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The clonal-selection theory of B- and T-cell development holds that B and T cells have a diverse array of antigen receptors before they ever encounter antigen. Increasingly, though, the idea is taking hold that antigen-specific interactions may, in fact, produce new receptors. Two studies now describe a powerful tool to allow further study of these issues, and the results may help to reconcile previous findings with the clonal-selection theory.

In a broad cross-tissue analysis, the authors show that a receptor called EDA2R steadily increases with age in both humans and animal models, and becomes even more active in conditions like obesity and diabetes, intensifying inflammation-like processes in muscle cells.

The phenotype and function of immune cells could change during spaceflight. Here the authors use simulated microgravity, coupled to validation with spaceflight data, to assess whether there are distinct gene expression changes in resting and TLR 7/8 stimulated PBMCs and found conserved changes in IFN signalling, the cytoskeleton, IL-6 and sirtuin signalling.

This isoform-centric microglia genomic atlas includes 35,879 novel human microglia isoforms identified by long-read RNA sequencing. A multi-ancestry quantitative trait locus meta-analysis of known and novel isoforms in 555 samples from 391 donors finds associations with genetic risk loci in Alzheimer’s and Parkinson’s diseases.

Researchers use extremely non-degenerate photon pairs to achieve two-photon absorption at levels 100-1,000 times that of degenerate two-photon absorption in direct-gap semiconductors. The technique enables the gated detection of sub-bandgap and sub-100-pJ mid-infrared radiation using large-bandgap detectors at room temperature.

Sex differences in fasting glucose and insulin have been identified, but the genetic loci underlying these differences have not. Here, the authors perform a meta-analysis of genome-wide association studies to detect sex-specific and sex-dimorphic loci associated with fasting glucose and insulin.

Strontium isotope analysis can be applied to animal and plant tissues to help determine their provenance. Here, the authors generate a strontium isoscape of sub-Saharan Africa using data from 2266 environmental samples and demonstrate its efficacy by tracing the African roots of individuals from historic slavery contexts.

Currently available platforms to study liver stage of Plasmodium species have limitations. Here, the authors show that primary human hepatocyte cultures in 384-well format support hypnozoite and other liver stage development and are suitable for drug and antibody screens.

A model that predicts the force behaviour for solid/liquid-dielectric multilayer stacks independent of actuator design, and solely based on the material properties, can be used to develop actuators that provide a steady force output under constant-voltage operation.

Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits.

Metastatic castration-resistant prostate cancer is treated with the microtubule-stabilizing drugs taxanes, but resistance ultimately develops. Here Galletti et al.show that ERG, a transcription factor commonly overexpressed in prostate cancers, confers taxane resistance by binding to soluble tubulin.

van Lengerich et al. developed a human TREM2 antibody with a transport vehicle (ATV) that improves brain exposure and biodistribution in mouse models. ATV:TREM2 promotes microglial energetic capacity and metabolism via mitochondrial pathways.

Temporal multi-omic analysis of tissues from rats undergoing up to eight weeks of endurance exercise training reveals widespread shared, tissue-specific and sex-specific changes, including immune, metabolic, stress response and mitochondrial pathways.

Single-cell multiomics can provide broad insights into gene/protein regulatory networks and cellular diversity. Here, authors develop nanoSPLITS, a nanodroplet splitting approach for global profiling of the transcriptome and proteome from same single cells via RNA sequencing and mass spectrometry-based proteomics.

Understanding the pathology in the lungs of patients with COVID-19 might provide clues as to the susceptibility of patients and how the SARS-CoV-2 virus can be fatal. Here the authors analyze cadaveric pulmonary tissue and show one group with high viral load, early death, inflammation and inflammatory damage, and another with low viral load, longer duration of disease, and more M2-like polarization and fibrotic lung damage.

Cyclic-di-GMP is a bacterial second messenger that binds to the regulatory ___domain of ATPases of some bacteria. Here, the authors report the crystal structure of this interaction, identify a cyclic-di-GMP binding mode, and show that this interaction might be important for bacterial biofilm formation.

In a phase 2 randomized control trial, intermittent senolytic therapy administered to postmenopausal women did not result in a reduction in the bone resorption marker, serum CTx, compared to control at 20 weeks.

It is known that exercise influences many human traits, but not which tissues and genes are most important. This study connects transcriptome data collected across 15 tissues during exercise training in rats as part of the Molecular Transducers of Physical Activity Consortium with human data to identify traits with similar tissue specific gene expression signatures to exercise.

Coherent noise affecting a random error correcting code is now shown to produce a transition between phases that accumulate and destroy magic.

Chromodomain Helicase DNA-binding (CHD) proteins have been implicated in neurodevelopmental processes. Here, the authors identify missense variants in CHD3 that disturb its chromatin remodeling activities and cause a neurodevelopmental disorder with macrocephaly and speech and language impairment.

Fluid shear stress plays a critical role in receptor-mediated signalling and has been shown to sensitize cancer cells to apoptosis. Here, Mitchellet al. introduce polymer micro- and nanoparticles tethered to tumour cells to amplify fluid shear stress effects, and find that they can enhance immune cytokine-mediated apoptosis of tumour cells in vitro and in vivo.

HIV vaccine development will be facilitated by having animal models that are predictive for translation to humans. Here, the authors use two nonhuman primate models to compare the effects of natural infection and different adjuvants on antigen persistence, diversity and humoral immunity.

Thousands of recombinant antibodies enriched for specificity against defined targets are assembled in multivalent mixtures with enhanced therapeutic activity.

Analysis of dendrite initiation, owing to filling of pores with lithium by means of microcracks, and propagation, caused by wedge opening, shows that there are two separate processes during dendrite failure of lithium metal solid-state batteries.

Technical challenges have previously hindered the detailed study of in vivo senescent cells. Here, the authors deeply characterize senescent skeletal cells across murine aging, establishing CD24 as a marker of osteolineage cells cleared by senolytics.

Identification of senescent cells in vivo remains a challenging task. Here the authors present and validate a senescence gene set called SenMayo enriched in human and murine aged tissues.

Reactivation of latent SIV with an IAP antagonist, coupled with immunotherapeutic approaches, reduced replication-competent SIV in lymph node CD4⁺ T cells in rhesus macaques. Further exploration targeting these pathways to reduce the HIV viral reservoir is warranted.

Multiomics analysis of right colon tissues identifies a distinct immune gene signature associated with greater risk of and shorter time to dysplasia in patients with primary sclerosing cholangitis, but not in patients with inflammatory bowel disease.

Cathy Laurie and colleagues detect mosaicism for large chromosomal abnormalities in peripheral blood in a subset of healthy individuals. They show that the frequency of such events increases with age and is associated with elevated risk of developing a subsequent hematological cancer.

Polymers are ubiquitous in batteries as binders, separators, electrolytes and electrode coatings. In this Review, we discuss the principles underlying the design of polymers with advanced functionalities to enable progress in battery engineering, with a specific focus on silicon, lithium-metal and sulfur battery chemistries.