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By combining left- and right-handed DNA-PAINT probes, Unterauer et al. achieve simple, robust, and highly multiplexed super-resolution. They show 13-plex neuronal maps, revealing nanoscale organization of cytoskeleton, organelles, and synapses.

Origins of replications are associated with potential G quadruplexes forming structures (G4s). Here the authors reveal the functional role of G4 elements in DNA replication initiation.

The nanoscale organization of the antigen-antibody complexes influences the therapeutic action of monoclonal antibodies. Here, the authors present a multi-target 3D RESI imaging assay for the nanometer spatial analysis of CD20 in complex with therapeutic monoclonal antibodies within intact cells, to analyse the interdependency between the mode of antibody binding and the therapeutic function.

Extracting quantitative information on biomolecular oligomerisation with high resolution remains a significant challenge. Here, the authors propose SPINNA, a framework that compares nearest-neighbour distances from experimental single-protein position data with those obtained from simulations based on a model of protein oligomerisation.

Material flows between ecosystems, though the degree to which ecosystems are coupled is under investigation. Here Gounand et al. analyze cross-ecosystem carbon flows and relate them to in situ functions, and report different dependencies on spatial flows across numerous ecosystems.

Changes in the tumour microenvironment have been associated with response and resistance to immunotherapy. Here, by performing longitudinal transcriptomic and spatial analysis, the authors report the exploratory analysis of their phase II trial of neoadjuvant chemotherapy alone or in combination with pembrolizumab (anti-PD1) in patients with advanced high-grade ovarian carcinoma.

Using intensive eDNA sampling in space and time across five rivers in Europe and North America, this study shows that eDNA gives relevant information on freshwater diversity and ecology across broad taxonomic groups, and with limited downstream transport. The findings demonstrate that eDNA is vital for freshwater biodiversity monitoring in a time of anthropogenic change.

Evolutionarily conserved gene modules mediate neurodegenerative dementia in a variety of mouse models and in postmortem brain tissue from patients.

Pseudokinases lack kinase activity, yet they impact cellular physiology through the regulation of bona fide signaling kinases. Here the authors describe the structure of the SgK223 pseudokinase and its adjacent domains, and identify regulatory interfaces required for self-assembly and downstream signaling.

Kovalski et al. perform a genome-wide CRISPRi screen for selective MYC mRNA translation regulators and identify RBM42 as a ribosome-associated protein that modulates translation of MYC and an oncogenic mRNA programme required for pancreatic cancer growth.

Resistance to anti-EGFR therapy is a clinical issue for patients with advanced head and neck cancers. Here, the authors show that therapy-resistant cancer cells enhance fatty acid metabolism, which can be therapeutically targeted by inhibiting peroxisome proliferator-activated receptor alpha (PPARα).

Filamin proteins are degraded by ASB2α E3 ubiquitin ligase and may affect T cell function. Here the authors show that increased levels of Filamin A and Filamin B in Th2 cells reduces allergic inflammation in mouse models through reduced Th2 cell recruitment into inflamed lungs.

Shwachman-Diamond syndrome (SDS) is a leukemia predisposition disorder that is caused by defective release of eIF6 during ribosome assembly. Here the authors show that acquired somatic EIF6 mutations are frequent in the hematopoietic cells from individuals with SDS and provide a selective advantage over non-modified cells.

Potent allogeneic CD8αβ⁺ CAR T cells devoid of alloreactive potential can be generated from human T-cell-derived induced pluripotent stem cells via the timed and calibrated expression of a CAR that substitutes for the T-cell receptor.

Blanpain and colleagues delineate lineage reprogramming following PTEN deletion in different prostate cancer-originating cells, demonstrating that in basal cells the NF-κB pathway and innate immunity control stem cell plasticity and tumor initiation.

Hypothalamus participates in systemic metabolic processes, while high calorie intake increases immune activation in the central nervous system. Here the authors show that reduced regulatory T cells in the hypothalamus contribute to elevated immune activation in a high calorie environment, thereby prompting a potential therapy target for metabolic diseases.

Here the authors identify GPATCH11 variants responsible for retinal dystrophy with neurological impairment and facial dysmorphy. They explore its function using a mouse model and demonstrate GPATCH11’s involvement in RNA regulation and splicing.

The authors introduce a single-molecule DNA-barcoding method, resolution enhancement by sequential imaging, that improves the resolution of fluorescence microscopy down to the Ångström scale using off-the-shelf fluorescence microscopy hardware and reagents.

We describe netrin-1 upregulation in a majority of human endometrial carcinomas and demonstrate that netrin-1 blockade, using the anti-netrin-1 antibody NP137, is effective both in a mouse model and in patients with endometrial carcinomas.

The nitrogen-fixing root nodule symbiosis evolved more than 90 million years ago. This innovation emerged by rewiring existing genetic programmes. More recently, this symbiosis convergently gained evolutionary stability in two legume lineages.

Neugebauer et al. show activation of the usually silenced embryonic factor DUX4 by herpesviruses in vitro and in patients, and demonstrate that depletion of DUX4 by nanobody degraders abrogates viral replication.

The authors identify a family of iron-binding proteins that is present in phytopathogenic bacteria, fungi and oomycetes. Some of these proteins are secreted, bind metals, protect the pathogen from H₂O₂-induced death, and are involved in plant infection.

Conventional selections of AAV capsid libraries are inefficient at searching sequence space. Here the authors report ‘Fit4Function’, a generalizable ML approach for systematically engineering multi-trait AAV capsids, and use this to predict cross-species traits of peptide-modified AAV capsids.

Idiopathic inflammatory myopathies are severe autoimmune diseases with poorly understood pathogenesis. In this study, the authors use Icos-deficient NOD mice as a model for myositis, as well as clinical samples, to demonstrate mitochondrial abnormalities and metabolic dysfunction, which can be reversed by treatment with the ROS scavenger, N-acetylcysteine (NAC).

The SPP1 tail completion protein, representative of a widespread family of essential phage proteins, is shown to play a role in capsid-tail attachment and to be essential for routing of phage DNA from the viral particle to the bacterial cytoplasm.

Delval, Hantute-Ghesquier, Sencio and colleagues demonstrate that depletion of age-associated senescent cells decreases pulmonary viral load and ameliorates early and late lung COVID-19 in a hamster model of aging.

The antigen-B-cell-receptor interaction is the driving force of terminal B cell development that spans from B cell activation to antibody secreting plasma cells. Here authors determine, using DNA-PAINT super-resolution microscopy, how antigen affinity and valency define antigen binding to BCR in an in vitro system allowing precision control of these parameters.

Changes in gene expression in the hippocampus and the cortex are pivotal for memory consolidation. Gräff and colleagues use a recognition task in mice to show that epigenetic post-translational modifications are rapidly activated in the hippocampus after learning, but induced with a delay in the cortex.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Bacteria produce small iron-binding molecules called siderophores, which are recognised by outer-membrane transporters. Here, the authors show that a Pseudomonas transporter recognises the siderophore enterobactin using extracellular loops distant from the pore, and propose that there is a second binding site deeper inside the structure.

The authors report TNFα-dependent hyperactivity in cortical microcircuits during remission in a mouse model of multiple sclerosis, a maladaptive response to the immune attack with behavioral changes.

Observations from the Lucy spacecraft of the small main-belt asteroid (152830) Dinkinesh reveals unexpected complexity, with a longitudinal trough and equatorial ridge, as well as the discovery of the first contact binary satellite.

Rhodococcus equiis an animal pathogen that sometimes causes opportunistic infections in immunocompromised patients. Speck et al. present the case of a 62-year-old male renal transplant recipient who presented with fever, hemoptysis and left-sided pleuritic chest pain. After numerous investigations, a diagnosis of R. equi infection with bacteremic pleuropneumonia and pseudotumor was made. This Case Study describes the diagnosis and management of R. equiinfection, which has a very varied clinical presentation in humans.

The proteome-wide characterization of proteostasis depends on robust approaches to determine protein half-lives. Here, the authors improve the accuracy and precision of mass spectrometry-based quantification, enabling reliable protein half-life determination in several non-dividing cell types.

Circadian disruption is implicated in the development of different human cancers. Here the authors show that chronic circadian disruption, through continuous jet lag, only moderately affects primary tumour growth but promotes cancer-cell dissemination and metastasis in a mouse model of spontaneous mammary tumorigenesis.

Experiments in mice show that expression of the oncogene SmoM2 induces basal cell carcinoma in the ear epidermis but not in the back skin, and that this difference in susceptibility is regulated by the extracellular matrix.

In mouse and human squamous cell carcinoma, loss of function of FAT1 promotes tumour initiation, malignant progression and metastasis through the activation of a hybrid epithelial-to-mesenchymal transition phenotype.

Netrin-1 is upregulated in cancer models that undergo spontaneous epithelial-to-mesenchymal transition, and its targeting blocks the progression of tumour cells to a late mesenchymal state, suggesting possible therapeutic applications.

DNA replication requires the loading of the replicative helicase onto the DNA molecule; in bacteria this was believed to be solely accomplished by DnaC and DnaI. Here the authors identify DciA as an ancestral and still widely distributed replicative helicase loader.

Blanpain and colleagues identify NR2F2 as a regulator of stemness and invasiveness that promotes tumor renewal and restricts differentiation to sustain squamous cell carcinomas.

Wang et al. use transcriptomic analysis to show that disruption of the transcription factor Lyl-1 in primitive macrophage progenitors results in defective differentiation that impacts on embryonic patterning and neurodevelopment. They also show that Lyl-1 disruption leads to a reduction in mature microglia, thus revealing its role in macrophage and microglial development

Epithelial-to-mesenchymal transition in tumour cells occurs through distinct intermediate states, associated with different metastatic potential, cellular properties, gene expression, and chromatin landscape

Spatially selective and temporally controlled stimulation of the spinal cord, together with rehabilitation, results in substantial restoration of locomotor function in humans with spinal cord injury.