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SLCO2A1 (also known as OATP2A1) is responsible for the transport of eicosanoids, including prostaglandins (PGs), as well as of a subset of nonsteroidal anti-inflammatory drugs (NSAIDs). Here, structures of SLCO2A1 bound to PGs and to four widely used drugs elucidate the molecular basis for PG and drug recognition.

Longitudinal metatranscriptomics in a prospective cohort of 1,164 adults hospitalized for COVID-19 reveals that azithromycin offered no apparent anti-inflammatory benefit but enriched the respiratory microbiome with potential pathogens and antimicrobial resistance genes.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

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.

Bacteria of the phylum Bacteroidota move by gliding and export proteins using a type-9 secretion system. Here, Liu et al. show that these two processes use a shared mechanism in which outer membrane proteins are covalently attached by disulfide bonds to a moving track structure inside the cell.

Intracellular pathogens hijack host gene expression to subvert cellular processes. Here, the authors show that Legionella pneumophila’s PieF effector inhibits the human CCR4-NOT deadenylation machinery, impacting mRNA poly(A) tail shortening and impairing cell division.

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

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Structural and biochemical studies of the β-barrel-assembly machinery from Flavobacterium johnsoniae reveal a subunit composition and assembly that are distinct from those of the canonical Escherichia coli complex.

The SLC45A4 gene encodes a neuronal polyamine transporter and is linked to pain response in humans and mice.

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.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

The complement receptor CD46 and the Notch-Jagged system are important for the differentiation of helper T cells. Kemper and colleagues demonstrate that Jagged1 is a physiological ligand for CD46 and is critical for the generation of T helper type 1 cells in humans.

The bacterial anti-phage defense systems known as ‘Zorya’ consist of a membrane protein complex (ZorAB) and soluble components of unclear function. Here, the authors solve cryo-EM structures of the ZorAB complex and show that the soluble component ZorE displays nickase activity and acts as an effector module.

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.

Transcription termination or pausing during DNA replication in bacteria and humans results in DNA damage with exposed 3′ single-stranded DNA ends and mutations.

Cryoelectron microscopy analyses of the counter-clockwise and clockwise states of the Salmonella Typhimurium C-ring reveal the structural bases for changes in rotation of the bacterial flagellum.

The uptake and elimination of beta-lactam antibiotics are facilitated by the proton-coupled peptide transporters. Here authors present cryo-EM structures of PepT2 in complex with the cefadroxil, amoxicillin and cloxacillin to reveal a mechanism of beta-lactam antibiotic recognition

The transmembrane export apparatus regulates protein secretion through bacterial type III secretion systems. New structural data indicate that MxiA, a major component of the apparatus, assembles in a nonameric ring. This and additional structural information provide a framework for understanding how protein secretion is controlled.

Breast cancer risk for BRCA1/BRCA2 mutation carriers varies depending on other genetic factors. Here, the authors perform a case-only genome-wide association study and highlight novel loci associated with breast cancer risk for BRCA1/BRCA2 mutation carriers.

Large-scale genome-wide analyses identify hundreds of genetic loci associated with hypothyroidism and thyroid hormone levels, demonstrating the potential of using polygenic risk scores to predict disease onset and progression.

Properdin is the only known positive regulator of the human complement system, stabilising the convertase C3 in the alternative pathway of complement activation. Here, the authors report the identification and characterisation of a species-specific properdin inhibitor CirpA, derived from tick saliva.

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

System xc- is a cystine transporter that is expressed in the plasma membrane and imports cystine in exchange for intracellular glutamate. Here, the authors present the cryo-EM structure of human system xc- both in the apo form and the glutamate bound state, and further supported by molecular dynamics and cell-based assays they discuss its cystine transport mechanism.

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

The twin-arginine translocation (Tat) pathway transports folded proteins across membranes in bacteria and plant chloroplasts; the crystal structure of TatC, an integral membrane protein and core component of this complex, is now presented.

Cryo-electron microscopy structures of PCFT in a substrate-free state and bound to the antifolate drug pemetrexed provide insights into how this protein recognizes folates and mediates their transport into cells.

Lipid droplet biogenesis is orchestrated by the conserved membrane protein Seipin via an unknown mechanism. Here, the authors use structural, biochemical and molecular dynamics simulation approaches to reveal the mechanism of lipid droplet formation by the yeast Seipin Sei1 and its partner Ldb16.

The LITMUS consortium provides a resource of rodent MASLD models benchmarked against metabolic, histologic and transcriptomic features that are relevant for human MASLD. The work is useful for selecting relevant rodent models for studying this common disease.

In this work, authors take a multiomics and microfluidics-based approach to elucidate the mechanism of endothelial damage in critical illness associated with SARS-CoV-2.

Previous studies identified an association between the 2q35 locus and breast cancer. Here, the authors show that a SNP at 2q35, rs4442975, is associated with oestrogen receptor positive disease and suggest that this effect is mediated through the downregulation of a known breast cancer gene, IGFBP5.