Bach, Cynthia et al. (2011) International Worm Meeting "Uncovering the mechanisms for the antioxidant-like properties of divalent manganese in Caenorhabditis elegans."

Srinivasan, Chandra, Bach, Cynthia

[International Worm Meeting, 2011]

Divalent manganese, Mn(II), has been thought to function as an effective superoxide radical scavenger in prokaryotic and eukaryotic organisms. Although previous studies on Caenorhabditis elegans have revealed that manganese supplementation increases the organism's tolerance to superoxide and thermal stress, the mechanism through which ionic manganese operates is not yet clearly understood. We hypothesize that Mn(II) provides its antioxidant-like properties through the activation of the DAF-16 forkhead transcription factor, which regulates expression of stress response and longevity genes. Reactive Oxygen Species (ROS) assays were performed, using 2',7'-dichlorfluorescein-diacetate to determine relative levels of ROS within the whole worms. Wild type C. elegans grown with Mn(II) supplementation contained decreased levels of ROS when exposed to paraquat (in vivo superoxide generator) treatment in comparison to worms raised on a normal diet, however lower levels were not observed under heat shock conditions. Additionally, TK22(mev-1), a strain known to overproduce superoxide, did not show a reduction in free radical levels when supplemented with Mn(II). Furthermore, a transgenic C. elegans strain containing a daf-16::GFP fusion(TJ356), was used to monitor nuclear localization of the transcription factor. Results indicate that prolonged exposure to Mn(II) did not fully alter localization of DAF-16 from the cytoplasm to the nucleus, suggesting that Mn(II) treatment does not induce a stress response. Finally, transgenic strains with a sod-3::GFP fusion(CF1553) and a hsp-16.2::GFP fusion(CL2070) were studied, as sod-3 and hsp-16.2 are downstream targets of DAF-16. Data illustrates that treatment with heat or paraquat stress does not cause an increase in upregulation of these genes. Although hsp-16.2 and sod-3 are both downstream targets of the DAF-16 transcription factor, data suggests that other factors or genes modulated by DAF-16 may be involved in providing manganese's antioxidant-like properties.

Rangel NA et al. (2012) Biometals "Unincorporated iron pool is linked to oxidative stress and iron levels in Caenorhabditis elegans."

Srinivasan C, Trinh K, Clement MH, Rangel NA, Lin L, Rakariyatham K, Bach A

[Biometals, 2012]

Free radicals or reactive oxygen species (ROS) are relatively short-lived and are difficult to measure directly; so indirect methods have been explored for measuring these transient species. One technique that has been developed using Escherichia coli and Saccharomyces cerevisiae systems, relies on a connection between elevated superoxide levels and the build-up of a high-spin form of iron (Fe(III)) that is detectable by electron paramagnetic resonance (EPR) spectroscopy at g=4.3. This form of iron is referred to as "free" iron. EPR signals at g=4.3 are commonly encountered in biological samples owing to mononuclear high-spin (S=5/2) Fe(III) ions in sites of low symmetry. Unincorporated iron in this study refers to this high-spin Fe(III) that is captured by desferrioxamine which is detected by EPR at g value of 4.3. Previously, we published an adaptation of Fe(III) EPR methodology that was developed for Caenorhabditis elegans, a multi-cellular organism. In the current study, we have systematically characterized various factors that modulate this unincorporated iron pool. Our results demonstrate that the unincorporated iron as monitored by Fe(III) EPR at g=4.3 increased under conditions that were known to elevate steady-state ROS levels in vivo, including: paraquat treatment, hydrogen peroxide exposure, heat shock treatment, or exposure to higher growth temperature. Besides the exogenous inducers of oxidative stress, physiological aging, which is associated with elevated ROS and ROS-mediated macromolecular damage, also caused a build-up of this iron. In addition, increased iron availability increased the unincorporated iron pool as well as generalized oxidative stress. Overall, unincorporated iron increased under conditions of oxidative stress with no change in total iron levels. However, when total iron levels increased in vivo, an increase in both the pool of unincorporated iron and oxidative stress was observed suggesting that the status of the unincorporated iron pool is linked to oxidative stress and iron levels.

Bennett KL (1988) Worm Breeder's Gazette "in situ hybridization to Ascaris embryos."

Bennett KL

[Worm Breeder's Gazette, 1988]

My laboratory is interested in isolating maternal and early embryonic mRNAs which segregate with, or are produced in, the two germ line precursor cells of the early nematode embryo. I propose a final assay for putative messages to be in situ hybridization to Ascaris embryos. Because the vitelline membrane of Ascaris is highly impermeable, it has been necessary to use frozen 10 m sections of eggs (sliced eggs!). This has worked well for the probes tested to date. A 1.0 kb subclone from the 26 S subunit of an Ascaris ribosomal gene ( Bach, et al., (1984) NAR 12-3:1313.) has been put into the SP6 transcription vector in both orientations. With the antisense transcript all cells of the paraformaldehyde-fixed embryos hybridize strongly to the hydrolyzed [35S] RNA probe, while the sense strand shows no hybridization above background. In order to determine the resolution of our assay and see if the two germ cells can be selectively hybridized, I have also used an RNA probe from the Ascaris satellite sequence which is lost from all the somatic lineages and retained in the germ line during chromatic diminution (Muller, et al., (1982) NAR 10-23:7493.). With 60 cell embryos (after diminution), the satellite probe shows high grain accumulation in the two primordial germ cells. The pattern seen in Ascaris looks much like the antibody staining with the anti-P granule antibodies in C. elegans, the two germ cells being covered with silver grains in this case. The sensitivity of the hybridization has yet to be tested, as both the ribosomal and satellite probes are abundant in the RNA and germ line genomic DNA, respectively. Helpful, current resource material on in situ hybridization techniques includes: Jorgensen, E. M. and R. L. Garber. Pro Mega Notes 10:2-5 (1987).

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.