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Panoptes, an anti-phage defence system against virus-mediated immune suppression, is revealed.

PRPS enzymes are crucial for making nucleotides needed to build DNA, RNA, and proteins. This study shows how gene duplications and emergent innovations evolved an ancestral PRPS enzyme into a multi-protein complex in mammals, allowing fine-tuned metabolic regulation vital for growth and adaptation.

Metabolic engineering guided by laboratory evolution enables upcycling of nylon by Pseudomonas putida.

Expression of VIM-2 leads to physiological trade-offs for bacterial pathogens that can be exploited to treat infections caused by multidrug-resistant bacteria.

A genome-wide CRISPR-based screen of Toxoplasma gondii during mouse infection reveals previously uncharacterized factors contributing to parasite virulence.

Zhang et al. uncover different dynamics underlying the maintenance and regulation of H3K9me3-enriched heterochromatin domains in mouse embryonic stem cells and propose that loss of H3K9me3 occurs through two distinct dynamic modes: passive dilution and active removal.

Nitrospira inopinata and probably most other comammox microorganisms can grow on the non-conventional substrate guanidine as the sole source of energy, reductant and nitrogen.

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).

Immunogenicity concerns preclude the use of bacterial kynureninases for cancer immunotherapy, while the human variant lacks the desired therapeutic effect. A human kynureninase enzyme has now been evolved to reach the activity and substrate specificity of its bacterial counterpart.

Genetic engineering of material-producing bacteria creates pigmented products.

A mechanism of lipid transport inhibition has been identified for a class of peptide antibiotics effective against resistant Acinetobacter strains, which may have applications in the inhibition of other Gram-negative pathogens.

Conventional type 1 dendritic cells perform antigen processing and priming of CD4⁺ and CD8⁺ T cells against tumour antigens, orchestrating their cross-talk to effect anti-tumour immunity.

Strain maps of cardiomyocyte nuclei during contraction indicate that, by integrating environmental mechanical cues, the nuclei of cardiomyocytes stabilize the fate of cells through the reorganization of epigenetically marked chromatin.

Chromosome-scale sequence assemblies of 20 diverse varieties of barley are used to construct a first-generation pan-genome, revealing previously hidden genetic variation that can be used by studies aimed at crop improvement

The intricate regulation of cell death pathways remains to be understood. Here the authors identify that PTPN23 functions as a cell death checkpoint to restrain apoptosis, necroptosis and pyroptosis via regulating the endosomal sorting of death receptors and Toll-like receptors.

Bioinformatic and chemoproteomic approaches resulted in the identification of a homolog of human dipeptidyl peptidase 4 in the gut bacterium Bacteroides thetaiotaomicron that regulates envelope integrity and community fitness.

Independent but complementary studies from Vakoc and Stegmaier identify and characterize a role for ETV6 in counteracting the transcriptional activity of EWS–FLI during Ewing sarcoma development, which may be targeted for therapeutic benefits.

Rare variant analyses identify a new type 2 diabetes risk allele near the LEP gene, which encodes leptin, and other risk alleles of intermediate penetrance in genes previously implicated in monogenic forms of diabetes.

A tethered macrocyclic peptide antibiotic class described here—which shows potent antibacterial activity against carbapenem-resistant Acinetobacter baumannii—blocks the transport of bacterial lipopolysaccharide from the inner membrane to its destination on the outer membrane through inhibition of the LptB₂FGC complex.

Obesity induces insulin resistance and impairs insulin signaling, causing diabetes. Here, the authors show that BMP and LGR signaling mediate communication between muscle, neuronal, and adipose tissues to enhance insulin signaling, identifying LGR as key in protecting against insulin resistance.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Callahan et al. show that GC and extra-GC sites spawn distinct MBC subsets. MBC precursors have open chromatin regions (OCRs) that will remain open in MBC progeny, with extra-GC and GC-derived MBCs having distinct OCRs and functions.

The rate of scale regeneration in zebrafish is controlled by the frequency of rhythmic travelling waves of Erk activity, which are broadcast from a central source to induce ring-like patterns of osteoblast tissue growth.

In mouse brain, neurotensin released into the basolateral amygdala by neurons in the paraventricular nucleus of the thalamus assigns positive or negative valence during associative learning.

Ghajar and colleagues report that astrocyte-deposited laminin-211 promotes the quiescence of disseminated tumor cells in the brain, in a manner dependent on the cytoplasmic sequestration of YAP by dystroglycan.

Upon physiological injury, hepatocytes transdifferentiate into biliary epithelial cells, a process involving molecular rewiring. Here, authors show that Sox4 organizes the early steps, acting as a pioneer factor to decommission hepatocyte enhancers and open chromatin around biliary genes.

Zebrafish can regenerate after paralyzing spine injuries and regain locomotor ability, unlike mammals. Here authors show that the neurogenic factor Hb-egf promotes spinal cord regeneration in zebrafish and is regulated by an enhancer that can similarly direct expression in the pro-regenerative setting of neonatal mice.

Cryo-EM structures of somatostatin 14- and octreotide-bound somatostatin receptor 2 reveal a flexible extracellular domain for recognizing different ligands and, together with functional assays, identify the basis of SSTR subtype selectivity.

Environmental exposures shape patterns of selection for mutations in clonal hematopoiesis. Cancer therapies promote the growth of clones with mutations that are strongly enriched in treatment-related myeloid neoplasms.