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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).

A combined sequencing technique assesses 18 patients with high-grade serous ovarian cancer over a multi-year period from diagnosis to recurrence and shows drug resistance typically arises from selective expansion of one or a few clones present at diagnosis.

There isn’t one single ‘early career experience’ in physics, and different subfields involve very different opportunities and challenges. Seven early career physicists who work on a range of research topics in different subfields discuss their views on the lessons we can learn from their professional lives.

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.

Mutational signature analysis of blood cells isolated from 23 chemotherapy-exposed samples and 9 nonexposed controls characterizes the effects of various drugs on mutational burden, signature exposure and cell types.

The authors analyze rare coding variants in 1990 individuals with congenital kidney anomalies, finding diagnostic variants in 14.1% of cases. They identify two new causal genes, ARID3A and NR6A1, along with 38 candidate genes, providing evidence for shared genetics with other developmental disorders.

The Perseverance rover detected polycyclic aromatic hydrocarbons preserved within sulfates in the fan and floor of Jezero crater on Mars, offering new insights into past habitability and the preservation of organic matter on Mars.

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.

In a previous clinical trial, the authors reported that SCFA-yielding biotherapy in adults with type 1 diabetes remodels the gut proteome and metabolome. Here, the show that colonization of the post-therapy microbiome into mice delayed diabetes and increased aryl-hydrocarbon receptor ligand and IgA production in the gut.

Using mathematical modeling of RSV and hMPV, this study found lowered transmissibility of hMPV and suppressive effects on hMPV transmission. Peak timing and magnitude of hMPV may shift due to RSV interventions, but the overall burden is small.

The influence of pregnancy on Long COVID is not well understood. Here, the authors use electronic health record data from the United States to compare the incidence of Long COVID in females after infection in pregnancy with matched non-pregnant females of reproductive age.

Here, the authors characterize the tempo and mode of lemur speciation with a phylogenomic dataset that also includes lorisiforms. They find that lemurs exhibited multiple bursts of diversification (without subsequent decline in diversification rate) with the highest diversification rates accompanied by high introgression rates.

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.

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

Kubota et al. find that white matter connections of ventral temporal cortex are innately organized by cytoarchitecture, category and eccentricity from birth, and also develop in parallel within each cytoarchitectonic area from infancy to adulthood.

A single-cell sequencing study using more than 30,000 tumour genomes from human ovarian cancers shows that whole-genome doubling is an ongoing mutational process that drives tumour evolution and disrupts immunity.

A study reports whole-genome sequences for 490,640 participants from the UK Biobank and combines these data with phenotypic data to provide new insights into the relationship between human variation and sequence variation.

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.

The authors show that extreme fire years in global forests align with rare fire weather extremes. Climate change has made such extremes 88-152% more probable. These findings highlight the need for action towards adaptation and mitigation of fire impacts.

Whole-genome sequencing of an ancient male Egyptian revealed a mixture of North African Neolithic and eastern Fertile Crescent ancestry, suggesting human migration between Egypt and Mesopotamia by the Old Kingdom period.

Haematopoiesis has high clonal diversity up to about 65 years of age, after which diversity drops precipitously owing to positive selection acting on a handful of clones that expand exponentially throughout adulthood.

The extent to which COVID-19 vaccination protects against long COVID is not well understood. Here, the authors use electronic health record data from the United States and find that, for people who received their vaccination prior to infection, vaccination was associated with lower incidence of long COVID.

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.

Ian Blair and colleagues use genome-wide linkage analysis and whole exome sequencing to identify mutations in the CCNF gene in large cohorts of amyotrophic lateral sclerosis and frontotemporal dementia patients. In addition to validating the mutations in international cohorts, the authors also show that mutant CCNFgene product affects ubiquitination and protein degradation in cultured cells.

Acyl carrier proteins (ACPs), a universal and highly conserved carrier of acyl intermediates during fatty acid and polyketide synthesis, are difficult to visualise. Here, the authors developed a facile, Raman spectroscopy-based method to detect ACP-substrate interactions.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

The authors use Patch-seq and electron microscopy datasets to relate synaptic connectivity to the transcriptomic cell type of different types of inhibitory neuron.

This study reports on excavations of hearths and stone artefacts from 20,000-year-old deposits at Dargan Shelter, which at an elevation of 1,073 m is believed to be the oldest occupied high-altitude site in Australia.

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.

US institutions and states are revamping hiring practices in an attempt to increase transparency about past misconduct in academia.

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.

In this study, Marshall et al. studied early immune responses in the lung and blood after an aerosol infection with BCG. Understanding which cells respond to this infection can help us understand how to design new tuberculosis vaccines.

Isolating and studying haematopoietic stem cells in young and aged mice demonstrates evolutionary processes related to blood production and provides a framework for interpreting future work using laboratory mice to study stem cell ageing.

Previously, authors have identified GW461484A (GW) as an inhibitor of the kinase Yck2 in the fungal pathogen Candida albicans. Here, they report the synthesis of GW analogs with improved pharmacological properties and activity in mouse models of systemic candidiasis.

Digoxin is a heart medicine extracted from plants, but how plants synthesize it is largely unknown. Here Carroll et al. identify a novel enzyme for digoxin biosynthesis, paving the way to produce digoxin and other structurally similar drugs in microbes.

Robbins and colleagues show that cigarette smoke-induced endothelial dysfunction enables atherosclerotic plaque macrophages to drive abdominal aortic aneurysm formation in a mouse model of atherosclerosis.

Infection by Plasmodium falciparum can manifest as diverse symptoms and outcomes with different treatment requirements. Here the authors use metabolomics, proteomics and transcriptomics data from 79 children to identify potential omics signatures that correlate with different extent and nature of inflammation to provide insights into the development of future treatments.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

The study provides a comprehensive transcriptomic atlas of the human gastrointestinal tract across the lifespan, highlighting inflammation-induced changes in epithelial stem cells that alter mucosal architecture and promote further inflammation.