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[
Bull Environ Contam Toxicol,
2016]
This study focused on assessing whether nickel (Ni) toxicity to the nematode Caenorhabditis elegans was affected by the molecular structure of the Ni salt used. Nematodes were exposed to seven Ni salts [Ni sulfate hexahydrate (NiSO4-6H2O), Ni chloride hexahydrate (NiCl2-6H2O), Ni acetate tetrahydrate (Ni(OCOCH3)2-4H2O), Ni nitrate hexahydrate (N2NiO6-6H2O), anhydrous Ni iodide (NiI2), Ni sulfamate hydrate (Ni(SO3NH2)2-H2O), and Ni fluoride tetrahydrate (NiF2-4H2O)] in an aquatic medium for 24h, and lethality curves were generated and analyzed. Ni fluoride, Ni iodide, and Ni chloride were most toxic to C. elegans, followed by Ni nitrate, Ni sulfamate, Ni acetate, and Ni sulfate. The LC50 values of the halogen-containing salts were statistically different from the corresponding value of the least toxic salt, Ni sulfate. This finding is consistent with the expected high bioavailability of free Ni ions in halide solutions. We recommend that the halide salts be used in future Ni testing involving aquatic invertebrates.
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Campbell, H., Lockley, J., Schaaf, N., Hvastkovs, E., Atkinson, J., Rudel, D.
[
International Worm Meeting,
2017]
Natural nickel (Ni) exposure occurs through volcanism and weathering of rocks. However, Ni's anthropogenic exposure has increased and overwhelmed natural exposure. Ni is a component in metal alloys and car exhaust. Ni is also an essential metal in plants and a component of cigarette smoke. Ni is highly allergenic and genotoxic, inducing carcinomas in industrial workers. Despite known Ni-induced DNA damage in prokaryotes, Ni-induced DNA damage has not been demonstrated in animals. Our data from genetic screens using Ni treatments on N2 animals and programmed cell death (PCD) mutant animals indicate Ni induces the apoptosis of germ cells in Caenorhabditis elegans. We have quantified Ni-induced germcell PCDs using an apoptotic gfp expression marker and dyes. Ni-induced PCDs rely upon genome surveillance as removal of
p53 reduces these Ni-induced PCDs. In a PCD mutant background, animals treated with Ni acquire mutations as demonstrated through the generation of heritable morphological phenotypes, i.e. Dpy, Unc, Bli, Rol, Muv, and Vul. Previously Ni's mutagenicity may have been masked through apoptosis of affected cells. Two models are proposed for Ni action. Direct-action implies Ni or Ni-generated reactive oxygen species (ROS) damages the DNA in an autonomous fashion. Indirect-action implies that Ni interacts with DNA packaging and repair proteins making DNA more susceptible to endogenous direct-acting mutagens. Genetic screens involving Ni-alone, ethyl methanesulfonte (EMS)-alone, and joint treatments were performed. Ni does not substantially enhance the mutagenicity of the direct-acting mutagen EMS. The joint treatment's effect appears additive in terms of number of mutations generated. Thus Ni putatively acts directly. Using an electrochemical assay, DNA harvested from Ni-treated worms shows damage in comparison to DNA from un-treated controls. Chemical reconstitution experiments using Ni, hydrogen peroxide and genomic DNA suggests Ni generates ROS as a part of its mechanism. We are identifying chemical changes to DNA upon Ni exposure. Preliminary mass spectrometry (MS) analysis of hydrolyzed Ni-damaged DNA in comparison to untreated DNA from the N2 strain shows accentuated molecular species and the generation of new m/z species corresponding to chemically modified DNA bases. Lastly we have compared Ni-induced DNA damage from strains isolated from highly volcanic regions (high Ni) to common laboratory stocks isolated from non-volcanic regions (low Ni) for both C. elegans and P. pacificus. Volcanic strains do not accrue as much damage as non-volcanic upon Ni exposure. This indicates compensatory genomic differences between strains based upon ecology and life history.
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[
Environ Toxicol,
2016]
To investigate the reproductive toxicity and underlying mechanism of nickel nanoparticles (Ni NPs), Caenorhabditis elegans (C. elegans) were treated with/without 1.0, 2.5, and 5.0 gcm(-2) of Ni NPs or nickel microparticles (Ni MPs). Generation time, fertilized egg numbers, spermatide activation and motility were detected. Results indicated, under the same treatment doses, that Ni NPs induced higher reproductive toxicity to C. elegans than Ni MPs. Reproductive toxicities observed in C. elegans included a decrease in brood size, fertilized egg and spermatide activation, but an increase in generation time and out-of-round spermatids. The reproductive toxicity of Ni NPs on C. elegans may be induced by oxidative stress. The reproductive toxicity in C. elegans induced by Ni NPs is consistent with our previous results in the rats. Therefore, C. elegans can be used as an alternative model to detect the early reproductive toxicity of Ni NPs exposure. 2016 Wiley Periodicals, Inc. Environ Toxicol, 2016.
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[
Neurotox Res,
2020]
Nickel (Ni) is a ubiquitous metal in the environment with increasing industrial application. While environmental and occupational exposure to Ni compounds has been known to result in toxicities to several organs, including the liver, kidney, lungs, skin and gonads, neurotoxic effects have not been extensively investigated. In this present study, we investigated specific neuronal susceptibility in a C. elegans model of acute Ni neurotoxicity. Wild-type worms and worms expressing green fluorescent protein (GFP) in either cholinergic, dopaminergic or GABAergic neurons were treated with NiCl<sub>2</sub> for 1h at the first larval (L1) stage. The median lethal dose (LD<sub>50</sub>) was calculated to be 5.88mM in this paradigm. Morphology studies of GFP-expressing worms showed significantly increasing degeneration of cholinergic, dopaminergic and GABAergic neurons with increasing Ni concentration. Significant functional changes in locomotion and basal slowing response assays reflected that cholinergic and dopaminergic neuronal function, respectively, were impaired due to Ni treatment. Interestingly, a small but significant number of worms exhibited shrinker phenotype upon Ni exposure but no loopy head foraging behaviour was observed suggesting that function of D-type GABAergic neurons of C elegans may be specifically attenuated while the RME subset of GABAergic neurons are not. GFP expression due to induction of glutathione S-transferase 4 (
gst-4), a target of Nrf2 homolog
skn-1, was increased in a P<sub>
gst-4</sub>::GFP worm highlighting Ni-induced oxidative stress. RT-qPCR verified upregulation of this expression of
gst-4 immediately after exposure. These data suggest that oxidative stress is associated with neuronal damage and altered behaviour due to developmental Ni exposure.
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[
BMC Syst Biol,
2008]
ABSTRACT: BACKGROUND: Large-scale evaluation of gene expression variation among Caenorhabditis elegans lines that have diverged from a common ancestor allows for the analysis of a novel class of biological networks - evolutionary gene coexpression networks. Comparative analysis of these evolutionary networks has the potential to uncover the effects of natural selection in shaping coexpression network topologies since C. elegans mutation accumulation (MA) lines evolve essentially free from the effects of natural selection, whereas natural isolate (NI) populations are subject to selective constraints. RESULTS: We compared evolutionary gene coexpression networks for C. elegans MA lines versus NI populations to evaluate the role that natural selection plays in shaping the evolution of network topologies. MA and NI evolutionary gene coexpression networks were found to have very similar global topological properties as measured by a number of network topological parameters. Observed MA and NI networks show node degree distributions and average values for node degree, clustering coefficient, path length, eccentricity and betweeness that are statistically indistinguishable from one another yet highly distinct from randomly simulated networks. On the other hand, at the local level the MA and NI coexpression networks are highly divergent; pairs of genes coexpressed in the MA versus NI lines are almost entirely different as are the connectivity and clustering properties of individual genes. CONCLUSION: It appears that selective forces shape how local patterns of coexpression change over time but do not control the global topology of C. elegans evolutionary gene coexpression networks. These results have implications for the evolutionary significance of global network topologies, which are known to be conserved across disparate complex systems.
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[
Chemosphere,
2016]
Contribution of chemical components in coal combustion related fine particulate matter (PM2.5) to its toxicity is largely unclear. We focused on heavy metals in PM2.5 to investigate their contribution to toxicity formation in Caenorhabditis elegans. Among 8 heavy metals examined (Fe, Zn, Pb, As, Cd, Cr, Cu, and Ni), Pb, Cr, and Cu potentially contributed to PM2.5 toxicity in wild-type nematodes. Combinational exposure to any two of these three heavy metals caused higher toxicity than exposure to Pb, Cr, or Cu alone. Toxicity from the combinational exposure to Pb, Cr, and Cu at the examined concentrations was higher than exposure to PM2.5 (100 mg/L). Moreover, mutation of
sod-2 or
sod-3 gene encoding Mn-SOD increased susceptibility in nematodes exposed to Fe, Zn, or Ni, although Fe, Zn, or Ni at the examined concentration did not lead to toxicity in wild-type nematodes. Our results highlight the potential contribution of heavy metals to PM2.5 toxicity in environmental organisms.
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[
Zootaxa,
2022]
Rhagovelia medinae sp. nov., of the hambletoni group (angustipes complex), and R. utria sp. nov., of the hirtipes group (robusta complex), are described, illustrated, and compared with similar congeners. Based on the examination of type specimens, six new synonymies are proposed: R. elegans Uhler, 1894 = R. pediformis Padilla-Gil, 2010, syn. nov.; R. cauca Polhemus, 1997 = R. azulita Padilla-Gil, 2009, syn. nov., R. huila Padilla-Gil, 2009, syn. nov., R. oporapa Padilla-Gil, 2009, syn. nov, R. quilichaensis Padilla-Gil, 2011, syn. nov.; and R. gaigei, Drake Hussey, 1947 = R. victoria Padilla-Gil, 2012 syn. nov. The first record from Colombia is presented for R. trailii (White, 1879), and the distributions of the following species are extended in the country: R. cali Polhemus, 1997, R. castanea Gould, 1931, R. cauca Polhemus, 1997, R. gaigei Drake Hussey, 1957, R. elegans Uhler, 1894, R. femoralis Champion, 1898, R. malkini Polhemus, 1997, R. perija Polhemus, 1997, R. sinuata Gould, 1931, R. venezuelana Polhemus, 1997, R. williamsi Gould, 1931, and R. zeteki Drake, 1953.
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[
Aquat Toxicol,
1998]
Predictive models for relative toxicity of divalent metal ions using ion characteristics have been produced with both Microtox(R), a 15 min microbial bioassay, and the 24 h Caenorhabditis elegans bioassay. Relative toxicity of mono-, di- and trivalent metal ions has also been successfully modeled using ion characteristics with the Microtox(R) bioassay. This study extends this approach to include longer exposure durations (24 h) and a more complex organism (metazoan). Twenty-four-hour LC50s (expressed as total and free ion concentrations) for the free-living soil nematode, C. elegans, were determined for Li: Na, Mg, K, Ca, Cr, Mn, Fe, Co, Ni, Cu, Zn, Sr, Cd, Cs, Ba, La, and Pb in an aqueous medium. Relative metal toxicity was predicted with least squares linear regression and several ion characteristics. Toxicity was most effectively predicted (r(2) = 0.85) with a two-variable model containing log K-OH (where K-OH is the first hydrolysis constant) and chi(m)(2)r (the covalent index). The first hydrolysis constant reflects a metal ion's tendency to bind to intermediate ligands such as biochemical groups with O donor atoms, while X(m)(2)r reflects binding to soft ligands such as those with S donor atoms. The use of LC50s based on free ion concentrations did not significantly improve model fit. The results of this study are consistent with earlier models generated with Microtox(R) data, with the exception of barium, which was much more toxic to C. elegans than would be predicted from the model. We conclude that, with thoughtful application, ion characteristics can be used to predict the relative toxicity of metal ions that
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[
Environ Pollut,
2021]
Mining activities in the world's largest platinum mining area in South Africa have resulted in environmental contamination with Pt (e.g., the Hex River's vicinity). The present study compared a Pt mining area with a non-mining area along this river in terms of (1) metal concentrations in different grain size fractions from soils and aquatic sediments; (2) the toxicological potential of aquatic sediments based on the Consensus-Based Sediment Quality Guideline (CBSQG); and (3) the chronic toxicity of aqueous eluates from soils and sediments to Caenorhabditis elegans. Platinum concentrations were higher in the mining area than in the non-mining area. For most metals, the sediment silt and clay fraction contained the highest metal concentrations. Based on the CBSQG, most sampling sites exhibited a high toxicological potential, driven by Cr and Ni. Eluate toxicity testing revealed that C. elegans growth, fertility, and reproduction inhibition were not dependent on mining activities or the CBSQG predictions. Toxicity was instead likely due to Cd, Fe, Mn, Ni, Pt, and Pb. In conclusion, the investigated region is loaded with a high geogenic background resulting in high reproduction inhibition. The mining activities lead to additional environmental metal contamination (particularly Pt), contributing to environmental soil and sediment toxicity.
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[
J Biol Chem,
1990]
The nematode Caenorhabditis elegans (C. elegans) expresses the regulatory subunit (R) of cAMP-dependent protein kinase at a level similar to the levels determined for R subunits in mammalian tissues. Approximately 60% of the C. elegans cAMP-binding protein is tightly associated with particulate structures by noncovalent interactions. Ionic detergents or 7 M urea solubilize particulate R. Solubilized and cytosolic R subunits have apparent Mr values of 52,000 and pI values of 5.5. cDNA and genomic DNA encoding a unique C. elegans R subunit were cloned and sequenced. The derived amino acid sequence contains 375 residues; carboxyl-terminal residues 145-375 are 69% identical with mammalian RI. However, residues 44-145 are markedly divergent from the corresponding regions of all other R sequences. This region might provide sufficient structural diversity to adapt a single R subunit for multiple functional roles in C. elegans. Antibodies directed against two epitopes in the deduced amino acid sequence of C. elegans R avidly bound nematode cytosolic and particulate R subunits on Western blots and precipitated dissociated R subunits and R2C2 complexes from solution. Immunofluorescence analysis revealed that the tip of the head, which contains chemosensory and mechanosensory neurons, and the pharyngeal nerve ring were enriched in R. The R subunit concentration is low during early embryogenesis in C. elegans. A sharp increase (approximately 6-fold) in R content begins several hours before the nematodes hatch and peaks during the first larval stage. Developmental regulation of R expression occurs at translational and/or post-translational levels. The 8-kilobase pair C. elegans R gene is divided into 8 exons by introns ranging from 46 to 4300 base pairs. The 5'-flanking region has no TATA box and contains preferred and minor transcription start sites.