Toe L et al. (1997) Lancet "Vector-parasite transmission complexes for onchocerciasis in West Africa."

Toe L, Unnasch TR, Tang J, Katholi CR, Back C

[Lancet, 1997]

BACKGROUND: In West Africa, there are two strains of the filarial parasite Onchocerca volvulus, which differ in their ability to induce ocular disease. Transmission studies have suggested that six sibling species of the parasite vector, the black fly Simulium damnosum sensu lato, allow development of the two strains of O volvulus with varying efficiency. We aimed to test the hypothesis of parasite-vector complexes, whereby the two parasite strains, known as forest and savanna, are preferentially transmitted by distinct groups of the species of S damnosum S l. METHODS: During 1993 and 1994, wild black flies were collected from 11 river basins within the area covered by the Onchocerciasis Control Programme (OCP). The flies were dissected and filarial larvae, ovaries, and malpighian tubules removed. Genomic DNA was extracted from larvae, and PCR amplification was used to classify O volvulus parasites as forest or savanna strains. PCR-amplified DNA from ovaries and malpighian tubules was used to distinguish sibling species of S damnosum s l. S yahense and S squamosum were distinguished by body colour. FINDINGS: 214 of 105105 flies dissected were infected with filarial larvae; 84 of these were infected with mature O volvulus parasites. Of the 35 savanna-dwelling infected flies. 17 carried forest-strain parasites and 18 savanna-strain parasites. Of the 45 infected flies identified as the forest dwelling sibling species. 20 carried savanna-strain parasites and 25 forest-strain parasites. No significant differences were found in the numbers of mature larvae of each strain carried by the forest-dwelling species of fly or in the number of forest and savanna larvae in savanna-dwelling vector species. INTERPRETATION: Vector-parasite transmission complexes do not currently play a part in the biology of O volvulus transmission in the area of the OCP in West Africa. This finding has important strategic implications for the future of efforts to control onchocerciasis in West Africa.

Toe L et al. (1998) Med Trop (Mars) "[A case of cross infection by Onchocerca volvulus and Onchocerca ochengi in Simulium damnosum S.L]."

Hougard JM, Bissan Y, Toe L, Adjami A

[Med Trop (Mars), 1998]

During a routine entomological survey conducted within the framework of the Program to Control Onchocerciasis in West Africa, a female simulium forest fly was found to be contaminated by 13 Onchocerca volvulus larvae and 7 Onchocerca ochengi larvae. The two Onchocerca species were identified using specific DNA probes. We speculate that cross infection could be related either to behavioral factors, e.g. interruption of blood meals on two different hosts, or developmental factors, e.g. asynchronous development of parasites of the same species or specific differences in the duration of parasite cycles. Further study will be needed to determine the incidence and scope of cross infection in areas where accurate assessment of the impact of vector control on transmission of onchocerciasis in man is required.

Toe L et al. (1997) Bull World Health Organ "Onchocerca volvulus: comparison of field collection methods for the preservation of parasite and vector samples for PCR analysis."

Unnasch TR, Back C, Adjami AG, Toe L, Tang JM

[Bull World Health Organ, 1997]

In recent years, methods for the identification of the filarial worm Onchocerca volvulus and its vector, blackflies of the Simulium damnosum complex (S. damnosum sensu lato (s.l.)), based on the amplification of parasite and vector DNA sequences with the polymerase chain reaction (PCR), have been developed. Routine application of these methods requires techniques for sample collection and preservation that are compatible with the limitations of field collection, yet preserve DNA in a form suitable for PCR. Two different methods for sample preservation were evaluated by the field collection teams and the DNA probe laboratory of the Onchocerciasis Control Programme in West Africa. The most successful involved the preservation of material from O. volvulus and its associated vectors in a dried state on microscope slides. Of over 1200 parasite samples preserved in this manner, more than 93% retained DNA yielding positive results in PCR analysis (1208/1291). Vector material (malpighian tubules and ovaries) preserved in the same manner on the same microscope slides also yielded DNA that was suitable for PCR.

Toe L et al. (1994) Am J Trop Med Hyg "DNA probe-based classification of Simulium damnosum s. l.-borne and human-derived filarial parasites in the onchocerciasis control program area."

Toe L, Merriweather A, Unnasch TR

[Am J Trop Med Hyg, 1994]

The development of polymerase chain reaction-based methods using strain- and species-specific DNA probes for Onchocerca volvulus has permitted classification of individual parasites from every stage of the parasite's life cycle. This technology has been applied on a large scale basis by Onchocerciasis Control Program (OCP) in West Africa. The primary objective of the OCP in using the DNA probes was to obtain accurate estimates of the annual transmission potential of the blinding strain of O. volvulus. The DNA probe classification of larvae collected throughout the OCP area demonstrated that larvae of less pathogenic strains of O. volvulus and other filarial parasites carried by Simulium damnosum s.l. have resulted in a significant overestimation of the annual transmission potential for blinding onchocerciasis. This effect is particularly pronounced along the southern border of the OCP, where the blinding and less pathogenic strains of O. volvulus coexist, and in the north of the control area, where animal parasites, particularly O. ochengi, may even predominate. A second objective of the OCP in applying the DNA probe technology was to determine the distribution of blinding and less pathogenic O. volvulus in infected individuals along the southern border of the control area. Results obtained from these studies have generally confirmed the distribution pattern established by previous epidemiologic studies. In addition, DNA probe classifications have demonstrated that in areas where the blinding and less pathogenic strains of O. volvulus coexist, a single individual may simultaneously be infected with both strains of the parasite.

Gurling M et al. (2014) Development "The DEP domain-containing protein TOE-2 promotes apoptosis in the Q lineage of C. elegans through two distinct mechanisms."

Gurling M, Talavera K, Garriga G

[Development, 2014]

Neuroblast divisions in the nematode Caenorhabditis elegans often give rise to a larger neuron and a smaller cell that dies. We have previously identified genes that, when mutated, result in neuroblast divisions that generate daughter cells that are more equivalent in size. This effect correlates with the survival of daughter cells that would normally die. We now describe a role for the DEP domain-containing protein TOE-2 in promoting the apoptotic fate in the Q lineage. TOE-2 localized at the plasma membrane and accumulated in the cleavage furrow of the Q.a and Q.p neuroblasts, suggesting that TOE-2 might position the cleavage furrow asymmetrically to generate daughter cells of different sizes. This appears to be the case for Q.a divisions where loss of TOE-2 led to a more symmetric division and to survival of the smaller Q.a daughter. Localization of TOE-2 to the membrane is required for this asymmetry, but, surprisingly, the DEP domain is dispensable. By contrast, loss of TOE-2 led to loss of the apoptotic fate in the smaller Q.p daughter but did not affect the size asymmetry of the Q.p daughters. This function of TOE-2 required the DEP domain but not localization to the membrane. We propose that TOE-2 ensures an apoptotic fate for the small Q.a daughter by promoting asymmetry in the daughter cell sizes of the Q.a neuroblast division but by a mechanism that is independent of cell size in the Q.p division.

Gurling M et al. (2015) Worm "The two faces of TOE-2."

Gurling M, Garriga G

[Worm, 2015]

The C. elegans Q lineage provides a unique context for studying how cells divide asymmetrically to generate cells fated to die. The Q cell divides to form the Q.a and Q.p neuroblasts, each of which divides to produce neurons and a cell that dies by apoptosis; however, these neuroblasts employ different mechanisms to divide asymmetrically.(1) We discovered 2 distinct roles for TOE-2, a protein previously shown to be a target of the C. elegans ERK ortholog MPK-1, in promoting apoptosis in each of these neuroblast divisions. In this commentary, we discuss possible molecular mechanisms by which TOE-2 promotes apoptosis. Specifically, we will discuss potential roles for TOE-2 interacting proteins, a possible nuclear function for TOE-2, and a potential link to the Wnt pathway.

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.