Petralanda I et al. (1988) Am J Trop Med Hyg "Parasite antigens are present in breast milk of women infected with Onchocerca volvulus."

Petralanda I, Yarzabal L, Piessens WF

[Am J Trop Med Hyg, 1988]

We used a noncompetitive two-site ELISA with 5 monoclonal antibodies to determine whether parasite antigens are present in breast milk from women infected with Onchocerca volvulus. Seven out of 13 available milk samples contained significant amounts of filarial antigens. Antigen indices in milk correlated with levels of microfilarodermia (Rs = 0.74, P less than 0.005). Antigen-containing milk samples markedly inhibited mitogen-induced proliferation of human mononuclear cells and activated cells within this population that suppressed the proliferative response of autologous lymphocytes to mitogens and antigens. These findings indicate that parasite products are present in breast milk of O. volvulus-infected women and suggest that these may induce immune tolerance and/or suppression in infants born of infected mothers.

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.

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.

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.

Basanez MG et al. (2000) Parasitology "Onchocerca-Simulium complexes in Venezuela: can human onchocerciasis spread outside its present endemic areas?"

Villamizar NJ, Frontado HL, Yarzabal L, Basanez MG

[Parasitology, 2000]

The compatibility between sympatric and allopatric combinations of Onchocerca volvulus-anthropophilic species of Simulium was studied in the north-eastern focus of human onchocerciasis as well as in a densely populated locality of the Amazonas State in Venezuela. The objectives were to test the conjecture that local adaptation exists between the parasite and its vectors (the Onchocerca-Simulium complex hypothesis), and assess the possibility of the infection spreading from its present distributional range. For the homologous combination, O. volvulus-S. metallicum cytospecies E in Anzoategui State (north-eastern focus), parasite yield was 45% in contrast to 1% for the heterologous, southern parasite-S. metallicum infection. This was significantly lower than the parasite yield (4-10%) expected after allowing for the effect of density-dependent limitation of infective larval output described in this paper for S. metallicum. The population of S. exiguum s.l. from southern Venezuela allowed no larval development beyond the L1 stage of either northern or southern parasites. Mechanisms for such refractoriness probably operate at the level of the thoracic muscles, not affecting microfilarial uptake or migration out of the bloodmeal. The parasite yield of southern O. volvulus in S. oyapockense s.l. flies biting man at Puerto Ayacucho (Amazonas) was about 1%, in agreement with the figures recorded for highly compatible sympatric combinations such as O. volvulus-S. ochraceum s.l. in Guatemala. No infective larval development of the northern parasite was observed in southern S. oyapockense. These results, together with considerations of typical worm burdens in the human host, presence/absence of armed cibaria in the simuliids, parasite-induced vector mortality, and fly biting rates, suggest a lower potential for onchocerciasis to spread between the northern and southern endemic areas of Venezuela than that between Amazonian hyperendemic locations and settlements outside this focus with high densities of S. oyapockense s.l.

Pepper ASR et al. (2003) Genetics "Genetic analysis of Caenorhabditis elegans glp-1 mutants suggests receptor interaction or competition."

Pepper ASR, Hubbard EJA, Killian DJ

[Genetics, 2003]

glp-l encodes a member of the highly conserved LIN-12/Notch family of receptors that mediates the mitosis/meiosis decision in the C. elegans germline. We have characterized three mutations that represent a new genetic and phenotypic class of glp-l mutants, glp-l(Pro). The glp-l(Pro) mutants display gainof-function germline pattern defects, most notably a proximal proliferation (Pro) phenotype. Each of three glp-l(Pro) alleles encodes a single amino acid change in the extracellular part of the receptor: two in the LIN-12/Notch repeats (LNRs) and one between the LNRs and the transmembrane domain. Unlike other previously described gain-of-function mutations that affect this region of LIN-12/Notch family receptors, the genetic behavior of glp-l(Pro) alleles is not consistent with simple hypermorphic activity. Instead, the mutant phenotype is suppressed by wild-type doses of glp-l. Moreover, a trans-heterozygous combination of two highly penetrant glp-l(Pro) mutations is mutually suppressing. These results lend support to a model for a higher-order receptor complex and/or competition among receptor proteins for limiting factors that are required for proper regulation of receptor activity. Double-mutant analysis with suppressors and enhancers of lin-12 and glp-l further suggests that the functional defect in glp-l(Pro) mutants occurs prior to or at the level of ligand interaction.

Flydal MI et al. (2010) Amino Acids "Superstoichiometric binding of L-Phe to phenylalanine hydroxylase from Caenorhabditis elegans: evolutionary implications."

Flydal MI, Teigen K, Siltberg-Liberles J, Martinez A, Mohn TC, Pey AL

[Amino Acids, 2010]

Phenylalanine hydroxylase (PAH) catalyzes the hydroxylation of L-Phe to L-Tyr. Dysfunctional PAH results in phenylketonuria and mammalian PAH is therefore highly regulated and displays positive cooperativity for L-Phe (Hill coefficient (h)=2). L-Phe does not bind to the regulatory ACT domain in full-length tetrameric human PAH and cooperativity is elicited by homotropic binding to the catalytic site (Thorolfsson et al. in Biochemistry 41:7573-7585, 2002). PAH from Caenorhabditis elegans (cePAH) is devoid of cooperativity for L-Phe (h=0.9), and, as shown in this work, structural analysis reveal an additional L-Phe binding site at the regulatory domain of full-length cePAH. This site involves the GA(S)L/ISRP motifs, which are also found in ACT domains of other L-Phe binding proteins, such as prephenate dehydratase. Isothermal titration calorimetry further demonstrated 2 binding sites per subunit for cePAH versus ~1 for hPAH. Steric occlusion of the regulatory site, notably by residues Lys215/Tyr216 from the adjacent catalytic domain, appears to hinder regulatory binding in full-length hPAH. Accordingly, the humanized mutant Q215K/N216Y of cePAH binds ~1.4 L-Phe/subunit. This mutant also displays high catalytic activity and certain positive cooperativity for L-Phe (h=1.4). Our results support that the acquisition of positive cooperativity in mammalian forms of PAH is accompanied by a closure of the regulatory L: -Phe binding site. Concomitantly, the function of the regulatory ACT domain appears to be adapted from amino acid binding to serving the communication of conformational changes among catalytic subunits.