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Here the authors use mRNA display to discover peptide inhibitors of BamA, an essential factor that catalyzes the membrane insertion of bacterial outer membrane proteins. They show that three peptides are antibacterial and inhibit BamA activity by a unique mechanism.

Myriad extracellular and intracellular cues regulate stem cell fate choice. Here, Liu et al. report intracellular pH dynamics as a previously unrecognized regulator to selectively mediate the secretory cell fate decision of the intestinal stem cell.

Antibiotics to treat carbapenem-resistant Acinetobacter baumannii infection are an urgent need. The cerastecins are potent, bactericidal and efficacious in animal models of infection, and may enable new treatment modalities targeting LOS transport.

Genome-wide association meta-analyses among 1.4 million individuals identify 318 new risk loci for type 2 diabetes and provide insight into the contribution of these risk variants to diabetes-related vascular outcomes.

Temporal multi-omic analysis of tissues from rats undergoing up to eight weeks of endurance exercise training reveals widespread shared, tissue-specific and sex-specific changes, including immune, metabolic, stress response and mitochondrial pathways.

Oncogenic gene fusions are frequent in childhood cancers but remain poorly understood and untargeted. Here, the authors identify 272 oncogenic fusions in transcriptomics data from 5190 childhood cancer patients, revealing their possible etiologies, their links with tumor progression and evolution, and their potential as therapeutic targets.

Photoelectrochemical devices based on III–V semiconductors have high performance potential but their cost and stability inhibit their wide application. Kang et al. make printed assemblies of GaAs-based photoelectrodes with separate optical and reactive interfaces, demonstrating water-splitting efficiency up to 13.1%.

Plasma levels of liver enzymes provide insights into hepatic function and related diseases. Here, the authors perform a genome-wide association study on three liver enzymes, identifying genetic variants associated with their plasma concentration as well as links to metabolic and cardiovascular diseases.

Multi-ancestry genome-wide association analyses identify new risk loci for Parkinson’s disease, and fine-mapping and co-localization analyses implicate candidate genes whose expression is associated with disease susceptibility.

This study uses gene expression predictors for the dorsolateral prefrontal cortex and other brain regions to perform a transcriptomic imputation analysis of schizophrenia, identifying 413 genic associations across 13 brain regions and 36 significantly enriched pathways.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

A multi-ancestry genome-wide association study of prostate cancer performed in 156,319 cases and 788,443 controls identifies 187 novel risk variants associated with the disease. Genetic risk scores associated with overall risk, and risk of aggressive disease in men of African ancestry.

The crystal structure of the fructose-2,6-bisphosphatase domain trapped during the reaction reveal a phosphorylated His 258, and a water molecule immobilized by the product, fructose-6-phosphate. The geometry suggests that the dephosphorylation step requires prior removal of the product for an ‘associative in-line’ phosphoryl transfer to the catalytic water.

The authors defined a roadmap for investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders. Their proof-of-concept study using the largest available common variant data sets for schizophrenia and volumes of several (mainly subcortical) brain structures did not find evidence of genetic overlap.

In a multicenter research program coordinated by the International Mouse Phenotyping Consortium, Spielmann et al. analyze the cardiac function and structure in ~4,000 monogenic mutant mice and identify 705 mouse genes involved in cardiac function, 75% of which have not been previously linked to cardiac heritable disease in humans. Using the UK Biobank human data, the authors validate the link between cardiovascular disease and some of the newly identified genes to illustrate the resource value and potential of their mutant mouse collection.

So far no enzymatic activity has been attributed to flagellin, the major component of bacterial flagella. Here the authors use bioinformatic analysis and identify a metallopeptidase insertion in flagellins from 74 bacterial species and show that recombinant flagellin and flagellar filaments have proteolytic activity.

A genome-wide survival study identifies variants at RIMS2 associated with progression of Parkinson’s disease to dementia and highlights divergence in the genetic architecture of disease onset and progression.

Keri Monda, Kari North, Christopher Haiman and colleagues report a meta-analysis of GWAS for body mass index that is composed of 39,144 individuals of African ancestry, followed by further genotyping in 32,268 individuals of African ancestry. The study also includes analysis of publicly available data from the GIANT consortium of ~124,000 individuals of European ancestry. The paper reports evidence for two new loci near GALNT10 and MIR148A.

The authors pooled resources to identify best practices and develop a new standardized protocol for estimating functional connectivity in rats with magnetic resonance imaging.

Using a multi-omics approach, the authors examine the molecular drivers of sexual dimorphism in the subcutaneous adipose tissue from sedentary and endurance-trained rats. These data provide a valuable resource for adipose tissue-related research.

Combined analysis of proton-proton collision data from the Large Hadron Collider at CERN by the CMS and LHCb collaborations leads to the observation of the extremely rare decay of the strange B meson into muons; the result is compatible with the standard model of particle physics, and does not show any signs of new physics, such as supersymmetry.

A small-molecule agonist for the cGAS–STING pathway has systemic activity in a mouse model of colon cancer.

The unfolded-protein response (UPR) protects cells from stress induced by the accumulation of unfolded proteins in the endoplasmic reticulum. As discussed here, an important role for the UPR has recently been described in the immune system, dysregulation of which could potentially contribute to autoimmunity.

The brain's capacity to respond to instructive capacity underlies behavioural learning, but how instructive experience acts on the juvenile brain, a period in which learning is often enhanced, remains unknown. Here, two-photon in vivo imaging is used to study the brains of zebra finches as they learn to sing. The results indicate that behavioural learning results when instructive experience is able to rapidly stabilize and strengthen synapses on the sensorimotor neurons that control the learned behaviour.

Horien and colleagues provide a roadmap to working with large, publically available imaging datasets.

The most comprehensive analysis to date of models of transcription-factor binding specificity reveals the best methods for predicting in vivo binding from in vitro data.