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Familial adenomatous polyposis (FAP) is an inherited gastrointestinal syndrome associated with duodenal adenoma formation. Here the authors show that IL17A-producing NKp44- group 3 innate lymphoid cells accumulate in FAP duodenal tissue and are associated with duodenal adenoma formation in patients with FAP.

TGF-β family cytokines control essential cell fate decisions via receptor regulated SMAD (R-SMAD) transcription factors. Here the authors identify an inner nuclear membrane phosphatase complex that dephosphorylates R-SMADs to inactivate TGF-β signaling.

Magnetic resonance imaging of swollen tendons suggests that the elasticity and stress relaxation of extracellular matrix depend on electrostatic repulsions between proteoglycans rather than on hydration-associated changes.

Using time-controlled CRISPR screens, the authors identify AKIRIN2 as a factor involved in the nuclear import of the proteasome.

Physical characterisation of proteins is challenging. Here the authors report single-molecule microfluidic diffusional sizing (smMDS) to enable calibration-free single-molecule diffusional-sizing based monitoring of protein hydrodynamic radii even within heterogenous multicomponent mixtures.

Skyrmions are topologically protected field configurations that appear as solutions of continuous quantum-field theories. Recently, they have been observed in magnetic bulk alloys, where a lattice of skyrmions is stabilized by an external magnetic field. In contrast, this study finds evidence for a skyrmion lattice as a spontaneous ground state, encoded into a magnetic spin texture on the atomic scale.

Genetic mechanisms of sex determination are still unknown in most amphibians. This study elucidates a mechanism behind amphibian sex determination by uncovering a sex-determining locus (bod1l gene and a Y-specific non-coding RNA, ncRNA-Y) in European green toads (Bufo(tes) viridis) which initiates male development.

The molecular joint of a nanorobotic arm can be wound up to store mechanical energy and then relaxed to drive the rotation of a DNA nanodevice.

Uncontrolled secretion of ECM proteins, such as collagen, can lead to excessive scarring. Here the authors describe membrane permeable peptides that target the interface of TANGO1 and cTAGE5, inhibit secretion of ECM components and could be of therapeutic benefit during wound healing and fibrotic processes.

The influence of stress relaxation of the extracellular matrix on the formation of intestinal organoids was investigated. It was shown that a stress-relaxing synthetic matrix promotes crypt budding through increased symmetry breaking and niche cell formation.

Examining the spatially resolved transcriptome of tissue sections promises advances in biomedical research. Here, the authors present xDBiT, a versatile, microfluidics-based approach to cost-effectively measure the spatial transcriptome of multiple tissue sections in parallel.

Obesity is associated with altered N-acylethanolamine levels (NAE). Here the authors show that deletion of the gene encoding N-acylphosphatidylethanolamine phospholipase D, a key enzyme for NAE synthesis, in intestinal cells of mice leads to the development of obesity and hepatic steatosis via a mechanism involving the gut-brain axis.

The authors perform parallel transcriptome sequencing, tRNA qPCR array, ribosome profiling and mass spectrometry across five stages of mouse neocortex development to model the dynamic transcriptome-to-proteome transition, discovering a critical prenatal window during which translational control is predominant.

In this work, the authors report that heparin oligosaccharides have a significant impact on the highly dynamic behaviour of netrin-1 by inducing hierarchical and distinct super assemblies leading to unique, yet unknown netrin-1 filament formation.

Multidrug resistance necessitates novel approaches to treating bacterial infections. Here, the authors apply their high-throughput screening and in silico prediction approaches to show that host receptor tyrosine kinases are good targets for host-directed therapies against intracellular bacteria.

A genetically encoded tension sensor module for measuring molecular forces at 3–5 pN along with tools for multiplexed tension sensing and data analysis reveal an intramolecular tension gradient across talin-1 during cell adhesion.

Two related papers show that cells disseminated from malignant lesions at early time points during tumorigenesis can contribute to metastases at distant organs and provide insights into the molecular basis of dissemination.

The spin direction of a single cobalt atom can be determined and manipulated using a scanning tunnelling microscope.

Patient-derived neuronal models highlight the importance of mitochondrial dysfunction during prolonged action potential firing in the context of the rare metabolic disease methylmalonic aciduria.

Nicole Soranzo and colleagues report a meta-analysis of genome-wide association datasets identifying 22 associations to 8 clinically relevant hematological traits. They also identify a long-range haplotype at 12q24 that includes variants associated with platelet counts as well as coronary artery disease and shows evidence of a selective sweep in Europeans.

Ageing is associated with a pronounced shift in mortality from cancer to degenerative diseases. Here, the authors show that in concordance with this shift, conserved transcriptional alterations during ageing across four vertebrates align with degenerative diseases but are opposite to those in cancer.

Mittasch et al. show that controlling cytoplasmic flow via focused-light-induced cytoplasmic streaming (FLUCS), a non-invasive technique, can be used to invert asymmetric cell division in Caenorhabditis elegans zygotes.

Austen et al. generated talin biosensors to study integrin-based force transduction. They report that extracellular rigidity sensing requires talin’s mechanical engagement and find talin isoform-dependent effects in integrin-mediated mechanosensing.

Tumour mutational burden (TMB), reflecting the number of mutations present in the DNA of a tumour, is a biologically appealing biomarker of a response to immune-checkpoint inhibitors (ICIs). Nonetheless, the clinical predictive value of TMB for ICI response has thus far been mixed, with robust associations seen only for a few ICI-responsive cancer types. In this Review, the authors summarize the available data on TMB and discuss ongoing research efforts to improve the clinical utility of this biomarker.