Cinar, Hediye N. et al. (2013) International Worm Meeting "Characterization of Vibrio parahaemolyticus virulence factors using Caenorhabditis elegans."

Franco, Augusto A., Cinar, Hediye N., Tall, Ben D., Hahn, Justin, Kim, Sungji, Grim, Christopher, Kothary, Mahendra, Sahu, Surasri N., Datta, Atin

[International Worm Meeting, 2013]

Vibrio parahaemolyticus (Vp), a Gram-negative marine bacterium, is an emerging pathogen causing gastroenteritis, wound infection, and septicemia. Gastroenteritis caused by Vp is associated with the production of thermostable direct (TDH) and TDH-related hemolysins (TRH), and the inflammatory responses are produced by effector proteins secreted by a type III secretion system (T3SS-2a, or b) contained within pathogenicity islands (1). In order to study innate immune responses to known virulence factors, and to discover new virulence factors, we used Caenorhabditis elegans as a host organism. Vp isolates, previously serotyped and characterized by PCR for the presence of T3SS-2, TRH, TDH, and urease genes, were tested using a C. elegans lethality assay for their virulence. Six groups of Vp strains, each representing the following genotypes, were tested in the C. elegans model: 1) urease+ trh+ tdh+ T3SS-2b+, 2) urease+ trh+ tdh- T3SS-2b + , 3) urease+ trh- tdh- T3SS-2b + , 4) urease+ trh- tdh+ T3SS-2a+ , 5) urease- trh- tdh- T3SS-2- , 6) urease- trh- tdh+ T3SS-2a + . Median survival rates of worms tested against Vp isolates ranged between five and sixteen days. Vp strains with functional urease gene loci resulted in shorter median survival rates of C. elegans. Our data suggest a strong correlation between the presence of Vp gene and C. elegans lethality. These results taken together with those previously reported by Honda et al.(2) that urease-positive, TDH- and TRH-negative strains were also capable of causing intestinal fluid accumulation in the rabbit ligated ileal loop assay, suggest a significant role for urease in disease development. Alternatively, urease might be needed to activate other virulence factor/s or a marker linked with a currently unknown virulence factor gene(s) in Vp. Further molecular and functional characterization of urease in C. elegans infection, is in progress. (1) Ham H, Orth K, 2012 (2) Honda S, et al. 1992.

Schlosser, A. et al. (2015) International Worm Meeting "Chronic exposure to pesticide residues exacerbates alpha-synuclein pathology in a Caenorhabditis elegans Parkinson's disease model."

Flaherty, D., Schlosser, A., Davis, M.

[International Worm Meeting, 2015]

Human health issues and disease have long been linked to environmental exposures which may be the greatest risk factors for the development of neurodegenerative diseases (Franco et al. 2010). Epidemiological studies show that exposure to environmental agents such as pesticides is a key contributor to the development and exacerbation of Parkinson's Disease (PD) (Franco et al. 2010). Intraneuronal inclusions, known as Lewy bodies, composed primarily of aggregated alpha-synuclein, are the primary causative formations associated with the loss of dopaminergic neurons and the development of PD (Baltazar et al. 2014; Brown et al. 2006). The loss of these neurons causes dysfunction of the basal ganglia and the subsequent inhibition of motor control, the defining characteristic of the disease (Baltazar et al. 2014). This study looks to assess the possible toxicological effects of chronic exposure to three common pesticides, chlorpyrifos, carbaryl and indoxacarb, at maximum tolerated residue levels set by the Environmental Protection Agency (EPA) in a Caenorhabditis elegans PD model. While the EPA employs strict regulations on individual pesticides, there are no regulations governing the mixing of pesticides. In this study, pesticides are tested both individually and as binary mixtures in order to investigate alpha-synuclein toxicity. Results from the study indicate that individually, these pesticides, with the exception of indoxacarb, have a noticeable effect on alpha-synuclein pathology. When combined to form binary mixtures, all pesticides have a drastic effect on alpha-synuclein pathology and mortality, despite being within EPA limits.

Otsuka AJ (1990) Worm Breeder's Gazette "ALTERATIONS IN UNC-44 ALLELES"

Otsuka AJ

[Worm Breeder's Gazette, 1990]

Preliminary analysis of six spontaneous unc-44 alleles indicates that alterations occur over a fairly large region in the genomic DNA. Southern analysis of two alleles from E. Hedgecock (rh1013 and rf1042) and four alleles (mn259, mn339, q331, and st200) from R. Herman and other labs (kindly provided by C. Kari, R. Herman, W. Li, and J. Shaw) indicated that restriction fragment differences from wild type are associated with all six alleles (see Franco et al., C. elegans Meeting abstracts, 1989). The construction of preliminary restriction maps of unc-44 cosmid (B0350 and C44A, kindly provided by A. Coulson and J. Sulston) and phage (DD#LRF1 and DD#LRF6) clones allows the approximate positioning of mutant changes. The absolute orientations of the cosmid and phage clones are based on positioning of these clones on the cosmid map. The overlapping of the cosmid and phage clones has not yet been demonstrated. Unfortunately, the cosmid isolate that could quickly clarify the situation (C02C3) deleted during growth. [See Figure 1]

Liu H et al. (2013) J Ethnopharmacol "Lifespan extension by n-butanol extract from seed of Platycladus orientalis in Caenorhabditis elegans."

Liu H, Liang F, Su W, Zhang Y, Li P, Xie X, Lv M, Pei Z, Wang Y, Wang N

[J Ethnopharmacol, 2013]

AIM OF THE STUDY: As a traditional Chinese medicine, seed of Platycladus orientalis(Linnaeus) Franco has been extensively used as a tonic and sedative remedy. The present study was conducted to investigate whether lifespan was extended and the mechanisms of n-butanol extract from seed of Platycladus orientalis (BSPO) in Caenorhabditis elegans. The findings could provide the pharmacological basis for a treatment in traditional medicine. MATERIALS AND METHODS: Lifespan extension by BSPO was evaluated under normal culture conditions and in a stress test. A possible mechanism of the anti-aging effect of BSPO, a change in the stress-resistance of related proteins, was also investigated in C. elegans. RESULTS: It has been shown that BSPO could significantly extend lifespan of C. elegans in a concentration dependent manner under normal culture conditions and stress. Further studies demonstrated that BSPO treatment significantly decreased reactive oxygen species (ROS) accumulation, up-regulated resistance to stress of related proteins, including glutathione S-transferase-4 (GST-4) and heat shock protein-16.2 (HSP-16.2), and reduced the amount of lipofuscin in transgenic C. elegans. CONCLUSION: These results indicated that BSPO extended the lifespan, which could be attributed to its direct ROS scavenging activity, reducing the amount of lipofuscin and increasing the expression of gens associated with resistance to stress. These obtained data provided valuable support for traditional clinical practice to extend lifespan and to provide tonic remedy.

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.

Shim KH et al. (1991) International C. elegans Meeting "CHARACTERIZATION OF UNC-44 cDNA CLONES"

Shim KH, Otsuka AJ

[International C. elegans Meeting, 1991]

The nematode, C. elegans, is an appropriate organism for the study of neuronal development. Some of 302 neurons can be visualized by use of the FITC fluorescence technique. It is of interest to determine how neuronal outgrowth is regulated during development and what mechanisms are involved at the cellular and molecular levels. The mechanisms and the characteristics of the molecules involved in axonal outgrowth are not well known. Mutations in unc-44 result in abnormal interconnections of the nervous system [Hedgecock et al., Devel. Biol. 111, 158-170, (1985)]. For example, the PDE (postdeirid) neurons in unc-44 show various abnormalities. The mutant axons have complex and variable defects including growth along inappropriate lateral, subventral, or subdorsal positions. The phasmid axons terminate just before they enter the ventral nerve cord at the posterior- end of the preanal region. The unc- 44 gene was cloned by transposon tagging [Franco et al., 7th C. elegans Meeting Abs., p. 76 (1989)]. Three cDNA clones were isolated (DD#PA013, DD#PA049, and DD#PA066) and sequence of DD#PA049 is being determined. The cDNA clones, DD#PA049 and DD#PA066 include the region corresponding to tlle insertion in the rhlO13 allele. The restriction map of DD#PA049 is similar to that of DD#PA066, but DD#PA013 showed a different pattern from DD#PA049 and DD#PA066. The cDNA sequence data demonstrate that DD#PA049 and DD#PA066 encode similar proteins, but the 3' untranslated regions are different. Toward the amino terminus, the DD#PA049 potential protein contains a 5-amino acid insertion relative to DD#A066, perhaps produced by alternative splicing.

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.