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[
Parasitol Today,
1993]
Globins are proteins commonly associated with oxygen transport in vertebrate blood, but the invertebrate phyla display a wide variety of globin types that reflect their disparate life styles and evolutionary history. It has been known for over 100 years that parasitic nematodes contain globins, but recent molecular investigations are only now beginning to shed some light on their curious properties. Mark Blaxter here describes the diversity of the different globins found in nematodes, and reviews emerging data on their evolution and function.
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Garey JR, Thomas WK, Dorris M, Frisse LM, Vanfleteren JR, De Ley P, Mackey LY, Vierstraete A, Liu LX, Scheldeman P, Blaxter ML, Vida JT
[
Nature,
1998]
Nematodes are important: parasitic nematodes threaten the health of plants, animals and humans on a global scale; interstitial nematodes pervade sediment and soil ecosystems in overwhelming numbers; and Caenorhabditis elegans is a favourite experimental model system. A lack of clearly homologous characters and the absence of an informative fossil record have prevented us from deriving a consistent evolutionary framework for the phylum. Here we present a phylogenetic analysis, using 53 small subunit ribosomal DNA sequences from a wide range of nematodes. With this analysis, we can compare animal-parasitic, plant-parasitic and free-living taxa using a common measurement. Our results indicate that convergent morphological evolution may be extensive and that present higher-level classification of the Nematoda will need revision. We identify five major clades within the phylum, all of which include parasitic species. We suggest that animal parasitism arose independently at least four times, and plant parasitism three times. We clarify the relationship of C. elegans to major parasitic groups; this will allow more effective exploitation of our genetic and biological knowledge of this model species.
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[
J Biol Chem,
1993]
The molecular components of the surface of the free-living nematode Caenorhabditis elegans have been identified by surface-specific radioiodination. Four compartments were defined by fractionation of labeled wild type (N2 strain) adult hermaphrodites. Organic solvents extracted cuticular lipids. Homogenization in detergents released a single, non-collagenous, hydrophobic protein. This is not glycosylated and is a heterodimer of 6.5- and 12-kDa subunits. The third compartment, proteins solubilized by reducing agents, included both the cuticular collagens and the heterodimer. Residual material corresponds to the cuticlin fraction. Larval stages showed a similar pattern, except that the dauer larva had an additional 37-kDa detergent-soluble protein. Other species of rhabditid nematodes displayed similar profiles, and comparison with parasitic species suggests that this simple pattern may be primitive in the Nematoda. A C. elegans strain mutant in cuticular collagen (
rol-6) had a pattern identical to that of wild type, but another morphological mutant (
dpy-3) [corrected] and several mutants that differ in surface reactivity to antibody and lectins (srf mutants) also had striking differences in surface labeling patterns.
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Mol Biochem Parasitol,
1994]
The globins of the nematode parasite Nippostrongylus brasiliensis have oxygen affinities 100-fold higher than the rodent host's haemoglobins. Two isoforms are found, one located in the cuticle, and the other in the body of the nematode. Both isoforms have been cloned and analysed for clues as to function and evolution. The body globin isoform is first expressed upon invasion of the mammalian host. The abundant cuticular globin is expressed only by adult nematodes in the gut, and differs significantly from the body globin. Both globins are found as trans-spliced
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[
Journal of Pesticide Science,
1984]
Juveniles of Caenorhabditis elegans were transformed to dumpy in the media containing methomyl (10 ug/ml) or aldoxycarb (500 ug/ml), but not in the media containing methylisothiocyanate (MITC). The dumpy did not recover to its normal structure even after being transferred to fresh medium, but underwent to adulthood with a lower reproduction rate. The progeny from the dumpy forms was normal in structure, however, its reproductivity was as low as one-third of normal ones. Longevity of the dumpy form and its progeny were longer than those of normal worms. Methomyl (1 ug/ml), MITC (1 ug/ml) and aldoxycarb (10 ug/ml) did not suppress population growth, but MITC (10 ug/ml) did for the first two weeks. The population growth was markedly suppressed at 100 ug/ml of methomyl, 20 ug/ml of MITC and 1000 ug/ml of aldoxycarb.
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[
Sci Total Environ,
2020]
The Deepwater Horizon (DWH) oil spill marked the largest environmental oil spill in human history, where it was estimated a large amount of the polycyclic aromatic hydrocarbons (PAHs) were released with crude oil into the environment. In this study, common PAH compounds were quantitatively determined in crude oil from the DWH spill by gas chromatography-mass spectroscopy (GC-MS). Twelve PAH compounds were identified and quantified from a 100x dilution of DWH crude oil: naphthalene (7800ng/mL), acenaphthylene (590ng/mL), acenaphtehen (540ng/mL), fluorene (2550ng/mL), phenanthrene (2910ng/mL), anthracene (840ng/mL), fluoranthene (490ng/mL), pyrene (290ng/mL), benzo(k) fluoranthene (1050ng/mL), benzo(b)fluoranthene (1360ng/mL), dibenz(a,h)anthracene (2560ng/mL), and benzo(g, h, i) perylene (630ng/mL). Toxicity assays using the nematode, Caenorhabditis elegans (C. elegans), indicated a single PAH compound naphthalene, exposure increased C. elegans germ cell apoptosis which may adversely affect progeny reproduction. The number of apoptotic germ cells significantly increased from 1.4 to 2.5 when worms were treated with 10g/mL of naphthalene and from 1.3 to 2.5 and 3.5 cells in presence of 1g/mL and 5g/mL of benzo(a)pyrene, respectively. Five CYP450 genes (CYP14A3, CYP35A1, CYP35A2, CYP35A5, and CYP35C1) were significantly upregulated following 500x dilution of dispersed crude oil exposure (p<0.05). These results suggest that CYP450s may play a role in bioactivation of PAHs in crude oil, resulting in DNA damage related germ cell apoptosis.
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[
Nematologica,
1983]
The quantities of Mg+2, Na+, K+, Mn+2, Ca+2 and Cu+2 required by the free-living nematode C. elegans were determined. An individual mineral deficieny was developed by deleting the mineral from the basal medium. Quantitative requirements of individual minerals were determined respectively by adding each mineral at various concentrations to the depleted medium. Serial subcultures and biological pre-treated media were used for the development of Mn+2, Ca+2 and Cu+2 deficiencies. It was found that most C. elegans were supported at 73 ug/ml Mg+2, 300 ug/ml Na+, 530 Ug/ml K+, 6.3 ug/ml Mn+2, 1500 ug/ml Ca+2 and 7.2 ug/ml Cu+2.
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[
Nematologica,
1993]
The carbohydrate requirement in the free-living nematode Caenorhabditis elegans was investigated. Glucose, fructose, sucrose, trehalose and glycogen were tested individually at concentrations of 0, 1.3, 6.5, 32.5, and 162.5 mg/ml as the energy source in a chemically defined medium containing C . briggsae Maintenance Medium (CbMM without glucose), 50 .mu.g/ml cytochrome c and 50 .mu.g/ml .beta.-sitosterol. Potassium acetate, used as the energy source in other studies, was not added to the medium. Therefore, carbohydrate was the major energy source for the nematode. At 32.5 mg/ml, glucose was found to support the maximal population at 80,000 nematodes/ml (100%), followed by glycogen (96%) and trehalose (73%). Population was significantly reduced when fructose (46%) or sucrose (26%) was the carbohydrate source. Toxicity was shown at 162.5 mg/ml for four carbohydrates tested, except glycogen. These results suggested that all five carbohydrates can be utilized as energy sources by C . elegans ; however, the degree of utilization of each carbohydate by C . elegans varied. Since glucose was best utilized by the nematode at 32.5 mg/ml, this concentration is recommended for future use in preparation in CbMM. Based on this study, the chemically defined medium that has been used for cultivation of C . elegans can also be modified to: CbMM (1x, with 32.5 mg/ml glucose), 50 .mu./ml cytochrome c and .mu.g/ml .beta.-sitosterol. Glucose (at 32.5 mg/ml) can be used as the major energy source in a chemically defined medium for the axenic cultivation of C . elegans .
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[
Int J Parasitol Drugs Drug Resist,
2016]
Macrocyclic lactones (ML) are important anthelmintics used in animals and humans against parasite nematodes, but their therapeutic success is compromised by the spread of ML resistance. Some ABC transporters, such as p-glycoproteins (Pgps), are selected and overexpressed in ML-resistant nematodes, supporting a role for some drug efflux proteins in ML resistance. However, the role of such proteins in ML transport remains to be clarified at the molecular level. Recently, Caenorhabditis elegans Pgp-1 (Cel-Pgp-1) has been crystallized, and its drug-modulated ATPase function characterized invitro revealed Cel-Pgp-1 as a multidrug transporter. Using this crystal structure, we have developed an in silico drug docking model in order to study the binding of ML and other anthelmintic drugs to Cel-Pgp-1. All tested ML bound with high affinity in a unique site, within the inner chamber of the protein, supporting that ML may be transported by Cel-Pgp-1. Interestingly, interacting residues delineate a ML specific fingerprint involving H-bonds, including T1028. In particular, benzofurane and spiroketal moieties bound to specific sub-sites. When compared with the aglycone ML, such as moxidectin and ivermectin aglycone, avermectin anthelmintics have significant higher affinity for Cel-Pgp-1, likely due to the sugar substituent(s) that bind to a specific area involving H-bonds at Y771. Triclabendazole, closantel and emodepside bound with good affinities to different sub-sites in the inner chamber, partially overlapping with the ML binding site, suggesting that they could compete for Cel-Pgp-1-mediated ML transport. In conclusion, this work provides novel information on the role of nematode Pgps in transporting anthelmintics, and a valuable tool to predict drug-drug interactions and to rationally design new competitive inhibitors of clinically-relevant nematode Pgps, to improve anthelmintic therapeutics.