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Fishing has had a profound impact on global reef shark populations, and the absence or presence of sharks is strongly correlated with national socio-economic conditions and reef governance.

Analyses of the TRACERx study unveil the relationship between tissue morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk of lung adenocarcinomas.

European river discharge observations suggest that catchments with similar flood generation processes produce similar extremes, enabling better predictability of megafloods using a continental scale perspective.

Results of the TRACERx study shed new light into the association between body composition and body weight with survival in individuals with non-small cell lung cancer, and delineate potential biological processes and mediators contributing to the development of cancer-associated cachexia.

The Wzc–Wza complex forms part of the bacterial extracellular polysaccharides synthesis machinery, where cycling of the Wzc between phosphorylation states is crucial to both synthesis and export. Here the authors report the structure of the Wzc octamer and provide insight into its regulation through phosphorylation.

Lassa virus infections in humans can result in severe disease, including hemorrhagic fever. Here the authors describe an mRNA-based Lassa virus vaccine that shows protection without requirement for neutralizing antibody in a guinea pig model of infection.

Ageing increases the risk of many diseases. Here the authors compare blood cell transcriptomes of over 14,000 individuals and identify a set of about 1,500 genes that are differently expressed with age, shedding light on transcriptional programs linked to the ageing process and age-associated diseases.

A transcriptomics study demonstrates cell-type-specific responses to differentially aged blood and shows young blood to have restorative and rejuvenating effects that may be invoked through enhanced mitochondrial function.

In lung adenocarcinoma, antibodies against endogenous retroviruses promote anti-tumour activity, and expression of endogenous retroviruses can predict outcomes of immunotherapy.

This paper describes molecular subtypes of cervical cancers, including squamous cell carcinoma and adenocarcinoma clusters defined by HPV status and molecular features, and distinct molecular pathways that are activated in cervical carcinomas caused by different somatic alterations and HPV types.

Bulk RNA sequencing of organs and plasma proteomics at different ages across the mouse lifespan is integrated with data from the Tabula Muris Senis, a transcriptomic atlas of ageing mouse tissues, to describe organ-specific changes in gene expression during ageing.

Using the GTEx data and others, a comprehensive analysis of adenosine-to-inosine RNA editing in mammals is presented; targets of the various ADAR enzymes are identified, as are several potential regulators of editing, such as AIMP2.

Comparative study of 81 genomes of parasitic and non-parasitic worms identifies gene family births and expanded gene families at key nodes in the phylogeny that are relevant to parasitism and proteins historically targeted for drug development.

Major histocompatibility complex (MHC) loss of heterozygosity, allele-specific mutation and measurement of expression and repression (MHC Hammer) detects disruption to human leukocyte antigens due to mutations, loss of heterogeneity, altered gene expression or alternative splicing. Applied to lung and breast cancer datasets, the tool shows that these aberrations are common across cancer and can have clinical implications.

Stimulus convergence and concomitant auditory cortex disinhibition are essential for fear learning.

The fungal pathogen Hymenoscyphus fraxineus is killing European common ash trees. Here, the authors sequence the genome of H. fraxineus and show that European populations were founded by two divergent haploid individuals introduced from Asia.

Unprecedented floods and droughts bring new challenges for risk reduction, as is clear from this analysis of the drivers of changing impacts in many cases worldwide, with implications for efficient governance and investment in integrated management.

A longitudinal evolutionary analysis of 126 lung cancer patients with metastatic disease reveals the timing of metastatic divergence, modes of dissemination and the genomic events subject to selection during the metastatic transition.

An analysis of 52 million births in 26 countries shows small reductions in preterm birth during the first to third months of lockdown. Further research is needed to examine causal pathways.

Measurements of subclonal expansion of ctDNA in the plasma before surgery may enable the prediction of future metastatic subclones, offering the possibility for early intervention in patients with non-small-cell lung cancer.

The MAGIC investigators report results of a large genome-wide association study meta-analysis to identify common variants influencing fasting glucose homeostasis. They further show that several of the newly discovered loci influencing glycemic traits are also associated with risk of type 2 diabetes.

The goal of the 1000 Genomes Project is to provide in-depth information on variation in human genome sequences. In the pilot phase reported here, different strategies for genome-wide sequencing, using high-throughput sequencing platforms, were developed and compared. The resulting data set includes more than 95% of the currently accessible variants found in any individual, and can be used to inform association and functional studies.

Mixed responses to targeted therapy within a patient are a clinical challenge. Here the authors show that TP53 loss-of-function cooperates with whole genome doubling which increases chromosomal instability. This leads to greater cellular diversity and multiple routes of resistance, which in turn promotes mixed responses to treatment.

The bispecific molecule tebotelimab, which blocks both PD-1 and LAG-3, is well tolerated as a monotherapy and in combination with the anti-HER-2 antibody margetuximab and elicits encouraging clinical activity in solid tumors with high LAG-3 levels and/or expression of IFN-γ-regulated genes.

This report from the 1000 Genomes Project describes the genomes of 1,092 individuals from 14 human populations, providing a resource for common and low-frequency variant analysis in individuals from diverse populations; hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites, can be found in each individual.

Pulmonary arterial hypertension (PAH) is characterised by progressive pulmonary vascular remodelling. Here, Arnold et al. develop a therapeutic antibody targeting osteoprotegerin and find it attenuates pulmonary vascular remodelling in multiple rodent models of PAH, alone or in combination with standard of care vasodilator therapy.

E1E2 spike on the hepatitis C virion is an important target for vaccine design. Here, the authors permute the subunits to generate E2E1 immunogens and show that mosaic nanoparticles displaying different E2E1 antigens elicit cross-neutralizing antibodies in rabbits.

To fully understand the potential shortcomings of SARS-CoV-2 vaccination, it is necessary to delineate the properties of the antibodies elicited, during immunization, and also infection. Through investigation of the SARS-CoV-2 spike-reactive B cell repertoire, authors identify following infection, a subset of B cells enriched and almost exclusively target a non-neutralizing S2 epitope present in aberrant forms.

Neutralizing nanobodies (Nb) are of considerable interest as therapeutic agents for COVID-19 treatment. Here, the authors functionally and structurally characterize Nbs that bind with high affinity to the receptor binding domain of the SARS-CoV-2 spike protein and show that an engineered homotrimeric Nb prevents disease progression in a Syrian hamster model of COVID-19 when administered intranasally.

The presence of earthworms is known to enhance the quality and moisture of soil in cool and wet climates. Evanset al. show that termites and ants can improve soil quality in warmer and drier climates—their presence results in elevated water infiltration and nitrogen content, leading to increased wheat yields.

The human germinal centre response to influenza virus vaccination is fuelled by the continued recruitment of naive B cells as well as pre-existing memory B cells.

Nanoparticles are a promising approach to increase immunogenicity of protein antigens for vaccines. Here, Brouwer et al. design self-assembling, two-component protein NPs that present native-like SOSIP trimers of HIV envelope protein and determine immunogenicity in a small animal model.

An immunoprecipitation-based protocol is developed to analyse DNA methylation in small quantities of circulating cell-free DNA, and can detect and classify cancers in plasma samples from several tumour types.

Megabodies, built by grafting nanobodies onto larger protein scaffolds, help alleviate problems of particle size and preferential orientation at the water–air interfaces during cryo-EM based structure determination experiments and are shown to be generalizable to soluble and membrane-bound proteins.

Enhancing rock weathering across UK croplands could deliver substantial atmospheric carbon dioxide removal alongside agricultural co-benefits, according to coupled climate–carbon–nitrogen cycle model simulations.

Observations of optical flares from AT2022tsd (the ‘Tasmanian Devil’) show that they have durations on the timescale of minutes, occur over a period of months, are highly energetic, are probably nonthermal and have supernova luminosities.

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.

The authors show that rare genetic variants contribute to large gene expression changes across diverse human tissues and provide an integrative method for interpretation of rare variants in individual genomes.

Kragel et al. identify a human functional magnetic resonance imaging signature of mesocorticolimbic activity specific to states of pleasure.

Mutations in the transcription factor FOXA1 that are common in prostate cancer result in gain-of-function effects that promote changes in the differentiation of tumour cells.

Knapp et al. analyse the heterogeneous molecular profiles and functions of CD49f human cord blood haematopoietic stem cells and report that a subset with CD33 expression has improved regenerative activity.

Two nanobodies that bind SARS-CoV-2 spike RBD are shown to block interaction with receptor ACE2 and thus neutralize the virus, and have an additive effect with antibody CR3022.

Randomised controlled experiments are the gold standard for scientific inference, but environmental and social scientists often rely on different study designs. Here the authors analyse the use of six common study designs in the fields of biodiversity conservation and social intervention, and quantify the biases in their estimates.

An epidural spinal cord stimulation system regulates blood pressure in the acute and chronic phases of spinal cord injury.

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.