Dusenbery DB (1975) J Exp Zool "The avoidance of D-tryptophan by the nematode Caenorhabditis elegans."

Dusenbery DB

[J Exp Zool, 1975]

In chemotactic studies employing countercurrent separation the nematode Caenorhabditis elegans was found to avoid D-tryptophan with a threshold in the range 10(-4) to 10(-3) M. There was no response to L-tryptophan up to 10(-2) M although it appeared to partially inhibit the response to D-tryptophan.

O'Connell EM et al. (2015) J Infect Dis "Targeting Filarial Abl-like Kinases: Orally Available, Food and Drug Administration-Approved Tyrosine Kinase Inhibitors Are Microfilaricidal and Macrofilaricidal."

Nutman TB, O'Connell EM, Bennuru S, Steel C, Dolan MA

[J Infect Dis, 2015]

BACKGROUND: Elimination of onchocerciasis and lymphatic filariasis is targeted for 2020. Given the coincident Loa loa infections in Central Africa and the potential for drug resistance development, the need for new microfilaricides and macrofilaricides has never been greater. With the genomes of L. loa, Onchocerca volvulus, Wuchereria bancrofti, and Brugia malayi available, new drug targets have been identified. METHODS: The effects of the tyrosine kinase inhibitors imatinib, nilotinib, and dasatinib on B. malayi adult males, adult females, L3 larvae, and microfilariae were assessed using a wide dose range (0-100 M) in vitro. RESULTS: For microfilariae, median inhibitory concentrations (IC50 values) on day 6 were 6.06 M for imatinib, 3.72 M for dasatinib, and 81.35 M for nilotinib; for L3 larvae, 11.27 M, 13.64 M, and 70.98 M, respectively; for adult males, 41.6 M, 3.87 M, and 68.22 M, respectively; and for adult females, 42.89 M, 9.8 M, and >100 M, respectively. Three-dimensional modeling suggests how these tyrosine kinase inhibitors bind and inhibit filarial protein activity. CONCLUSIONS: Given the safety of imatinib in humans, plans are underway for pilot clinical trials to assess its efficacy in patients with filarial infections.

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.

Shakambari G et al. (2017) ACS Omega "Agro Waste Utilization for Cost-Effective Production of l-Asparaginase by Pseudomonas plecoglossicida RS1 with Anticancer and Acrylamide Mitigation Potential."

Shakambari G, Ashokkumar B, Varalakshmi P, Sameer Kumar R

[ACS Omega, 2017]

Agricultural wastes such as the peels of onion and garlic were used as a supplement along with l-asparagine for the very first time to produce increased yield of l-asparaginase by <i>Pseudomonas plecoglossicida</i> RS1. Statistical optimization strategies such as response surface methodology were used to generate a medium composition containing extracts of 0.9 (v/v) of garlic peel waste and 0.5% (v/v) onion peel waste along with 0.2% (w/w) l-asparagine, which yielded a twofold increase in the enzyme activity compared to the unsupplemented minimal (M-9) medium. The presence of l-asparagine content in the peel extract was confirmed by high-performance liquid chromatography. Further, l-asparaginase was purified to homogeneity, and identity was confirmed by matrix-assisted laser desorption ionization time-of-flight analysis. The application of the purified l-asparaginase as a therapeutic was studied in HeLa cells which showed a p53-mediated G₂ cell cycle arrest. Moreover, the purified l-asparaginase showed effective acrylamide mitigation in vitro, at 6 IU, and its effective degradation was also demonstrated by the effect on chemotactic index of <i>Caenorhabditis elegans</i> and the restoration of the cognitive abilities of <i>C. elegans</i> which was coexposed to acrylamide and l-asparaginase compared to that exposed to acrylamide alone. Thus, l-asparaginase, with multipotent applications, was produced by effective waste utilization for economical commercial production.

Abraham D et al. (1989) Am J Trop Med Hyg "Immunity to larval Brugia malayi in BALB/c mice: protective immunity and inhibition of larval development."

Grieve RB, Christensen BM, Abraham D, Holy JM

[Am J Trop Med Hyg, 1989]

The objective of this study was to analyze the immune response of mice to the larval stages of Brugia malayi. Male BALB/c mice were inoculated with 3 doses of irradiated third-stage larvae (L-3) of B. malayi and were subsequently challenged with L-3 implanted ip within diffusion chambers. After 3 weeks, larvae were recovered to determine their viability, length, and stage of development. A significant reduction in parasite survival was observed in immunized mice. Furthermore, larvae recovered from immunized mice were significantly shorter than larvae recovered from control mice. All larvae recovered from immunized mice were L-3, whereas 96% of larvae recovered from controls were fourth-stage larvae (L-4). Sera collected from control and immunized mice were tested for the presence of antibodies reactive with L-3 and L-4 antigens using an indirect fluorescent antibody assay employing frozen larval cross-sections as antigen. Sera recovered after challenge of control mice reacted with internal, but not surface, antigens of L-3 and L-4. Alternatively, sera from immunized mice reacted with both internal and external antigens of both L-3 and L-4.

Wypijewska A et al. (2012) Biochemistry "7-methylguanosine diphosphate (m(7)GDP) is not hydrolyzed but strongly bound by decapping scavenger (DcpS) enzymes and potently inhibits their activity."

Wypijewska A, Darzynkiewicz E, Davis RE, Jemielity J, Bojarska E, Lukaszewicz M, Stepinski J

[Biochemistry, 2012]

Decapping scavenger (DcpS) enzymes catalyze the cleavage of a residual cap structure following 3' 5' mRNA decay. Some previous studies suggested that both m(7)GpppG and m(7)GDP were substrates for DcpS hydrolysis. Herein, we show that mononucleoside diphosphates, m(7)GDP (7-methylguanosine diphosphate) and m(3)(2,2,7)GDP (2,2,7-trimethylguanosine diphosphate), resulting from mRNA decapping by the Dcp1/2 complex in the 5' 3' mRNA decay, are not degraded by recombinant DcpS proteins (human, nematode, and yeast). Furthermore, whereas mononucleoside diphosphates (m(7)GDP and m(3)(2,2,7)GDP) are not hydrolyzed by DcpS, mononucleoside triphosphates (m(7)GTP and m(3)(2,2,7)GTP) are, demonstrating the importance of a triphosphate chain for DcpS hydrolytic activity. m(7)GTP and m(3)(2,2,7)GTP are cleaved at a slower rate than their corresponding dinucleotides (m(7)GpppG and m(3)(2,2,7)GpppG, respectively), indicating an involvement of the second nucleoside for efficient DcpS-mediated digestion. Although DcpS enzymes cannot hydrolyze m(7)GDP, they have a high binding affinity for m(7)GDP and m(7)GDP potently inhibits DcpS hydrolysis of m(7)GpppG, suggesting that m(7)GDP may function as an efficient DcpS inhibitor. Our data have important implications for the regulatory role of m(7)GDP in mRNA metabolic pathways due to its possible interactions with different cap-binding proteins, such as DcpS or eIF4E.

Sese BT et al. (2009) J Toxicol Environ Health A "Toxicity of polycyclic aromatic hydrocarbons to the nematode Caenorhabditis elegans."

Reid BJ, Grant A, Sese BT

[J Toxicol Environ Health A, 2009]

The presence of polycyclic aromatic hydrocarbons (PAHs) in the environment has attracted much concern owing to their mutagenic and carcinogenic properties. Regulatory authorities have favored the use of biological indicators as an essential means of assessing potential toxicity of environmental pollutants. This study aimed to assess the toxicity of acenaphthene, phenanthrene, anthracene, fluoranthene, pyrene, and benzo[a]pyrene to Caenorhabditis elegans by measuring LC50 and EC50 values for growth and reproduction. The exposure to all chemicals was carried out in aqueous medium. All PAHs showed a low acute toxicity to C. elegans. There was no significant mortality in C. elegans after 24 h of exposure at PAH concentrations within (and indeed above) their respective solubility limits. Prolonged exposure (72 h) at high concentrations for acenaphthene (70,573 microg/L), phenanthrene (3758 microg/L), anthracene (1600 microg/L), fluoranthene (1955 microg/L), pyrene (1653 microg/L), and benzo[a]pyrene (80 microg/L) produced mortality. Results also showed that reproduction and growth were much more sensitive parameters of adverse response than lethality, and consequently may be more useful in assessing PAH toxicity using C. elegans. In comparison with previous studies, C. elegans was found to be approximately 2-fold less sensitive to acenaphthene, 5-fold less sensitive to phenanthrene, and 20-fold less sensitive to fluoranthene than Daphnia magna. However, the 48-h LC50 for benzo[a]pyrene (174 microg/L) reported in the present study with C. elegans was similar to that reported elsewhere for Daphnia magna (200 microg/L). Although C. elegans indicated greater sensitivity to benzo[a]pyrene than Artemia salina (174 microg/L vs. 10000 microg/L), the organism showed less sensitivity to pyrene (8 microg/L vs. 2418 microg/L), fluoranthene (40 microg/L vs. 2719 microg/L), and phenanthrene (677 microg/L vs. 4772 microg/L) than Artemia salina. Caenorhabditis elegans, while not the most sensitive of species for PAH toxicity assessment, may still hold applicability in screening of contaminated soils and sediments.

Manalo RVM et al. (2020) Pharm Biol "Caffeine reduces deficits in mechanosensation and locomotion induced by L-DOPA and protects dopaminergic neurons in a transgenic Caenorhabditis elegans model of Parkinson's disease."

Medina PMB, Manalo RVM

[Pharm Biol, 2020]

CONTEXT: L-DOPA is the first-line drug for Parkinson's disease (PD). However, chronic use can lead to dyskinesia. Caffeine, which is a known neuroprotectant, can potentially act as an adjunct to minimise adverse effects of L-DOPA. OBJECTIVES: (Rhabditidae) strain UA57 overexpressing tyrosine hydroxylase (CAT-2) when treated with caffeine, L-DOPA or their combinations. MATERIALS AND METHODS: =20). Meanwhile, mechanosensation and locomotion under vehicle (0.1% DMSO), L-DOPA (60mM), caffeine (10mM) or 60mM L-DOPA + 10 or 20mM caffeine (60LC10 and 60LC20) treatments were scored for 3days. RESULTS: Taken together, we show that caffeine can protect DAergic neurons and can reduce aberrant locomotion and loss of sensation when co-administered with L-DOPA, which can potentially impact PD treatment and warrants further investigation.

Buyannemekh K et al. (2024) Dev Biol "Left/right asymmetrically expressed ephrin and Flamingo proteins regulate lateralized axon growth in C. elegans."

Buyannemekh K, Bertrand V, Villoutreix P

[Dev Biol, 2024]

While the nervous system of bilaterian animals is mainly left-right (L-R) symmetric at the anatomical level, some molecular and functional L-R asymmetries exist. However, the extent of these molecular asymmetries and their functional consequences remain poorly characterized. C. elegans allows to study L-R asymmetries in the nervous system with single-neuron resolution. We have previously shown that a neural bHLH transcription factor, HLH-16/Olig, is L-R asymmetrically expressed in the AIY neuron lineage and regulates AIY axon projections in a L-R asymmetric manner. Here, by combining a candidate approach and single-cell RNA sequencing data analysis, we identify the ephrin protein EFN-2 and the Flamingo protein FMI-1 as downstream targets of HLH-16 that are L-R asymmetrically expressed in the AIY lineage. We show that EFN-2 and FMI-1 collaborate in the L-R asymmetric regulation of axonal growth. EFN-2 may act via a non-canonical receptor of the L1CAM family, SAX-7. Our study reveals novel molecular L-R asymmetries in the C. elegans nervous system and their functional consequences.

Pohl C (2011) Commun Integr Biol "Left-right patterning in the C. elegans embryo: Unique mechanisms and common principles."

Pohl C

[Commun Integr Biol, 2011]

The development of bilateral symmetry during the evolution of species probably 600 million years ago brought about several important innovations: It fostered efficient locomotion, streamlining and favored the development of a central nervous system through cephalization. However, to increase their functional capacities, many organisms exhibit chirality by breaking their superficial left-right (l-r) symmetry, which manifests in the lateralization of the nervous system or the l-r asymmetry of internal organs. In most bilateria, the mechanisms that maintain consistent l-r asymmetry throughout development are poorly understood. This review highlights insights into mechanisms that couple early embryonic l-r symmetry breaking to subsequent l-r patterning in the roundworm Caenorhabditis elegans. A recently identified strategy for l-r patterning in the early C. elegans embryo is discussed, the spatial separation of midline and anteroposterior axis, which relies on a rotational cellular rearrangement and non-canonical Wnt signaling. Evidence for a general relevance of rotational/torsional rearrangements during organismal l-r patterning and for non-canonical Wnt signaling/planar cell polarity as a common signaling mechanism to maintain l-r asymmetry is presented.