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Escherichia coli form pili structures in order to initiate infection of the urinary tract. Here, Thanassi et al., have solved the structures of pili assembly intermediates and provided insights into their biogenesis and assembly.

Ultrafast Sample placement on Existing tRees (UShER) is an efficient method that facilitates the addition of new SARS-CoV-2 genome sequences onto the existing phylogeny, aiding in real-time analysis of viral evolution during the COVID-19 pandemic.

Biochemical analyses show that in the Escherichia coli type I pilus the plug domain controls activation of usher by masking the substrate-binding site in the C-terminal domains when usher is in resting state.

Mutations in PCDH15 cause deafness and blindness in Usher syndrome 1 F, but gene therapy is difficult because the PCDH15 sequence is too large for AAV vectors. Here, the authors engineered a miniPCDH15 that fits in AAV and rescues hearing in mouse Usher syndrome 1F models.

The Csu pili of the multidrug-resistant nosocomial pathogen Acinetobacter baumannii assemble into an ultrathin zigzag architecture secured by a clinch mechanism that provides the pilus with high mechanical stability and superelasticity.

The structure of a pilus assembly intermediate reveals the timing of subunit polymerization and how chaperone–subunit complexes are transferred from N-terminal to C-terminal domains of the usher in the formation of bacterial pili.

The crystal structure of the FimD usher traversed by the tip complex of a type 1 pilus demonstrates the mechanism by which pilus subunits are assembled and translocated during pilus elongation.

A small molecule identified from high-throughput screening and optimization specifically stabilizes a disease-linked CLRN1 protein, delivering it to its site of action at the plasma membrane and preserving hearing in a new mouse model for Usher syndrome type III.

Zubair Ahmed and colleagues identify homozygous mutations in CIB2, a gene that encodes a calcium- and integrin-binding protein, that cause Usher syndrome type 1J and nonsyndromic deafness DFNB48. CIB2 is required for hair cell development and retinal photoreceptor cells in zebrafish and Drosophila melanogaster.

Pili are crucial virulence factors in many Gram-negative pathogens; these surface structures enable bacteria to interact with, and attach to structures in, their environment and can also facilitate horizontal gene transfer. In this Review, Waksmanet al. examine recent advances in our structural understanding of various pilus systems in Gram-negative bacteria and discuss their functional implications.

DNA hybridisation thermodynamics parameters underlie rational design of oligonucleotides for diagnostics and nanotechnology. Here, the authors present an accurate method to measure the free energy of a given DNA structure at specific temperature and buffer conditions.

Chronic SARS-CoV-2 infections have been hypothesised to be sources of new variants. Here, the authors use large-scale genome sequencing data to identify mutations predictive of chronic infections, which may therefore be relevant in future variants.

The long-term natural history of long-COVID is not well understood. In this population-based cohort study from Scotland, the authors describe symptom prevalence and health-related quality of life up to 18 months after a positive SARS-CoV-2 test and compare with matched test-negative controls.

In addition to their role in apoptosis, caspases are also involved in mediating non-apoptotic events. Here the authors show that the Drosophilamyosin family member CRINKLED and its mammalian counterpart act as substrate adaptor that facilitate caspase-mediated cleavage and localised kinase activity.

Human genetic loci that associate with composition of the oral microbiome are identified using saliva-derived DNA, where the same host genetics also shapes oral health and genetic variation in oral bacteria.

Cadherin is essential for mechanotransduction and myosin-adaptor-harmonin complexes anchor it to actin. Here the authors present the structures of myosin 7 MF2 domains bound to the harmonin PDZ3c domain and give insights into myosin-adaptor-harmonin complex assembly.

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).

Antibiotic resistance poses a critical global health threat. Here, the authors identify a carbapenem resistant clone of uropathogenic Escherichia coli with atypical virulence features as an increasing cause of urinary tract infection

Emerging SARS-CoV-2 variants of concern were detected early and multiple cases of virus spread not captured by clinical genomic surveillance were identified using high-resolution wastewater and clinical sequencing.

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.

White-tailed deer are an important reservoir of SARS-CoV-2 in the USA and continued monitoring of the virus in deer populations is needed. In this genomic epidemiology study from Ohio, the authors show that the virus has been introduced multiple times to deer from humans, and that it has evolved faster in deer.

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.

Bacterial pili are surface fibers that must resist high shearing forces to remain associated with their target. The Escherichia coli type 1 pilus chaperone FimC serves as a 'sensor', ensuring that only stable pilins become incorporated into the growing fiber.

A new phylogenomic method is developed that can detect recombinations in virus lineages in pandemic-scale datasets.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

Large genes require dual adeno-associated viral (AAV) vectors for in vivo delivery/expression, but current methods have limitations. Here the authors develop and functionally evaluate REVeRT, an efficient and flexible dual AAV vector technology based on reconstitution via mRNA trans-splicing.

Association analyses in over 1 million individuals identify 535 new loci influencing blood pressure traits. The results provide new insights into blood pressure regulation and highlight shared genetic architecture between blood pressure and lifestyle exposures.

Walmsley and colleagues report that systemic hypoxia induces persistent loss of histone H3K4me3 marks and epigenetic reprogramming in neutrophil progenitors, resulting in long-term impairment of subsequent neutrophil effector functions.

The identity of the tip link, which converts mechanical force to channel opening in hair cells, has been controversial, with different groups promoting cadherin 23 or protocadherin 15. A new paper in Nature shows that both proteins are involved.

There is limited understanding of SARS-CoV-2 intra-host evolution and subsequent transmission and adaptations in the context of persistent infection. Here, the authors describe sequential persistent SARS-CoV-2 infections that led to the emergence, transmission and further evolution of a novel Omicron BA.1.23 lineage.

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.

Retinitis pigmentosa (RP) is the most common type of inherited retinal dystrophy without effective treatments. Here, authors apply prime editing (PE) system to correct the point mutation in a preclinical RP mouse model. In vivo treatment achieves genome editing and restores mice vision.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

The majority of incident HIV infections in Eastern and Southern Africa occur in the general population. Here, the authors harmonise data from eight open population-based cohort studies from six countries and describe individual and community-level risk factors for HIV acquisition.

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.