Hawkins EG et al. (2015) Genetics "A novel cholinergic action of alcohol and the development of tolerance to that effect in Caenorhabditis elegans."

Davies AG, Martin I, Bettinger JC, Brings VE, Kondo LM, Chan CL, Blackwell GG, Hawkins EG, Judy ME

[Genetics, 2015]

Understanding the genes and mechanisms involved in acute alcohol responses has the potential to allow us to predict an individual's predisposition to developing an alcohol use disorder. To better understand the molecular pathways involved in the activating effects of alcohol and the acute functional tolerance that can develop to such effects, we characterized a novel ethanol-induced hypercontraction response displayed by Caenorhabditis elegans. We compared body size of animals prior to and during ethanol treatment and showed that acute exposure to ethanol produced a concentration-dependent decrease in size followed by recovery to their untreated size by 40 min despite continuous treatment. An increase in cholinergic signaling, leading to muscle hypercontraction, is implicated in this effect because pretreatment with mecamylamine, a nicotinic acetylcholine receptor (nAChR) antagonist, blocked ethanol-induced hypercontraction, as did mutations causing defects in cholinergic signaling (cha-1 and unc-17). Analysis of mutations affecting specific subunits of nAChRs excluded a role for the ACR-2R, the ACR-16R, and the levamisole-sensitive AChR and indicated that this excitation effect is dependent on an uncharacterized nAChR that contains the UNC-63 -subunit. We performed a forward genetic screen and identified eg200, a mutation that affects a conserved glycine in EAT-6, the -subunit of the Na(+)/K(+) ATPase. The eat-6(eg200) mutant fails to develop tolerance to ethanol-induced hypercontraction and remains contracted for at least 3 hr of continuous ethanol exposure. These data suggest that cholinergic signaling through a specific -subunit-containing nAChR is involved in ethanol-induced excitation and that tolerance to this ethanol effect is modulated by Na(+)/K(+) ATPase function.

Hawkins, E.G. et al. (2015) International Worm Meeting "Tolerance to a cholinergic activating effect of alcohol requires a specific function of the EAT-6 Na+/K+-ATPase."

Kondo, L.M., Davies, A.G., Hawkins, E.G., Martin, I., Bettinger, J.C.

[International Worm Meeting, 2015]

Alcohol (ethanol) produces activating and depressing behavioral effects in humans. We have investigated the basis for an activating effect of ethanol in C. elegans that produces body hypercontraction. Acute ethanol exposure induces a shortening of the animal that requires normal acetylcholine levels and a functional UNC-63 acetylcholine receptor (AChR) subunit. Elimination of the two receptors currently known to contain the UNC-63 subunit, the ACR-2R and the levamisole-sensitive AChR, do not alter sensitivity to ethanol. This suggests that UNC-63 may be acting in an unidentified receptor to mediate this effect of ethanol. AChRs in mammals have been implicated in mediating activating effects of ethanol, and genetic variation in AChR subunit-encoding genes has been associated with the development of alcoholism in humans. We are pursuing the tissue-specific requirements for unc-63 expression for its role in this ethanol effect.The hypercontracted animals show a recovery of pre-treatment body length despite continuous exposure to ethanol (and a gradual increase in internal ethanol concentration). This observation suggests that a physiological tolerance is developing to the drug. We identified the eat-6(eg200) mutation as a mutant that fails to develop tolerance to this ethanol effect. An examination of several existing alleles of eat-6 found that mutants with strong effects on pharyngeal pumping did not alter the response to ethanol-induced hypercontraction, whereas the ad601 allele, which resembles the eg200 mutant in having weak effects on pumping but strong effects on aldicarb sensitivity, does alter the maintenance of tolerance to ethanol. These data suggest that eg200 and ad601 alter a specific function of the Na+/K+-ATPase that is important for the development and/or maintenance of tolerance to ethanol for this cholinergic activating effect of ethanol. One possibility that we are testing, is that EAT-6 has a structural relationship with an ethanol-sensitive AChR, and that the mutations eg200 and ad601 prevent desensitization or compensatory trafficking of that receptor.

Jason Pellettieri et al. (2002) West Coast Worm Meeting "pom-1 is a Conserved Regulator of Cell Polarity and Cell Division in the C. elegans Embryo and Fission Yeast"

Jason Pellettieri, Geraldine Seydoux, Stuart Kim, Valerie Reinke

[West Coast Worm Meeting, 2002]

Polarization of the C. elegans zygote depends on cortically enriched proteins (e.g. the evolutionarily conserved PARs) and two cytoplasmic proteins (MEX-5/6) that function together to localize cytoplasmic determinants (e.g. PIE-1) in response to a polarity cue associated with the sperm asters.

Schierenberg E "Laser-induced cell fusion."

Schierenberg E

In recent years a number of different techniques have been developed to fuse cells of various origin in order to obtain hybrids with qualities different from each of the original cells. In many cases, one wants to fuse large numbers of cells (e.g. to generate hybridomas), and fusion occurs more or less randomly (e.g. Kohler and Milstein, 1975). With other methods, individual cells have been fused under controlled conditions (e.g., McGrath and Solter, 1984). So far a prerequisite for fusing two preselected cells has been that they must be isolated away

Calabrese EJ et al. (2024) Ageing Res Rev "HORMESIS DETERMINES LIFESPAN."

Calabrese V, Agathokleous E, Kapoor R, Hayes AW, Calabrese EJ, Pressman P, Nascarella M, Dhawan G

[Ageing Res Rev, 2024]

This paper addresses how long lifespan can be extended via multiple interventions, such as dietary supplements [e.g., curcumin, resveratrol, sulforaphane, complex phytochemical mixtures (e.g., Moringa, Rhodiola)], pharmaceutical agents (e.g., metformin), caloric restriction, intermittent fasting, exercise and other activities. This evaluation was framed within the context of hormesis, a biphasic dose response with specific quantitative features describing the limits of biological/phenotypic plasticity for integrative biological endpoints (e.g., cell proliferation, memory, fecundity, growth, tissue repair, stem cell population expansion/differentiation, longevity). Evaluation of several hundred lifespan extending agents using yeast, nematode (Caenorhabditis elegans), multiple insect and other invertebrate and vertebrate models (e.g., fish, rodents), revealed they responded in a manner [average (mean/median) and maximum lifespans] consistent with the quantitative features [i.e., 30-60% greater at maximum (Hormesis Rule)] of the hormetic dose response. These lifespan extension features were independent of biological model, inducing agent, endpoints measured and mechanism. These findings indicate that hormesis describes the capacity to extend life via numerous agents and activities and that the magnitude of lifespan extension is modest, in the percentage, not fold, range. These findings have important implications for human aging, genetic diseases/environmental stresses and lifespan extension, as well as public health practices and long-term societal resource planning.

Schulenburg, Hinrich et al. (2011) International Worm Meeting "Experimental test of the consequences of host-parasite coevolution."

Laehnemann, David, EL Masri, Leila, Michiels, Nicolaas K., Guenther, Patrick, Schulenburg, Hinrich

[International Worm Meeting, 2011]

The coevolution between host and parasite is believed to be associated with high evolutionary dynamics affecting various life-history characteristics and the underlying genetics. We use experimental evolution between the nematode host Caenorhabditis elegans and its microparasite Bacillus thuringiensis to explore the consequences of coevolution. Our current results demonstrate that B. thuringiensis evolves into two very distinct phenotypes in response to either coevolution with the host (e.g., maintenance of virulence, no biofilm production) or evolution in the absence of an antagonist (e.g., loss of virulence, pronounced biofilm production). The host C. elegans shows similar although less pronounced adaptations (e.g., increased resistance, reduced body size). Based on genomic analyses, we are currently exploring the underlying molecular genetics. Our study provides experimental evidence for the high selective dynamics that result from host-parasite coevolution.

Ishii N et al. (2002) Free Radic Biol Med "Protein oxidation during aging of the nematode Caenorhabditis elegans."

Goto S, Ishii N, Hartman PS

[Free Radic Biol Med, 2002]

The nematode Caenorhabditis elegans has proven a robust genetic model for studies of aging, including the roles of oxidative stress and protein damage. In this review, we focus on the genetics of select long-lived (e.g., age-1, daf-2, daf-16) and short-lived (e.g., mev-1) mutants that have proven useful in revealing the relationships that exist among oxidative stress, life span, and protein oxidation. The former are known to control an insulin/IGF-1-like pathway in C. elegans, while the latter affect mitochondrial function.

Mohamed ASA et al. (2000) Journal of Pesticide Science "Lethal activity of galo- and condensed tannins against the free-living soil-inhabiting nematode, Caenorhabditis elegans."

Mohamed ASA, Sato M, Islam SQ, Yamasaki T, Mori T

[Journal of Pesticide Science, 2000]

Great amounts of structurally diverse tannins are annually produced. Tannins have been well known as food phytochemicals (e.g. 3T-O-a-L-arabinopyranosyl-ent-epicatechin-(2a->O-7,4a->8)-epicat echin in cacao mass), medicinal properties (e.g. geraniin in Geranium thunbergii as tonic or antidiarrhoic) or tanning materials for leather manufacture (e.g. wattle tannins in Acacia mollissima). Recently, condensed tannin dimers (procyanidins B-1 and B-3) and its polymers were isolated from Pinus densiflora and characterized as members of the oviposition-stimulating multicomponent system in pine for the cerambycid beetle, Monochamus alternatus. Condensed tannins have also been regarded as antifeedants for phytophagous insects. A marine phlorotannin preparation, polymer of phloroglucinol, obtained from the brown alga Sargassum furvellum inhibits growth of the green algae Dunaliella and Enteromorpha spp. This paper describes isolation and identification of gallo- and condensed tannins and their nematicidal acitivity against the soil-inhabiting nematode, Caenorhabditis elegans.

Li Z et al. (2019) J Hazard Mater "Multi-generational obesogenic effects of sulfomethoxazole on Caenorhabditis elegans through epigenetic regulation."

Li Z, Yin D, Cui C, Yu Z, Ai F

[J Hazard Mater, 2019]

Increasing concerns are earned on the multigenerational hazards of antibiotics due to the connection between their mother-children transfer via cord blood and breast milk and obesity in the children. Currently, Caenorhabditis elegans was exposed to sulfamethoxazole (SMX) over 11 generations (F0-F10). Indicators of obesogenic effects and gene expressions were measured in each generation and also in T11 to T13 that were the offspring of F10. Biochemical analysis results showed that SMX stimulated fatty acids in most generations including T13. The stimulation was resulted from the balance between enzymes for fatty acid synthesis (e.g., fatty acid synthetase) and those for its consumption (e.g., fatty acid transport protein). Gene expression analysis demonstrated that the obesogenic effects of SMX involved peroxisome proliferator activated receptors (PPARs, e.g., nhr-49) and insulin/insulin-like signaling (IIS) pathways (e.g., ins-1, daf-2 and daf-16). Further epigenetic analysis demonstrated that SMX caused 3-fold more H3K4me3 binding genes than the control in F10 and T13. In F10, the most significantly activated genes were in metabolic and biosynthetic processes of various lipids, nervous system and development. The different gene expressions in T13 from those in F10 involved development, growth, reproduction and responses to chemicals in addition to metabolic processes.

Waldmann R et al. (1998) Curr Opin Neurobiol "H+-gated cation channels: nruonal acid sensors in the NaC/DEG family of ion channels."

Waldmann R, Lazdunski M

[Curr Opin Neurobiol, 1998]

Ion channels in the amiloride-sensitive Na+ channel/degenerin (NaC/DEG) family of cation channels have very diverse functions. They can be constitutively active (e.g. the epithelial Na+ channel), gated by a ligand (e.g. the peptide-gated channel FaNaC or H+-gated cation channels [ASICs]) or possibly activated by stretch (degenerins of Caenorhabditis elegans). Despite this functional diversity, the heterologous expressed channels share the following properties: permeability to Na+, inhibition by the diuretic amiloride and no voltage gating. This review will focus on recent advances in this ion channel family, with special emphasis on H+-gated cation channels.