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[
J Steroid Biochem Mol Biol,
1998]
Physiological responses due to steroid hormones and retinoids are regulated by their cognate receptors and dehydrogenases. The origins of either regulatory mechanism are not fully understood. Here we examine the origins of the human 11beta-hydroxysteroid dehydrogenase-type 2, which regulates access of glucocorticoids to cells, and 17beta-hydroxysteroid dehydrogenase-type 2, which regulates access of androgens and estrogens to cells. Sequence comparisons trace their ancestry to homologs in Caenorhabditis elegans. These C. elegans proteins most closely resemble mammalian all-trans and 11-cis-retinol dehydrogenases. The similarity is sufficient -37% to 43% identity to suggest that one or more of the C. elegans homologs metabolizes a retinoid. Receptors for retinoids, but not for androgens, estrogens or glucocorticoids have been identified in C. elegans, suggesting that retinoid-mediated gene transcription is more ancient than that for adrenal and sex steroids. We propose that the hydroxysteroid dehydrogenase-type 2 mechanism for regulating the androgen, estrogen and glucocorticoid concentrations in mammals descended from that for regulating retinoid concentrations. Interestingly, E. coli contains a protein with strong sequence similarity to mammalian retinol dehydrogenases. Sequence comparisons and phylogenetic analysis indicate that the E. coli protein may be an example of horizontal transfer from a eukaryote ancestor.
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[
Worm,
2014]
Mutually exclusive selection of one exon in a cluster of exons is a rare form of alternative pre-mRNA splicing, yet suggests strict regulation. However, the repertoires of regulation mechanisms for the mutually exclusive (ME) splicing in vivo are still unknown. Here, we experimentally explore putative ME exons in C. elegans to demonstrate that 29 ME exon clusters in 27 genes are actually selected in a mutually exclusive manner. Twenty-two of the clusters consist of homologous ME exons. Five clusters have too short intervening introns to be excised between the ME exons. Fidelity of ME splicing relies at least in part on nonsense-mediated mRNA decay for 14 clusters. These results thus characterize all the repertoires of ME splicing in this organism.
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[
International C. elegans Meeting,
1991]
A microbial exometabolite (ME) has been isolated which inhibits egg- laying in Caenorhabditis elegans. Nematodes exposed to active concentrations of the factor, and maintained at 22C in axenic culture ( liver extract medium), mature and grow normally. Eggs are fertilized and larvae develop and move within eggs as in untreated nematodes. However, eggs are not laid, though occasionally hatch occurs within the gonad. In shake culture of the microbe, active yellow-pigmented ME appears at 3-4 days. A concentration of 8 parts ME: 1 part liver extract completely inhibits egg-laying. Concentrations of 4 ME: 1 liver extract and 2 ME: 1 liver extract, inhibit egg-laying about 50 and 25%, respectively. Sections from nematodes exposed to extracts of a microbe showing similar properties examined by transmission electron microscopy indicated that the constrictor and dilator muscles associated with vulval function in egg-laying appear normal. ME is thermostable (at 100C for 5 min.), and the active fraction does not pass through 6,000-8,000 MW dialysis tubing. About one-half of the activity is lost when ME is dialyzed through 12,000 14,000 MW membrane tubing, suggesting the presence of at least two active fractions. Trypsinization obliterated activity. Thus far, the double control experiment with trypsin inhibitor has not yielded definitive results. SDS gel electrophoresis of boiled ME, with molecules below 8,000 MW removed by dialysis, revealed several strong protein bands, one or more of which may be ME. ME purification and characterization studies continue.
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[
Biosci Rep,
2003]
Thank you so very much for inviting me to be here. It gives me a mingled sense of humility at how much I owe to others, and of joy that the collective work on the worm has been recognized in this way.
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[
Chembiochem,
2003]
Thank you so very much for inviting me to be here. It gives me a mingled sense of humility at how much I owe to others, and of joy that the collective work on the worm has been recognised in this way.
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[
Int J Dev Biol,
2000]
1969 was a landmark year. But for me it was not Neil Armstrong's giant leap or Woodstock heralding the beginning of the end of the sixties that sticks in my mind. It was a visit I made to Cambridge to meet a "bloke who is starting a new project to study some sort of worm", as my head of department at the Medical Research Council's National Institute of Medical Research informed me...
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[
Genes Dev,
2002]
The CM domain is a cysteine-rich DNA-binding motif first recognized in proteins encoded by the Drosophila set determination gene doublesex (Erdman and Burtis 1993; Zhu et al. 2000). As the name doublesex (dsx) suggests, this gene has functions in both sexes: Its transcripts undergo sex-specific alternative splicing, so that it can encode either a male-specific isoform, DSX(M), or a female-specific isoform, DSX(F) (Baker and Wolfner 1988; Burtis and Baker 1989). These proteins have the same N-terminal DNA-binding domain, but different C termini that confer different regulatory properties on the two forms. The expression of DSX(M) directs male development, and the expression of DSX(F) directs female development, throughout most of the somatic tissues of the fruit fly.
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[
Dev Biol,
2002]
In mammals, one of the two somatic X chromosomes in the female is inactivated, thereby equalizing X chromosome-derived transcription in the two sexes, a process known as dosage compensation. In the germline, however, the situation is quite different. Both X chromosomes are transcriptionally active during female oogenesis, whereas the X and Y chromosomes are transcriptionally silent during male spermatogenesis. Previous studies suggest that Caenorhabditis elegans germline X chromosomes might have different transcriptional activity in the two sexes in a manner similar to that in mammals. Using antibodies specific to H3 methylated at either lysine 4 or lysine 9, we show that the pattern of site-specific H3 methylation is different between X chromosomes and autosomes as well as between germline X chromosomes from the two sexes in C. elegans. We show that the pachytene germline X chromosomes in both sexes lack Me(K4)H3 when compared with autosomes, consistent with their being transcriptionally inactive. This transcriptional inactivity of germline X chromosomes is apparently transient in hermaphrodites because both X chromosomes stain brightly for Me(K4)H3 after germ nuclei exit pachytene. The male single X chromosome, on the other hand, remains devoid of Me(K4)H3 staining throughout the germline. Instead, the male germline X chromosome exhibits a high level of Me(K9)H3 that is not detected on any other chromosomes in either sex, consistent with stable silencing of this chromosome. Using mutants defective in the sex determination pathway, we show that X-chromosomal Me(K9)H3 staining is determined by the sexual phenotype, and not karyotype, of the animal. We detect a similar high level of Me(K9)H3 in male mouse XY bodies, suggesting an evolutionarily conserved mechanism for silencing the X chromosome specifically in the male germline.
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[
Cancer Research,
1999]
It is an honor and a great pleasure to introduce Dr. Robert Horvitz to you as the 1998 recipient of the Alfred Sloan Prize of the General Motors Cancer Research Foundation. Let me begin by telling you a little bit about Bob's
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[
Worm Breeder's Gazette,
1982]
We've (Stan Himmelhodst and I) completed a cryo-ultromicrotory study showing the feasibility of en force labelling of ultrathin sections with molecular members of various types. The MC lines have been submitted to Eyrptli Parasitology. The results also include successful immuno-labelling. Anyone interested in details can write to me. Respectfully, B. M. Zuckerman