Engineered RNA molecules have been designed from scratch to precisely turn off protein expression and implement multi-input universal logic gates in Escherichia coli. The cover depicts an RNA circuit for computing NAND logic in the process of being switched off.

See Kim et al

Evolution of the modern organophosphate-degrading enzyme methyl parathion hydrolase from an ancestral dihydrocoumarin hydrolase is subject to a highly constrained adaptive landscape, making just five mutations both necessary and sufficient for the switch in function.

See Tokuriki et al

A metabolic tracing strategy was used for efficient determination of glycolytic thermodynamics revealing near-equilibrium glycolytic steps. The flow of sand represents glycolytic flux, with the narrowing of the hourglass depicting a thermodynamic bottleneck. The colors of the molecules represent the extent of deuterium labeling.

See Park et al.

Macrophages kill intracellular bacteria such as Mycobacterium tuberculosis (Mtb) through lysosome acidification, which serves to promote autophagic degradation of Mtb. To avoid this fate, virulent Mtb abundantly generates terpene nucleoside 1-TbAd, which acts as an antacid, regulating the pH of host lysosomes and therefore the degradation of the bacteria.

See Buter et al.

Caenorhabditis elegans worms were found to excrete an N-acylated glutamine that promotes exit from dauer diapause and accelerates sexual maturation of hermaphrodites. The cover depicts adult male (aqua colored) and hermaphrodite (magenta colored) C. elegans.

See Ludewig et al.

Chinese hamster ovary (CHO) cells have been engineered with genetic circuits for small-molecule-inducible expression of glycosyltransferases that modulate monoclonal antibody N-glycosylation. The cover depicts the secretion of glycosylated antibodies emerging from a Golgi circuit.

See Chang et al.

Before petunia flowers open, terpenoids are produced in the tube and emitted into the bud’s headspace. These volatile compounds then diffuse into the pistil, where they affect growth, seed yield, and the pistil microbiome in the developing flower.

See Boachon et al.

In the nanoFleming screen, library bacterial cells (artificially colored cyan) producing potential antibacterial compounds are encapsulated with sensor cells (artificially colored purple) in nanoliter reactor droplets. The production of an active antibiotic by a library cell restricts growth of the sensor strain, resulting in smaller colonies.

See Schmitt et al.

The use of chemoproteomics enabled the identification of new covalent targets of the oncometabolite fumarate in cells. The cover depicts chemoproteomics as a radar for reactivity with cellular structures in the background and the nucleus at the center.

See Meier et al.

A new method was developed that analyzes ibrutinib-induced changes of chromatin and chemosensitivity in chronic lymphocytic leukemia (CLL) cells in order to identify and prioritize treatment-specific vulnerabilities. The cover depicts CLL cells (green) and normal lymphocytes (orange). Chromatin fibers, which represent epigenetic cell states, are shown inside each cell.

See Schmidl et al.

Directed evolution of a set of 12 small-molecule-responsive biosensors and their integration into Escherichia coli “marionette” strains enables researchers to precisely control gene expression in bacteria, as conceptualized on the cover illustration of a bacterium being manipulated by a scientific puppeteer.

See Meyer et al.

Structures of G-protein-coupled receptors (GPCRs) in five main classes have advanced our knowledge about the mode of action of these receptors in normal and disease contexts and will continue to support the design of drugs to target them. This issue features structures of three members of the prostanoid receptor subfamily of GPCRs, EP3, EP4, and TP, shown here as structural models on a phylogenetic tree based on GPCR sequence. Also highlighted in the tree are those GPCRs (circled) represented by at least one solved structure.

See Audet et al.