The splicing code, decoded

For many years, researchers have attempted to define the combinatorial rules that control alternative splicing. Barash et al. now report a code, implemented in a web tool, that predicts tissue-specific alternative splicing with high accuracy. To construct the algorithm, they analyzed a large amount of data profiling alternatively spliced exons in diverse mouse tissues, known RNA binding sites and sequence motifs, exon-intron organization characteristics, evolutionary conservation and RNA fold structure.

Barash, Y. et al. Nature 465, 53–59 (2010).

Stem cells

Making mechanosensitive sensory hair cells

Damage to mechanosensitive sensory hair cells found in the mammalian inner ear can result in permanent hearing loss and balance problems because these cells do not regenerate. Oshima et al. report a protocol to generate such cells, which could eventually be used in therapies. Starting with embryonic stem cells and induced pluripotent stem cells, they identified conditions for differentiation into hair cell–like cells that exhibited characteristic hair cell morphologies and were responsive to mechanical stimulations.

Oshima, K. et al. Cell 141, 704–716 (2010).


A bold application of optogenetics

Functional magnetic resonance imaging measures brain activity by detecting blood oxygenation level–dependent (BOLD) signals. For a long time, the link between BOLD signals and neural firing has been hard to demonstrate. Using optogenetic tools to excite specific sets of neurons, Lee et al. now show that neuronal activity elicits BOLD signals. The unification of these two powerful methods will open new possibilities for mapping large-scale neural circuits in the brains of live animals.

Lee, J.H. et al. Nature 465, 788–792 (2010).


Digital ELISA

The enzyme-linked immunosorbent assay, ELISA, is not sensitive enough to detect proteins found in very low concentrations in biological samples. Rissin et al. describe a 'digital ELISA', which can be used to detect proteins in serum at concentrations as low as 10−15 M. Using an on-bead ELISA format, they capture proteins of interest and distribute the beads into femtoliter-volume well arrays, where they image them by fluorescence microscopy. The percentage of fluorescent beads is proportional to the concentration of the protein in the sample.

Rissin, D.M. et al. Nat. Biotechnol. 28, 595–599 (2010).


High-throughput single-molecule force spectroscopy

Typical single-molecule force spectroscopy procedures require substantial time and effort to acquire multiple measurements. Halvorsen and Wong describe a centrifuge force microscope in which the instrument components and sample—consisting of thousands of beads bound to a coverslip via a DNA tether and receptor-antigen pair—are on a rotating arm. Centrifugal force pulls the beads from the surface, and visualizing the rupture events yields thousands of parallel measurements of receptor unbinding.

Halvorsen, K. & Wong, W.P. Biophys. J. 98, L53–L55 (2010).