Isolation of the closed circular form of the transposable element Tc1 in Caenorhabditis elegans

The mobilization of Tc1, a transposable element in the genome of the roundworm Caenorhabditis elegans, has been investigated. Genomic blot hybridization has shown that Tc1 exists in very different numbers in the genomes of two closely related strains of C. elegans: there are approximately 30 copies of Tc1 in the Bristol strain, whereas in the Bergerac strain there are 200-300. Most of these Tc1 elements are structurally highly conserved although there exists a second form which contains a HindIII restriction site (Tc1 (Hin) form) and comprises approximately 10% of the population. Excision of Tc1 from its chromosomal location in the Bergerac strain is indicated by the presence, on genomic blots, of a minor band corresponding to the size of the uninserted restriction fragment. Here we describe the recovery of extrachromosomal linear and closed circular copies of Tc1 from the Bergerac strain, presumably a result of Tc1 excision.     

Lymphopenia and lymphocyte transformation in alcoholics

Summary The basis of peripheral blood lymphopenia observed in patients with chronic alcoholism and liver disease was investigated by examining the effect of sera of these patients on in vitro transformation of normal human peripheral blood lymphocytes. A positive correlation was demonstrated between the serum inhibition of phytohaemagglutinin- and pokeweed mitogen-induced transformation and the degree of lymphopenia. Thus serum factors may contribute to the observed lymphopenia by inhibiting lymphocyte production in vivo.This study was supported by grants from the National Health and Medical Research Council of Australia, Royal Australasian College of Physicians and Alfred Hospital Henry Laurie Scholarship Fund.     

Aberrant thymus tissue in rat and mouse thyroid

Résumé Dans différentes lignées de souris et de rats, on a souvent trouvé du tissu thymique d'aspect normal au voisinage ou dans la thyroide mme. Les animaux thymectomisés dovient tre examinés pour contrôler la présemce d'un tissu thymique aberrant.

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Research assistant professor, supported by Bertha H. and Henry Buswell Ressearch Fellowship.

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This work was supported in part by USPHS research grant No CA 05203 from the National Caucer Institute.     

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.