known to promote these opposing effects dynamically integrate to shape cells and tissue systems.

The sensitivities of a set of bacterial metal-sensing transcriptional regulators explain how a protein, such as the cobalt chelatase CbiK, is metalated with its cognate metal in cells rather than mis-metalated with more tightly binding metals.

A study of retrotransposon activity repurposes a retroelement called R2Tocc to create a programmable system called STITCHR that enables diverse genome edits including efficient, scarless large payload insertions.

Estimates of global total biomass (the mass of all living things) and anthopogenic mass (the mass embedded in inanimate objects made by humans) over time show that we are roughly at the timepoint when anthropogenic mass exceeds total biomass.

The authors use time-resolved metabolomics and microfluidics to characterize enhanced heterotroph chemoattraction to metabolites released from cyanobacteria during early stages of phage infection.

Alexander disease is a rare neurodegeneration caused by mutations in a glial gene GFAP. Here, Wang and colleagues show in animal models of Alexander disease that GFAP mutant brain and cells have greater tissue and cellular stiffness and greater activation of mechanosensitive signaling cascade.

Immunostimulatory antibodies have strong potential as anti-cancer therapeutics. Here Elliott et al. show that conformational rigidity determines agonistic activity of antibodies targeting CD40 and 4-1BB and demonstrate further enhancement of agonism through disulfide engineering.

Insoluble protein expression continues to be a bottleneck for biotechnology. Here, Chilkoti and colleagues report a method for generating and identifying hypersoluble intrinsically disordered protein fusion tags to improve soluble protein expression and rescue protein function.

Knockout studies using CRISPR–Cas9 identify PCDH10 as a selective host cellular receptor for western equine encephalitis virus.

The International Union for Conservation of Nature’s Global Ecosystem Typology has been developed to provide a systematic framework for data on all of Earth’s ecosystems in a unified theoretical context to support biodiversity conservation and ecosystem services.

The competition between grassland vegetation and microbes for phosphorus controls how plant productivity responds to elevated CO₂, according to free-air CO₂ enrichment experiments on phosphorus-limited grasslands.

Sea level fall with the growth of the Antarctic Ice Sheet 34 million years ago, and the shift in nutrients and carbon from continental margins to the ocean, initially provided a negative feedback that slowed global cooling and ice sheet expansion.

DNA glycosylases license expression of a set of pollen-specific, highly expressed maize genes that are of interest not only because of their transposon-like DNA methylation but also because of their predicted importance in cell wall modification.

Improved base editors are generated by continuous evolution.

Invasive Spartina grasses accumulate high levels of intracellular dimethylsulfoniopropionate (DMSP). Here, the authors report the isolation and characterization of the genes involved in DMSP biosynthesis and show that administration of DMSP by root uptake or overexpression of the DMSP biosynthesis genes results in salinity and drought tolerance in Arabidopsis.

In situ analysis of natural Crocosphaera populations revealed diel cycling of transcript abundances for a range of metabolic pathways, indicating that these cyanobacteria are dominant nitrogen fixers and contributors to primary productivity.

Large-scale land transactions can promote agricultural intensification but may be accompanied by negative socioeconomic and environmental consequences. Estimated carbon emissions from converting transacted lands to large-scale farms can reach up to 2.26 Gt, with the majority emitting from Africa, Southeast Asia, Latin America and Oceania; mitigation strategies are discussed.

Few aerobic hyperthermophilic microorganisms are known to degrade polysaccharides. Here, Nou et al. use genomic information to enrich and optical tweezers to isolate an aerobic hyperthermophilic bacterium that can grow at 65–87.5 °C using polysaccharides as sole carbon sources.

Genome-wide association studies (GWASs) of mice provide an alternative means of identifying genes and genetic variants that are important for human physiology and disease. This Review describes the various resources and strategies for GWASs of mice, emphasizing their advantages and pitfalls relative to human studies.

This work identified cyclic peptide inhibitors of a mammalian N-terminal cysteine oxidase, ADO, through mRNA display, one of which was used as a scaffold to graft substrate moieties, allowing key interactions to be assessed through structural and biochemical approaches.

Abraham Palmer and colleagues use genotyping by sequencing to perform genome-wide association studies on CFW mice for behavioral, physiological and gene expression traits. They find many QTLs and incorporate expression QTL analysis to prioritize specific genes at loci of interest that underlie different complex traits.

Shi and Li et al. show that SARS-CoV-2 Omicron subvariants have increased capacity to infect primary human nasal tissue using a distinct entry route that depends on matrix metalloproteinases as opposed to TMPRSS2 used by previous variants, which enables evasion from antiviral factors.

Zhang et al. show that dynamin forms a helical structure with actin and, upon disruption, enhances branched actin polymerization, constituting a dynamic cycle to regulate actin cytoskeleton mechanical strength.

Fragment-based drug design is an efficient yet challenging approach for developing therapeutics. Here, the authors employ structure-based docking screens of vast fragment libraries to identify inhibitors of 8-oxoguanine DNA glycosylase, a difficult drug target implicated in cancer and inflammation.

Evolution affects microbial community composition, but it is still unknown how commonly compositions change, and how predictable such changes are. Using experimental evolution, Meroz et al. show that compositional changes typically occur within ~400 generations, and are predictable by a bottom-up approach.

High-affinity antibodies are often identified through directed evolution but deep leaning methods hold great promise. Here the authors report RESP, a pipeline for efficient identification of high affinity antibodies, and apply this to the PD-L1 antibody Atezolizumab.

EDI048 is a gastrointestinal-targeted Cryptosporidium PI(4)K inhibitor that undergoes a predictable metabolism and limits systemic exposure without compromising its anti-parasitic activity.