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A cross-reactive antibody and T cell response is identified in a large portion of patients with multisystem inflammatory syndrome in children.

A combination of palaeoclimate proxies and simulations shows that a common mechanism controls El Niño variation in cold and warm states, which supports expectations of more extreme El Niño occurrence in the future.

Human norovirus pathogenesis is incompletely understood due to a lack of appropriate animal disease models. Here, Green et al. show norovirus replication in chromogranin A-positive enteroendocrine cells and other epithelial cells in tissue from a pediatric intestinal transplant recipient with severe gastroenteritis.

Implantation of lung tissue into humanized mice enables in vivo study of the human immune response to pathogens.

How folded proteins are translocated across membranes is unknown for eukaryotes. Here, the authors propose a concerted translocation mechanism used by the AAA-ATPase Bcs1 to retro-translocate fully folded Rieske iron-sulfur protein across mitochondrial inner membrane.

Artificial self-assembling systems such as anion receptors or ‘binders’ are largely unexplored for therapeutic applications. Here, the authors report self-assembling trimetallic cryptands containing copper, zinc or manganese that encapsulate a range of anions, are highly toxic to human cancer cell lines and show metal-dependent selectivity towards cancer vs. healthy cells linked to the selective inhibition of multiple kinases.

Anti-CTLA4 therapy has not been comprehensively explored for the treatment of metastatic renal cell carcinoma (mRCC). Here, in a pilot study of anti-CTLA4 therapy with or without cryoablation in mRCC, the authors report that the combination is feasible and enhances immune infiltration in patients with metastatic clear cell histology.

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.

Quantum dots with different size emit light at different wavelengths but also different brightness, which complicates analysis of fluorescence images. Here, the authors synthesize multicolour brightness-equalized quantum dots by controlling the composition and structure of core-shell HgCdSeS-CdZnS nanocrystals.

It is unclear why certain tissues are more susceptible to the consequences of aneuploidy. Here, in Drosophila, Gogendeau et al.identify aneuploidy as the cause of lengthened G1 and premature differentiation in both neural and adult intestinal stem cells, which prevents cells with abnormal genomes from cycling.

The authors determined high-resolution cryo-EM structures of the lentiviral intasome — the nucleoprotein complex that inserts viral DNA into a host chromosome — and show that the architecture comprising 16 integrase subunits is critical for its function.

Bacteria and archaea use tripartite ATP-independent periplasmic (TRAP) transporters to import essential nutrients. Davies et al. report a high resolution structure of a TRAP and show that it uses an ‘elevator-with-an operator’ mechanism.

An initial draft of the human pangenome is presented and made publicly available by the Human Pangenome Reference Consortium; the draft contains 94 de novo haplotype assemblies from 47 ancestrally diverse individuals.

Psoriasis is a partially heritable skin disorder, the genetic basis of which is not fully understood. Here, the authors use genome-wide association meta-analysis to discover psoriasis susceptibility loci and genes, which encode existing and potential new drug targets.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

ATE1 is a highly specific enzyme hijacking tRNA from ribosomal pathways to install an arginine onto proteins as a post-translational modification. Here, the authors describe the structures of yeast ATE1 with or without its tRNA cofactor. ATE1 recognizes and selects tRNA in a unique mechanism.

Risk of isolation is expected to disproportionately affect racial minority populations in the U.S. as sea level rise increases. Communities with more renters, older adults, and lower-income populations will also be impacted.

There is a need for development of efficient delivery vehicles for the treatment of inherited retinal degeneration with gene therapy. Here, Gautam et al., show that surface modifications of lipid nanoparticles with PEG variants alters their cellular tropism allowing gene editing in diverse retinal cell types in mice.

Rocks and dust from the asteroid Bennu contain some of the molecular building blocks of life on Earth, such as amino acids and nucleobases. They also carry ammonia that formed billions of years ago in cold, distant regions of our Solar System.

A phase I trial of a neoantigen-targeting personalized cancer vaccine led to durable and polyfunctional T cell responses and antitumour recognition, and was associated with no recurrence in patients with high-risk clear cell renal cell carcinoma.

Whipworms are large parasites causing chronic disease in humans and other mammals. Here, the authors show how larvae create tunnels inside the gut lining and reveal the early host response to infection via Isg15 in mice and murine caecaloids.

Raman and fluorescence spectra, consistent with several species of aromatic organic molecules, are reported in the Crater Floor sequences of Jezero crater, Mars, suggesting multiple mechanisms of organic synthesis, transport, or preservation.

Necroptosis is a regulated form of inflammatory cell death driven by activated MLKL. Here, the authors identify a mutation in the brace region that confers constitutive activation, leading to lethal inflammation in homozygous mutant mice and providing insight into human mutations in this region.

Here, the authors describe an early synziphosurine from the Lower Ordovician Fezouata Shale of Morocco, which exhibits traits that elucidate the long-contentious relationships between crown euchelicerates and their sister taxa, and also clarifies euchelicerate body plan evolution.

Neutrophils employ several mechanisms to control the growth of fungi, including enzymes, reactive oxygen species, extracellular traps, and formation of “swarms”. Here, Hopke et al. study how the different mechanisms work together, using an in vitro assay with human neutrophils and clusters of live Candida cells.

Lee et al. identify SHMT and one-carbon metabolism as a metabolic vulnerability conferred by LKB1 and KEAP1 loss in KRAS-mutant lung cancer.

Binding-activated optical sensors are powerful tools, but their development can be slow and laborious. Here, authors introduce a platform to expedite biosensor discovery and evolution using genetically encodable fluorogenic amino acids.

In this immunological ancillary study of the PREVAC trial, the authors show that approved Ebola virus vaccines induce memory T-cell responses that persist during the five year follow-up after initial vaccination.

Pancreatic ductal carcinoma (PDAC) is characterized by an immunosuppressive tumor microenvironment (TME) enriched in stromal cells. Here the authors show that TSG-6-positive cancer associated fibroblasts modulate myeloid cell responses and that TSG-6 targeting improves response to immune checkpoint inhibitors in preclinical PDAC models.

Ongoing hydrogen loss from two sibling exoplanets provides support for the role of such hydrogen loss in the evolution of close-orbiting sub-Neptunes.

A design pipeline is presented whereby binding proteins can be designed de novo without the need for prior information on binding hotspots or fragments from structures of complexes with binding partners.

It is thought that polyphenols inhibit organic matter decomposition in soils devoid of oxygen. Here the authors use metabolomics and genome-resolved metaproteomics to provide experimental evidence of polyphenol biodegradation and maintained soil microbial community metabolism despite anoxia.

Spatial metabolomics are used to describe the location and chemistry of small molecules involved in metabolic phenotypes. Here, Conroy et al. present a bioinformatic pipeline to analyze MALDI data and show that it can be used to identify actionable targets such as glycogen in fibrotic lungs of both human and mice.

The contribution of transposable elements and endogenous retroviruses to renal fibroinflammation is currently unknown. Here, the authors comprehensively profile the expression of transposable elements and endogenous retroviruses (ERVs) in kidneys of patients and mouse disease models and find expression of ERVs in diseased kidneys activate cytosolic nucleotide sensors contributing to cytokine release and renal fibroinflammation.

An international conference about gentrification gathered scholars, activists and practitioners to discuss urban changes worldwide that are displacing poorer residents to develop upscale areas.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

A rare case of asymptomatic dominantly inherited Alzheimer’s reveals confined tau pathology and unique proteomic features, highlighting potential resilience mechanisms decades beyond expected onset.

A study comparing the pattern of single-nucleotide variation between unique and duplicated regions of the human genome shows that mutation rate and interlocus gene conversion are elevated in duplicated regions.

Analysis of genomes, epigenomes and transcriptomes of developing sea urchins with divergent life histories shows how natural selection can reshape developmental gene regulatory networks.

Drug resistance to current antimalarials is rising and new drugs and targets are urgently needed. Here the authors identify Plasmodium falciparum acyl-CoA synthetase 10 as a new target whose inhibition leads to a decrease in triacylglycerols.

Luan et al. find that CTCF shapes the transcriptional landscape in part by suppressing the initiation of upstream antisense transcription at hundreds of divergent gene promoters.

If the activity of genetically specified neurons is silenced in a temporally precise fashion, the roles of different cell classes in neural processes can be studied. Members of the class of light-driven outward proton pumps are now shown to mediate powerful, safe, multiple-colour silencing of neural activity. The gene archaerhodopsin-3 (Arch) enables near 100% silencing of neurons in the awake brain when virally expressed in the mouse cortex and illuminated with yellow light.

The authors find that mice fed a diet with reduced levels of branched-chain amino acids have improved metabolic health, and in males but not females, lifelong feeding of such a diet reduces frailty and extends life span.