The ribosomal translation of genetic material into protein polymers serves as an archetype for the elegance and complexity possible in biological processes. Effraim et al. (p 947) probed the limits of substrate selection in this process, studying translational efficiency with misloaded amino acids. In an unrelated study, Kawakami et al. (p 888) further employed misloaded amino acids to create a self-cyclizing peptide sequence. The enabled keyboard featured on the cover highlights both our current paradigms in ribosomal translation as well as the open questions and engineering potential that remain. Cover art by Erin Dewalt, based on an original image from iStockphoto.com, © Paul Cowan.

The structure of a protein is a key determinant of its function, but the relationship of a protein's structure to its dynamics, motions and conformational variations is also important. This issue presents a collection of articles that discuss our current understanding of protein dynamics and of the methods used to study the dynamics of proteins at the individual level as well as their interactions with the larger biological systems in which they function. Cover art by Erin Dewalt, based on an image of a plowed field reminiscent of a protein energy landscape (original image from www.fotosearch.com).

Mutant synthetases allow selective labeling. Ngo et al. (p 715) describe the combination of azidonorleucine, a non-natural amino acid that can be used in 'click' reactions, with a mutant methionyl-tRNA synthetase selective for this new residue, which allows for the specific modification of proteins in mutant cell strains within mixed cell cultures. The cover shows a three-dimensional topographic rendering of an infection of mouse macrophages by Escherichia coli labeled with azidonorleucine and further modified with a fluorescent dye. Cover art by Erin Dewalt, based on an original image from Julie A. Champion.

DNA-encoded libraries. Clark et al. (p 647) describe a new method for synthesizing DNA-encoded libraries that uses double-stranded DNA coding and a combination of enzymatic and chemical synthesis in a split-and-pool format. With this approach, the authors synthesized two libraries, the larger of which contains just over 800 million molecules, and rapidly selected novel, potent kinase inhibitors. The cover shows a microscopic view of affinity selection for DNA-linked compounds that bind to p38 MAP kinase. Cover art by Erin Dewalt, based on images provided by Kenneth Lind and Matthew Clark.

Biological catalysis includes a wide and expanding range of chemical reactions mediated by proteins and nucleic acids. Many of these reactions have been extensively charted with increasingly sophisticated biochemical and structural techniques. However, our understanding of the chemical and physical basis for these transformations, as well as our ability to predict and manipulate them, remain limited. This map provides direction for those seeking to access new compounds via known enzyme functions. Cover art by Erin Dewalt, based on an original image from iStockphoto.com, © AdrianHillman.

An inhibitor 'hijacks' kinase regulation. Okuzumi et al. (p 484) investigated the mechanism by which the ATP-competitive Akt inhibitor A-443654 induces hyperphosphorylation of Akt regulatory sites. Using chemical genetic tools, the authors found that inhibitor binding, rather than pathway feedback, directly triggers Akt hyperphosphorylation (see also News and Views by Frye and Johnson on p 448). The cover shows Akt in contact with two regulatory kinases, PDK and mTORC2, and an analog of A-443654. Cover art by Erin Dewalt.

A small molecule defines an ecological network. Apterostigma dentigerum, a species of fungus-growing ants, utilizes Pseudonocardia actinobacteria to protect a desired species of fungus from the parasitic Escovopsis fungus. Oh et al. (p 391) use a suite of known and modified methods to first isolate the bacteria, and then isolate and characterize the small molecule that serves as an antifungal agent. The discovery of this new natural product, named dentigerumycin, will allow further studies on this interesting mutualistic community. This image shows a member of the ant colony at work in the fungal garden. Cover art by Erin Boyle, based on a photo provided by Michael Poulsen.

Because of their contributions to ecosystems and economies at the local and global scales, plants have been the subject of scientific investigations for centuries. Historically, botanical sciences have focused on plants as organisms or parts of ecological niches, but advances in genetics and molecular biology have led to a deeper understanding of plant cellular biology. In parallel, more recent postgenomic and systems biology approaches have offered a more integrated view of plant biology from molecules to ecosystems. In this issue, we highlight several emerging areas of plant chemical biology that bring the molecular processes of plant biology into greater focus. Cover by Erin Boyle based on a photograph by Siede Preis featuring an engraving of bamboo plants on aluminum (Getty images).

Compounds direct differentiation of human embryonic stem cells (hESCs) to pancreatic progenitors. Chen et al. (p 258) isolated (-)-indolactam V (ILV) from a high-content screen, and when added to definitive endoderm that had been derived from hESCs, ILV increased the number of cells that express the pancreatic marker Pdx1. Pdx1 and other pancreatic lineage markers, such as FOXA2, were monitored by immunocytochemistry. ILV acted synergistically with FGF10, a known contributor to pancreatic development, to produce the Pdx1-positive cells shown here (see also News and Views by Wright, p 195). Cover art by Erin Boyle, based on images provided by Douglas Melton.

Engineering alkaloids in plants. Runguphan and O'Connor (p 151) transform an engineered alkaloid biosynthetic gene into Catharanthus roseus to metabolically reprogram the plant's alkaloid pathway. When transgenic plant cultures were fed modified substrates, the plants produced unnatural alkaloid compounds (see also News and Views by Ryan and Moore on p 140). The cover shows a mosaic of C. roseus plants and tissue culture representing the various stages of the genetic engineering and plant transformation processes. Cover art by Erin Boyle based on images provided by Weerawat Runguphan.

Fluorescent proteins keep time in vivo. Using rational design and saturation mutagenesis, Subach et al. (p 118) created three fluorescent timers based on mCherry with slow, medium and fast maturation rates. The authors then used the 'medium' timer to track trafficking of a membrane protein to its final destination (see also News and Views by Daunert, p 70). In this image, the clock numbers are colonies of bacteria that have been expressing the fast fluorescent timer protein for the number of hours indicated by the clock numeral, yielding a real-time display of the conversion from blue to red fluorescence. Cover art by Erin Boyle, based on an image provided by Fedor Subach.

Proteasomal substrate selection. Prakash et al. (p 29) mixed and matched a ubiquitin tag and an unstructured region, two signals for proteasomal targeting, on the protein complex components barnase and barstar. Attaching ubiquitin to barstar and an unstructured region to barnase resulted in degradation of barnase through an in trans targeting mechanism (see also News and Views by Wandless on p 3). Barstar modified with four ubiquitin domains is shown targeting the unstructured region of barnase to the proteasome. Cover art by Erin Boyle based on images provided by Sumit Prakash and Tomonao Inobe.