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Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

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.

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).

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Investigating how proteins acquire specific metals in cells is challenging. Here, the authors use a cyanobacterial Mn^II-cupin (MncA) as a metal trap to test predictions of metalation, and determine metal-preferences by refolding MncA in buffered competing metals.

Brown dwarfs are small stars that are believed to be made of a warm dense plasma that cannot support hydrogen fusion as larger stars do. Here, the authors present a method for studying the properties, such as resistivity, of warm dense plasmas in the laboratory.

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.

Myoglobin is a hemeprotein that reversibly binds oxygen and gives muscle its red color. Here, the authors report a genetic variant in the MB gene that associates with myoglobinopathy, an autosomal dominant progressive myopathy, and altered oxygen binding properties of the mutant protein.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

TGF-β signaling is required for microglial homeostasis, however the source of ligands in the adult brain is unknown. Here, the authors show that microglial homeostasis relies on microglia-derived TGF-β1 ligand via an autocrine mechanism, which is also important for astrocyte homeostasis.

The sensitivities of a set of bacterial metal-sensing transcriptional regulators explain how a protein, such as the cobalt chelatase CbiK, is metalated with its cognate metal in cells rather than mis-metalated with more tightly binding metals.

The connection between metal binding to proteins and availabilities of different metals in cells has been unclear. Here, the authors report a metalation-calculator that takes into account competition between metals and their variable accessibility, and thereby elucidate in vivo metal occupancies of three different proteins, CobW, YeiR and YjiA.

Safely opening university campuses has been a major challenge during the COVID-19 pandemic. Here, the authors describe a program of public health measures employed at a university in the United States which, combined with other non-pharmaceutical interventions, allowed the university to stay open in fall 2020 with limited evidence of transmission.

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

Frontal fibrosing alopecia (FFA) features lichenoid cutaneous inflammation and scarring hair loss. Here, Tziotzios et al. identify four genetic loci associated with FFA by GWAS followed by Bayesian fine-mapping, co-localisation and HLA imputation which highlights HLA-B*07:02 as a risk factor.

Copper is vital to most cells, but too much is lethal. The structure of a protein that pumps copper ions out of the cytosol provides insight into both the pumping mechanism and how certain mutations in the protein cause disease. See Article p.59

The Ni(ii) affinity of Ni(ii) sensor InrS is attuned to buffered Ni(ii) concentrations, explaining why these two parameters co-vary for different metals over many orders of magnitude.

Bacteria possess transcription factors whose DNA-binding activity is altered upon binding to specific metals, but the binding of metals is not specific in vitro. Here, Osman et al. show that tight regulation of buffered intracellular metal concentrations is a prerequisite for metal specificity.

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.

An emerging view is that high-fidelity metal selection by the proteins involved in metal homeostasis is pivotal to ensure that the correct metals bind to nascent metalloproteins. A new study demonstrates that the AztA zinc exporter performs this function by using tandem metal-binding domains to entrap some of the wrong metals in nonproductive complexes.

A genome-wide association study for attention deficit/hyperactivity disorder (ADHD) identifies 12 loci and implicates neurodevelopmental pathways and conserved regions of the genome as being involved in underlying ADHD biology.

Metallothioneins sequester cadmium and surplus atoms of copper and zinc to prevent aberrant metal-catalyzed reactions. The identification of a 'cryptic' copper metallothionein in the bacterium that causes tuberculosis suggests that bacterial metallothioneins may be more widespread than previously suspected.

Metalloproteins constitute up to one-third of the total cellular cohort of proteins, and cells have evolved elaborate mechanisms for scavenging and storing metal atoms. In this Review, the authors summarize the homeostatic mechanisms by which bacteria and archaea ensure that metalloproteins receive and bind the correct metal.

Using whole-genome data for single-nucleotide polymorphism and results from genome-wide association studies, the authors show that people’s preference for pairing with those with similar phenotypic traits has genetic causes and consequences.

Transcriptomic and proteomic profiling of blood samples from individuals with COVID-19 reveals immune cell and hematopoietic progenitor cell alterations that are differentially associated with disease severity.

Past genome-wide associate studies have identified hundreds of genetic loci that influence body size and shape when examined one trait at a time. Here, Jeff and colleagues develop an aggregate score of various body traits, and use meta-analysis to find new loci linked to body shape.

Chassis-independent recombinase-assisted genome engineering (CRAGE) enables the integration of plasmids encoding biosynthetic gene clusters into the chromosomes of diverse bacteria to optimize production of natural products in non-native strains.

Stabilization of DNA quadruplex structures (G4) is lethal for cells with a compromised DNA repair pathway. Here, the authors show that CX-5461, a small molecule in clinical trials as RNA polymerase inhibitor, has G4-stablization properties and can be repurposed to target DNA repair-defective cancers cells.

Exome sequencing and copy number analysis are used to define genomic aberrations in early sporadic pancreatic ductal adenocarcinoma; among the findings are mutations in genes involved in chromatin modification and DNA damage repair, and frequent and diverse somatic aberrations in genes known as embryonic regulators of axon guidance.

This study identifies the most abundant Cu²⁺- and Mn²⁺-containing proteins in the periplasm of a cyanobacterium and determines that the cellular compartment in which each of those proteins fold is responsible for the insertion of the correct metal ion into the metalloprotein.

Ozone depletion has altered conditions at the Earth’s surface and interacts with climate change. This Review assesses the effects on humans and ecosystems, including implications for food and water security, and the mitigating and ongoing influence of the Montreal Protocol.

Analysis of changes in functional groups of species and potential drivers of environmental change for protected areas across the world’s major tropical regions reveals large variation between reserves that have been effective and those experiencing an erosion of biodiversity, and shows that environmental changes immediately outside reserves are nearly as important as those inside in determining their ecological fate.

The structures of three intermediate states of photosystem II, which is crucial for photosynthesis, have been solved at room temperature, shedding new light on this process.

Ammar Al-Chalabi, Jan Veldink and colleagues perform a genome-wide association study for amyotrophic lateral sclerosis (ALS) in 15,156 cases and 26,242 controls. They identify three new genome-wide-significant variants and establish ALS as a complex trait with a polygenic architecture, but with a distinct and important role for low-frequency variants.