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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.

Remotely sensed NDVI data and contemporary field data from 84 grasslands on 6 continents show increasing divergence in aboveground plant biomass between sites in different bioclimatic regions.

A description is given of the ENCODE effort to provide a complete catalogue of primary and processed RNAs found either in specific subcellular compartments or throughout the cell, revealing that three-quarters of the human genome can be transcribed, and providing a wealth of information on the range and levels of expression, localization, processing fates and modifications of known and previously unannotated RNAs.

New treatments are needed for muscle invasive bladder cancers. Here, the authors show that combined Pparg activation and MEK inhibition using FDA approved drugs shrinks tumor volume and induces a Basal/Squamous-to-Luminal shift in the urothelium as well as in invading tumors.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

The genomic sequences of 12 Drosophila species for conserved elements and describe the relationship between conservation and function for many specific sequence motifs.

Lithium nitride is the only stable binary alkali metal-nitrogen compound and shows promise for energy applications involving the transport of lithium ions. Here, the authors demonstrate that lithium nitride nanostructures can be grown as fibres and sheets despite the absence of a van der Waals gap.

The species threat abatement and restoration (STAR) metric quantifies the contributions that abating threats and restoring habitats offer towards reducing species’ extinction risk in specific places.

Infection of African green monkeys with SIV is associated with reduced pathogenicity. Here the authors explore the requirement of differentiated NK cell populations in a pathogenic Rhesus macaque model of SIV infection and show administration of IL-21 and IFNα rescues terminally differentiated NK cells, similarly to what found in African green monkeys, and limits the SIV reservoir in antiretroviral therapy treated macaques.

After compiling literature data on mammal parasites across urban and non-urban areas, the authors show that mammals in urban areas have more parasites overall without disproportionately more zoonotic ones, as is commonly thought.

In this immunological ancillary study of the PREVAC trial, the authors show that approved Ebola virus vaccines induce memory T-cell responses that persist during the five year follow-up after initial vaccination.

Exponential growth of toxigenic Streptococcus pyogenes M1_UK lineage accounted for most of the 2022/2023 invasive infection upsurge in the UK. Authors provide evidence that M1_UK first emerged in 2008, has genetic evidence of enhanced fitness, and has disseminated to 3 continents.

A rare case of asymptomatic dominantly inherited Alzheimer’s reveals confined tau pathology and unique proteomic features, highlighting potential resilience mechanisms decades beyond expected onset.

Genome-wide nucleotide composition varies greatly among species. Here, the authors show that genomic G + C composition is driven by mutation bias but is also modified by natural selection or biased gene conversion.

The next step after sequencing a genome is to figure out how the cell actually uses it as an instruction manual. A large international consortium has examined 1% of the genome for what part is transcribed, where proteins are bound, what the chromatin structure looks like, and how the sequence compares to that of other organisms.

Using a single-nucleus multi-omics approach, a study jointly profiles the reorganization of the epigenome and the three-dimensional chromatin conformation during the development of the human hippocampus and prefrontal cortex.

The human leukocyte antigen allele HLA-B*15:01 is associated with asymptomatic SARS-CoV-2 infection due to pre-existing T cell immunity.

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.

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.

Without mitigation, relative sea-level rises under current climate change projections will exceed the capacity of coastal habitats such as mangroves and tidal marshes to adjust, leading to instability and profound changes to coastal ecosystems.

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.

Climate change and land use change may have independent or interactive effects on species’ distributions. Here, the authors show that changes in bird, lepidopteran and plant ranges across Great Britain are often explained by individual or additive effects of land conversion and temperature change.

Sporadic surface melt over the West Antarctic Ice Sheet is not fully understood. Here, the authors report on an extensive melting episode in the Ross Ice Shelf area in 2016 and use comprehensivein situobservations and model simulations to highlight the role of the strong El Niño event.

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.

Steve Brown and colleagues report an analysis of 20 phenotyping tests, including 413 data parameters, across 449 mutant mouse alleles. They identify widespread pleiotropy and assign putative functions to genes that lacked previous phenotypic annotation.

Animal propulsors—wings and fins—typically bend during motion. Here, the authors analysed video data on animal propulsor bending and find that, for propulsion within inertially dominated flows, the flexion angles and the positions of the point of flexion are similar across the animal kingdom.

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 strategy for inferring phase for rare variant pairs is applied to exome sequencing data for 125,748 individuals from the Genome Aggregation Database (gnomAD). This resource will aid interpretation of rare co-occurring variants in the context of recessive disease.

A genomic constraint map for the human genome constructed using data from 76,156 human genomes from the Genome Aggregation Database shows that non-coding constrained regions are enriched for regulatory elements and variants associated with complex diseases and traits.

Neutrophils are the first responders in acute inflammatory events such as acute respiratory distress syndrome and tend to home to lung capillaries during acute inflammation, where they can cause tissue damage by diapedesis and secretion of specific molecules. Here the authors show that nanoparticles coated with agglutinated proteins selectively target activated neutrophils in inflamed lungs and can be used for imaging and therapeutic purposes.

Non-ribosomal peptide synthetases (NRPSs) are multi-modular enzymes assembling complex natural products. Here, the structures of a Thermobifida fusca NRPS condensation domain bound to the substrate-bearing peptidyl carrier protein (PCP) domain provide insight into the mechanisms of substrate selectivity and engagement within the catalytic pocket.

Alzheimer’s disease is associated with changes in astrocytes. Here the authors investigated the astrocyte translatome associated with amyloid-ß and tau pathology.

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

Molnupiravir is an antiviral that forces lethal error catastrophe in SARS-CoV-2 RNAs. Here, the authors confirm the mechanism of action of molnupiravir in humans using samples obtained from the UK’s AGILE phase IIa clinical trial investigating the antiviral efficacy of the drug against SARS-CoV-2. No treatment-associated SARS-CoV-2 mutations were identified.

A secure framework that harmonizes storage and querying of clinical and genetic data using blockchain technology was developed to support combined genotype–phenotype queries, improving transparency into how and when health information is used.

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.

Colorectal tumors with mutated KRAS and APC require the amino acid transporter SLC7A5 to drive tumorigenesis. Mechanistically, SLC7A5 drives transcriptional and metabolic reprogramming by maintaining intracellular amino acid levels, leading to enhanced protein synthesis.

H3K27ac HiChIP analysis helps to identify promoter-interacting expression quantitative trait loci (pieQTLs) in five common immune cell types. Some pieQTLs overlap with nontranscribed promoters that act as enhancers.

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.

Sequencing data from two large-scale studies show that most of the genetic variation influencing the risk of type 2 diabetes involves common alleles and is found in regions previously identified by genome-wide association studies, clarifying the genetic architecture of this disease.

IMPDH and GMPR have similar active sites, but their reactions cause opposite effects on the guanine nucleotide pool. Biochemical and crystallographic evidence point to cofactor conformation as distinguishing the two reaction mechanisms and demonstrate that GMPR can substitute for IMPDH, prompting further investigations of this metabolic cycle.