Dedkhad W et al. (2018) Parasit Vectors "Immune responses of Aedes togoi, Anopheles paraliae and Anopheles lesteri against nocturnally subperiodic Brugia malayi microfilariae during migration from the midgut to the site of development."

Joshi D, Bartholomay LC, Hempolchom C, Dedkhad W, Christensen BM, Saeung A

[Parasit Vectors, 2018]

BACKGROUND: Lymphatic filariasis is a mosquito-borne disease caused by filarioid nematodes. A comparative understanding of parasite biology and host-parasite interactions can provide information necessary for developing intervention programmes for vector control. Here, to understand such interactions, we choose highly susceptible filariasis vectors (Aedes togoi and Anopheles lesteri) as well as Anopheles paraliae, which has lower susceptibility, infected them with nocturnally subperiodic (NSP) Brugia malayi microfilariae (mf) and studied the exsheathment, migration and innate immune responses among them. METHODS: Mosquito-parasite relationships were systematically investigated from the time mf entered the midgut until they reached their development site in the thoracic musculature (12 time points). RESULTS: Results showed that exsheathment of B. malayi mf occurred in the midgut of all mosquito species and was completed within 24 h post-blood meal. The migration of B. malayi mf from the midgut to thoracic muscles of the highly susceptible mosquitoes Ae. togoi and An. lesteri was more rapid than in the low susceptibility mosquito, An. paraliae. Melanisation and degeneration, two distinct refractory phenotypes, of mf were found in the midgut, haemocoel and thoracic musculature of all mosquito species. Melanisation is a complex biochemical cascade that results in deposition of melanin pigment on a capsule around the worms. Also, some biological environments in the body are inhospitable to parasite development and cause direct toxicity that results in vacuolated or degenerated worms. Even though Ae. togoi is highly susceptible to B. malayi, melanisation responses against B. malayi mf were first noted in the haemocoel of Ae. togoi, followed by a degeneration process. In contrast, in An. lesteri and An. paraliae, the degeneration process occurred in the haemocoel and thoracic musculature prior to melanisation responses. CONCLUSION: This study provides a thorough description of the comparative pathobiology of responses of mosquitoes against the filarial worm B. malayi.

Dedkhad W et al. (2018) Acta Trop "Effects of cross-mating on susceptibility of synonymous mosquitoes, Anopheles paraliae and Anopheles lesteri to infection with nocturnally subperiodic Brugia malayi."

Taai K, Hempolchom C, Joshi D, Christensen BM, Saeung A, Bartholomay LC, Dedkhad W

[Acta Trop, 2018]

In Southeast Asia, Anopheles lesteri (recently synonymized with An. paraliae) is a competent vector for Plasmodium parasites, but its ability to transmit parasites that cause lymphatic filariasis has yet to be determined. In this study, the susceptibility of An. lesteri and An. paraliae to Brugia malayi parasites was determined by comparing with the control mosquito, Aedes togoi. We found that the infection prevalence per infected mosquito in An. paraliae was significantly lower than that in Ae. togoi in all experiments (p< 0.05). Reciprocal crosses (female An. paraliae x male An. lesteri) produced highly susceptible F₁-hybrid progeny, with increased infection prevalence when compared to parental stocks (p< 0.05). Subsequently, the possibilities of introgression between high and low/moderate parasite susceptibility genes were investigated by cross-mating experiments (parental, reciprocal crosses, back crosses and repeated backcrosses). The results showed the possibility of introgression of B. malayi-susceptible genes between An. paraliae (low/moderate susceptibility) and An. lesteri (high susceptibility) based on increasing or decreasing susceptibility and normal larval development in the thoracic muscles of F₃-hybrids. Additionally, melanization, an innate immune response with proven involvement in the susceptibility or refractoriness of mosquitoes to B. malayi parasites, was examined. Parasite degeneration and cell aggregation, and melanization were observed for first-stage larvae in the thoracic muscle fibers of hybrid mosquitoes.

Reamtong O et al. (2019) Exp Parasitol "Immunome and immune complex-forming components of Brugia malayi identified by microfilaremic human sera."

Reamtong O, Saeung A, Sakolvaree Y, Loymek S, Thiangtrongjit T, Sookrung N, Rujimongkon K, Chaicumpa W, Thammapalo S

[Exp Parasitol, 2019]

Adult Brugia malayi proteins with high potential as epidemiological markers, diagnostic and therapeutic targets, and/or vaccine candidates were revealed by using microfilaremic human sera and an immunoproteomic approach. They were HSP70, cytoplasmic intermediate filament protein, independent phosphoglycerate mutase, and enolase. Brugia malayi microfilaria-specific proteins that formed circulating immune complexes (ICs) were investigated. The IC-forming proteins were orthologues of hypothetical protein Bm1_12480, Pao retrotransposon peptidase family protein, uncoordinated protein 44, NAD-binding domain containing protein of the UDP-glucose/GDP-mannose dehydrogenase family which contained ankyrin repeat region, ZU5 domain with C-terminal death domain, C2 domain containing protein, and FLJ90013 protein of the eukaryotic membrane protein family. Antibodies to these proteins were not free in the microfilaremic sera, raising the possible role of the IC-forming proteins in an immune evasion mechanism of the circulating microfilariae to avoid antibody-mediated-host immunity. Moreover, detection of these ICs should be able to replace the inconvenient night blood sampling for microfilaria in an evaluation of efficacy of anti-microfilarial agents.

Quartey MO et al. (2021) Sci Rep "The A(1-38) peptide is a negative regulator of the A(1-42) peptide implicated in Alzheimer disease progression."

Pennington PR, Heistad RM, Nyarko JNK, Barnes JR, Bolanos MAC, Parsons MP, Knudsen KJ, De Carvalho CE, Leary SC, Mousseau DD, Buttigieg J, Maley JM, Quartey MO

[Sci Rep, 2021]

The pool of -Amyloid (A) length variants detected in preclinical and clinical Alzheimer disease (AD) samples suggests a diversity of roles for A peptides. We examined how a naturally occurring variant, e.g. A(1-38), interacts with the AD-related variant, A(1-42), and the predominant physiological variant, A(1-40). Atomic force microscopy, Thioflavin T fluorescence, circular dichroism, dynamic light scattering, and surface plasmon resonance reveal that A(1-38) interacts differently with A(1-40) and A(1-42) and, in general, A(1-38) interferes with the conversion of A(1-42) to a -sheet-rich aggregate. Functionally, A(1-38) reverses the negative impact of A(1-42) on long-term potentiation in acute hippocampal slices and on membrane conductance in primary neurons, and mitigates an A(1-42) phenotype in Caenorhabditis elegans. A(1-38) also reverses any loss of MTT conversion induced by A(1-40) and A(1-42) in HT-22 hippocampal neurons and APOE 4-positive human fibroblasts, although the combination of A(1-38) and A(1-42) inhibits MTT conversion in APOE 4-negative fibroblasts. A greater ratio of soluble A(1-42)/A(1-38) [and A(1-42)/A(1-40)] in autopsied brain extracts correlates with an earlier age-at-death in males (but not females) with a diagnosis of AD. These results suggest that A(1-38) is capable of physically counteracting, potentially in a sex-dependent manner, the neuropathological effects of the AD-relevant A(1-42).

Tangrodchanapong T et al. (2020) Front Pharmacol "Frondoside A Attenuates Amyloid- Proteotoxicity in Transgenic Caenorhabditis elegans by Suppressing Its Formation."

Tangrodchanapong T, Sobhon P, Meemon K

[Front Pharmacol, 2020]

Oligomeric assembly of Amyloid- (A) is the main toxic species that contribute to early cognitive impairment in Alzheimer's patients. Therefore, drugs that reduce the formation of A oligomers could halt the disease progression. In this study, by using transgenic <i>Caenorhabditis elegans</i> model of Alzheimer's disease, we investigated the effects of frondoside A, a well-known sea cucumber <i>Cucumaria frondosa</i> saponin with anti-cancer activity, on A aggregation and proteotoxicity. The results showed that frondoside A at a low concentration of 1 M significantly delayed the worm paralysis caused by A aggregation as compared with control group. In addition, the number of A plaque deposits in transgenic worm tissues was significantly decreased. Frondoside A was more effective in these activities than ginsenoside-Rg3, a comparable ginseng saponin. Immunoblot analysis revealed that the level of small oligomers as well as various high molecular weights of A species in the transgenic <i>C. elegans</i> were significantly reduced upon treatment with frondoside A, whereas the level of A monomers was not altered. This suggested that frondoside A may primarily reduce the level of small oligomeric forms, the most toxic species of A. Frondoside A also protected the worms from oxidative stress and rescued chemotaxis dysfunction in a transgenic strain whose neurons express A. Taken together, these data suggested that low dose of frondoside A could protect against A-induced toxicity by primarily suppressing the formation of A oligomers. Thus, the molecular mechanism of how frondoside A exerts its anti-A aggregation should be studied and elucidated in the future.

Viney ME et al. (2004) Naturwissenschaften "Is dauer pheromone of Caenorhabditis elegans really a pheromone?"

Viney ME, Franks NR

[Naturwissenschaften, 2004]

Animals respond to signals and cues in their environment. The difference between a signal (e.g. a pheromone) and a cue (e.g. a waste product) is that the information content of a signal is subject to natural selection, whereas that of a cue is not. The model free-living nematode Caenorhabditis elegans forms an alternative developmental morph (the dauer larva) in response to a so-called 'dauer pheromone', produced by all worms. We suggest that the production of 'dauer pheromone' has no fitness advantage for an individual worm and therefore we propose that 'dauer pheromone' is not a signal, but a cue. Thus, it should not be called a pheromone.

Schaeffer JM et al. (1990) J Antibiot (Tokyo) "Cochlioquinone A, a nematocidal agent which competes for specific [3H]ivermectin binding sites."

Williamson JM, Schaeffer JM, Bergstrom AR, Liesch JM, Goetz MA, Frazier EG

[J Antibiot (Tokyo), 1990]

Cochlioquinone A, isolated from the fungus Helminthosporium sativum, was found to have nematocidal activity. Cochlioquinone A is a competitive inhibitor of specific [3H]ivermectin binding suggesting that cochlioquinone A and ivermectin interact with the same membrane receptor.

Desta IT et al. (2016) J Lab Autom "Detecting and Trapping of a Single C. elegans Worm in a Microfluidic Chip for Automated Microplate Dispensing."

Giakoumidis N, Mustafa N, AlGharibeh N, Orozaliev A, Al-Sharif A, Song YA, Desta IT, Gunsalus KC

[J Lab Autom, 2016]

Microfluidic devices offer new technical possibilities for a precise manipulation of Caenorhabditis elegans due to the comparable length scale. C. elegans is a small, free-living nematode worm that is a popular model system for genetic, genomic, and high-throughput experimental studies of animal development and neurobiology. In this paper, we demonstrate a microfluidic system in polydimethylsiloxane (PDMS) for dispensing of a single C. elegans worm into a 96-well plate. It consists of two PDMS layers, a flow and a control layer. Using five microfluidic pneumatic valves in the control layer, a single worm is trapped upon optical detection with a pair of optical fibers integrated perpendicular to the constriction channel and then dispensed into a microplate well with a dispensing tip attached to a robotic handling system. Due to its simple design and facile fabrication, we expect that our microfluidic chip can be expanded to a multiplexed dispensation system of C. elegans worms for high-throughput drug screening.

Ailion M et al. (2017) Curr Biol "Genetics: Master Regulator or Master of Disguise?"

Malik HS, Ailion M

[Curr Biol, 2017]

The pha-1 gene of Caenorhabditis elegans was originally heralded as a master regulator of organ differentiation. A new study suggests instead that pha-1 actually serves no role in development and instead is a component of a selfish genetic element.

Gokul G et al. (2020) Curr Biol "Extracellular Proteostasis: Laying Siege to Pathogens."

Singh J, Gokul G

[Curr Biol, 2020]

How protein homeostasis is maintained in the extracellular space remains poorly studied. A recent study employed a Caenorhabditis elegans model to carry out a systematic analysis of the extracellular proteostasis network and uncovered its role in combating a pathogenic attack.