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An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Alzheimer’s disease has been associated with increased structural brain aging. Here the authors describe a model that predicts brain aging from resting state functional connectivity data, and demonstrate this is accelerated in individuals with pre-clinical familial Alzheimer’s disease.

Design of a two-component protein array enables robust formation of complex large-scale ordered biologically active materials.

Microtubules (MT) form higher-order structures such as asters, but the molecular pathway underlying aster formation remains unclear. Here authors demonstrate that the kinesin-14, HSET, clusters with soluble (nonMT) tubulin via its N-terminal tail domain and thereby promotes MT aster formation.

Serotonin signaling is well known for modulating animal behavior. Here the authors discovered it plays a developmental role in regulating actomyosin contractility driven cellular mechanics and tissue flows during gastrulation of insect and bird.

A small molecule that restores the integrity of the intestinal barrier provides a novel therapeutic strategy for inflammatory bowel diseases.

A. Kemal Topaloglu and colleagues report the identification of mutations in the neurokinin B receptor and its ligand in families with severe congenital gonadotropin deficiency and pubertal failure. These findings indicate that neurokinin B is a central regulator of human gonadal function.

Temporal lobe epilepsy (TLE) can be unresponsive to treatment. Here, the authors show that treatment with D-Serine mitigates TLE and acts on neurons and glia, attenuating neuronal loss and reducing astro- and microgliosis in rodents.

Immune checkpoint blockade (ICB) benefits only a small subset of patients with small cell lung cancer (SCLC) and the mechanisms driving benefit are poorly understood. Here, the authors show that elevated Notch signaling predicts clinical benefit in ICB in relapsed SCLC.

Acetylcholine signaling by the parasympathetic nervous system is crucial for proper insulin release. Alejandro Caicedo and his colleagues now show that such cholinergic signaling in human pancreatic islets is instead locally derived by pancreatic alpha cells—a finding that may have an impact on future drug development to treat diabetes.

Streptococcus dysgalactiae subsp. equisimilis is closely related to Streptococcus pyogenes and colonises the same sites in humans. This study examines cross-species transmission interactions and genetic exchange in a high disease burden setting.

Neuroinflammation is observed in Alzheimer’s disease. Here the authors show that 15 proteins related to inflammation found in CSF can potentially be used as a prognostic biomarker.

Cryo-electron microscopy structures of the bacterial O-antigen ligase WaaL, combined with genetics, biochemistry and molecular dynamics simulations, provide insight into the mechanism by which WaaL catalyses the biosynthesis of lipopolysaccharide.

Information about atmospheric conditions far back in Earth's history is embedded in the isotopic composition of fossil microbes. Such studies are technically demanding, but hold considerable promise.

Mammals detect the nutrient content, palatability and potential toxicity of food through taste buds that are present mainly in the tongue. In this Review, Roper and Chaudhari discuss the taste bud cells, receptors and transmitters that are involved in taste detection, how these cells communicate with sensory afferent fibres, and peripheral taste coding.

Streptococcus dysgalactiae subsp. equisimilis (SDSE) is an emerging cause of human infection closely related to Streptococcus pyogenes. Here the authors investigate the degree of genomic similarity between the two species and assess implications for development of vaccines.

How taste information is encoded and transmitted from the periphery to the cortex is not well understood. Here the authors provide evidence for population-based coding of taste by demonstrating that more than half of individual geniculate ganglion neurons are broadly tuned to basic taste stimuli.

During development, new arteries can arise from pre-existing veins; the cell fate switch involved occurs gradually and before the onset of blood flow in mouse embryo hearts.

Characterization of gustatory neural pathways has suffered due to a lack of molecular markers. Here, the authors report single cell RNA sequencing and unbiased transcriptome analyses to reveal major distinctions between gustatory and somatosensory neurons and subclusters of gustatory neurons with unique molecular and functional profiles.

Vaccination is effective in protecting from COVID-19. Here the authors report immune responses and breakthrough infections in twice-vaccinated patients receiving anti-TNF treatments for inflammatory bowel disease, and find dampened vaccine responses that implicate the need of adapted vaccination schedules for these patients.

Discovery of causal variants for monogenic disorders has been facilitated by whole exome and genome sequencing, but does not provide a diagnosis for all patients. Here, the authors propose a Full Spectrum of Intolerance to Loss-of-Function (FUSIL) categorization that integrates gene essentiality information to aid disease gene discovery.

TGF-β plays a key role in fibrosis. β-catenin is common transcription factor in major TGF-β profibrotic signaling pathways and binds competitively to either TCF or Foxo transcription factors. In human kidney biopsies, the authors found that β-catenin/Foxo interaction was negatively correlated, while that of β-catenin/TCF was positively correlated with kidney fibrosis. They further identified β-catenin/Foxo-dependent protection against TGF-β-induced profibrotic changes in tubular cells and kidney fibrosis.

Azevedo et al. conduct a machine learning-based analysis of structural MRI data from multiple cohorts. The authors identify Alzheimer’s disease-like neuroimaging phenotypes associated with poorer cognitive performance in a healthy UK Biobank cohort, potentially highlighting a population at risk of Alzheimer’s disease.

Bret Moore et al. from the International Mouse Phenotyping Consortium report the identification of 347 mouse genes that influence ocular phenotypes when knocked out. 75% of the identified genes have not previously been associated with any ocular pathology.

Inglese et al. develop a predictive model that computes multi-regional statistical morpho-functional mesoscopic traits from T1-weighted magnetic resonance imaging scans. Their model reliably discriminates people with Alzheimer’s disease-related pathologies from those without.