Temporal hyperacuity in the electric sense of fish

It has recently become evident that sensory thresholds for certain tasks are lower than those expected from the properties of individual receptors. This perceptual capacity, termed hyperacuity, reveals the impressive information-processing abilities of the central nervous system. Although much is known about spatial hyperacuity, temporal hyperacuity has received little attention. Here we demonstrate that an electric fish, Eigenmannia, can detect modulations in the timing (phase) of an electrical signal at least as small as 400 ns. Such sensitivity exceeds the temporal resolution of individual phase-coding afferents. This hyperacuity results from a nonlinear convergence of parallel afferent inputs to the central nervous system; subthreshold inputs from particular areas of the body surface accumulate to permit the detection of these extremely small temporal modulations.     

Molecular mimicry: a critical look at exemplary instances in human diseases

Molecular mimicry, the concept that antigenic determinants of microorganisms resemble antigenic determinants of the host, is frequently cited as a plausible mechanism to account for the association of infection and autoimmune disease. Based on analogous sequences of amino acids or on cross-reactions of monoclonal antibodies, numerous examples of such mimicry have been reported. There are, however, no clear examples of a human disease caused by molecular mimicry.     

Cascades of multisite phosphorylation control Sic1 destruction at the onset of S phase

Multisite phosphorylation of proteins has been proposed to transform a graded protein kinase signal into an ultrasensitive switch-like response. Although many multiphosphorylated targets have been identified, the dynamics and sequence of individual phosphorylation events within the multisite phosphorylation process have never been thoroughly studied. In Saccharomyces cerevisiae, the initiation of S phase is thought to be governed by complexes of Cdk1 and Cln cyclins that phosphorylate six or more sites on the Clb5-Cdk1 inhibitor Sic1, directing it to SCF-mediated destruction. The resulting Sic1-free Clb5-Cdk1 complex triggers S phase. Here, we demonstrate that Sic1 destruction depends on a more complex process in which both Cln2-Cdk1 and Clb5-Cdk1 act in processive multiphosphorylation cascades leading to the phosphorylation of a small number of specific phosphodegrons. The routes of these phosphorylation cascades are shaped by precisely oriented docking interactions mediated by cyclin-specific docking motifs in Sic1 and by Cks1, the phospho-adaptor subunit of Cdk1. Our results indicate that Clb5-Cdk1-dependent phosphorylation generates positive feedback that is required for switch-like Sic1 destruction. Our evidence for a docking network within clusters of phosphorylation sites uncovers a new level of complexity in Cdk1-dependent regulation of cell cycle transitions, and has general implications for the regulation of cellular processes by multisite phosphorylation.