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FASEB J,
2016]
Nematodes lack a heme biosynthetic pathway and must acquire heme from exogenous sources. Given the indispensable role of heme, this auxotrophy may be exploited to develop drugs that interfere with heme uptake in parasites. Although multiple heme-responsive genes (HRGs) have been characterized within the free-living nematode Caenorhabditis elegans, we have undertaken the first study of heme transport in Brugia malayi, a causative agent of lymphatic filariasis. Through functional assays in yeast, as well as heme analog, RNAi, and transcriptomic experiments, we have shown that the heme transporter HRG-1 (BmHRG-1) is indeed functional in B. malayi In addition, BmHRG-1 localizes both to the endocytic compartments and cell membrane when expressed in yeast cells. Transcriptomic sequencing revealed that BmHRG-1, BmHRG-2, and BmMRP-5 (all orthologs of HRGs in C. elegans) are down-regulated in heme-treated B. malayi, as compared to non-heme-treated control worms. Likely because of short gene lengths, multiple exons, other HRGs in B. malayi (BmHRG-3, -4, -5, and -6) remain unidentified. Although the precise mechanisms of heme homeostasis in a nematode with the ability to acquire heme remains unknown, this study clearly demonstrates that the filarial nematode B. malayi is capable of transporting exogenous heme.-Luck, A. N., Yuan, X., Voronin, D., Slatko, B. E., Hamza, I., Foster, J. M. Heme acquisition in the parasitic filarial nematode Brugia malayi.
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PLoS One,
2019]
Further characterization of essential systems in the parasitic filarial nematode Brugia malayi is needed to better understand its biology, its interaction with its hosts, and to identify critical components that can be exploited to develop novel treatments. The production of glycophosphatidylinositol-anchored proteins (GPI-APs) is essential for eukaryotic cellular and physiological function. In addition, GPI-APs perform many important roles for cells. In this study, we characterized the B. malayi GPI-anchored proteome using both computational and experimental approaches. We used bioinformatic strategies to show the presence or absence of B. malayi GPI-AP biosynthetic pathway genes and to compile a putative B. malayi GPI-AP proteome using available prediction programs. We verified these in silico analyses using proteomics to identify GPI-AP candidates prepared from the surface of intact worms and from membrane enriched extracts. Our study represents the first description of the GPI-anchored proteome in B. malayi and lays the groundwork for further exploration of this essential protein modification as a target for novel anthelmintic therapeutic strategies.
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Int J Parasitol,
2016]
A homologue of the ecdysone receptor has been identified and shown to be responsive to 20-hydroxyecdysone in Brugia malayi. However, the role of this master regulator of insect development has not been delineated in filarial nematodes. Gravid adult female B. malayi cultured in the presence of 20-hydroxyecdysone produced significantly more microfilariae and abortive immature progeny than control worms, implicating the ecdysone receptor in regulation of embryogenesis and microfilarial development. Transcriptome analyses identified 30 genes whose expression was significantly up-regulated in 20-hydroxyecdysone-treated parasites compared with untreated controls. Of these, 18% were identified to be regulating transcription. A comparative proteomic analysis revealed 932 proteins to be present in greater amounts in extracts of 20-hydroxyecdysone-treated adult females than in extracts prepared from worms cultured in the absence of the hormone. Of the proteins exhibiting a greater than two-fold difference in the 20-hydroxyecdysone-treated versus untreated parasite extracts, 16% were involved in transcriptional regulation. RNA interference (RNAi) phenotype analysis of Caenorhabditis elegans orthologs revealed that phenotypes involved in developmental processes associated with embryogenesis were significantly over-represented in the transcripts and proteins that were up-regulated by exposure to 20-hydroxyecdysone. Taken together, the transcriptomic, proteomic and phenotypic data suggest that the filarial ecdysone receptor may play a role analogous to that in insects, where it serves as a regulator of egg development.
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Biochem Soc Trans,
1995]
Modification, by the addition of lipid-derived groups, is an important determinant of the correct expression of a variety of polypeptides involved in signal transduction. Myristic and palmitic acid are the predominant fatty acids attached to proteins in eucaryotes. Myristic acid is normally linked, cotranslationally, via an amide bond to an N-terminal glycine. In contrast, palmitic acid attachment occurs post-translationally via an alkali-labile ester or thioester linkage...
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Curr Biol,
2019]
How does physiological state affect the reproductive behavior of an organism? Two new studies in Caenorhabditis elegans implicate an ancient serotonergic neuronal circuit in the link between these two outputs- reproductive behavior and physiology.
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MicroPubl Biol,
2021]
Gamete fusion is a pivotal step during fertilization to create an organism of the next generation. In C. elegans, since oocytes have no thick egg coat like the zona pellucida, perhaps spermatozoa directly bind to and fuse with the oocyte plasma membrane (PM). Thus, C. elegans is an excellent model to investigate how a spermatozoon and an oocyte fuse together.
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Food Chem X,
2022]
Aimed at exploring the impact of fatty acid side chains on the anthocyanins, n-valeric acid, n-decanoic acid and myristic acid were used to grafting onto the blueberry anthocyanins, and the acylating degree value of the of n-valeric acid acylated anthocyanins (Va-An), n-decanoic acid acylated anthocyanins (De-An) and myristic acid acylated anthocyanins (My-An) reached 6.43 %, 7.56% and 8.38 %, respectively. After acylation modification, the octanol-water partition coefficient of the anthocyanins increased from -0.20 (native anthocyanins, Na-An) to 0.65 (Va-An), 0.66 (De-An) and 0.72 (My-An), respectively, indicating the increasement of the lipid solubility. Besides, although the DPPH clearance of acylated anthocyanins was lower than that of native anthocyanins, the inhibition ratio of β-carotene bleaching and malonaldehyde reduction effect of the acylated blueberry anthocyanins in Caenorhabditis elegans were both stronger than that of native anthocyanins, which might be caused by the improvement of lipid solubility of the anthocyanins.
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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 F<sub>1</sub>-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 F<sub>3</sub>-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.
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Elife,
2020]
An intricate stem cell niche boundary formed by finger-like extensions generates asymmetry in stem cell divisions.
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MicroPubl Biol,
2023]
In this study, we developed an efficient co-conversion marker, using the conserved <i>
dpy-10</i> gene, to facilitate creation and detection of CRISPR/Cas9-mediated targeted genomic changes in an emerging male/female nematode model system, <i>Caenorhabditis nigoni</i> .