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Citizen science taps the efforts of non-experts. Here, authors describe Drugit, an extension of the crowdsourcing game Foldit, and its use in designing a non-peptide binder of Von Hippel Lindau E3 ligase for use with proteolysis targeting chimeras.

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.

Nature's speciality is to direct and control the reactivity of species, which are otherwise fatally destructive. However, the processes and design rules required to achieve such precise control are not clear. A de novo designed metalloprotein that stabilizes an otherwise unstable organic radical has now been developed to guide our understanding.

In a mouse model, maternal obesity during pregnancy can lead to fatty liver disease in the offspring, driven by aberrant developmental programming of Kuppfer cells.

Neonates are thought to have impaired immune responses, yet, paradoxically, they can also demonstrate hyperinflammation. Ulas et al. show that a neonatal burst of the alarmins S100A8 and S100A9 activates a distinct innate immune response without dangerous hyperinflammation.

Neonatal immune responses are known to differ to those of an adult immune response. Here Dreschers and colleagues, compare macrophage populations derived from cord blood or adult peripheral blood and show a metabolic impairment of glycolysis in macrophages derived from cord blood which may impair response to infective scenarios such as sepsis.

A randomized crossover trial showed that transition to a Western diet resulted in pro-inflammatory changes, whereas transition to an African heritage diet rich in fruits and vegetables, legumes and fermented products led to opposite effects.

Metabolic processes may be different in immune cells between neonates and adults. Here the authors measure metabolic changes in human monocytes from different aged donors and find enhanced oxidative phosphorylation fueling myeloid differentiation in neonates which contrasts glycolytic responses in early childhood and more effective inflammatory response.

It is unclear if early pathological changes in normal-appearing multiple sclerosis (MS) tissue are reflected by molecular changes in microglia, which might contribute to lesion initiation. Here, authors demonstrate significant intrinsic differences in the human microglial transcriptome between grey and white matter regions, isolated from MS and non-neurological control donors, and show early microglial changes related to MS pathology.

Swarm Learning is a decentralized machine learning approach that outperforms classifiers developed at individual sites for COVID-19 and other diseases while preserving confidentiality and privacy.

The next step after sequencing a genome is to figure out how the cell actually uses it as an instruction manual. A large international consortium has examined 1% of the genome for what part is transcribed, where proteins are bound, what the chromatin structure looks like, and how the sequence compares to that of other organisms.

Chest CT is emerging as a valuable diagnostic tool for clinical management of COVID-19 associated lung disease. Here, the authors present a multinational study on the application of deep learning algorithms for COVID-19 diagnosis against multiple lung conditions as controls.

Peripheral stimuli can induce acute immune training and tolerance in the brain and lead to long-lasting epigenetic reprogramming of microglia; these changes alter pathology in mouse models of stroke and Alzheimer’s pathology .

Duy and Weise et al. combined human functional integrative genomics with mouse experimental biology to reveal a neuroprogenitor-based genetic subtype of human hydrocephalus with defective neurogenesis and altered brain–fluid biomechanics.

Rapid urbanization can be associated with adverse health implications. de Mast and colleagues compare urban and rural Tanzanian populations using multi-omics and observe that urbanization is associated with an elevated but reversible inflammatory state.

Synthetic embryo models have arisen as an approach to probe early development in vitro, facilitating the study of difficult to access stages. Here the authors present a simple system for generating embryo-like structures that resemble peri-implantation mouse embryos.

Within a human cohort, wide variation can occur with constitutively expressed proteins. Aschenbrenner and colleagues found that individuals with lower CRELD1 expression have decreased frequencies of naive CD4⁺ T cells. Mice with conditional Creld1 deficiency also exhibit a phenotype associated with immunological aging.

The authors establish inducible Cxcr4-CreER-based fate mapping as a universal means to identify bone-marrow-derived myeloid cells in the injured brain and demonstrate that Cxcr4 deficiency affects the innate immune response and outcome after stroke.

Salvagno et al. demonstrated that blocking tumour-associated macrophages in breast cancer enhances the efficacy of chemotherapeutics by promoting intratumoural type I interferon responses.

Microorganisms from the terrestrial subsurface are understudied. Here, Anantharamanet al. analyse aquifer sediments and groundwater by genome-resolved metagenomics and reconstruct 2,540 genomes representing the majority of known bacterial phyla as well as 47 new phylum-level lineages.

High-density lipoprotein (HDL) has beneficial effects in coronary artery disease. Latz and colleagues show that HDL's benefits stem at least in part by activating an anti-inflammatory program dependent on the transcription factor ATF3.

The explosion of single-cell and systems approaches in immunology risks leaving the uninitiated behind. This guide to systems immunology is designed for immunologists who want an introduction to the area.

Christina Warinner and colleagues report a high-resolution characterization of the oral microbiome isolated from the dental tissues of adult skeletons dating to 1100 CE and showing evidence of periodontal disease. They show the long-term carriage of a diverse range of opportunistic pathogens in the oral cavity and reconstruct the genome of the periodontal pathogen Tannerella forsythia.

In mice aged 12–18 months, chronic administration of low-dose Δ⁹-tetrahydrocannabinol (THC) improves performance in behavioral learning and memory tasks, whereas a similar administration in younger mice (aged 2 months) impairs performance.

Reduction in key air pollutants, especially particulate carbon, can help mitigate Arctic warming with associated benefits for global climate and human health, according to Earth system model simulations under future emissions scenarios.