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Polyamines prevent the action of kinases on acidic phosphorylatable motifs in spliceosomal proteins, thus providing a mechanism for metabolite-mediated regulation of alternative splicing in cells.

Schweighauser, Shi, Murzin and colleagues report cryo-EM structures of tau filaments from individuals with P301L or P301T MAPT mutations. P301L tau filaments adopted a distinct three-lobed fold, while P301T filaments had either a variant of the three-lobed fold or a V-shaped fold.

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).

Two products of the anal microbiome improve the specificity and sensitivity of diagnosing high-grade precursor lesions to anal cancer over cytology.

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.

Enzyme engineering is opening up new chemistries. Here, the authors report enzymes engineered to contain two biological active sites — also showing that one site can be converted to a metal-complex catalyst — and demonstrate the utility of such dual sites in a range of catalytic processes.

A comprehensive analysis of models of brain metastasis and multiple cohorts of patient samples identifies a targetable molecular mechanism underlying the resistance to whole-brain radiotherapy that can inform patient selection for personalized radiotherapy.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

Known genetic loci account for only a fraction of the genetic contribution to Alzheimer’s disease. Here, the authors have performed a large genome-wide meta-analysis comprising 409,435 individuals to discover 6 new loci and demonstrate the efficacy of an Alzheimer’s disease polygenic risk score.

Analysis of 2,170 SARS-CoV-2 sequences from the first wave of the COVID-19 epidemic in Spain provides insights into transmission patterns and the effects of lockdown on the emergence of new variants.

Laser spectroscopy measurements of the fermium isotopic chain show a smooth trend in the nuclear size of heavy actinide elements, and diminishing shell effects on the size evolution compared with lighter nuclei.

Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.

The development of innovative strategies for the capture and biodegradation of nanoplastics is sought after. Now, artificial hydrolytic active sites are incorporated into non-catalytic membrane nanopores generating pore-based biocatalytic nanoreactors that depolymerize polyethylene terephthalate plastic nanoparticles.

City-level analysis of data from the SALURBAL project shows vast heterogeneity in life expectancy across cities within the same country, in addition to substantive differences in causes of death among nine Latin American countries, revealing modifiable factors that could be leveraged by municipal-level policies aimed toward improving health in urban environments.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

Ferroplasma acidiphilum is a member of the order Thermoplasmatales, commonly found in extreme environments characterized by low pH and high concentrations of ferrous iron and other heavy metals. Analysis of the F. acidiphilum proteome reveals that an unusually high percentage of cellular proteins are iron-metalloproteins.

Analysis of HbA1c and FPG levels across 117 population-based studies demonstrates regional variation in prevalence of previously undiagnosed screen-detected diabetes using one or both measures and suggests that use of elevated FPG alone could underestimate diabetes prevalence in low- and middle-income countries.

Ru-pyrochlores find their way as alternative anodes of PEM water electrolyzers, and their high performance is owing to Ru sites embedded in RuMnO_x surface layers. Here, a water electrolyser with Y₂MnRuO₇ and only 0.2 mgRu cm⁻² has been tested with significant durability.

In this study, Juan-Mateu et al. discover microexons that modulate insulin secretion in the pancreas in response to glucose levels in beta cell lines and mouse islets. Human genetic variants modulating these islet microexons are associated with type 2 diabetes risk.

Temperature shapes the adaptation and composition of microbiomes, but whether their enzymes drive the thermal response remains unknown. Using an analysis of seven enzyme classes from worldwide marine microbiome data, this study shows that enzyme thermal properties explain microbial thermal plasticity and they are both finely tuned by the thermal variability of the environment.

Methanonatronarchaeia are a distinct class-level lineage of extremely halophilic methanogens, which lack features of classical methanogenesis and have a high intracellular concentration of potassium, suggesting potassium-based osmoprotection.

Paul Pharoah and colleagues report the results of a large genome-wide association study of ovarian cancer. They identify new susceptibility loci for different epithelial ovarian cancer histotypes and use integrated analyses of genes and regulatory features at each locus to predict candidate susceptibility genes, including OBFC1.

Genome-wide analysis identifies 30 loci associated with bipolar disorder, allowing for comparisons of shared genes and pathways with other psychiatric disorders, including schizophrenia and depression.

Beam shaping methods can generate optical fields with nontrivial topologies, which are invariant against perturbations and thus interesting for information encoding. Here, the authors introduce the realization of framed optical knots to encode programs with the conjoined use of prime factorization.

Dissimilatory sulfate reduction in archaeon ‘Candidatus Vulcanisaeta moutnovskia’ is distinct from bacterial sulfate reduction and sheds light on the evolution of sulfur metabolism.

Analysis of the spread of the 20E (EU1) variant of SARS-CoV-2 through Europe suggests that international travel and insufficient containment, rather than increased transmissibility, led to a resurgence of infections.

In the absence of complete genomes, the metabolic capabilities of uncultured ARMAN-like archaea have been uncertain. Here, Golyshina et al. apply an enrichment culture technique and find that the ungapped genome of the ARMAN-like archaeon Mia14 has lost key metabolic pathways, suggesting dependence on the host archaeon Cuniculiplasma divulgatum.

Oleispira antarctica is an oil-degrading bacterium found in the cold and deep sea. Here Kube et al. report the genome sequence of O. antarcticaand provide a comprehensive functional genetic and protein structural analysis, revealing insights into how this organism has adapted to its cold environment.