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Here, a combination of forward genetics and genome-wide association analyses has been used to show that variation at a single genetic locus in Arabidopsis thaliana underlies phenotypic variation in vegetative growth as well as resistance to infection. The strong enhancement of resistance mediated by one of the alleles at this locus explains the allele's persistence in natural populations throughout the world, even though it drastically reduces the production of new leaves.

The effect of knots on protein stability and folding kinetics is not well understood. Here the authors combine optical tweezer experiments and calculations to experimentally determine the energy cost for knot formation, which indicates that knotted proteins evolved specific folding pathways because knot formation in unfolded chains is unfavorable.

Whilst superconductivity usually appears when magnetic order is suppressed, the role of charge is less known. Here, Kawasaki et al. report a charge density wave (CDW) above the superconducting transition induced by an in-plane magnetic field in Bi₂Sr_2-x La _x CuO₆, with the CDW onset temperature scaling with the pseudogap temperature.

A trans-ancestry genome-wide association study of serum urate levels identifies 183 loci influencing this trait. Enrichment analyses, fine-mapping and colocalization with gene expression in 47 tissues implicate the kidney and liver as key target organs and prioritize potential causal genes.

Serum urate concentration can be studied in large datasets to find genetic and epigenetic loci that may be related to cardiometabolic traits. Here the authors identify and replicate 100 urate-associated CpGs, which provide insights into urate GWAS loci and shared CpGs of urate and cardiometabolic traits.

Mutations that impact the function of the Arp2/3 complex are known to cause inborn errors of immunity. Here the authors describe biallelic null mutations in the ARPC5 subunit of Arp2/3 that disrupt actin function and cytokine signaling, causing infections, autoimmunity, inflammation and dysmorphisms.

Neutrophilic inflammation is a hallmark of many monogenic autoinflammatory diseases. Here the authors report a case series of three unrelated boys with perinatal-onset of neutrophilic cutaneous small vessel vasculitis and systemic inflammation, and identify de novo truncating and missense variants in the Src-family tyrosine kinase LYN.

Causally linking a mutation to clinical phenotypes in rare hereditary diseases is both challenging and illuminating. Here the authors identify PI3Kɣ mutations in a patient with immune dysregulation, and recapitulate the phenotypes in PI3Kɣ-deficient mice by exposing them to natural microbiota from pet-shop mice.

Initial results from phase I/II lentiviral gene therapy trials provide early evidence supporting its safety and efficacy in treating patients with X-linked chronic granulomatous disease.

Transcriptomic, proteomic and immune repertoire profiling reveals distinct peripheral features of MIS-C and pediatric COVID-19, including elevated soluble spike protein levels, more pronounced type II IFN-dependent gene expression and a higher B cell mutation rate in patients with MIS-C.

Local probing into the microscopic degrees of freedom is highly desired to understand emergent exotic quantum phases. Here, the authors report a canted ferromagnetic phase preceded by local point symmetry breaking at low temperature in Ba₂NaOsO₆, acquired by probing into the spin, orbital and lattice degrees of freedom.

If vortex cores within a superconductor can trap electrostatic charge, the cores will experience a repulsive Coulomb interaction. Evidence from NMR measurements indeed suggests that above some threshold magnetic field, the Abrikosov vortex lattice becomes unstable.

Chromatin neighbourhoods, formed by CTCF, have been proposed to isolate enhancers and their target genes from other regulatory elements. Here, the authors provide evidence that while CTCF binding does regulates mammary-specific super-enhancers, CTCF sites are relatively porous borders.

The common ABCG2 variant Q141K contributes to hyperuricemia and gout risk. Here, using a human interventional study and a new orthologous mouse model, the authors report a tissue specific pathobiology of the Q141K variant, and support a significant role for ABCG2 in urate excretion in both the kidney and intestine.

Tissue-resident marcophages have both generic and tissue-specific functions, but how the latter functions are imbued is still unclear. Here the authors show that peritoneal macrophages express a specialised genetic programme to utilise the locally enriched glutamate for a metabolic setting that facilitates protective in situ immunity.

Nikolich-Žugich and colleagues describe a unique subset of human T cells with a naive phenotype and the ability to rapidly produce cytokines in response to engagement of the T cell antigen receptor.

T cells proliferate in response to cues provided by antigen-presenting cells or high concentrations of cytokines. Krummel and colleagues reveal a distinct requirement for the cytoskeletal protein septin 7 for cytokine-driven bystander T cell proliferation.

Lupus-like disease is driven by NETs enriched in mitochondrial DNA.

Many receptors of the immune system are composed of ligand-binding subunits combined with signalling subunits. Here, Matthew Call and Kai Wucherpfennig review recent studies on the assembly and architecture of these receptors and discuss the implications of these studies.

Combinations of fluorescently labeled peptide–major histocompatability (pMHC) tetramers are used to simultaneously detect T cells with multiple antigen specificities from human blood samples. Also in this issue, Hadrup et al. present a very similar combinatorial encoding approach.