Search

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).

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.

OSM is an IL-6 family cytokine that can signal via type I receptor complex (OSM/gp130/LIFR) or type I receptor complex (OSM/gp130/OSMR). Here, the authors report cryo-EM structures of the two types of OSM receptor complexes and provide insights for modulation of OSM signaling in therapeutics.

Landward barrier migration facilitates erosion of shoreface-exposed marsh and lagoon carbon stocks at rates outpacing backbarrier carbon accumulation, thus demonstrating the ephemeral nature of blue carbon storage along transgressive coasts.

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.

Here, cryo-electron microscopy structures reveal how the chemokine receptor CXCR4 oligomerizes and how it is regulated by its physiological ligand CXCL12, the small-molecule drug AMD3100 and the monoclonal antibody REGN7663.

The ecological importance of microclimate variation is increasingly recognized. This Perspective discusses the extent to which favourable microclimates (in other words, areas with temperature and precipitation within the niche of a species) can facilitate adaptation, plasticity, colonization of new patches and, ultimately, persistence under global change.

TDP-43 gains function due to perturbed autoregulation in a Tardbp knock-in mouse model of ALS-FTD, leading to aberrant Mapt splicing and a paucity of parvalbumin interneurons. Phenotypic heterogeneity is exploited to yield modifiers of disease.

Mucopolysaccharidosis type I (MPSI) is a lysosomal storage disease caused by insufficient iduronidase (IDUA) activity. Here, the authors use an ex vivo genome editing approach to overexpress IDUA in human hematopoietic stem and progenitor cells and show it can phenotypically correct MSPI in mouse model.

Wireless miniaturized implantable temperature sensors enable real-time monitoring of the progression of inflammatory bowel diseases, as shown in a mouse model of Crohn’s-disease-like ileitis.

Understanding the mode of small-molecule binding to amyloid filaments is critical for diagnosing and treating neurodegeneration. The authors use cryo-EM to reveal a stacked binding motif which may hasten design of diagnostics and therapeutics.

Streptomyces bacteria undergo two modes of cell division: formation of cross-walls in hyphae, leading to multicellular compartments, and septation for release of unicellular spores. Here, Bush et al. identify a protein that is important for both cell division modes in Streptomyces, likely by contributing to stabilization of the divisome.

Interleukin-17A homodimers preferentially interact with heterodimeric IL-17 receptors. By solving the crystal structure of an IL-17A homodimer in complex with a single IL-17RA receptor subunit, the authors reveal conformational changes in IL-17A that lead to exclusion of a second IL-17RA subunit.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

Cell seeding on scaffolds for regenerative tissue engineering presents a regulatory and manufacturing hurdle. Here, the authors report on the development of a cell free conductive scaffold which can support tissue regeneration without cell seeding, demonstrating application in bladder repair.

Ribofuranose residues are installed on O-antigens of bacterial polysaccharides by a dual-activity enzyme that uses phosphoribosyl-5-phospho-d-ribosyl-α-1-diphosphate as a sugar donor and also catalyzes phosphate hydrolysis.

The AKAP79 scaffold protein couples plasma membrane Ca²⁺ influx in neurons to activation of calcineurin, which in turn activates NFAT. Analysis of this interaction shows that AKAP79 and NFAT bind the same interface on calcineurin, but the affinity of the calcineurin-AKAP79 interaction is finely balanced to promote calcineurin recruitment to the scaffold while still allowing calcineurin release for NFAT activation.

Computational design incorporating modular buried hydrogen networks produces highly orthogonal protein heterodimers.

Circulating tumour DNA profiling in early-stage non-small-cell lung cancer can be used to track single-nucleotide variants in plasma to predict lung cancer relapse and identify tumour subclones involved in the metastatic process.

Structural genomics and binding studies show that a cyclic peptide produced by Streptomyces griseus, griselimycin, exhibits high binding selectivity for diverse DNA polymerase binding sites of various infectious Gram-negative bacteria.

RNA sequencing data and tumour pathology observations of non-small-cell lung cancers indicate that the immune cell microenvironment exerts strong evolutionary selection pressures that shape the immune-evasion capacity of tumours.

Primary biliary cirrhosis is an autoimmune liver disease with poor therapeutic options. Here Cordell et al. a perform meta-analysis of European genome-wide association studies identifying six novel risk loci and a number of potential therapeutic pathways.

Genomic and phenomic screens of 827 wheat landraces from the A. E. Watkins collection provide insight into the wheat population genetic background, unlocking many agronomic traits and revealing haplotypes that could potentially be used to improve modern wheat cultivars.

Hydrogen evolution technologies for a future carbon-free energy economy require efficient catalysts which can be implemented on a large scale. Here, the authors prepare a composite electrode from readily available elements, whereby a metal-organic framework boosts catalytic performance by enabling rapid proton transport.

Oxycodone withdrawal triggered distinct transcriptomic changes in the ventral tegmental area, nucleus accumbens and medial prefrontal cortex in mice with and without chronic pain, with histone deacetylase 1 (HDAC1) as a common upstream regulator. A novel HDAC1/HDAC2 inhibitor reduced behavioral manifestations of oxycodone withdrawal.

Wu et al. utilize multiparametric analysis of early-stage human NSCLC to characterize a population of Vδ1 T cells displaying a resident memory and effector memory phenotype, which were associated with ongoing remission.

A robust, cost-effective technique based on whole-exome sequencing data can be used to characterize immune infiltrates, relate the extent of these infiltrates to somatic changes in tumours, and enables prediction of tumour responses to immune checkpoint inhibition therapy.

A survey of T cell repertoire evolution in the tumors, healthy tissue and blood of patients with early-stage untreated lung cancer offers an opportunity to monitor and identify neoantigen-specific T cells for personalized immunotherapy.

Poor material biocompatibility of implanted medical devices endangers patient safety and impairs device functionality. Here, durable zwitterion grafts attached onto polymeric surfaces via plasma functionalization lead to superhydrophilic materials for safer and more durable devices.

Atmospheric warming may reduce CO₂ emissions from hardwater lakes by reducing the duration of ice cover, increasing lake water pH and favouring CO₂ sequestration.

TRACERx Lung: Intratumoral transcriptional heterogeneity, which often hinders the development of clinically useful RNA-expression-biased biomarkers for cancer, can now be overcome with an approach for the identification of clonal expression biomarkers.

In this Review, Chan and colleagues discuss the need for improved management options for hypospadias and describe advances in urethral tissue engineering and barriers to clinical application of tissue-engineered constructs in hypospadias repair.