Fang Ng L et al. (2014) Free Radic Biol Med "The mitochondria-targeted antioxidant MitoQ extends lifespan and improves healthspan of a transgenic Caenorhabditis elegans model of Alzheimer disease."

Ping Sit K, Cheah I, Wenk MR, Kiat Goo C, Shui G, Fun Cheong W, Gruber J, Halliwell B, Fang Ng L

[Free Radic Biol Med, 2014]

-Amyloid (A)-induced toxicity and oxidative stress have been postulated to play critical roles in the pathogenic mechanism of Alzheimer disease (AD). We investigated the in vivo ability of a mitochondria-targeted antioxidant, MitoQ, to protect against A-induced toxicity and oxidative stress in a Caenorhabditis elegans model overexpressing human A. Impairment of electron transport chain (ETC) enzymatic activity and mitochondrial dysfunction are early features of AD. We show that MitoQ extends lifespan, delays A-induced paralysis, ameliorates depletion of the mitochondrial lipid cardiolipin, and protects complexes IV and I of the ETC. Despite its protective effects on lifespan, healthspan, and ETC function, we find that MitoQ does not reduce DCFDA fluorescence, protein carbonyl levels or modulate steadystate ATP levels or oxygen consumption rate. Moreover, MitoQ does not attenuate mitochondrial DNA (mtDNA) oxidative damage. In agreement with its design, the protective effects of MitoQ appear to be targeted specifically to the mitochondrial membrane and our findings suggest that MitoQ may have therapeutic potential for A- and oxidative stress-associated neurodegenerative disorders, particularly AD.

Ju J et al. (2023) Aquat Toxicol "The growth toxicity and neurotoxicity mechanism of waterborne TBOEP to nematodes: Insights from transcriptomic and metabolomic profiles."

Wu X, Zhu Y, Wang Y, Ma S, Ju J, Zhang C, Ge W, Mao W

[Aquat Toxicol, 2023]

Tris(2-butoxy) ethyl phosphate (TBOEP) is a typical organophosphorus flame retardant (OPFR), which has been detected in natural water bodies and drinking water and has reached a certain concentration. As a new type of organic pollutant, the environmental health risk of TBOEP needs to be assessed urgently. Here, Caenorhabditis elegans were exposed to 0, 50, 500, and 5000 ng/L TBOEP in water for 72 h. The results showed that TBOEP exposure caused concentration-dependent inhibition to the growth of nematodes, while exposure to 5000 ng/L TBOEP significantly inhibited the locomotor behavior of nematodes. Transcriptomic and metabolomic analysis showed that the disturbances in neurotransmitter transmission and amino acid, carbohydrate, and lipid metabolism were the reason for the neurotoxicity and growth toxicity of TBOEP to nematodes. These results provide basic data and a theoretical basis for evaluating the environmental health risks of organophosphorus flame retardants.

van der Most MA et al. (2023) Ecotoxicol Environ Saf "Contrasting dose response relationships of neuroactive antidepressants on the behavior of C. elegans."

van den Brink NW, van der Most MA, Estruch IM

[Ecotoxicol Environ Saf, 2023]

Antidepressant prescriptions are on a rise worldwide and this increases the concerns for the impacts of these pharmaceuticals on nontarget organisms. Antidepressants are neuroactive compounds that can affect organism's behavior. Behavior is a sensitive endpoint that may also propagate effects at a population level. Another interesting aspect of antidepressants is that they have shown to induce non-monotonic dose-response (NMDR) curves. While such NMDR relationships may have clear implications for the environmental risk, the resolution of current studies is often too coarse to be able to detect relevant NMDR. Therefore, the current study was performed into the behavioral effects (activity, feeding and chemotaxis) in Caenorhabditis elegans as the model organism of the selective serotonin reuptake inhibitors fluoxetine and sertraline and the acetylcholinesterase inhibiting pesticide chlorpyrifos, using a wide range of concentrations (ng/l to mg/l). In order to statistically examine the non-monotonicity, nonlinear regression models were applied to the results. The results showed a triphasic dose-response relationship for activity and chemotaxis after exposure to fluoxetine, but not to sertraline or chlorpyrifos. Effects of fluoxetine already occurred at low concentrations in the range of ng/l while sertraline only showed effects at concentrations in the μg/l range, similar to chlorpyrifos. The different responses between fluoxetine and sertraline, both SSRIs, indicate that response patterns may not always be extrapolated from chemicals with the same primary mode of action. The effects of fluoxetine at low concentrations, in a non-monotonic manner, confirm the relevance of examining such responses at low concentrations.

Yu Y et al. (2021) Chemosphere "Glutamatergic transmission associated with locomotion-related neurotoxicity to lindane over generations in Caenorhabditis elegans."

Chen X, Chen H, Hua X, Yang Y, Xiang M, Yu Y, Wang Z, Han Y

[Chemosphere, 2021]

Organochlorine pesticide lindane in the environment and biota results in the potential risks on ecosystem and human health. Lindane can adversely affect the locomotion and nervous system, yet the potential neurotoxicity of lindane over generations remains uncertain. In this study, the neurotoxicity and underlying mechanisms in Caenorhabditis elegans (C. elegans) were investigated after parental (P0) exposure to lindane at environmentally relevant concentrations over generations. Exposure to lindane at concentrations of 10-100 ng/L significantly decreased body bends and head thrashes in P0 generation. Significant decrease of fluorescence labeled different neurotransmitters, and clear morphological changes by exposure to lindane at 10-100 ng/L suggested that lindane could induce the neuronal damage in C. elegans. During the transgenerational process, decreased locomotive behaviors were also observed in F1-F3 generations, and head thrashes returned to normal levels in F4 generation. Moreover, lindane exposure down-regulated the expression of dat-1, dop-1, glr-1 and mod-1genes, while up-regulated unc-30 gene in P0 generation, which recovered to normal levels in F4 generation. Interestingly, eat-4 continued to be regulated from inhibition to stimulation in P0-F4 generations, suggesting that glutamatergic transmission may more contribute to the neurotoxicity of lindane over generations.

Zain MM et al. (2016) Trop Life Sci Res "The Effect of Macrocyclic Lactones-Ivermectin Exposure on Egg Hatching and Larval Development of Caenorhabditis elegans."

Zain MM, Him NA, Yahaya ZS

[Trop Life Sci Res, 2016]

To date, the ivermectin resistance in nematode parasites has been reported and many studies are carried out to determine the causes of this problem. A free-living Caenorhabditis elegans is used as a model system for this study to investigate the response of C. elegans to ivermectin exposure by using larval development assay. Worms were exposed to ivermectin at concentration from 1 ng/mL to 10 ng/mL and dimethyl sulphoxide (DMSO) as a control. The developments of the worms were monitored for 24, 48, 72, and 96 hours until the worms become adults. Results indicated that worms' growth began to be affected by ivermectin at a concentration of 5 ng/mL, while at the concentration of 6, 7, 8, 9, and 10 ng/mL, the growth of worms were inhibited compared to control worms. Further study of the protein expression in C. elegans should be done to investigate the up-regulated and down-regulated proteins involve in ivermectin resistance.

Hussain R et al. (1981) J Immunol "IgE responses in human filariasis. I. Quantitation of filaria-specific IgE."

Ottesen EA, Hussain R, Hamilton RG, Adkinson NF, Kumaraswami V

[J Immunol, 1981]

We have developed a noncompetitive solid phase radioimmunoassay to quantitate human IgE antibodies against soluble adult antigens of Brugia malayi (B.m.), a filarial parasite, in sera of patients with various forms of clinical filariasis in Madras, India. A single reference serum was shown to contain 23 micrograms/ml of B.m.-specific IgE by depletion analysis and was used as a standard serum throughout the study. The levels of specific IgE ranged in the patients sera from 2 to 23,000 ng/ml. When these individuals were divided into clinical groups, the individuals with tropical pulmonary eosinophilia had the highest levels (mean = 8630 ng/ml) and were significantly higher than all the other groups (p less than 0.001). The lowest levels were seen in patients with circulating microfilariae (mean = 30.5 ng/ml). Patients exhibiting lymphatic obstruction (i.e., chronic pathology group) had levels slightly higher than microfilaremics (mean = 68 ng/ml) but were not significantly different (p less than 0.1). Surprisingly, individuals living in endemic areas but who had no clinical signs of filariasis also showed appreciable levels of B.m.-specific IgE (mean = 55 ng/ml). The B.m.-specific IgE represented 0.1 to 48% of the total IgE. High percentages of specific IgE may be responsible for evoking allergic symptomatology in patients with tropical pulmonary eosinophilia.

Haldimann P et al. (2011) J Biol Chem "The novel hydroxylamine derivative NG-094 suppresses polyglutamine protein toxicity in Caenorhabditis elegans."

Goloubinoff P, Muriset M, Vigh L, Haldimann P

[J Biol Chem, 2011]

Aggregation-prone polyglutamine (polyQ) expansion proteins cause several neurodegenerative disorders, including Huntington disease. The pharmacological activation of cellular stress responses could be a new strategy to combat protein conformational diseases. Hydroxylamine derivatives act as co-inducers of heat-shock proteins (HSPs) and can enhance HSP expression in diseased cells, without significant adverse effects. Here, we used Caenorhabditis elegans expressing polyQ expansions with 35 glutamines fused to the yellow fluorescent protein (Q35-YFP) in body wall muscle cells as a model system to investigate the effects of treatment with a novel hydroxylamine derivative, NG-094, on the progression of polyQ diseases. NG-094 significantly ameliorated polyQ-mediated animal paralysis, reduced the number of Q35-YFP aggregates and delayed polyQ-dependent acceleration of aging. Micromolar concentrations of NG-094 in animal tissues with only marginal effects on the nematode fitness sufficed to confer protection against polyQ proteotoxicity, even when the drug was administered after disease onset. NG-094 did not reduce insulin/insulin-like growth factor 1-like signaling, but conferred cytoprotection by a mechanism involving the heat-shock transcription factor HSF-1 that potentiated the expression of stress-inducible HSPs. NG-094 is thus a promising candidate for tests on mammalian models of polyQ and other protein conformational diseases.

Hunter CP et al. (1991) International C. elegans Meeting "NON-AUTONOMY OF HER-1 FUNCTION IMPLICATES CELL INTERACTIONS IN C. ELEGANS SEX DETERMINATION."

Hunter CP, Wood WB

[International C. elegans Meeting, 1991]

Activity of the her-l gene is required for normal male development in C. elegans. Loss-of-function her-l mutations cause feminization of XO animals (normally male) to produce fertile hermaphrodites, while gain-of-function her-l mutations cause masculinization of XX animals ( normally hermaphrodite) to produce pseudo-males. Genetic analysis indicated that her-l functions early in the hierarchy of regulatory interactions among the major sex determination genes (1). We have analyzed her-l genetic mosaics to determine which cells must express her-l for wild-type male development. If her-l functions cell- autonomously, then in XO animals her-l (+) cells will follow male fates, and her-1(-) cells will follow hermaphrodite fates. If her-l or a her-l regulated activity functions non-autonomously, then the her-l genotype of a cell may not determine its sexual phenotype. The phenotypes of XO her-l genetic mosaics are variable, but clearly show that both her-1(-) and her-l (+) cells can follow either hermaphrodite or male fates. We conclude that her-l is neither necessary nor sufficient to cell-autonomously determine male sexual phenotypes and, therefore, that her-l or a her-l regulated activity must be able to function non-autonomously. The observed patterns of non-autonomous effects suggest that many or all cells express and respond to her-l activity. These findings implicate cell interactions in C. elegans sex determination. Earlier genetic analysis indicated that her-l might directly control tra-2 activity (1). Molecular characterization of the gene products of her-l and tra-2 (see abstracts by M. Perry et al. and P. Kuwabara et al) is consistent with a model in which a secreted ligand encoded by her-l interacts with a cell-surface receptor encoded by tra-2. We will discuss the possible role of such an interaction in coordinating the sex determination decision.

Forrester S et al. (2007) Foodborne Pathog Dis "Evaluation of the pathogenicity of Listeria spp. in Caenorhabditis elegans."

Schwab U, Wiedmann M, Hoose WA, Milillo SR, Forrester S

[Foodborne Pathog Dis, 2007]

Caenorhabditis has proven to be a useful model for studying host-pathogen interactions as well as the ability of nematodes to serve as vectors for the dispersal of foodborne pathogens. In this study, we evaluated whether C. elegans can serve as a host for Listeria spp. While there was an effect of growth media on C. elegans killing, C. elegans exposed to L. monocytogenes and L. innocua pregrown in Luria-Bertani medium showed reduced survival when compared to nonpathogenic E. coli OP50, while L. seeligeri showed survival similar to E. coli OP50. In a preference assay, C. elegans preferred E. coli over L. monocytogenes and L. innocua, but showed no preference between L. monocytogenes and L. innocua. A gentamicin assay indicated that L. monocytogenes did not persist within the C. elegans intestinal tract. Our findings that L. monocytogenes and L. innocua strains tested have equally deleterious effects on C. elegans and that L. monocytogenes did not establish intestinal infection conflict with other recently published results, which found intestinal infection and killing of C. elegans by L. monocytogenes. Further studies are thus needed to clarify the interactions between L. monocytogenes and C. elegans, including effects of environmental conditions and strain differences on killing and intestinal infection.

Hong K et al. (1992) Worm Breeder's Gazette "A Method for Direct DNA Sequence Analysis of PCR Amplified DNAThat Works Very Well"

Driscoll MA, Hong K

[Worm Breeder's Gazette, 1992]

We have begun DNA sequence analysis of 50 recessive mec-4 mutations. By combining aspects of a few different protocols we have come up with a method for sequencing of PCR products that is reliable and gives high quality data. We hope that this protocol may be of use to others involved in sequencing projects! A. Generation of the template DNA for sequence analysis 1. Amplify genomic DNA in standard PCR reaction. We use 2 g genomic DNA and approximately .5 g each primer (our primers average 21 bp in length) in 100 l reaction volume. 2 Run an agarose gel to assay the concentration of amplified DNA. Ideally, the concentration of DNA should be at least 1 g in 10 l. If the DNA concentration is very low, either ethanol precipitate to concentrate it for the next step or reamplify. Also if large visible amounts of primers remain, it is good to remove them as outlined in Step 4 below. 3 Amplify one strand of DNA. In separate experiments we have used either a new primer internal to the original boundaries of the PCR product or we reused on of the original primers for the single stranded amplification. Both approaches work quite well. Usually we use 10 l of the DNA generated in Step 1 above (About 1 g if possible) and about 200 ng of primer in 100 l volume. 4. Purify the ss amplified DNA away from unincorporated primers by passing over Miniprep Spun Columns form Pharmacia. Alternatively, make homeade columns with Sephacryl S-400. 5. Check DNA concentration on an agarose gel. For certain success, about 2 g of single-stranded DNA is used in each sequencing reaction. If the DNA concentration is too low, DNA can be ethanol precipitated to concentrate the sample or a second single-stranded amplification step is suggested. The amount of DNA template is very important. B. Denaturation of the template and annealing of sequencing primer 1. Add 8 l of template DNA and 1 l of 1 M NaOH to a 1.5 ml microcentrifuge tube; incubate at room temperature for 10 minutes 2. Add 1 l of 1 M HCl to neutralize the solution and then immediately add 2 l (about 200 ng) of sequencing primer (from the complementary strand, of course) and 2 l of sequencing buffer (as in Sequenase kit from US Biochemical). Note: perform this step on each tube individually, ie., if you are doing 10 reactions do not add HCl to each tube and then go back and add primers. Neutralize the first tube and add the appropriate primer and buffer and then start the next tube. This is important. 3. Incubate at 37 C for 15 minutes to allow the primer to anneal to template DNA C. Sequencing reactions Reactions are according to instructions in the USB Sequenase kit with a few changes: Labelling reaction: -14 l annealed DNA (the entire reaction prepared above) -1 l DMSO (added fresh) -1 l DTT. 0.1 M -2 l diluted dITP mix (1:5 dilution) -0.5 l 35S -2 l diluted sequenase* *When diluting Sequenase for reactions the dilution mix is made as follows: enzyme dilution buffer, 6.5 l pyrophosphatase, 0.5 l Sequenase, 1 l as usual, do this just before starting reactions Termination reaction: Although the starting volume is slightly larger than in the USB protocol, still add 4 l of labelled DNA into 2.5 l of each dITP for termination reactions, add 4 l stop solution. Notes: 1. We can read at least 400 bp for each reaction. 2. This procedure works very well for sequencing double stranded plasmid DNA.