Muscular thin films for building actuators and powering devices

We demonstrate the assembly of biohybrid materials from engineered tissues and synthetic polymer thin films. The constructs were built by culturing neonatal rat ventricular cardiomyocytes on polydimethylsiloxane thin films micropatterned with extracellular matrix proteins to promote spatially ordered, two-dimensional myogenesis. The constructs, termed muscular thin films, adopted functional, three-dimensional conformations when released from a thermally sensitive polymer substrate and were designed to perform biomimetic tasks by varying tissue architecture, thin-film shape, and electrical-pacing protocol. These centimeter-scale constructs perform functions as diverse as gripping, pumping, walking, and swimming with fine spatial and temporal control and generating specific forces as high as 4 millinewtons per square millimeter.     

Domesticated nature: shaping landscapes and ecosystems for human welfare

Like all species, humans have exercised their impulse to perpetuate and propagate themselves. In doing so, we have domesticated landscapes and ecosystems in ways that enhance our food supplies, reduce exposure to predators and natural dangers, and promote commerce. On average, the net benefits to humankind of domesticated nature have been positive. We have, of course, made mistakes, causing unforeseen changes in ecosystem attributes, while leaving few, if any, truly wild places on Earth. Going into the future, scientists can help humanity to domesticate nature more wisely by quantifying the tradeoffs among ecosystem services, such as how increasing the provision of one service may decrease ecosystem resilience and the provision of other services.     

A single IGF1 allele is a major determinant of small size in dogs

The domestic dog exhibits greater diversity in body size than any other terrestrial vertebrate. We used a strategy that exploits the breed structure of dogs to investigate the genetic basis of size. First, through a genome-wide scan, we identified a major quantitative trait locus (QTL) on chromosome 15 influencing size variation within a single breed. Second, we examined genetic variation in the 15-megabase interval surrounding the QTL in small and giant breeds and found marked evidence for a selective sweep spanning a single gene (IGF1), encoding insulin-like growth factor 1. A single IGF1 single-nucleotide polymorphism haplotype is common to all small breeds and nearly absent from giant breeds, suggesting that the same causal sequence variant is a major contributor to body size in all small dogs.     

Mercury cratering record viewed from MESSENGER's first flyby

Morphologies and size-frequency distributions of impact craters on Mercury imaged during MESSENGER's first flyby elucidate the planet's geological history. Plains interior to the Caloris basin displaying color and albedo contrasts have comparable crater densities and therefore similar ages. Smooth plains exterior to Caloris exhibit a crater density approximately 40% less than on interior plains and are thus volcanic and not Caloris impact ejecta. The size distribution of smooth-plains craters matches that of lunar craters postdating the Late Heavy Bombardment, implying that the plains formed no earlier than 3.8 billion years ago (Ga). At diameters less than or equal to 8 to 10 kilometers, secondary impact craters on Mercury are more abundant than primaries; this transition diameter is much larger than that on the Moon or Mars. A low density of craters on the peak-ring basin Raditladi implies that it may be younger than 1 Ga.     

Inactivation of TNF signaling by rationally designed dominant-negative TNF variants

Tumor necrosis factor (TNF) is a key regulator of inflammatory responses and has been implicated in many pathological conditions. We used structure-based design to engineer variant TNF proteins that rapidly form heterotrimers with native TNF to give complexes that neither bind to nor stimulate signaling through TNF receptors. Thus, TNF is inactivated by sequestration. Dominant-negative TNFs represent a possible approach to anti-inflammatory biotherapeutics, and experiments in animal models show that the strategy can attenuate TNF-mediated pathology. Similar rational design could be used to engineer inhibitors of additional TNF superfamily cytokines as well as other multimeric ligands.     

Discovery and directed evolution of a glyphosate tolerance gene

The herbicide glyphosate is effectively detoxified by N-acetylation. We screened a collection of microbial isolates and discovered enzymes exhibiting glyphosate N-acetyltransferase (GAT) activity. Kinetic properties of the discovered enzymes were insufficient to confer glyphosate tolerance to transgenic organisms. Eleven iterations of DNA shuffling improved enzyme efficiency by nearly four orders of magnitude from 0.87 mM-1 min-1 to 8320 mM-1 min-1. From the fifth iteration and beyond, GAT enzymes conferred increasing glyphosate tolerance to Escherichia coli, Arabidopsis, tobacco, and maize. Glyphosate acetylation provides an alternative strategy for supporting glyphosate use on crops.     

A new strategy for the synthesis of glycoproteins

Posttranslational modifications of proteins regulate many biological processes, including metabolism, signal transduction, and gene expression. The synthetic challenges associated with generating homogeneous populations of selectively modified proteins, however, have hindered detailed studies of the effects of these modifications on protein structure and function. Here, we report an approach to the cotranslational synthesis of selectively glycosylated proteins in which the modified amino acid is genetically encoded. We show that myoglobin containing beta-N-acetylglucosamine (GlcNAc)-serine at a defined position can be expressed in Escherichia coli in good yield and with high fidelity. The beta-GlcNAc moiety can be recognized by a saccharide-binding protein, or subsequently modified with a galactosyltransferase to build more complex carbohydrates. This approach should be generally applicable to other posttranslational modifications such as protein phosphorylation, acetylation, and methylation.     

Racemization of Amino Acids in Dipeptides Shows COOH > NH2 for Non-Sterically Hindered Residues

The relative rates of racemization for amino acid residues at the NH(2) and COOH ends of 37 different dipeptides were determined. In nine dipeptides containing alanine, leucine, phenylalanine, aspartic acid, and methionine, the amino acid residue racemized faster at the COOH-terminal position than at the NH(2)-terminal position (COOH > NH(2)). The sterically hindered amino acids isoleucine and valine showed NH(2) > COOH. Six proline dipeptides showed NH(2) > COOH. Intramolecular effects have been invoked to explain these surprising results.