Roussell DL et al. (1994) Parasitol Today "Germ-line determination in Caenorhabditis and Ascaris: will a helicase begin to unravel the mystery?"

Bennett KL, Roussell DL, Gruidl ME

[Parasitol Today, 1994]

How cell lineages are established during development in higher eukaryotes is being addressed by geneticists and by developmental and molecular biologists. In Drosophila melanogaster, a gene corresponding to a germ-line-specific RNA helicase, vasa, has been shown to be a component o f the posteriorly localized germ granules o f the developing embryo. A putative RNA helicase, glh-I r which appears germ-line specific in its expression, has recently been reported from the free-living nematode Caenorhabditis elegans. Parasitologists studying the nematode Ascaris lumbricoides var. suum have found it to be a useful complement to Caenorhabditis. Deborah Roussell, Michael Gruidl and Karen Bennett predict that Ascaris will be valuable in determining the role played by germ-line helicases in development.

Joshua P Ellwitz et al. (2001) International C. elegans Meeting "Intrinsically Thermotolerant Substrains Of C. elegans Maintain Their IT State, Show Increased Longevity, And Elevated Hsp16 Levels."

Karen A McFarland, Nicole D Smith, Joshua P Ellwitz, Karen E Stine, Glenn E White, Rebecca A Buonpane

[International C. elegans Meeting, 2001]

The response to external stresses has been studied in a number of organisms including C. elegans with the heat shock response being a classic example. We reported at the 12th International C. elegans Meeting (Smith et al., page 787) the isolation of substrains of N2 which demonstrated an intrinsic thermotolerance (defined as a significantly increased survival probability when taken from either 16 or 25 o C to 37 o C for two hours as compared to controls). These substrains were designated N2IT# (intrinsically thermotolerant) to distinguish these from EMS induced mutations which also can confer intrinsic thermotolerance. We report here that over two years after these N2ITs were isolated, that they are still maintaining their intrinsic thermolerance. In our most recent experiment (March, 2001), using N2IT6, we observed a survival probability (SP) = 0.33 as compared to a SP = .029 for the controls. Because of continual concerns that perhaps it was microenvironment that was inducing this intrinsically thermotolerant substrain of N2s, we tested three different 'lots' of N2s obtained from the CGC. When tested, these three different lots of N2s also demonstrated SPs < 0.1, which implies that it is not the microenvironment of the petri dish that is producing these IT substrains. We have examined one of our substrains, designated N2IT6, for evidence of heat shock protein induction. Western blot analysis indicated significantly elevated hsp16 levels when compared to unshocked controls (thanks to Peter Candido for the anti-hsp16 antibody). Coomassie stained SDS gels do not show any elevated hsp70 levels. Because of the poor quality of many commercial antibodies against heat shock proteins, we have initiated RT-PCR studies on total RNA preparations from both N2IT6 and N2 controls. At this time, we are analyzing levels of hsp 70 and hsp 16 mRNA in these worms. Studies will also be initiated to look at hsp60 and hsp90 mRNA levels in N2IT6. The stress response is designed to help the organism survive a stress that it otherwise would not, and it has been noted in other systems that the response to stress often comes at a price for the organism such as a shortened lifespan. Therefore, we decided to see what impact the IT state would have on the lifespan of these intrinsically thermotolerant worms. We performed several longevity studies comparing N2IT6 to N2 controls. Four separate experiments, involving approximately 40 worms/experiment, were conducted at 25 o C. Average lifespan for N2 Controls was 11.5 + 0.5 days. Average lifespan for N2IT6 was 13.5 + 0.7 days, which represents a 17% increase in average lifespan for the N2IT6 substrain. It was noted in every experiment that at least 2-3 worms lived significantly longer than the mean (18 - 19 days). The F1s from these extremely long lived worms were saved and are now maintained as our N2IT6 substrain. We are currently examining N2IT6 for its longevity at 16 o C versus 25 o C. In summary, we have been able to maintain our N2IT substrains for over 2 years now. In addition to their intrinsic thermotolerance, they show increased longevity and elevated hsp16 levels. At the meeting, we will also be reporting on our RT-PCR studies examining mRNA levels for the various hsp genes.

Kreutzer MA et al. (1994) Worm Breeder's Gazette "Expression Studies of the Putative Caenorhabditis elegans cyclin A and B Genes"

Richards JP, Bennett KL, Kreutzer MA

[Worm Breeder's Gazette, 1994]

Expression studies of the putative Caenorhabditis elegans cyclin A and B genes Monique A. Kreutzer, James P. Richards and Karen L. Bennett, University of Missouri-Columbia, Columbia, Missouri 65212. We have cloned putative A, B1 and B2 cyclins from C. elegans. Cyclin B1 and B2 are single copy genes while cyclin A belongs to a multigene family. Cyclin A and B2 each correspond to single transcripts while cyclin B1 recognizes three transcripts. The C. elegans temperature sensitive germline defective mutants fem-1, fem-3 gf) and glp4 were used to analyze cyclin germline expression. When hybridizing C. elegans cyclin A or B2 to the mutant RNAs that produce no oocytes, the cyclin A and B2 messages are significantly reduced. When normal numbers of oocytes are produced, the cyclin A and B2 messages are at wild type levels. Therefore, the cyclin A and B2 transcripts appear to be primarily maternal with some somatic component. Consistent with a somatic component, cyclin A and B2 cDNAs cross-hybridize to Ascans intestinal poly A+ RNA. Hybridization of the cyclin B1 cDNA to these germline defective RNAs suggest that the cyclin B1 transcripts are differentially expressed in the germline. The two larger cyclin B1 transcripts appear to be primarily maternal and the smallest transcript appears to be sperm- specific. The observation that two polyadenylation signals are present in the cyclin B1 3'UTR, as well as results using cyclin B1 probes from specific regions of the B1 3'UTR, suggests that two of the three cyclin B1 transcripts are produced by polyadenylation a~ different sites. There is precedence in mice and flies for producing tissue-specific transcripts by different use of the cyclin B 3'UTRs. It has been shown in mouse that cyclin B1 hybridizes to four differentially expressed transcripts, one of which is testis- specific. Two of these mouse transcripts differ in the choice of polyadenylation sites and therefore in the lengths of their 3'UTRs (Chapman and Wolgemuth (1992) MoL Repro.Dev. 33, 259-269). In Drosophila, the cyclin B cDNA detects two female-specific transcripts that are made by splicing of a region of the cyclin B 3'UTR (Dalby and Glover (1992) Development 115, 989-997). In summary, our initial findings show that the C. elegans cyclin As and Bs are highly expressed in the germline and also suggest that the three cyclin B1 transcripts are differentially expressed in oocytes and sperm.

Quartey MO et al. (2021) Sci Rep "The A(1-38) peptide is a negative regulator of the A(1-42) peptide implicated in Alzheimer disease progression."

Pennington PR, Heistad RM, Nyarko JNK, Barnes JR, Bolanos MAC, Parsons MP, Knudsen KJ, De Carvalho CE, Leary SC, Mousseau DD, Buttigieg J, Maley JM, Quartey MO

[Sci Rep, 2021]

The pool of -Amyloid (A) length variants detected in preclinical and clinical Alzheimer disease (AD) samples suggests a diversity of roles for A peptides. We examined how a naturally occurring variant, e.g. A(1-38), interacts with the AD-related variant, A(1-42), and the predominant physiological variant, A(1-40). Atomic force microscopy, Thioflavin T fluorescence, circular dichroism, dynamic light scattering, and surface plasmon resonance reveal that A(1-38) interacts differently with A(1-40) and A(1-42) and, in general, A(1-38) interferes with the conversion of A(1-42) to a -sheet-rich aggregate. Functionally, A(1-38) reverses the negative impact of A(1-42) on long-term potentiation in acute hippocampal slices and on membrane conductance in primary neurons, and mitigates an A(1-42) phenotype in Caenorhabditis elegans. A(1-38) also reverses any loss of MTT conversion induced by A(1-40) and A(1-42) in HT-22 hippocampal neurons and APOE 4-positive human fibroblasts, although the combination of A(1-38) and A(1-42) inhibits MTT conversion in APOE 4-negative fibroblasts. A greater ratio of soluble A(1-42)/A(1-38) [and A(1-42)/A(1-40)] in autopsied brain extracts correlates with an earlier age-at-death in males (but not females) with a diagnosis of AD. These results suggest that A(1-38) is capable of physically counteracting, potentially in a sex-dependent manner, the neuropathological effects of the AD-relevant A(1-42).

Danielle Thierry-Mieg et al. (2003) Worm Breeder's Gazette "www.wormgenes.org , a new gene centered database"

Vahan Simonyan, Michel Potdevin, Mark Sienkiewicz, Yuji KOHARA, Jean Thierry-Mieg, Danielle Thierry-Mieg, Tadasu SHIN-I

[Worm Breeder's Gazette, 2003]

Wormgenes is a new resource for C.elegans offering a detailed summary about each gene and a powerful query system.

Tangrodchanapong T et al. (2020) Front Pharmacol "Frondoside A Attenuates Amyloid- Proteotoxicity in Transgenic Caenorhabditis elegans by Suppressing Its Formation."

Tangrodchanapong T, Sobhon P, Meemon K

[Front Pharmacol, 2020]

Oligomeric assembly of Amyloid- (A) is the main toxic species that contribute to early cognitive impairment in Alzheimer's patients. Therefore, drugs that reduce the formation of A oligomers could halt the disease progression. In this study, by using transgenic <i>Caenorhabditis elegans</i> model of Alzheimer's disease, we investigated the effects of frondoside A, a well-known sea cucumber <i>Cucumaria frondosa</i> saponin with anti-cancer activity, on A aggregation and proteotoxicity. The results showed that frondoside A at a low concentration of 1 M significantly delayed the worm paralysis caused by A aggregation as compared with control group. In addition, the number of A plaque deposits in transgenic worm tissues was significantly decreased. Frondoside A was more effective in these activities than ginsenoside-Rg3, a comparable ginseng saponin. Immunoblot analysis revealed that the level of small oligomers as well as various high molecular weights of A species in the transgenic <i>C. elegans</i> were significantly reduced upon treatment with frondoside A, whereas the level of A monomers was not altered. This suggested that frondoside A may primarily reduce the level of small oligomeric forms, the most toxic species of A. Frondoside A also protected the worms from oxidative stress and rescued chemotaxis dysfunction in a transgenic strain whose neurons express A. Taken together, these data suggested that low dose of frondoside A could protect against A-induced toxicity by primarily suppressing the formation of A oligomers. Thus, the molecular mechanism of how frondoside A exerts its anti-A aggregation should be studied and elucidated in the future.

Hodgkin JA (1998) International Journal of Developmental Biology "Seven types of pleiotropy."

Hodgkin JA

[International Journal of Developmental Biology, 1998]

Pleiotropy , a situation in which a single gene influences multiple phenotypic tra its, can arise in a variety of ways. This paper discusses possible underlying mechanisms and proposes a classification of the various phenomena involved.

Tuck S (2011) Curr Biol "Extracellular vesicles: budding regulated by a phosphatidylethanolamine translocase."

Tuck S

[Curr Biol, 2011]

Recent work on a Caenorhabditis elegans transmembrane ATPase reveals a central role for the aminophospholipid phosphatidylethanolamine in the production of a class of extracellular vesicles.

Viney ME et al. (2004) Naturwissenschaften "Is dauer pheromone of Caenorhabditis elegans really a pheromone?"

Viney ME, Franks NR

[Naturwissenschaften, 2004]

Animals respond to signals and cues in their environment. The difference between a signal (e.g. a pheromone) and a cue (e.g. a waste product) is that the information content of a signal is subject to natural selection, whereas that of a cue is not. The model free-living nematode Caenorhabditis elegans forms an alternative developmental morph (the dauer larva) in response to a so-called 'dauer pheromone', produced by all worms. We suggest that the production of 'dauer pheromone' has no fitness advantage for an individual worm and therefore we propose that 'dauer pheromone' is not a signal, but a cue. Thus, it should not be called a pheromone.

Schaeffer JM et al. (1990) J Antibiot (Tokyo) "Cochlioquinone A, a nematocidal agent which competes for specific [3H]ivermectin binding sites."

Williamson JM, Schaeffer JM, Bergstrom AR, Liesch JM, Goetz MA, Frazier EG

[J Antibiot (Tokyo), 1990]

Cochlioquinone A, isolated from the fungus Helminthosporium sativum, was found to have nematocidal activity. Cochlioquinone A is a competitive inhibitor of specific [3H]ivermectin binding suggesting that cochlioquinone A and ivermectin interact with the same membrane receptor.