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Computationally designed TRI2-2 miniprotein inhibitor broadly neutralizes multiple SARS-CoV-2 Omicron variants and confers post-exposure protection in mice against BQ.1.1, XBB.1.5, and BA.2.86 challenge when administered intranasally.

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).

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

Amateur and professional astronomers share with Nature what they observed and what data they collected when the Moon blocked the Sun.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Jayavelu, Samaha et al., apply machine learning models on hospital admission data, including antibody titers and viral load, to identify patients at high risk for Long COVID. Low antibody levels, high viral loads, chronic diseases, and female sex are key predictors, supporting early, targeted interventions.

By coupling robotic cell culture systems with artificial intelligence–powered image analysis, Schiff et al. identify previously unseen characteristics of Parkinson’s disease in patient skin cells that distinguish them from healthy controls.

Alterations in the tumour suppressor genes STK11 and/or KEAP1 can identify patients with advanced non-small-cell lung cancer who are likely to benefit from combinations of PD-(L)1 and CTLA4 immune checkpoint inhibitors added to chemotherapy.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Showdown over Trump’s border-wall plan could bring key agencies to a halt.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

Immune receptors regulate immune responses and are key cancer immunotherapy targets. Here, the authors designed helical concave scaffolds to bind convex sites in immune receptors, creating high-affinity protein binders for TGFβRII, CTLA-4, and PD-L1. Co-crystal structures confirmed their therapeutic potential.

Computationally designed genetically encoded proteins can be used to target surface proteins, thereby triggering endocytosis and subsequent intracellular degradation, activating signalling or increasing cellular uptake in specific tissues.

Post-acute sequelae of SARS-CoV-2 (PASC) is still not well understood. Here the authors provide patient reported outcomes from 590 hospitalized COVID-19 patients and show association of PASC with higher respiratory SARS-CoV-2 load and circulating antibody titers, and in some an elevation in circulating fibroblast growth factor 21.

Solid organ transplant recipients are at increased risk of infectious disease and have unique molecular pathophysiology. Here the authors use host-microbe profiling to assess SARS-CoV-2 infection and immunity in solid organ transplant recipients, showing enhanced viral abundance, impaired clearance, and increased expression of innate immunity genes.

There is little question that supplemental fluoride strengthens teeth and reduces decay. But at what cost?

Exposure to volatile chemical products happens during or in the vicinity of product use and through ambient air; the latter pathway is neglected in exposure estimates. This study shows that both pathways should be considered in efforts to develop safer and more sustainable products and to achieve cleaner air.

The role of IgG glycosylation in the immune response has been studied, but less is known about IgM glycosylation. Here the authors characterize glycosylation of SARS-CoV-2 spike specific IgM and show that it correlates with COVID-19 severity and affects complement deposition.

Fluorescent protein reporters based on GFP exist, but have intrinsic disadvantages. Here the authors incorporate pH, Ca²⁺ and protein–protein interaction sensing modalities into de novo designed mini-fluorescence-activating proteins (mFAPs), with increased photostability and smaller size, which bind a range of DFHBI chromophore variants.

Hetero-oligomeric proteins offer many advantages for bioengineering efforts but are difficult to make from scratch. Here, authors present a simple method for creating pseudosymmetric hetero-oligomers from input symmetrical proteins.

The elucidation of general principles for designing β-barrels enables the de novo creation of fluorescent proteins.

A case–control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.

The assumption that boron concentration is a conservative property in seawater may not hold in polar seas where there is sea ice formation, ice melt and brine release, according to an analysis of Arctic brines, snow and sea ice samples.

The authors show PTEN mutations, which can cause both congenital hydrocephalus and autism spectrum disorder, disrupt CSF homeostasis and brain connectivity in mice. Reducing mTORC1 activation ameliorates ventricular enlargement and neuronal deficits.

Here, the authors computationally designed and produced small protein antagonists to target IL-6 and IL-1β signaling to develop modulators of CRS.

Jiang et al. developed a computational method to design repeat proteins with multiple structured loops that are buttressed by extensive hydrogen bond networks. The designs were further functionalized into high-affinity peptide-binding proteins.

Here, the authors constructed a deep-learning approach to design closed repeat proteins with central binding pockets—a step towards designing proteins to specifically bind small molecules.

The GREGoR consortium provides foundational resources and substrates for the future of rare disease genomics.

Here, the authors use computational screening and a chemogenetic analysis of transgenic mice to show that Gα_s-coupled G-protein-coupled receptors on exhausted CD8⁺ T cells are involved in suppression of effector functions and inhibition of the protective effects of immune checkpoint immunotherapy.

A deep-learning-based strategy is used to design artificial luciferases that catalyse the oxidative chemiluminescence of diphenylterazine with high substrate specificity and catalytic efficiency.

In this work the authors provide a computational workflow for the parallel, from scratch, design of proteins to rapidly explore the shape diversity of protein folds.

Multisystem inflammatory syndrome in children (MIS-C) is a rare complication of SARS-CoV-2 infection that can result in serious illness in the paediatric population but our understanding of this syndrome is in its infancy. Translational studies in 2020 leveraging immune profiling have laid the foundation to enable further discovery in MIS-C.

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus with unclear immune cell involvement. Here the authors generate a single cell transcriptomic dataset with 400k cells from the esophageal mucosa of active EoE patients, remission EoE patients, and healthy individuals to characterise esophageal cellular composition, phenotype and interaction in this disease.

SARS-CoV-2 induces mild infection in ferret model. Here, Ryan et al. characterise optimal infection dosage inducing upper respiratory tract (UTR) viral shedding, progression time of viral shedding, and pathology in ferrets and finally provide evidence for protection after re-challenge.

Trials in rhesus macaques show that a subunit vaccine against SARS-CoV-2, comprising the spike protein receptor-binding domain displayed on a nanoparticle protein scaffold, produces a robust protective response against the virus.

The trRosetta neural network was used to iteratively optimise model proteins from random 100-amino-acid sequences, resulting in ‘hallucinated’ proteins, which when expressed in bacteria closely resembled the model structures.

Matthew Meyerson and colleagues report whole-exome and whole-genome sequencing of 55 small intestine neuroendocrine tumors. They identify recurrent somatic mutations in CDKN1B, implicating cell cycle dysregulation in the pathogenesis of these tumors.

Whole-genome sequencing of 25 metastatic melanomas and matched germline DNA in humans reveals that the highest mutation load is associated with chronic sun exposure, and that the PREX2 gene is mutated in approximately 14 per cent of cases

Molecular systems with coincident cyclic and superhelical symmetry axes have considerable advantages for materials design as they can be lengthened or shortened by changing the length of the monomers. Now a systematic approach to generate modular repeat protein oligomers with combined symmetry that can be extended by repeat propagation has been developed.

Roy et al. describe a generalized method for computationally designing miniproteins selective for a single integrin heterodimer and conformational state. The designed αvβ6 inhibitor remains monomeric and maintains biological activity following aerosolization and shows excellent efficacy in bleomycin induced lung fibrosis.

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.

COVID-19 disease is less common in children than adults, but the extent to which SARS-CoV-2 infections are missed through symptom-driven testing is not well understood. In this study, the authors show that approximately 1% of children seeking care for reasons other than COVID-19 at a Seattle hospital in March/April 2020 were seropositive for SARS-CoV-2.

A hyper-stable de novo protein mimic of interleukin-2 computationally designed to not interact with a regulatory T-cell specific receptor subunit has improved therapeutic activity in mouse models of melanoma and colon cancer.