Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
Rissin et al. increase the sensitivity of sandwich ELISA by segregating beads bearing a single enzyme-labeled immunoconjugate into femtoliter-volume reaction chambers. As the small volume of each well permits detection of extremely low levels of fluorescence, protein abundance is determined by counting the number of fluorescent wells as a percentage of the number of wells containing beads.
Insects are biotechnologically important producers of recombinant proteins and materials, and their biology as crop pests has substantial economic consequences. Xiang et al. map cytosine methylation genome-wide at single-base resolution in the silkworm, opening the door for global studies of epigenetic DNA modification in insects.
Smith et al. use time-lapse imaging to study the conversion of mouse embryonic fibroblasts to induced pluripotent stem cells. By reconstructing movies of single cells over a two-week period, they identify an early phenotypic change characteristic of cells that are successfully reprogrammed.
RNA-Seq enables rapid sequencing of total cellular RNA and should allow the reconstruction of spliced transcripts in a cell population. Trapnell et al. achieve this and transcript quantification using only paired-end RNA-Seq data and an unannotated genome sequence, and apply the approach to characterize isoform switching over a developmental time course.
Human embryonic stem cells are generally cultured as adherent monolayers, but large-scale production of these cells for clinical applications would require the development of culture conditions amenable to growth in bioreactors. Steiner et al. show that human embryonic stem cells can be derived, grown and differentiated in suspension.
Synthetic genetic circuits may be used to program cells to respond to physiological conditions with predictable dynamic behaviors. Kemmer et al. describe the engineering of a mammalian circuit that maintains homeostasis of a bloodstream metabolite within a physiologically appropriate range.
Plant pattern-recognition receptors (PRRs) confer resistance to infection by many microbes by recognizing conserved molecules important for pathogen viability. Lacombe et al. show that transfer of a PRR from a wild species to tobacco and tomato plants renders them resistant to several bacterial phytopathogens.
Many proteases are important drug targets, but identification of their substrates remains challenging. By using polymers to selectively isolate N-terminal peptides generated by proteolysis of complex samples, Kleifeld et al. identify substrates of clinically relevant proteases with broad specificity.
Spinal muscular atrophy is an autosomal recessive disease of motor neurons caused by lack of the SMN gene. Foust et al. achieve long-term correction of the disease phenotype in a mouse model by intravenous delivery of SMN using the viral vector scAAV9.
In acute myeloid leukemia, a sub-population of quiescent cancer cells, called leukemia stem cells, is thought to be responsible for chemotherapy resistance and eventual recurrence of the disease. Saito et al. show that treatment with granulocyte colony-stimulating factor can overcome resistance to standard therapy by inducing cell cycle entry of the leukemia stem cells.
Hepatitis C virus research is hampered by the inability to detect individual infected cells. Jones et al. achieve this by imaging the translocation of a fluorescent reporter protein after cleavage by a viral protease in living or fixed cells.
Efficient siRNA delivery remains a key challenge to realizing the full potential of RNAi-based therapeutics. Semple et al. accomplish unprecedented potency for liposome-mediated siRNA delivery by applying rational design to refine an empirically identified cationic lipid widely regarded as the benchmark for use in lipid nanoparticles.
James et al. describe a method for efficient differentiation of human embryonic stem cells into endothelial cells using TGFβ inhibition. Sustained expansion and maintenance of endothelial cells is shown to depend on expression of the vascular transcription factor Id1.
Gene therapy vectors based on adeno-associated virus tend to accumulate in the liver, limiting their utility for targeting other organs. Using site-directed mutagenesis of the capsid surface, Asokan et al. generate a variant that efficiently transduces a wide range of muscle groups while avoiding the liver.
The intrinsic variation between mass spectrometry data collected from replicate samples is a major hurdle to realizing the full potential of shotgun proteomics. Griffin et al. present a simple method to compare label-free quantifications between technical and biological replicates.