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The CARD11-BCL10-MALT1 (CBM) complex governs canonical NF-κB signaling and MALT1 protease activation downstream of TCR stimulation. Here, the authors evaluate the contribution of the E3 ligases LUBAC and TRAF6 in controlling CBM activity, using Jurkat and primary human T cells. Unlike TRAF6, LUBAC is largely dispensable for activating NF-κB, but it modifies BCL10 and regulates MALT1 protease activity by controlling substrate selectivity.

Crohn’s disease is associated with disturbances in the B-cell compartment and secreted antibodies. Here, the authors reveal impaired colonic dimeric IgA responses in patients with Crohn’s disease and verify this phenotype in murine models, demonstrating that mitochondrial dysfunction drives defective mucosal humoral immunity.

Teichoic acid is bound to peptidoglycan (wall teichoic acid, WTA) or to membrane glycolipids (lipoteichoic acid, LTA) in most Gram-positive bacteria. Here, the authors identify a putative ligase required for the assembly of LTA, but not WTA, and important for Streptococcus pneumoniae virulence in mouse models.

Hepatocyte organoids derived directly from human tissue enable long-term hepatocyte expansion and can be combined with portal mesenchyme and cholangiocyte organoids to form a donor-specific periportal liver assembloid system.

The omentum is the main metastatic site for ovarian cancer. Here, the authors present a human cell atlas of both benign and omentum metastatic ovarian cancer, providing insights into established metastatic sites but also of the omentum pre-metastatic niche.

Niobium tungsten oxides block structures, consisting of ReO3-type blocks of specific sizes, are promising fast-charging negative electrode materials. Here, the authors propose a partially disordered Nb12WO33 structure that enhances the Li-ion storage performance.

Here authors identify GluN2D-containing NMDA receptors on interneurons as a specific target for rapid antidepressant action. Blocking GluN2D restores stress-impaired plasticity and mimics the effects of ketamine with fewer side effects.

The success of allogeneic hematopoietic stem cell transplantation for the treatment of haematological cancers is limited by the morbidity and mortality associated with graft-versus-host disease (GVHD). Here the authors show that the microbial metabolite desaminotyrosine contributes to graft-versus-leukemia responses while protecting against GVHD and promoting mTORC1 and STING-dependent intestinal regeneration.

Chan et al. generate a high-resolution spatiotemporal atlas of healing hearts and reveal cellular networks of lesion repair, including macrophage–fibroblast interactions that control late-stage fibrosis and immune niches that induce cardiomyocyte de-differentiation.

Endosomal function depends on luminal ion homeostasis. Here the authors identify TMEM9 and TMEM9B as inhibitory subunits of endosomal ClC-3 to ClC−5 that prevent endosomal swelling and disease by regulating their Cl⁻/H⁺ exchange and trafficking.

A molecular mechanism is revealed through which commensal bacteria modulate intestinal epithelial barrier function.

The filamentous fungus expression system Thermothelomyces heterothallica (C1) is a protein expression system that may be useful for large scale antibody production. Here the authors characterise the production of a human monoclonal antibody that neutralises SARS-CoV-2 and compare functional properties in vitro and in animal models to antibodies produced using other methods.

Hofer et al. show that fasting promotes the synthesis of spermidine, which stimulates eIF5A hypusination to induce autophagy and increase lifespan in various species in a conserved manner.

By using cryo-EM and biochemical assays, Loeff et al. reveal the mechanistic basis for the protective function of the oxidoreductase PYROXD1 that maintains the activity of the tRNA ligase complex under aerobic conditions.

Efstathiou et al. describe an Argonaute-dependent endoplasmic reticulum (ER)-associated RNA silencing pathway that acts together with ER-associated protein degradation to preserve ER homeostasis and function.

Antimicrobial peptide LL37 can bind nucleic acids and potentiate their sensing by endosomal TLRs. Here the authors show that LL37 binds to RNA from neutrophil extracellular traps (NETs), which amplifies inflammation and production of more LL37 and NETs via TLR8/13, suggesting that LL37 contribution to psoriasis may be fueled by NET-associated RNA.

CLPP-deficiency-driven mitochondrial dysfunction in brown adipose tissue leads to the accumulation of d-2-hydroxyglutarate, in turn promoting lipid-droplet enlargement by altering gene expression and epigenetically regulating nuclear stiffness.

Analyses of atmospheric samples at a high-altitude site show that methylated forms of arsenic, emitted via biological processes, represent an important share of arsenic deposition. These forms are transported from both marine and terrestrial systems.

Long-read single-cell RNA sequencing is capable of detecting isoform-level gene expression and genomic alterations such as mutations and gene fusions, thereby providing cell-specific genotype-phenotype information. Here, the authors use long-read scRNA-seq on metastatic ovarian cancer samples and detect cell-type specific isoforms and gene fusions that may otherwise be misclassified in short-read data.

Remaining drug-tolerant persistent (DTP) cancer cells limit the efficacy of targeted therapy in EGFR, ALK and KRAS mutant non-small cell lung cancer (NSCLC). Here, the authors show that focal adhesion kinase (FAK)-YAP signalling supports DTP cells promoting residual disease and targeting this pathway improved tumour response in NSCLC preclinical models.

A technique to detect the release of N-terminal fragments of Drosophila adhesion G-protein-coupled receptors (aGPCRs) provides insight into the dissociation of aGPCRs, and shows that receptor autoproteolysis enables non-cell-autonomous activity of aGPCRs in the brain.

Many enzymes form homo-oligomers, but it is often not clear why. This study follows the evolution self-assembly in citrate synthases across their phylogeny and finds it to be variable and not obviously related to enzyme function.

Pneumococcal infection of the cerebrospinal fluid results in bacterial lysis, the release of toxic factors and induction of neuroinflammation. Here, the authors show that the virulence factor pneumolysin enhances the neuroinflammatory response to Streptococcus pneumoniae by the enhancement of endocytosis.

Zeziulia et al. identify the proton-activated Cl⁻ channel ASOR/TMEM206 as necessary for shrinkage of macropinosomes, which is needed for downstream sorting events.

Hippocampal theta oscillations support encoding of spatial information during navigation, yet their role in locomotion is poorly understood. Here the authors demonstrate that hippocampal theta oscillations regulate the speed of locomotion in rodents through a hippocampo-lateral septal-hypothalamic pathway.

This study uncovers a critical link between DNMT3A-driven CHIP and heart failure and, in particular, it shows that DNMT3A inactivation in monocytes boosts the release of HB-EGF, which activates fibroblasts inducing diffuse fibrosis in the heart.

Imaging of lipid bilayers using light microscopy is challenging. Here the authors label cells using a short chain click-compatible ceramide to visualize mammalian and bacterial membranes with expansion microscopy.

ZNF524 is a newly described protein that binds to telomeres, the ends of linear chromosomes. ZNF524 promotes the presence of two members of the shelterin complex, TRF2/RAP1, at telomeres, and prevents genomic instability.

Fat culturing remains a challenging task in the process of producing optimal cultivated meat. Here, using antibiotic-free culture conditions, the authors establish bovine adipose-derived stem cell spheroids as building blocks for the fabrication of cultured fat.

Metalloproteinase inhibitors are leads for drug development, but their biosynthetic pathways are often unknown. Here the authors show that the acyl branched warhead of actinonin and matlystatins derives from an ethylmalonyl-CoA-like pathway and the structural diversity of matlystatins is due to the activity of a decarboxylase-dehydrogenase enzyme.

Urinary albumin-to-creatinine ratio (UCAR) is associated with various clinical outcomes such as kidney disease and cardiovascular disease. Here, the authors report genome-wide meta-analysis in over 500,000 individuals and find 68 UACR loci, followed by statistical fine-mapping, gene prioritization and experimental validation in flies.

The herbivorous horseradish flea beetle sequesters plant toxins to defend against predators. Here the authors identify glucosinolate transporters expressed in the beetle Malpighian tubules and provide evidence that these reabsorb glucosinolates from the tubule lumen to prevent their loss by excretion.

This protocol describes an approach to generate chemically modified aptamers using CuAAC click chemistry. Such aptamers possess extended interaction properties and can be identified by in vitro selection procedures using established SELEX strategies.

Gut Bacteroides deploy several polysaccharide utilization loci (PULs) to forage diverse dietary and host-derived glycans. Here, the authors identify the RNA-binding protein RbpB and a family of noncoding RNAs as key players in post-transcriptional PUL regulation, further showing that ablation of RbpB in Bacteroides thetaiotaomicron compromises colonization in the mouse gut in a diet-dependent manner.

KDM4C regulates cathepsin L-mediated histone H3 N-terminal tail clipping through grainyhead-like 2 (GRHL2) methylation in breast cancer. This link between the cellular redox state and chromatin remodeling might represent a therapeutic target in KDM4C-amplified tumors.

Citrate synthase from the cyanobacterium Synechococcus elongatus is shown to self-assemble into Sierpiński triangles, a finding that opens up the possibility that other naturally occurring molecular-scale fractals exist.

Krisai et al. compare brain structure and cognitive function in elderly patients with and without atrial fibrillation using brain MRI and cognitive testing. They find that atrial fibrillation is associated with more brain lesions and lower cognitive function, but the cognitive impairment occurs primarily through direct effects of the arrhythmia rather than through brain damage.

Lavdovskaia, Hanitsch, Linden et al. provide a comprehensive roadmap of mitoribosome biogenesis and establish that mitochondria use a unique pathway for the assembly of their translation machinery.

Using large-scale single-nucleus transcriptomics, Nicin et al. report insights into human cardiac hypertrophy, caused by pressure overload, at single-cell resolution. The authors show that intercellular communication, particularly via the Eph receptor tyrosine kinase EPHB1, is impaired in human cardiomyopathy.

Deubiquitinase OTULIN targets linear (M1-linked) ubiquitin chain patches on cytosolic Salmonella Typhimurium to modulate NEMO, IKKα/IKKβ and NF-ĸB signalling and regulate secretion of pro-inflammatory cytokines and bacterial proliferation.

Optogenetic tools enable precise experimental control of the behaviour of cells. Here, the authors introduce a genetically-encoded two-protein system that enables silencing of excitable cells such as neurons and cardiomyocytes using blue light, and demonstrate its utility both in vitro and In vivo.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

Bacteriophage T4 uses an enzyme known as ADP-ribosyltransferase ModB to modify the translational apparatus of bacteria it infects, not only by ADP-ribosylating proteins, but also by attaching entire RNA chains in a process known as RNAylation.

Microtubules are a ubiquitous eukaryotic cytoskeletal element typically consisting of 13 protofilaments arranged in a hollow cylinder. Using CryoEM and subvolume averaging, Ferreira and Pražák et al. show that Plasmodium does not adhere to a single microtubule structure. Instead, the cytoskeleton changes substantially to produce a unique, fit for purpose structure and organisation at each stage of its life cycle.

The attachment of polymers to protein molecules is known to shield them from biological breakdown. Here, the authors apply this concept to an asparaginase, in order to prevent its deactiviation by host immune responses during leukaemia treatment.

Personalised medicine requires cell cultures from defined genetic backgrounds, but providing sufficient numbers of cells is a challenge. Here the authors develop gene cocktails to expand primary cells from a variety of different tissues and species, and show that expanded endothelial and hepatic cells retain properties of the differentiated phenotype.