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Macrophages are pleiotropic and can have different functions and phenotypes. Here the authors show that a population of macrophages, previously described as pro-fibrotic, can be induced through Notch2 blockade and that in a mouse lung injury and fibrosis model this macrophage population does not promote inflammation or fibrosis.

Beck et al. conducted single-cell and spatial profiling of embryonal tumors with multilayered rosettes, finding that malignant cellular hierarchies are driven by developmental programs and specific members of the chromosome 19 microRNA cluster.

In contrast to their clinical success as inhibitors and targeting agents, antibodies have generally been ineffective as receptor agonists. Here, Romei et al. leverage a natural homotypic interface to tune antibody geometry, enabling optimization of agonist activity for multiple therapeutic targets.

Comprehensive analyses of 178 lung squamous cell carcinomas by The Cancer Genome Atlas project show that the tumour type is characterized by complex genomic alterations, with statistically recurrent mutations in 11 genes, including TP53 in nearly all samples; a potential therapeutic target is identified in most of the samples studied.

Scaffold proteins are known to have an important role in signal transduction but their mechanisms of activation are still unclear. In this Review, recent studies that have shed light on the function of cytoplasmic scaffold proteins in immune-cell signalling are discussed.

Fibroblastic reticular cells (FRCs) provide structural support and soluble factors necessary for proper lymph node organization and function. Turley and colleagues use scRNA-seq to identify a unique Gremlin1-expressing FRC subset that is found in T cell zones. Grem1⁺ FRCs support the survival of resident cDCs and are necessary to promote T cell immunity.

UBE2W catalyzes the ubiquitination of protein N-termini but its substrate spectrum is largely unknown. Here, the authors discover mAbs selective for peptides derived from N-terminally ubiquitinated proteins, solve the structure of a peptide-bound mAb and apply the mAbs to map endogenous UBE2W substrates by proteomics.

The Arctic tundra is a relatively young biome. Here, the authors sample 32 angiosperm clades encompassing 3600+ species and find that both long-term dispersal and in situ speciation may have contributed to Arctic flora assembly, in association with landscape, climate and sea-level changes since the early Late Miocene.

Naive T cells can spend hours 'sampling' dendritic cells before making a stable conjugate with a single dendritic cell. It is the antigen 'dose' that determines how long this process takes.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

Crystal structures of human BRAF kinase domain with MEK and an ATP analog or with 14-3-3 reveal how ATP exerts a negative regulatory effect on the kinase and how this effect is relieved by dimeric 14-3-3.

Classical type 1 dendritic cells (cDC1s) are essential for activation of antiviral and anticancer T cell responses. Murphy and colleagues describe a genetic circuit that involves the transcription factors Nfil3, Id2 and Zeb2. This circuit imposes a molecular switch that allows cDC1 specification and development.

Metal–organic frameworks (MOFs) are attractive electrodes for supercapacitors but generally suffer from low electric conductivity and chemical stability. Here the authors report stable conductive MOFs based on hexaminobenzene linker with volumetric and areal capacitances in excess of 700 F per cm³ and 15 F per cm², respectively.

The SARS-CoV-2 protein ORF8 functions as a mimic of histone H3 to disrupt host cell epigenetic regulation.

Relatives of patients with amyotrophic lateral sclerosis have an unexpectedly high incidence of schizophrenia. Here, the authors show a genetic link between the two conditions, suggesting shared neurobiological mechanisms.

Macrophage colony-stimulating factor (M-CSF) induces the proliferation of mononuclear phagocytes, and DAP12 is needed for their function. Colonna and colleagues show that DAP12 is also needed for M-CSF-induced stabilization of β-catenin.

A screen of the ReFRAME library of approximately 12,000 known drugs for antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) identified several candidate compounds with suitable activities and pharmacological profiles, which could potentially expedite the deployment of therapies for coronavirus disease 2019 (COVID-19).

Inclusions containing TDP43 are linked to pathologies in several neurodegenerative diseases such as ALS and FTD. Pathogenic TDP43 mutations are now found to shorten the protein's half-life in individual neurons. Stimulating autophagy with inhibitors improves TDP43 clearance and localization.

The Cancer Genome Atlas consortium reports on their genome-wide characterization of somatic alterations in colorectal cancer; in addition to revealing a remarkably consistent pattern of genomic alteration, with 24 genes being significantly mutated, the study identifies new targets for therapeutic intervention and suggests an important role for MYC-directed transcriptional activation and repression.

Lipid second messengers are thought to be important in T cell activation. Two studies show the spatial-temporal organization of these lipids during immunological synapse formation and raise new questions about their functions.

This paper reports integrative molecular analyses of urothelial bladder carcinoma at the DNA, RNA, and protein levels performed as part of The Cancer Genome Atlas project; recurrent mutations were found in 32 genes, including those involved in cell-cycle regulation, chromatin regulation and kinase signalling pathways; chromatin regulatory genes were more frequently mutated in urothelial carcinoma than in any other common cancer studied so far.

The Cancer Genome Atlas Research Network reports an integrative analysis of more than 400 samples of clear cell renal cell carcinoma based on genomic, DNA methylation, RNA and proteomic characterisation; frequent mutations were identified in the PI(3)K/AKT pathway, suggesting this pathway might be a potential therapeutic target, among the findings is also a demonstration of metabolic remodelling which correlates with tumour stage and severity.

An integrative genomic analysis of several hundred endometrial carcinomas shows that a minority of tumour samples carry copy number alterations or TP53 mutations and many contain key cancer-related gene mutations, such as those involved in canonical pathways and chromatin remodelling; a reclassification of endometrial tumours into four distinct types is proposed, which may have an effect on patient treatment regimes.

Mesangial cells are stromal cells that are important for kidney glomerular homeostasis and the glomerular response to injury. This Perspective reviews advances in our understanding of mesenchymal stromal cell function and describes how these insights can inform our understanding of mesangial cells and their role in disease.

Immunological synapse formation is essential for T cell activation. A recent paper in Science reports that immunological and neurological synapses utilize a common molecule, agrin.

Hot-band absorption based anti-Stokes fluorescence of ICG for evaluating the thermal state of the tumor and multi-organ imaging.

The Cancer Genome Atlas Network describe their multifaceted analyses of primary breast cancers, shedding light on breast cancer heterogeneity; although only three genes (TP53, PIK3CA and GATA3) are mutated at a frequency greater than 10% across all breast cancers, numerous subtype-associated and novel mutations were identified.

The study of topological defects in matter is a topic of extensive interest, but it remains challenging when it concerns non-equilibrium active matter. The authors experimentally and computationally demonstrate that obstacles immersed in a two-dimensional active liquid crystal can pin a type of defects and slow down the dynamics of nearby defects.

Although most immunologists do not routinely combine experiments with theoretical and mathematical modeling, new insights can be gained from this interdisciplinary approach. But what makes a good theoretical model?

The glomerulus is a difficult-to-isolate structure that is often poorly represented in single-cell kidney preparations. This protocol describes the isolation of high-quality mouse glomerular cells for high-throughput analyses.

This article aims to make the methodology behind the recent spate of papers reportingin situimmune-cell imaging more accessible to the reader and to highlight potential artefacts so that the reader can analyse the data more critically.