Ras farnesyltransferase inhibitors suppress the phenotype resulting from an activated ras mutation in Caenorhabditis elegans.

Attachment of Ras protein to the membrane, which requires farnesylation at its C terminus, is essential for its biological activity. A promising pharmacological approach of antagonizing oncogenic Ras activity is to develop inhibitors of farnesyltransferase. We use Caenorhabditis elegans vulval differentiation, which is controlled by a Ras-mediated signal transduction pathway, as a model system to test previously identified farnesyltransferase inhibitors. We show here that two farnesyltransferase inhibitors, manumycin and gliotoxin, suppress the Multivulva phenotype resulting from an activated let-60 ras mutation, but not the Multivulva phenotype resulting from mutations in the lin-1 gene or the lin-15 gene, which act downstream and upstream of let-60 ras, respectively, in the signaling pathway. These results are consistent with the idea that the suppression of the Multivulva phenotype of let-60 ras by the two inhibitors is specific for Ras protein and that the mutant Ras protein might be more sensitive than wild-type Ras to the farnesyltransferase inhibitors. This work suggests that C. elegans vulval development could be a simple and effective in vivo system for evaluation of farnesyltransferase inhibitors against Ras-activated tumors.

Evolution of Outcrossing in Experimental Populations of Caenorhabditis elegans

Caenorhabditis elegans can reproduce exclusively by self-fertilization. Yet, males can be maintained in laboratory populations, a phenomenon that continues to puzzle biologists. In this study we evaluated the role of males in facilitating adaptation to novel environments. For this, we contrasted the evolution of a fitness component exclusive to outcrossing in experimental populations of different mating systems. We introgressed a modifier of outcrossing into a hybrid population derived from several wild isolates to transform the wild-type androdioecious mating system into a dioecious mating system. By genotyping 375 single-nucleotide polymorphisms we show that the two populations had similar standing genetic diversity available for adaptation, despite the occurrence of selection during their derivation. We then performed replicated experimental evolution under the two mating systems from starting conditions of either high or low levels of diversity, under defined environmental conditions of discrete non-overlapping generations, constant density at high population sizes (N = 10(4)), no obvious spatial structure and abundant food resources. During 100 generations measurements of sex ratios and male competitive performance showed: 1) adaptation to the novel environment; 2) directional selection on male frequency under androdioecy; 3) optimal outcrossing rates of 0.5 under androdioecy; 4) the existence of initial inbreeding depression; and finally 5) that the strength of directional selection on male competitive performance does not depend on male frequencies. Taken together, these results suggest that androdioecious males are maintained at intermediate frequencies because outcrossing is adaptive.

Marini Becichemi Scodrensis elegans ac docta in C. Plinium Praelectio, eiusdem Pinii praefatio in libros historiae naturalis ... eiusdem Scodrensis collectanea in primum Plinii ... Nicolai Perotti Pontificis Sipo[n]tini Commentariolus in eundem primum Plinii librum, Cornelii Vitelli in eundem primum enarratiuncula perquam erudita.

CCBE S. XVI, B, 570

Quinti Sereni Sammonici ... De re medica, siue Morborum curationibus liber tum elegans tum humanae saluti perquàm utilis, & diligenter emendatus ; item Gabrielis Humelbergij Rauenspurgensis, medici, in Q. Sereni librum medicinalem Commentarii.

Mode of access: Internet.

Bartholomaei Bertazolii ... Tractatvs clavsvlarvm instrvmentalivm ... Cvi ad extremvm eivsdem avtoris elegans admodvm Repetitio adnexa est L. Si quis maior, C. De transactionibus. Indice rerum memoria dignarum, ita & serie alphabetica ordinatè digesto, accedente.

Prefatory dedication signed: Io. Baptista Bertazolus.

Philiberti Pingonii Sabaudi ... Sindon euangelica : accesserunt Hymni aliquot, Insignis Bulla pontificia, elegans Epist. Francisci Adorni Ies. de peregrinatione memorabili.

Edit16,

Dissertatio botanica de passiflora ... : quam, cum consensu amplis. facult. medicae, in reg. academi Upsalensi /

In Linné's Amoenitates academicae, v. 1 [ed. 1] 1749, p. 244-279; [ed. 2] 1749, and ed. 3, 1787, p. 211-242. cf. Hulth, Bibl. Linn. (1907) p. 42.

Descriptions of a new genus of plants named Araujia, and of a new species of Passiflora [P. racemosa].

Transactions of the Linnean society of London, 1818, xii, p. 62-75, 3 pl.

Tractatvs de crimine laesae maiestatis insignis, et elegans ...

Title vignette.

Functionality, Robustness and Control of Nonlinear Network Dynamics: Modeling and Understanding the C. elegans Connectome

Thesis (Ph.D.)--University of Washington, 2016-06

CemaT1 is an active transposon within the Caenorhabditis elegans genome

The maT clade of transposons is a group of transposable elements intermediate in sequence and predicted protein structure to mariner and T-C transposons, with a distribution thus far limited to a few invertebrate species. In the nematode Caenorhabditis elegans, there are eight copies of CemaT1 that are predicted to encode a functional transposase, with five copies being >99% identical. We present evidence, based on searches of publicly available databases and on PCR-based mobility assays, that the CemaT1 transposase is expressed in C. elegans and that the CemaT transposons are capable of excising in both somatic and germline tissues. We also show that the frequency of CemaT1 excisions within the genome of the N2 strain of C. elegans is comparable to that of the Tc1 transposon. However, unlike T-C transposons in mutator strains of C elegans, maT transposons do not exhibit increased frequencies of mobility, suggesting that maT is not regulated by the same factors that control T-C activity in these strains. Finally, we show that CemaT1 transposons are capable of precise transpositions as well as orientation inversions at some loci, and thereby become members of an increasing number of identified active transposons within the C. elegans genome. (C) 2004 Elsevier B.V. All rights reserved.