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Bacterial growth rate depends on the number of active ribosomes and translation elongation rate. Matamouros et al. show that Corynebacterium glutamicum, a gram-positive model species, uses a different strategy than Escherichia coli during slow growth by strongly reducing the translation elongation rate while keeping a high number of active ribosomes.

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.

Spatial molecular imaging analysis of human pancreatic adenocarcinomas describes multicellular neighborhoods in the tumor microenvironment. Ligand–receptor analysis using optimal transport-based SCOTIA identifies interleukin-6 as a mediator of chemoresistance.

This study describes sensing of circulating cell-free DNA after stroke as the mechanism leading to recurrent ischemic events.

Arya et al. report that migrating neutrophils resolve acute inflammation by releasing exosomes associated with nuclear DNA. This process is distinct from the release of neutrophil extracellular traps, and relies on the lamin B receptor.

Identifying genes involved in MYC-driven lymphoma reveals therapeutic vulnerabilities. Here, the authors show by using CRISPR knockout screens in primary cells in vivo that the GATOR1 complex suppresses MYC-driven lymphomagenesis, and that GATOR1-deficient lymphomas are sensitive to mTOR inhibitors.

The interaction between MyD88 and ERK is necessary for RAS-dependent transformation and cancer cell survival. Here, the authors identify benzimidazole compound EI-52 as a disrupter of this interaction and demonstrate its therapeutic efficacy in tumours via ERK dysregulation and the induction of immunogenic cell death.

α-ketoglutarate (αKG) is an intermediate in the tricarboxylic acid cycle that is required in the nucleus for genomic DNA demethylation by Tet3. Here, the authors show that the enzyme glutamate dehydrogenase, which converts glutamate to αKG, is redirected from the mitochondria to the nucleus.

Accumulation of advanced glycation end products such as carboxymethyllysine (CML) has been associated with aging but their molecular roles are largely unclear. Here, the authors use proteomics to identify CML sites and show that CML formation affects protein homeostasis and cell proliferation.

Antifungal azoles inhibit ergosterol biosynthesis, but how that leads to fungistatic or fungicidal activities in many pathogenic fungi is poorly understood. Here, Schuster, Kilaru & Steinberg show that azole lethality in the plant pathogens Zymoseptoria tritici and Magnaporthe oryzae is due to a combination of reactive oxygen species-induced apoptosis and macroautophagy.

Petite yeast cells lack the mitochondrial genome, which impairs growth. Vowinckel et al. identify the causes behind this growth impairment, linked to amino acid deficiencies that result from iron metabolism defects and an inhibited tricarboxylic cycle.

Mutations in the hexosamine pathway key enzyme glutamine fructose-6-phosphate amidotransferase (GFAT-1) improve protein quality control and extend C. elegans lifespan. Here the authors present the crystal structures of full-length human GFAT-1 alone and with bound ligands and perform activity assays, which show that gain-of-function in the longevity-associated G451E variant is caused by a loss of feedback regulation.

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.

In E. coli, FtsA and FtsZ control the place and time of cell division. Here, the authors use in vitro experiments to show how FtsA can follow FtsZ treadmilling and that downstream proteins form dynamic copolymers with FtsA to initiate division.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

There is a need for effective antiviral drugs against RSV infection. Conducting an RSV repurposing screen using the ReFRAME library Sake et al. identify lonafarnib as an RSV fusion protein inhibitor, characterize its binding site within the viral protein and show its antiviral effects in a mouse model.

A deleterious mutation in the tomato transcription factor SSP2 was enriched during domestication. Repairing the deleterious mutation in cultivated tomato by base editing leads to compact growth and early fruit yield.

In this paper and the related paper from Lugli and colleagues the authors show that high levels of NaCl inside the tumor have a beneficial effect on CD8⁺ T cells and their ability to control tumor growth as a result of enhanced T cell receptor activity.

There is a clinical need for effective and efficacious vaccines for Epstein-Barr virus (EBV) that induce substantive and protective immunity. Here the authors use a combined lymph-node targeted adjuvant and subunit vaccine against EBV and show the induction and effectiveness in a human leukocyte antigen expressing murine model.’

The development of innovative strategies for the capture and biodegradation of nanoplastics is sought after. Now, artificial hydrolytic active sites are incorporated into non-catalytic membrane nanopores generating pore-based biocatalytic nanoreactors that depolymerize polyethylene terephthalate plastic nanoparticles.

Nonselective engagement of GPCR signaling pathways by GPCR-targeting drugs can reduce treatment efficacy and cause side effects. The authors show that signaling selectivity in CB2R can be tuned by reshaping allosteric networks, offering insights for more precise therapies.

Dynamic changes in 2′-O-methylation of rRNA in human cells lead to ribosome heterogeneity and result in altered translation of select mRNAs, correlating with changes in cellular phenotypes.

Liebers and colleagues present a prospective non-interventional trial in 80 individuals with hematologic cancer investigating the potential of ex vivo drug response profiling and show it to be clinically feasible.

Here the authors show that antibody-dependent phagocytosis of ring-stage P. falciparum parasites is mediated by merozoite antigens and is a strong predictor of protection following challenge in a controlled human malaria infection study in semi-immune Kenyan adults.

In a phase I/II dose-escalation clinical trial, the mRNA COVID-19 vaccine BNT162b1 elicits specific T cell and antibody responses that suggest it has protective potential.

Taniguchi et al. structurally analyse nuclear pore complex architecture in situ during differentiation, which is associated with mechanical constraints on the nuclear envelope. They link nuclear pore complex elasticity to nuclear envelope integrity in differentiation.

The changes in super-enhancer (SE) landscape of cancers are mainly attributed to cell-intrinsic genomic alterations. Here, the authors perform epigenomic profiling on primary colorectal cancers (CRCs) and their matched normal tissues and show that local tumour microenvironment induces a SE activation and that its target, PDZK1IP1 promotes CRC growth.

Bradyzoites are a quiescent form of Toxoplasma gondii enclosed in cysts during chronic infections. Here, Christiansen et al. develop a human myotube-based in vitro culture model of cysts that are infectious to mice and characterize their metabolism in comparison to fast replicating tachyzoites.

The ability of the fungal pathogen Candida albicans to undergo yeast-to-hypha transition is believed to be a key virulence factor. Here, Dunker et al. show that a filament-deficient strain is attenuated in a mouse model of intraperitoneal infection, but remains virulent in a mouse model of systemic candidiasis.

In a non-prespecified interim analysis of a phase 1 trial, autologous PRAME-directed TCR T cell therapy was safe and elicited durable responses in patients with recurrent and/or treatment-refractory PRAME⁺ advanced solid tumors, including melanoma and synovial sarcoma.

In order to find a general treatment for cancer, this study found that MTH1 activity is essential for the survival of transformed cells, and isolated two small-molecule inhibitors of MTH1, TH287 and TH588 — in the presence of these inhibitors, damaged nucleotides are incorporated into DNA only in cancer cells, causing cytotoxicity and eliciting a beneficial response in patient-derived mouse xenograft models.

Engineered erythropoietin receptor scaffolds equipped with extracellular sensor domains and modular intracellular domains that couple to endogenous signaling pathways enable modular reprogramming of designer membrane-bound receptors.

Collignon et al. report that Mettl3-mediated m⁶A RNA methylation promotes developmental pausing in embryonic stem cells and blastocysts by establishing transcriptional dormancy.

The molecular mechanisms explaining racial disparity in breast cancer mortality are not completely elucidated. Here, the authors show that an African-associated SNP in American breast cancer patients, leads to higher levels of microRNA miR-1304-3p which promotes cancer by increasing lipids availability.

The enzymatic breakdown of the lipid sphingomyelin is associated with various infectious diseases. Here, the authors introduce trifunctional sphingomyelin derivatives for the visualisation of sphingomyelin distribution and sphingomyelinase activity in infection processes.

Modelling of acidic zeolites, one of the key industrial catalysts, under realistic operating conditions is currently limited to specific cases. Here, the authors report a machine learning framework allowing for accurate high-throughput modelling.

Some cyanobacteria excrete nitrite when the supply of inorganic carbon is limiting, but the underlying mechanisms are unclear. Here, Kraus et al. identify a conserved protein that interacts with nitrite reductase, thus regulating nitrogen metabolism and promoting nitrite excretion.

‘Gasdermin-mediated pyroptosis can induce anti-tumor immune responses. Here the authors report a toolbox of gasdermin D variants for induction of pyroptosis, showing that, when combined with intratumoral expression of cytokines (IL-1β, IL-12, or IL-18), anti-tumor immune responses in preclinical models are enhanced.

Antibody diversification relies on the intentional mutagenesis of immunoglobulin genes for adaptive immune responses. Here, the authors identified a CTLH E3 ubiquitin ligase complex that co-opts FAM72A to recruit and degrade the UNG2 base excision repair factor to permit mutagenesis.

The production of eicosanoids by neutrophils during the neonatal period is necessary for the self-renewal and maintenance of alveolar macrophages during lung development.

SARS-CoV-2 variants with mutations in spike have emerged during the pandemic. Magaret et al. show that in Latin America, efficacy of the Ad26.COV2.S vaccine against moderate to severe–critical COVID-19 varied by sequence features, antibody escape scores, and neutralization impacting features of the SARS-CoV-2 variant.

Tick evasin proteins block the inflammatory activity of mammalian chemokines. In this work, the authors report that structure-based modification of class A3 evasins alters their chemokine selectivity, suggesting these evasins could be engineered for targeted anti-inflammatory therapy.

The authors explore sequence-encoded molecular grammar underlying the liquid liquid phase-separation of the human RNA polymerase II C-terminal domain and demonstrate that phase-separation appears to accelerate on phosphorylation by CDK7.

The yeast Saccharomyces cerevisiae is powerful for studying human G protein-coupled receptors as they can be coupled to its mating pathway. Here the authors engineer baker’s yeast to produce human sterols and show that vertebrate G protein coupled receptors are more sensitive in this membrane environment.

Waning immunity to SARS-CoV-2 is of concern. Here the authors follow spike- and nucleocapsid specific immunity in convalescent individuals for 9 months observing a decline in antibody levels but persisting T cell response. Vaccination approximately 11 months after infection boosts antibody and T cell immunity.

Protein kinase transition between different conformational states is controlled by autophosphorylation. Here, the authors demonstrate that the c-terminal Tyr530 is a de facto c-Src autophosphorylation site  and identify a critical c-terminal palindromic phospho-motif that controls the interplay between substrate and enzyme-acting kinases during autophosphorylation.

Protection afforded by inorganic minerals is assumed to make mineral-associated organic carbon less susceptible to loss under climate change than particulate organic carbon. However, a global study of soil organic carbon from drylands suggests that this is not the case.

Using new optogenetic tools to induce distinct ion fluxes, a study shows that these discrete signals trigger different metabolic and transcriptional pathways that allow plants to respond to specific types of stress.