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Overactive bladder (OAB) is a challenging clinical condition and treatment can include behavioral therapy or antimuscarinic agents. A placebo effect has been reported in randomized controlled studies of antimuscarinic agents for OAB. In this Review, Mangera and colleagues assess the response to placebo in OAB and describe a positive placebo effect in OAB outcome parameters. Reasons for the placebo effect and its potential use will also be discussed.

HIV-1 binds host CD4⁺ T cells via its gp120 envelope glycoprotein that undergoes changes to allow ‘opening’ of the envelope trimer, exposure of gp41 and binding to the CCR5 co-receptor. Compound 18A inhibits HIV-1 infection by blocking some of these conformational changes.

Fibroblasts play critical roles in tissue homeostasis, but in pathologic states they can drive fibrosis, inflammation, and tissue destruction. Here, Faust et al. find that healthy human synovial fibroblasts under the influence of adjacent adipocytes have altered lipid metabolism driven by cortisol signaling. Both adipocytes and these characteristics are lost in inflammatory arthritis.

Understanding host–guest interactions and structural changes within porous materials is crucial for enhancing gas storage properties. Here, the authors combine cryogenic loading of gases with high pressure crystallography and computational techniques to obtain atomistic detail of adsorption-induced structural and energetic changes in ZIF-8.

Measurements of subclonal expansion of ctDNA in the plasma before surgery may enable the prediction of future metastatic subclones, offering the possibility for early intervention in patients with non-small-cell lung cancer.

The transition between conducting and non-conducting states of K⁺ channels has been explained by conformational changes at the intracellular entrance to the conduction pathway. Here authors demonstrate that control over K⁺ currents in Kir channels is not explained by the canonical pore-gating model, as conduction is not impaired by a constricted inner helix bundle.

Understanding the emergence, evolution, and transmission of antibiotic resistance genes (ARGs) is essential to combat antimicrobial resistance. Here, Munk et al. analyse ARGs in hundreds of sewage samples from 101 countries and describe regional patterns, diverse genetic environments of common ARGs, and ARG-specific transmission patterns.

A study finds that a protease called granzyme K can activate the entire complement cascade, explaining how it can drive destructive inflammation in inflammatory diseases such as rheumatoid arthritis.

A randomized trial in patients hospitalized with COVID-19 showed no benefit and potentially increased harm associated with the use of convalescent plasma, with subgroup analyses suggesting that the antibody profile in donor plasma is critical in determining clinical outcomes.

Analyses of the TRACERx study unveil the relationship between tissue morphology, the underlying evolutionary genomic landscape, and clinical and anatomical relapse risk of lung adenocarcinomas.

Understanding the immune response to SARS-CoV-2 is dependent on being able to distinguish COVID-19 immune responses from cross-reactive immune responses to other coronaviruses. Here the authors show that choice of antigens and whether an ICS, ELISPOT or T cell proliferation assay is used has a major effect on this discriminatory ability.

Physical activity has been linked to lower risks of colorectal and breast cancer. Here, the authors present a Mendelian randomisation analysis supporting a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer.

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.

Understanding the effect of vaccination on emerging SARS-CoV-2 variants of concern is of increasing importance. Here, James et al. report that two doses of vaccination with the Pfizer-BioNTech vaccine induce more robust immune responses to the B.1.1.7 and B.1.351 SARS-CoV-2 lineages than does natural infection.

The identification of Escherichia coli ycfD and human MINA53 and NO66 as ribosomal amino acid hydroxylases defines a role for 2-oxoglutarate/iron-dependent oxygenases in translational regulation.

Genetic susceptibility loci for oropharyngeal cancer have been reported but these studies have not always examined human papillomavirus (HPV) status. Here, the authors perform genome-wide analysis taking into account HPV16 serology status and report two independent loci in the HLA region, suggesting the protective role of HLA variants against HPV infection.

Cardelino leverages variant information from single-cell RNA-seq data for inferring clonal tree configuration and mapping cells to their clone of origin.

Industrial whaling drove several species to near extinction. From an analysis of 50 whole-genomes from fin whale populations, this study shows that the fin whale population in the Eastern North Pacific was reduced 99% during whaling but has maintained genomic diversity, whereas the Gulf of California population remained small and isolated, resulting in increased genetic load.

The integration of nano-molecules into microelectronic circuitry is challenging. Here, the authors provide a scalable method for contacting a self-assembled monolayer of nanoparticles with a single layer of graphene that produces single-electron effects, in the form of a Coulomb staircase, with a yield of at least 70%.

Automated pathotyping of synovial tissue in arthritis is a major unmet need. Here, the authors develop and demonstrate the efficacy of an automated tissue and cellular pathotyping tool for inflammatory arthritis.

Somatic mutations obtained from laser microdissected biopsies of human tissues are used to reconstruct the developmental phylogenies of these tissues back to the zygote.

Lim and colleagues present the UK PROSECO study where they assess humoral and cellular immune responses to one, two and three doses of vaccination against SARS-CoV-2 in patients with B-cell malignancies in a prospective observational study.

Foliar spray of double-stranded RNA carried on clay particles or BioClay affords protection against multiple life stages of whitefly in crop hosts. The sprayed dsRNA makes its way to the vasculature of plants and is taken up by whiteflies during feeding.

Identifying causal variants and genes in genome-wide association studies remains a challenge, an issue that is ameliorated with larger sample sizes. Here the authors meta-analyze kidney function genome-wide association studies to identify new loci and fine-map loci to home in on variants and genes involved in kidney function.

The Cancer Genome Atlas Network describe their multifaceted analyses of primary breast cancers, shedding light on breast cancer heterogeneity; although only three genes (TP53, PIK3CA and GATA3) are mutated at a frequency greater than 10% across all breast cancers, numerous subtype-associated and novel mutations were identified.

Single-cell transcriptomic and proteomic data from synovial tissue from individuals with rheumatoid arthritis classify patients into groups based on abundance of cell states that can provide insights into pathology and predict individual treatment responses.

Thrombospondin-1 (TSP-1) activates latent TGF-β in the extracellular matrix. Here the authors show that inappropriate activation of latent TGF-β in murine, bovine and human lung by monocyte-produced TSP-1 causes pulmonary hypertension, and that interference with the activation process prevents disease development.

Excavation in Island New Guinea reveals features associated with the Pacific Lapita cultural complex as well as sustained local cultural traditions from 3,480–3,060 years ago, contemporary with the earliest known Lapita settlements 700 km away. This supports New Guinea as a springboard for Lapita dispersal throughout the Pacific and illuminates their origins.

The solutiuon structure of the GAGA DMA-binding domain reveals an N-terminally extended zinc finger structure which wraps around one turn of the DNA, a result which helps to set limits on the mechanism of nucleosome remodelling.

Insufficient AHR activation has been suggested in SLE, and augmenting AHR activation therapeutically may prevent CXCL13⁺ T_PH/T_FH differentiation and the subsequent recruitment of B cells and formation of lymphoid aggregates in inflamed tissues.

In a 15-year whole-ecosystem, single-factor experiment, stopping experimental mercury loading results in rapid decreases in methylmercury contamination of fish populations and almost complete recovery within the timeframe of the study.

A machine-learning approach accounting for methodological differences in studies and complex interactions among taxa allows independent soil studies to be combined at the taxonomy-based level to assess bacterial community structure.

The Cancer Genome Atlas consortium reports on their genome-wide characterization of somatic alterations in colorectal cancer; in addition to revealing a remarkably consistent pattern of genomic alteration, with 24 genes being significantly mutated, the study identifies new targets for therapeutic intervention and suggests an important role for MYC-directed transcriptional activation and repression.

Using the GTEx data and others, a comprehensive analysis of adenosine-to-inosine RNA editing in mammals is presented; targets of the various ADAR enzymes are identified, as are several potential regulators of editing, such as AIMP2.

Major histocompatibility complex (MHC) loss of heterozygosity, allele-specific mutation and measurement of expression and repression (MHC Hammer) detects disruption to human leukocyte antigens due to mutations, loss of heterogeneity, altered gene expression or alternative splicing. Applied to lung and breast cancer datasets, the tool shows that these aberrations are common across cancer and can have clinical implications.

This report identifies oncogenic fusions in individuals with breast cancer involving the genes encoding NOTCH and MAST, recurring in approximately 5–7% of studied cases. The fusions show growth-promoting properties that suggest that they may represent targetable events in a subset of people with breast cancer.

SHP2 promotes RAS-driven MAPK signalling, but it is unclear why cancer cells with distinct KRAS mutations exhibit differential sensitivity to SHP2 inhibition. Here the authors show that KRAS Q61H is decoupled from SHP2- mediated upstream regulation, thus Q61H pancreatic cancer cells maintain MAPK signalling and are refractory to SHP2 inhibitors.

Neuronal PAS domain protein 4 (NPAS4) is an immediate early gene, but its role in striatal circuits in drug seeking behaviour is not understood. Here the authors show that exposure to cocaine in mice results in induction of NPAS4 in a subset of nucleus accumbens (NAc) neurons, and in D2-neurons of the NAc it contributes to cocaine-associations and cocaine seeking behaviour.

Analyses of multiregional tumour samples from 421 patients with non-small cell lung cancer prospectively enrolled to the TRACERx study reveal determinants of tumour evolution and relationships between intratumour heterogeneity and clinical outcome.

Phenotypic variation and diseases are influenced by factors such as genetic variants and gene expression. Here, Barbeira et al. develop S-PrediXcan to compute PrediXcan results using summary data, and investigate the effects of gene expression variation on human phenotypes in 44 GTEx tissues and >100 phenotypes.

The ATLAS Collaboration reports a measurement of the ratio of the decay rates of W bosons to τ leptons and muons, in agreement with universal lepton couplings as postulated in the standard model of particle physics.

The ATLAS experiment at the Large Hadron Collider reports a search for charged-lepton-flavour violation in decays of Z bosons into a τ lepton and an electron or muon of opposite charge.