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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).

Development of a generalized method for dual site-specific incorporation of nonnatural photocaged and photoreactive amino acids into proteins expressed in live cells enabled engineering of a photoreactive photoactive antibody fragment.

Phage genomes are readily engineered using retron recombineering.

Genome editing tools are developed through large-scale characterization of bacterial retrons.

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.

m⁶A modifications are measured in living cells with a fluorescent reporter.

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.

SUGAR-TARGET is a modular platform for the homogeneous synthesis of enzymes with controlled N-linked glycosylation using a one-step immobilization/purification method.

The sodium salts in corn stover hydrolysates have been identified as important inhibitors for cellulosic ethanol production. Adaptive evolution generated a robust yeast that converted both glucose and xylose into biofuel. Subsequent reverse engineering created a genetically defined yeast with equivalent performance to the evolved strain.

Neurons are subjected to strains due to body movements and their locations within organs and tissues. Here the authors show that UNC-70/β-spectrin and TBC-10 dynamically maintain attachment of the axon within the epidermis non-cell-autonomously by stabilizing hemidesmosome attachment, preventing axon degeneration.

Pathogenic variants of DDX3X are associated with neurodevelopmental disorders (NDD) and cancer. Here, the authors perform saturation genome editing of DDX3X to test the functional impact of 12,776 variants, develop a machine learning classifier to identify variants relevant for NDD, and show that DDX3X predominantly acts as a tumour suppressor in cancer.

Engineering of a bacterial-derived retron system enhances production of reverse-transcribed DNA for genome-editing applications in bacteria, yeast and human cells.

Microbial production of aromatic amino acid (AAA)-derived chemicals remains an outstanding metabolic engineering challenge. Here, the authors engineer baker’s yeast for high levels p-coumaric acid production by rewiring the central carbon metabolism and channeling more flux to the AAA biosynthetic pathway.

Whole-genome sequencing and phenotype data sharing are introduced in a national health system to streamline diagnosis and to discover coding and non-coding variants that cause rare diseases.

Circular RNAs are exported from the nucleus by Ran-GTP, exportin-2 and IGF2BP1 in a mechanism analogous to protein export rather than mRNA export.

Whole-genome sequencing of chronic lymphocytic leukemia from 485 patients identifies putative coding and noncoding drivers of disease. Genomically defined subgroups show distinct clinical and biological characteristics.

Circular RNAs can contribute to tumour progression. Here the authors show that two circular RNAs, circCsnk1g3 and circAnkib1 promote sarcoma growth by controlling the expression of interferon related genes and pro-inflammatory factors in sarcoma cells

A survey of the CD4⁺ T cells in human melanomas indicates that immune evasion is mediated through direct stimulation of neoantigen-specific tumour-reactive regulatory T cells by HLA class II-positive melanoma cells.

Analyses of expression profiles from whole blood of 31,684 individuals identify cis-expression quantitative trait loci (eQTL) effects for 88% of genes and trans-eQTL effects for 37% of trait-associated variants.

Burrows, Denckla and colleagues performed a systematic review to evaluate the available evidence linking climate change to mental health outcomes.

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.

Chromodomain Helicase DNA-binding (CHD) proteins have been implicated in neurodevelopmental processes. Here, the authors identify missense variants in CHD3 that disturb its chromatin remodeling activities and cause a neurodevelopmental disorder with macrocephaly and speech and language impairment.

This is an issue edsumm for ng1939. Identification of the Palaeocene/Eocene thermal maximum in a marine sedimentary sequence. It shows that sea surface temperatures near the North Pole increased from roughly 18 degrees Celsius to over 23 degrees Celsius — such warm values imply the absence of ice and thus exclude the influence of ice-albedo feedbacks on this Arctic warming.

Stig Bojesen, Georgia Chenevix-Trench, Alison Dunning and colleagues report common variants at the TERT-CLPTM1L locus associated with mean telomere length measured in whole blood. They also identify associations at this locus to breast or ovarian cancer susceptibility and report functional studies in breast and ovarian cancer tissue and cell lines.

Hesitancy and resistance towards vaccination is a challenge for public health. Here the authors determine psychological characteristics associated with COVID-19 vaccine hesitancy or resistance attitudes in the UK and Ireland.

Gain-of-function mutations altering the PWWP ___domain of DNMT3A are identified as a new cause of microcephalic dwarfism. These mutations abrogate DNMT3A binding to H3K36me2 and H3K36me3 and lead to aberrant DNA methylation of Polycomb-marked regions.

In-depth interviews are a versatile form of qualitative data collection used by researchers across the social sciences. In this Primer, Knott et al. describe the stages and challenges involved in designing and conducting interviews, how to analyse the data and strategies to overcome challenges.

The ATLAS Collaboration reports the observation of the electroweak production of two jets and a Z-boson pair. This process is related to vector-boson scattering and allows the nature of electroweak symmetry breaking to be probed.

The measurement of the total cross-section of proton–proton collisions is of fundamental importance for particle physics. Here, the first measurement of the inelastic cross-section is presented for proton–proton collisions at an energy of 7 teraelectronvolts using the ATLAS detector at the Large Hadron Collider.

The ATLAS Collaboration reports a measurement of the ratio of the decay rates of W bosons to τ leptons and muons, in agreement with universal lepton couplings as postulated in the standard model of particle physics.

Cortical thickness is asymmetric, and cortical thinning occurs with age and in disease. Here the authors investigate if both cortices thin at the same rate or if the thicker hemisphere declines faster in aging and in Alzheimer’s disease.

The ATLAS experiment at the Large Hadron Collider reports a search for charged-lepton-flavour violation in decays of Z bosons into a τ lepton and an electron or muon of opposite charge.

Despite the identification of genetic risk loci for late-onset Alzheimer’s disease (LOAD), the genetic architecture and prediction remains unclear. Here, the authors use genetic risk scores for prediction of LOAD across three datasets and show evidence suggesting oligogenic variant architecture for this disease.

Quantum electrodynamics predicts a rare process in which light is scattered by light. The ATLAS Collaboration reports signs of this elusive effect in the collisions of ultra-relativistic lead ions.

As phase 1 of the Earth Microbiome Project, analysis of 16S ribosomal RNA sequences from more than 27,000 environmental samples delivers a global picture of the basic structure and drivers of microbial distribution.