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[
WormBook,
2005]
Protein kinases are one of the largest and most influential of gene families: constituting some 2% of the proteome, they regulate almost all biochemical pathways and may phosphorylate up to 30% of the proteome. Bioinformatics and comparative genomics were used to determine the C. elegans kinome and put it in evolutionary and functional context. Kinases are deeply conserved in evolution, and the worm has family homologs for over 80% of the human kinome. Almost half of the 438 worm kinases are members of worm-specific or worm-expanded families. Such radiations include genes involved in spermatogenesis, chemosensation, Wnt signaling and FGF receptor-like kinases. The C. briggsae kinome is largely similar apart from the expanded classes, showing that such expansions are evolutionarily recent.
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[
1998]
The free-living nematode Caenorhabditis elegans has emerged rapidly as an organism with which to study many basic biological phenomena, particularly those related to development. This can ben evidenced numerically in many ways; for example, the number of presentations at the biennial C. elegans meeting has increased over sevenfold, from 80 in 1979 to 569 in 1995. In addition to numerous review articles, several books are devoted to this nematode, its attributes and various foci of interest. The three preliminary attributes that have rendered C. elegans a popular model system are overviewed briefly in the following three sections. The attributes that have rendered C. elegans popular with developmental biologists have also been exploited to examine specific areas in radiation biology, DNA repair, and mutagenesis. Several of the basic DNA repair pathways operative in C. elegans have been elucidated. Also, a number of biological end points such as survival and mutagenesis, have been examined so as to address the various mechanisms by which C. elegans accommodates DNA damage. Central to these efforts has been the isolation and characterization of radiation-sensitive (rad) mutants that modify various biological responses. In particular, these studies provide insights into damage processing, particularly as related to development and aging.
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[
1999]
Caenorhabditis elegans is a free-living soil nematode that is commonly used as a biological model. Recently, much work has been done using the nematode as a toxicological model as well. Much of the work involving C. elegans has been performed in aquatic media, since it lives in the interstitial water of soil. However, testing in soil would be expected to more accurately reproduce the organism's normal environment and may take into consideration other factors not available in an aquatic test, i.e., toxicant availability effects due to sorption, various chemical interactions, etc. This study used a modification of a previous experimental protocol to determine 24h LC50 values for Cu in a Cecil series soil mixture, and examined the use of CuCl2 as a reference toxicant for soil toxicity testing with C. elegans. Three different methods of determining percent lethality were used, each dependent on how the number of worms missing after the recovery process was used in the lethality calculations. Only tests having >/= 80% worm recovery and >/= 90% control survival were used in determining the LC50S, by Probit analysis. The replicate LC50 values generated a control chart for each method of calculating percent lethality. The coefficient of variation (CV) for each of the three methods was </= 14%. The control charts and the protocol outlined in this study are intended to be used to assess test organism health and to monitor precision of future soil toxicity tests with C.
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[
Adv Exp Med Biol,
2010]
Nematode neuropeptide systems comprise an exceptionally complex array of approximately 250 peptidic signaling molecules that operate within a structurally simple nervous system of approximately 300 neurons. A relatively complete picture of the neuropeptide complement is available for Caenorhabditis elegans, with 30 flp, 38 ins and 43 nlp genes having been documented; accumulating evidence indicates similar complexity in parasitic nematodes from clades I, III, IV and V. In contrast, the picture for parasitic platyhelminths is less clear, with the limited peptide sequence data available providing concrete evidence for only FMRFamide-like peptide (FLP) and neuropeptide F (NPF) signaling systems, each of which only comprises one or two peptides. With the completion of the Schmidtea meditteranea and Schistosoma mansoni genome projects and expressed sequence tag datasets for other flatworm parasites becoming available, the time is ripe for a detailed reanalysis ofneuropeptide signalingin flatworms. Although the actual neuropeptides provide limited obvious value as targets for chemotherapeutic-based control strategies, they do highlight the signaling systems present in these helminths and provide tools for the discovery of more amenable targets such as neuropeptide receptors or neuropeptide processing enzymes. Also, they offer opportunities to evaluate the potential of their associated signaling pathways as targets through RNA interference (RNAi)-based, target validation strategies. Currently, within both helminth phyla, theflp signaling systems appear to merit further investigation as they are intrinsically linked with motor function, a proven target for successful anti-parasitics; it is clear that some nematode NLPs also play a role in motor function and could have similar appeal. At this time, it is unclear if flatworm NPF and nematode INS peptides operate in pathways that have utility for parasite control. Clearly, RNAi-based validation could be a starting point for scoring potential target pathways within neuropeptide signaling for parasiticide discovery programs. Also, recent successes in the application of in planta-based RNAi control strategies for plant parasitic nematodes reveal a strategy whereby neuropeptide encoding genes could become targets for parasite control. The possibility of developing these approaches for the control of animal and human parasites is intriguing, but will require significant advances in the delivery of RNAi-triggers.