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[
International C. elegans Meeting,
1991]
Some 7-alkoxy-2,2-dimethylchromenes (precocenes) adversely affect caenorhabditids. Some symptomps caused by them could partially be compensated by exogenous insect juvenile hormone analogue (JHA) methopren (Fodor et al., 1982, 1989; Fodor & Timar, 1989, Gen. Comp. Endocrinol.). Precocenes are suspected pro-mutagenes, which might be activated by epoxydases in some tissues and the JHA may act as a competitor. Whether precocenes could be used as selective agents for getting mutants resistant to free radicals, eleven biologically active analog were tested according to Szabad et al. (Mut. Res., 1981) by determining the frequency of mitotic recombination in untreated and P-- treated Drosophila melanoqaster. The results were practically negative but inconclusive, as the precocenes inactivated in the medium within a few hours. Just below its toxic concentration (at a dose of 150 ug/ml NGM medium), however, precocene II did significantly decrease the average life span of the amphimictic strain of C. remanei at 25 C from 8 days to 6. Whether the adverse effect on the life span can or cannot be compensated is under study.
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[
General & Comparative Endocrinology,
1989]
Fourteen 7-alkoxy-2,2-dimethylchromenes were synthetized and studied in JH competition experiments: prococenes (Ps) PI and PII, and synthetic analogs (PAs) including (i) three with both antiallatal and P-like activities: 7-ethoxy-PII (7-EPII); 7-(
prop-2-ynyloxy)-2,2-dimethylchromene (PPI); and 6-methoxy-7-(
prop-2-yynyloxy)-2,2-dimethylchromene (PPIII); (ii) six without antiallatal activity, exerting P-like activity in nematodes; and (iii) three without either antiallatal or P-like activity, but with a strong nematocidal effect. Within the dose range 8-1000 ug/ml, different concentrations of each PA were applied to nematode growth medium which did or did not contain 1000 ug methoprene (a juvenile hormone analog JHA)/ml. Plates inoculated with Caenorhabditis embryos were incubated and scored for developmentally affected survivors. The JHA did not compete with any PA mentioned as (iii). It competed moderately with some nonantiallatal PAs (8-Me-PPI, 8-MeO-PPI, and 3,4-diCl-PPI) with strong P-like and nematocidal activities. The JHA competed most efficiently with all Ps, antiallatal PAs, and two nonantiallatal PAs (PPII and thio-PI) which exerted severe P-like activities in nematodes. Parameters assumed to be indicators of the P-like (rather than nematocidal) activity of the PAs proved more sensitive to the JHA than those of nematocidal activity. Whether the JH-compensable P-like activity of some PAs can be regarded as a real anti-JH action needs further clarification.
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[
J Neurosci,
2003]
Thermotactic behavior in Caenorhabditis elegans is sensitive to both a worm's ambient temperature (T-amb) and its memory of the temperature of its cultivation (T-cult). The AFD neuron is part of a neural circuit that underlies thermotactic behavior. By monitoring the fluorescence of pH-sensitive green fluorescent protein localized to synaptic vesicles, we measured the rate of the synaptic release of AFD in worms cultivated at temperatures between 15 and 25degreesC, and subjected to fixed, ambient temperatures in the same range. We found that the rate of AFD synaptic release is high if either T-amb > T-cult or T-amb > T-cult, but AFD synaptic release is low if T-amb congruent to T-cult. This suggests that AFD encodes a direct comparison between T-amb and T-cult.
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[
International C. elegans Meeting,
1981]
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[
Trends Mol Med,
2007]
Transforming growth factor beta1 (TGFbeta1), an important pleiotropic, immunoregulatory cytokine, uses distinct signaling mechanisms in lymphocytes to affect T-cell homeostasis, regulatory T (T(reg))-cell and effector-cell function and tumorigenesis. Defects in TGFbeta1 expression or its signaling in T cells correlate with the onset of several autoimmune diseases. TGFbeta1 prevents abnormal T-cell activation through the modulation of Ca(2+)-calcineurin signaling in a Caenorhabditis elegans Sma and Drosophila Mad proteins (SMAD)3 and SMAD4-independent manner; however, in T(reg) cells, its effects are mediated, at least in part, through SMAD signaling. TGFbeta1 also acts as a pro-inflammatory cytokine and induces interleukin (IL)-17-producing pathogenic T-helper cells (T(h) IL-17 cells) synergistically during an inflammatory response in which IL-6 is produced. Here, we will review TGFbeta1 and its signaling in T cells with an emphasis on the regulatory arm of immune tolerance.
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[
Genomics,
1995]
Recently, a novel family of genes with a region of homology to the mouse T locus, which is known to play a crucial, and conserved, role in vertebrate development, has been discovered. The region of homology has been named the T-box. The T-box domain of the prototypical T locus product is associated with sequence-specific DNA binding activity. In this report, we have characterized four members of the T-box gene family from the nematode Caenorhabditis elegans. All lie in close proximity to each other in the middle of chromosome III. Homology analysis among all completely sequenced T-box products indicates a larger size for the conserved T-box domain (166 to 203 residues) than previously reported. Phylogenetic analysis suggests that one C. elegans T-box gene may be a direct ortholog of the mouse Tbx2 and Drosophila omb genes. The accumulated data demonstrate the ancient nature of the T-box gene family and suggest the existence of at least three separate T-box-containing genes in a common early metazoan ancestor to nematodes and vertebrates.
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[
Glycobiology,
2006]
The common O-glycan core structure in animal glycoproteins is the core 1 disaccharide Galbeta1-3GalNAcalpha1-Ser/Thr, which is generated by addition of Gal to GalNAcalpha1-Ser/Thr by core 1 UDP-Gal:GalNAcalpha1-Ser/Thr beta1,3-galactosyltransferase (core 1 beta3-Gal-T or T-synthase, EC2.4.1.122)(2). Although O-glycans play important roles in vertebrates, much remains to be learned from model organisms such as the free-living nematode Caenorhabditis elegans, which offer many advantages in exploring O-glycan structure/function. Here we report the cloning and enzymatic characterization of T-synthase from C. elegans (Ce-T-synthase). A putative C. elegans gene for T-synthase, C38H2.2, was identified in GenBank by a BlastP search using the human T-synthase protein sequence. The full-length cDNA for Ce-T-synthase, which was generated by PCR using a C. elegans cDNA library as the template, contains 1,170 bp including the stop TAA. The cDNA encodes a protein of 389 amino acids with typical type-II membrane topology and a remarkable 42.7% identity to the human T-synthase. Ce-T-synthase has 7 Cys residues in the lumenal domain including 6 conserved Cys residues in all of the orthologs. The Ce-T-synthase has 4 potential N-glycosylation sequons, whereas the mammalian orthologs lack N-glycosylation sequons. Only one gene for Ce-T-synthase was identified in the genome-wide search and it contains 8 exons. Promoter analysis of the Ce-T-synthase using green fluorescent protein constructs show that the gene is expressed at all developmental stages and appears to be in all cells. Unexpectedly, only minimal activity was recovered in the recombinant, soluble Ce-T-synthase secreted from a wide variety of mammalian cell lines, whereas robust enzyme activity was recovered in the soluble Ce-T-synthase expressed in Hi-5 insect cells. Vertebrate T-synthase requires the molecular chaperone Cosmc, but our results show that Ce-T-synthase does not require Cosmc, and might require invertebrate-specific factors for formation of the optimally active enzyme. These results show that the Ce-T-synthase is a functional ortholog to the human T-synthase in generating core 1 O-glycans and opens new avenues to explore O-glycan function in this model organism.
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[
Int J Syst Evol Microbiol,
2007]
A yellow-pigmented, Gram-positive, aerobic, non-motile, non-spore-forming, irregular rod-shaped bacterium (strain TAN 31504(T)) was isolated from the bacteriophagous nematode Caenorhabditis elegans. Based on 16S rRNA gene sequence similarity, DNA G+C content of 69.5 mol%, 2,4-diaminobutyric acid in the cell-wall peptidoglycan, major menaquinone MK-11, abundance of anteiso- and iso-fatty acids, polar lipids diphosphatidylglycerol and phosphatidylglycerol and a number of shared biochemical characteristics, strain TAN 31504(T) was placed in the genus Leucobacter. DNA-DNA hybridization comparisons demonstrated a 91 % DNA-DNA relatedness between strain TAN 31504(T) and Leucobacter chromiireducens LMG 22506(T) indicating that these two strains belong to the same species, when the recommended threshold value of 70 % DNA-DNA relatedness for the definition of a bacterial species by the ad hoc committee on reconciliation of approaches to bacterial systematics is considered. Based on distinct differences in morphology, physiology, chemotaxonomic markers and various biochemical characteristics, it is proposed to split the species L. chromiireducens into two novel subspecies, Leucobacter chromiireducens subsp. chromiireducens subsp. nov. (type strain L-1(T)=CIP 108389(T)=LMG 22506(T)) and Leucobacter chromiireducens subsp. solipictus subsp. nov. (type strain TAN 31504(T)=DSM 18340(T)=ATCC BAA-1336(T)).
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[
Worm Breeder's Gazette,
1987]
We have accomplished a ten year long project aimed to learn whether competition between the juvenile hormone (JH) analogue methoprene (JHA) and precocenes (P's) (chromene derivatives capable to destruct the JH producing organ (CA) in sensitive insect species tissue specifically) in C. elegans (Fodor, et. al., Gen. Comp. Endcr. 46: p. 99 (1982)) can or cannot be explained by a comparable 'anti-JH' action of P's in nematodes. Neither JH or CA like organ has been discovered in nematodes so far. There are only a few indirect data showing that insect juvenile hormones may influence certain nematodes pathogenizing insects. We adopted a 'structure/activity' approach including design, synthesis and test P analogues on nematodes in the presence and absence of JHA. If (at least part of) those analogues which capable to destruct the CA of a sensitive insect (Locusta migratoria) were also effective in nematodes and their effect could be compensated by JHA exogenously, then this hormone (analogue) should play a physiological role in the P-poisoned nematodes. If those P's could be competed by JHA, which proved effective (as 'anti-JH' compounds) in insects, but those which exerted only aspecific toxicity could not be, then it would be logical to suggest, that P's are the same kind of 'suicide compounds' for nematodes as for insects. More than 200 P derivatives were synthesized (Tim r, Hosztafi) and tested on C. elegans (Fodor) and L. migratoria (Kiss). After a detailed quantitative structure/activity relation (QSAR) analysis ( Dinya, et. al., QSAR Strat. Des. Bioact. Compd. Proc. Eur. Symp. Struct.-Act. Relat. 5th (1984) Publ. 1985) several new P analogue were designed, synthesized and tested on L. migratoria and on C. remanei var. Bangaloriensis. (We choose this nematode strain because half of its population consists of males, therefore it is easy to distinguish male adultoids from other type of retarded worms.) Altogether, 121 molecules were retested C. remanei and 17 of them was found to exert some significant biological effect. These compounds were retested again several times both in the absence and in the presence of 1 mg/ml NGM dose of JHA: altogether, more that 144,000 C. remanei embryos were counted, treated and scored afterwards. The tests on nematodes were carried out as described in our attached paper. The most characteristic data concerning precocene activity in nematodes were the following: (1) LC50: the half lethal dose (in g/ml) at which half of the embryos develops to worms (calculated by probit analysis); (2) AD50: the dose ( g/ml) at which half of the embryos develops to normal adults; (3) EC50: the dose ( g/ml) at which half of the nematodes on the plates found as 'normal' fertile adults; (4) The maximum frequency of 'adultoid mini worms' during the experiments. [See Figures 1- 2] The main conclusions are the following: About structure/activity relations: (1) All the three (P1-P3) precocene is effective in nematodes and their effects can be compensated by exogenous JHA. (2) The longer the chain of the R7 substituent the less the effect of the compounds in nematodes. (3) The 7-proparglyoxy analogues are much more effective in nematodes than any other C7 substituted compound. (compare P1 to TT51; P2 to K460; P3 to TT80; TT56 to TT58 or 3,4-diCl-P1 (inactive) to FI121.) (4) The asymmetrically disubstituted analogues are much more effective than the symmetrically disubstituted ones (compare TT80 to K460). It is true, if R7 is longer than R6. (5) Me substitution at C5 position inactivates the originally potent P's (compare TT58 to TT51) but restore the activity of originally inactive (for instance, 7-sBuO-P1) analogues (compare it to TT56). 8-MeO substitution eliminate specific P activity (compare TT51 to K464). (6) Both 8-Me and 8-MeO substitution increase toxic rather than JH compatible biological activity of P's. 8-MeO analogues are more toxic than 8-Me ones, but the consequences of the action of 8-MeO compounds in nematodes can be cured more efficiently by JHA than those concerning 8-Me compounds (compare TT100 to K475). About JHA competition experiments: JHA competed the effects of all precocenes which effected both insects and nematodes. However, the data concerning K354 and FI121 show, that there are analogues which effective only in nematodes and their effects can also be cured by exogenous JHA. Although there are aspecifically toxic analogues (like K454 or 2,3,5-triMe-7 propargO-P1) which cannot be compensated by methoprene, we cannot conclude, that our data unambiguously support the idea of existence JH-like hormones in nematodes. It seems very probable, however, that JH-like compounds can interfere with the lethal metabolism of P's.
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[
Genome,
1997]
The T-box gene family consists of members that share a unique DNA binding domain. The best characterized T-box gene, Brachyury or T, encodes a transcription factor that plays an important role in early vertebrate development. Seven other recently described mouse T-box genes are also expressed during development. In the nematode Caenorhabditis elegans, four T-box genes have been characterized to date. In this study, we describe three new C. elegans T-box genes, named
Ce-tbx-11,
Ce-tbx-12, and
Ce-tbx-17.
Ce-tbx-11 and
Ce-tbx-17 were uncovered through the sequencing efforts of the C. elegans Genome Project.
Ce-tbx-12 was uncovered through degenerate PCR analysis of C. elegans genomic DNA.
Ce-tbx-11 and
Ce-tbx-17 are located in close proximity to the four other previously described T-box genes in the central region of chromosome III. In contrast,
Ce-tbx-12 maps alone to chromosome II. Phylogenetic analysis of all known T-box domain sequences provides evidence of an ancient origin for this gene family.