Search

The site-selective functionalization of C(sp²)–H bonds is a powerful strategy for the synthesis of structurally diverse compounds with broad applicability. Here the authors show ruthenium-catalysed regiodivergent methods for the installation of silyl synthetic handles at both ortho and meta sites within arenes.

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).

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

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.

The team of authors led by Seon-Kyeong Jang use whole-genome sequencing data and show that rare genetic variants explain much of the ‘missing heritability’ in smoking behaviours. These results help address a long-standing mystery in behavioural genetics.

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.

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.

Traditional, top-down governance approaches alone will not bend the curve of biodiversity loss, and must be combined with small-scale interventions that can spark systemic change. Mobilizing behaviour change towards biodiversity-positive practices is as a promising leverage point, but requires a nuanced understanding of how people perceive and value nature.

Within-sibship genome-wide association analyses using data from 178,076 siblings illustrate differences between population-based and within-sibship GWAS estimates for phenotypes influenced by demographic and indirect genetic effects.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Based on phylogenomic and geometric morphometric analyses of 132 anglerfish species, the authors infer a Cretaceous origin of the clade and show that bathypelagic anglerfish are undergoing rapid phenotypic diversification despite inhabiting a relatively homogeneous deep-sea habitat.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

Dimethyl fumarate (DMF) is an anti-inflammatory drug proposed as a treatment for COVID19. Here the results are reported from a randomised trial testing DMF treatment in 713 patients hospitalised with COVID-19. DMF was not associated with any improvement in day 5 outcomes.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

An analysis of rare genetic variants reveals that they influence human traits through similar biological pathways to common ones. The work deepens our understanding of how this type of variant affects complex traits.

Analysis of 46 newly sequenced or re-sequenced Tausch’s goatgrass (Aegilops tauschii) accessions establishes the origin of the bread wheat (Triticum aestivum) D genome from genetically and geographically discrete Ae. tauschii subpopulations.

Mackay and colleagues show that distinct programs of tissue residency are induced in CD8⁺ and CD4⁺ T_RM cell subsets, a difference attributable to the activity of the transcription factor Runx3.

A genome-wide association meta-analysis study here shows novel genetic loci to be associated to body fat percentage, and describes cross-phenotype association that further demonstrate a close relationship between adiposity and cardiovascular disease risk.

A case–control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.

The tunability of covalently bound cationic and anionic moieties of zwitterionic materials makes them attractive for potential applications. A family of zwitterions exhibiting molecular disorder and plasticity allows their use as a solid-state conductive matrix.

Understanding how a supporting material can change the surface chemistry of the nanoparticle catalysts that it hosts is critical to tuning catalytic properties. Experimental Hammett studies and density functional theory calculations show that differences in reactivity can be attributed to differences in the electron density at metal active sites, which arises from differences in electron donation from the support.

Imbalanced proteostasis is associated with diverse diseases, including ischemia/reperfusion injury in the heart. Here the authors show that the ATF6 arm of the unfolded protein response can be pharmacologically activated with a small molecule in vivo, providing protection from ischemia/reperfusion injury in the heart, the brain, and the kidney.

McGaha and colleagues review recent research on the metabolic programs of tumor-associated macrophages across cancer types and discuss their implications on potential therapeutic vulnerabilities.

More than 1 in 10 babies born in the UK are suspected of having an infection. Here the authors show that newborn babies with signs of infection (raised C-Reactive Protein levels) have exaggerated leg reflexes and pain-related brain activity following a heel prick blood test, suggesting they may be more sensitive to pain.

Long-term data for 34 butterfly species evidence that population responses to climate change vary with adaptation to local conditions and niche position. Local adaptation implies negative effect of climatic anomalies independently of niche position.

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

Adjuvanting the lipid and the encapsulated messenger RNA-encoded antigen in lipid-nanoparticle mRNA vaccines can enhance the efficiency of mRNA delivery and the activation of the immune responses, as shown for a COVID-19 vaccine in mice.

Investigation of variation in three cohorts has identified multiple genetic signals associated with the pregnancy-specific liver disorder, intrahepatic cholestasis of pregnancy, giving insight into the disease which can cause preterm birth and stillbirth.

A trans-ancestry genome-wide association study of serum urate levels identifies 183 loci influencing this trait. Enrichment analyses, fine-mapping and colocalization with gene expression in 47 tissues implicate the kidney and liver as key target organs and prioritize potential causal genes.

Genome-wide data from 400 individuals indicate that the initial spread of the Beaker archaeological complex between Iberia and central Europe was propelled by cultural diffusion, but that its spread into Britain involved a large-scale migration that permanently replaced about ninety per cent of the ancestry in the previously resident population.

An improved, single-cell lineage-tracing system, based on deep detection of naturally occurring mitochondrial DNA mutations with simultaneous readout of transcriptional states and chromatin accessibility, is used to define the clonal architecture of haematopoietic stem cells.

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.

Amalio Telenti, Craig Venter and colleagues report common, low-frequency and rare variants associated with blood metabolite levels using whole-genome sequencing and comprehensive metabolite profiling in 1,960 individuals. They identify 246 metabolites whose levels are associated with genetic variation at 101 loci.

Two spider toxins are shown to target the Na_v1.1 subtype of sodium channel specifically, shedding light on the role of these channels in mechanical pain signalling.

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.

Most people who are infected with SARS-CoV-2 seroconvert within a few weeks, but the determinants and duration of the antibody response are not known. Here, the authors characterise these features of the immune response using data from a large representative community sample of the UK population.

Splicing is regulated by cis-acting elements in pre-mRNAs such as exonic or intronic splicing enhancers and silencers. Here the authors show that exonic splicing enhancers are enriched in exons compared to introns due to mutational bias coupled with purifying selection on the protein code.