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Wilson RK, Metzstein MM, Ainscough R, Waterston RH, Coulson AR, Craxton M, Thomas K, Dear S, Qiu L, Staden R, Berks M, Halloran N, Thierry-Mieg J, Hillier L, Sulston JE, Du Z, Durbin RM, Hawkins TL, Green P
[
Nature,
1992]
The long-term goal of this project is the elucidation of the complete sequence of the Caenorhabditis elegans genome. During the first year methods have been developed and a strategy implemented that is amenable to large-scale sequencing. The three cosmids sequenced in this initial phase are surprisingly rich in genes, many of which have mammalian homologues.AD - MRC Laboratory of Molecular Biology, Cambridge, UK.FAU - Sulston, JAU - Sulston JFAU - Du, ZAU - Du ZFAU - Thomas, KAU - Thomas KFAU - Wilson, RAU - Wilson RFAU - Hillier, LAU - Hillier LFAU - Staden, RAU - Staden RFAU - Halloran, NAU - Halloran NFAU - Green, PAU - Green PFAU - Thierry-Mieg, JAU - Thierry-Mieg JFAU - Qiu, LAU - Qiu LAU - et al.LA - engPT - Journal ArticleCY - ENGLANDTA - NatureJID - 0410462RN - 0 (Cosmids)SB - IM
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[
J Biochem,
1997]
The full-length cDNA coding for a putative copper transporting P-type ATPase (Cu2+-ATPase) was cloned from Caenorhabditis elegans. The putative Cu2+-ATPase is a 1,238-amino acid protein, and highly homologous to the Menkes and Wilson disease gene products mutations of which are responsible for human defects of copper metabolism. The Saccharomyces cerevisiae mutant with a disrupted CCC2 gene (yeast Menkes/Wilson disease gene homologue) was rescued by the cDNA for the C. elegans Cu2+-ATPase but not by the cDNA with an Asp-786 (an invariant phosphorylation site) to Asn mutation, suggesting that the C. elegans Cu2+-ATPase functions as a copper transporter in yeast. The expressed C. elegans protein was detected in yeast vacuolar membranes by immunofluorescence microscopy. The yeast expression system may facilitate further studies on copper transporting P-type ATPases.
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[
MicroPubl Biol,
2021]
Saul-Wilson Syndrome (SWS) is an ultra-rare, autosomal dominant skeletal dysplasia syndrome discovered in 1990; only 16 patients have been identified to date (Saul and Wilson 1990; Ferreira et al. 2018, OMIM#: 618150). The disease is characterized by short stature, various craniofacial abnormalities, shortened fingers and toes, and speech and physical developmental delay (Ferreira 2020). SWS is caused by a missense mutation in the COG4 gene, resulting in a G516R residue change. Other pathogenic mutations have been observed in this gene and all are clustered at the C-terminal end of the protein (R724W, R729W, R729A, E764A). These are associated with Congenital Disorder of Glycosylation type 2j (CDGIIj). This is a recessive disease characterized by mild psychomotor delay, mild dysmorphic features, epilepsy, and defective sialylation (Reynders et al. 2009). Besides the mild developmental delay, this disease seems to share virtually no phenotypic similarity with SWS.
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[
Pesticide Biochemistry & Physiology,
1990]
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Van der Gaag, Victoria L., Edison, Arthur S., Muzio, Cole J., Asif, Muhammad Zaka, Nocilla, Kelsey A., Guo, Jane
[
MicroPubl Biol,
2021]
1-Hydroxyphenazine (1-HP) is a small molecule produced by Pseudomonas aeruginosa, a bacterium that is used for pathogenesis models in C. elegans (Cezairliyan et al., 2013; Mahajan-Miklos, Tan, Rahme, & Ausubel, 1999). 1-HP is an especially interesting toxin to study as it has been shown to interact with human cells causing ciliary-slowing associated with dyskinesia and ciliostasis (Wilson et al., 1987). Prior research in our lab has shown that this molecule is toxic to C. elegans, with an LD50 between 150 and 200 M, but C. elegans can glycosylate 1-HP, which detoxifies the molecule (Stupp et al., 2013).
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[
Nanotoxicology,
2019]
An adverse outcome pathway (AOP) is a framework that organizes the mechanistic or predictive relationships between molecular initiating events (MIEs), key events (KEs), and adverse outcomes (AOs). Previously, we intensively investigated the molecular mechanism that underlies toxicity caused by AgNPs in the nematode Caenorhabditis elegans. Using transcriptomics, functional genetics, and various molecular/biochemical tools, we identified oxidative stress as the major mechanism underlying toxicity and reproduction failure as the outcome. With this information, here we conducted a case study of building an AOP to link oxidative stress with reproductive toxicity. To validate this AOP, we filled the gaps by conducting further experiments on its elements, such as NADPH oxidase, ROS formation, PMK-1 P38 MAPK activation, HIF-1 activation, mitochondrial damage, DNA damage, and apoptosis. The establishment of a causal link between the MIE and AO is critical for the construction of an AOP. Therefore, causal relationships between each KE and AO were verified by using functional genetic mutants of each KE. By combining these experimental data with our previously published results, we established causal relationships between the MIE, KEs, and AO using a Bayesian network (BN) model, culminating in an AOP entitled 'NADPH oxidase and P38 MAPK activation leading to reproductive failure in C. elegans ( https://aopwiki.org/aops/207)' . Overall, our approach shows that an AOP can be developed using existing data and further experiments can be conducted to fill the gaps between the MIE, KEs, and the AO. This study also shows that BN modeling has the potential to identify causal relationships in an AOP.
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[
Parasitology,
1990]
Rigorous proofs applicable to the routes of migration of Strongyloides ratti and Nippostrongylus brasiliensis skin-penetrating juveniles inside the rat are extended. By applying the inequality principle (Tindall & Wilson, 1988) it was confirmed with a probability of error of 1 in 10(10) that N. brasiliensis larvae applied to the skin passed through the lungs on their way to the intestine. Taking the analysis further, migrating larvae of S. ratti or N. brasiliensis were extracted from the nose or lungs, respectively, of donor rats and transferred to recipients by stomach tube to assay their ability to colonize the intestine. Results showed that (a) changes undergone by each parasite in its proven, specific transit site were essential before larvae could establish in the intestines of recipients, (b) these changes could be monitored by morphological criteria, and [corrected] (c) these changes were not completed until larvae had been in the nose or lung for a significant period. It follows from (c) that anywhere in the body of the host, termed a 'nursery', that supports a substantial amount of this mandatory development must be detectable by the conventional procedure of sampling at autopsy. Conversely, absence of parasites judged by sampling at autopsy is positive proof that a site is not a nursery when sampling is timed in relation to reliable estimates of overall kinetics (Tindall & Wilson, 1990), and with control information on the efficiency of sampling. Comparative data from sampling at autopsy using the same extraction techniques for both species met these criteria: they demonstrated that no part of the head of the rat was a nursery for N. brasiliensis, and that the lung did not serve in this capacity for S. ratti.(ABSTRACT TRUNCATED AT 250 WORDS)
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[
Parasitology,
1982]
Unsuckled mother rats given a 1 h suckling stimulus 3 h after subcutaneous injection of an exact dose of homogonic Strongyloides ratti allow fewer worms to develop in their intestines by day 9 than nulliparous rats (Wilson & Simpson, 1981). This effect is studied in more detail in terms of the length of time between weaning and stimulus (W leads to S) and injection and stimulus (I leads to S). It was observable with a W leads to S of 30 h but this and a period of 5 h were less effective than 24 h. With W leads to S constant at 24 h, significantly more worms developed in mothers when I leads to S was 24 h compared to 3 h and 10 h (P less than 0.005). The data, combined with those from nulliparous controls, are presented as a measure of the change with time of numbers of larvae in that compartment of the system which gives access to the stimulated mammary gland. It is argued that the particular compartment is the local lymph node draining the injection site and that the kinetics deduced are applicable to migration in the rat in general.
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[
CBE Life Sci Educ,
2012]
Scientists routinely integrate information from various channels to explore topics under study. We designed a 4-wk undergraduate laboratory module that used a multifaceted approach to study a question in molecular genetics. Specifically, students investigated whether Caenorhabditis elegans can be a useful model system for studying genes associated with human disease. In a large-enrollment, sophomore-level laboratory course, groups of three to four students were assigned a gene associated with either breast cancer (
brc-1), Wilson disease (
cua-1), ovarian dysgenesis (
fshr-1), or colon cancer (
mlh-1). Students compared observable phenotypes of wild-type C. elegans and C. elegans with a homozygous deletion in the assigned gene. They confirmed the genetic deletion with nested polymerase chain reaction and performed a bioinformatics analysis to predict how the deletion would affect the encoded mRNA and protein. Students also performed RNA interference (RNAi) against their assigned gene and evaluated whether RNAi caused a phenotype similar to that of the genetic deletion. As a capstone activity, students prepared scientific posters in which they presented their data, evaluated whether C. elegans was a useful model system for studying their assigned genes, and proposed future directions. Assessment showed gains in understanding genotype versus phenotype, RNAi, common bioinformatics tools, and the utility of model organisms.
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[
Parasitology,
1982]
A prediction of the hypothesis of Wilson (1977, 1980 a, b) to account for larval migration of homogonic Strongyloides ratti in the host is that the pattern of invasion of the mammary gland of a lactating rat will be quantitatively similar on both sides and independent of the point of entry into the body. Twenty-one suckled mother rats in 6 experiments in which live 75Se-labelled 3rd-stage homogonic larvae were injected under the skin of the upper flank had an overall distribution of label 30 h post-injection, as a percentage of the initial dose, in the quadrants, I (rear, injection side, II (rear, opposite injection side), III (front, injection side) and IV (front, opposite injection side) of the mammary gland as follows: 27.4%, 1.27%, 1.98% and 1.24%. Quantitative changes in mammary label between 30 and 48 h post-injection using live larvae, differences between mothers and virgins, and results after injection of heat-killed labelled larvae, confirm that the pattern is representative of the behaviour of normal (unlabelled) worms when injected. The theory is therefore disproved. The findings are put forward as the first quantitative evidence for major lymphatic involvement in migration of a skin-penetrating roundworm. They need confirmation in similar experiments in which worms are allowed to penetrate the skin naturally. The role of isotope-labelled larvae versus traditional methods of estimating parasite content of host tissue is discussed.