Proteomic screen finds pSer/pThr-binding domain localizing Plk1 to mitotic substrates

We have developed a proteomic approach for identifying phosphopeptide binding domains that modulate kinase-dependent signaling pathways. An immobilized library of partially degenerate phosphopeptides biased toward a particular protein kinase phosphorylation motif is used to isolate phospho-binding domains that bind to proteins phosphorylated by that kinase. Applying this approach to cyclin-dependent kinases (Cdks), we identified the polo-box domain (PBD) of the mitotic kinase polo-like kinase 1 (Plk1) as a specific phosphoserine (pSer) or phosphothreonine (pThr) binding domain and determined its optimal binding motif. This motif is present in known Plk1 substrates such as Cdc25, and an optimal phosphopeptide containing the motif disrupted PBD-substrate binding and localization of the PBD to centrosomes. This finding reveals how Plk1 can localize to specific sites within cells in response to Cdk phosphorylation at those sites and provides a structural mechanism for targeting the Plk1 kinase domain to its substrates.     

Global biodiversity,biochemical kinetics,and the energetic-equivalence rule

The latitudinal gradient of increasing biodiversity from poles to equator is one of the most prominent but least understood features of life on Earth. Here we show that species diversity can be predicted from the biochemical kinetics of metabolism. We first demonstrate that the average energy flux of populations is temperature invariant. We then derive a model that quantitatively predicts how species diversity increases with environmental temperature. Predictions are supported by data for terrestrial, freshwater, and marine taxa along latitudinal and elevational gradients. These results establish a thermodynamic basis for the regulation of species diversity and the organization of ecological communities.     

Farming and the fate of wild nature

World food demand is expected to more than double by 2050. Decisions about how to meet this challenge will have profound effects on wild species and habitats. We show that farming is already the greatest extinction threat to birds (the best known taxon), and its adverse impacts look set to increase, especially in developing countries. Two competing solutions have been proposed: wildlife-friendly farming (which boosts densities of wild populations on farmland but may decrease agricultural yields) and land sparing (which minimizes demand for farmland by increasing yield). We present a model that identifies how to resolve the trade-off between these approaches. This shows that the best type of farming for species persistence depends on the demand for agricultural products and on how the population densities of different species on farmland change with agricultural yield. Empirical data on such density-yield functions are sparse, but evidence from a range of taxa in developing countries suggests that high-yield farming may allow more species to persist.     

Large-scale copy number polymorphism in the human genome

The extent to which large duplications and deletions contribute to human genetic variation and diversity is unknown. Here, we show that large-scale copy number polymorphisms (CNPs) (about 100 kilobases and greater) contribute substantially to genomic variation between normal humans. Representational oligonucleotide microarray analysis of 20 individuals revealed a total of 221 copy number differences representing 76 unique CNPs. On average, individuals differed by 11 CNPs, and the average length of a CNP interval was 465 kilobases. We observed copy number variation of 70 different genes within CNP intervals, including genes involved in neurological function, regulation of cell growth, regulation of metabolism, and several genes known to be associated with disease.     

Understanding overbidding: using the neural circuitry of reward to design economic auctions

We take advantage of our knowledge of the neural circuitry of reward to investigate a puzzling economic phenomenon: Why do people overbid in auctions? Using functional magnetic resonance imaging (fMRI), we observed that the social competition inherent in an auction results in a more pronounced blood oxygen level-dependent (BOLD) response to loss in the striatum, with greater overbidding correlated with the magnitude of this response. Leveraging these neuroimaging results, we design a behavioral experiment that demonstrates that framing an experimental auction to emphasize loss increases overbidding. These results highlight a role for the contemplation of loss in understanding the tendency to bid "too high." Current economic theories suggest overbidding may result from either "joy of winning" or risk aversion. By combining neuroeconomic and behavioral economic techniques, we find that another factor, namely loss contemplation in a social context, may mediate overbidding in auctions.     

Synteny and collinearity in plant genomes

Correlated gene arrangements among taxa provide a valuable framework for inference of shared ancestry of genes and for the utilization of findings from model organisms to study less-well-understood systems. In angiosperms, comparisons of gene arrangements are complicated by recurring polyploidy and extensive genome rearrangement. New genome sequences and improved analytical approaches are clarifying angiosperm evolution and revealing patterns of differential gene loss after genome duplication and differential gene retention associated with evolution of some morphological complexity. Because of variability in DNA substitution rates among taxa and genes, deviation from collinearity might be a more reliable phylogenetic character.     

A metagenomic survey of microbes in honey bee colony collapse disorder

In colony collapse disorder (CCD), honey bee colonies inexplicably lose their workers. CCD has resulted in a loss of 50 to 90% of colonies in beekeeping operations across the United States. The observation that irradiated combs from affected colonies can be repopulated with naive bees suggests that infection may contribute to CCD. We used an unbiased metagenomic approach to survey microflora in CCD hives, normal hives, and imported royal jelly. Candidate pathogens were screened for significance of association with CCD by the examination of samples collected from several sites over a period of 3 years. One organism, Israeli acute paralysis virus of bees, was strongly correlated with CCD.     

Detection of radial crossbridge force by lattice spacing changes in intact single muscle fibers

Time-resolved lattice spacing changes were measured (10-millisecond time resolution) by x-ray diffraction of synchrotron radiation in single intact muscle fibers of the frog Rana temporaria undergoing electrically stimulated tension development during application of stretches and releases. Ramp releases, which decreased fiber length at constant speed, caused a lattice expansion. After the ramp, increasing tension during recovery was accompanied by lattice compression. Ramp stretches caused a compression of the lattice. While the fiber was held at a constant length after the stretch, tension decreased and lattice spacing increased. These observations demonstrate the existence of a previously undetected radial component of the force generated by a cycling crossbridge. At sarcomere lengths of 2.05 to 2.2 micrometers, the radial force compresses the myofilament lattice. Hence, the myofilament lattice does not maintain a constant volume during changes in force.     

Serum globulin in myasthenia gravis: inhibition of alpha-bungarotoxin binding to acetylcholine receptors

Serum factors that inhibit the binding of (125)I-labeled alpha-bungarotoxin to the acetylcholine receptor extracted in detergent from denervated rat muscle were detected by a sensitive assay. The serum of at least 5 and possibly 11 out of 15 patients with myasthenia gravis showed inhibitory activity that was localized to the globulin fraction. No controls showed inhibitory activity. The demonstration of inhibitory globulins may help explain the involvement of the immune system in the pathophysiology of the neuromuscular junction in patients with myasthenia gravis.