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[
ACS Omega,
2020]
Depleted uranium (DU) is an emerging heavy metal pollutant with considerable environmental and occupational concerns. Its radiotoxicity is known to be low. However, its chemical toxicity should not be ignored. In order to explore the chemical toxicity of DU, the effects of uranyl nitrate, prepared from DU, on the model organism <i>Caenorhabditis elegans</i> were investigated. Chronic exposure to DU did not affect the lifespan or reproduction of the worm. DU had little effect on the physiological processes of <i>C. elegans</i>. Additionally, DU treatment did not make <i>C. elegans</i> more susceptible to UV, heat, or oxidative stress. Interestingly, chronic exposure of DU decreased the <i>in vivo</i> reactive oxygen species-scavenging ability through inhibiting the expression of antioxidant genes <i>ctl</i>-1, <i>ctl</i>-2, <i>ctl</i>-3, <i>gst</i>-7, and <i>gst</i>-10. Chronic but not acute exposure of DU induced a statistically significant degeneration of the dopaminergic (DAergic) neurons of treated worms and promoted the increase of -synuclein aggregation and DAergic neurotoxicity. These findings may raise the public concerns regarding DU as an etiologic agent of Parkinson's disease and underline its potential neurotoxicity.
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[
Toxicol Sci,
2009]
Depleted uranium (DU) is a dense and heavy metal used in armor, ammunition, radiation shielding, and counterbalances. The military usage has led to growing public concern regarding the health effects of DU. In this study, we used the nematode, Caenorhabditis elegans, to evaluate the toxicity of DU and its effects in knockout strains of metallothioneins (MTs), which are small thiol-rich proteins that have numerous functions, such as metal sequestration, transport, and detoxification. We examined nematode viability, the accumulation of uranium, changes in MT gene expression by quantitative reverse transcription-PCR, and the induction of green fluorescent protein under the control of the MT promoters, following exposure to DU. Our results indicate that (1) DU causes toxicity in a dose-dependent manner; (2) MTs are protective against DU exposure; and (3) nematode death by DU is not solely a reflection of intracellular uranium concentration. (4) Furthermore, only one of the isoforms of MTs, metallothionein-1 (
mtl-1), appears to be important for uranium accumulation in C. elegans. These findings suggest that these highly homologous proteins may have subtle functional differences and indicate that MTs mediate the response to DU.
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[
Toxicol Sci,
2007]
Depleted uranium (DU) is an extremely dense metal that is used in radiation shielding, counterbalances, armor and ammunition. In light of the public concerns about exposure to DU and its potential role in Gulf War Syndrome, this study evaluated the neurotoxic potential of DU using focused studies on primary rat cortical neurons and the nematode C. elegans. We examined cell viability, cellular energy metabolism, thiol metabolite oxidation, and lipid peroxidation following exposure of cultured neurons to DU, in the form of uranyl acetate. We concurrently evaluated the neurotoxicity of uranyl acetate in C. elegans using various neuronal-green fluourescent protein reporter strains to visualize neurodegeneration. Our studies indicate that uranyl acetate has low cytotoxic potential, and uranium exposure does not result in significant changes in cellular energy metabolism, thiol metabolite oxidation, or lipid peroxidation. Furthermore, our C. elegans studies do not show any significant neurodegeneration following uranyl acetate exposure. Together, these studies suggest that DU, in the form of uranyl acetate, has low neurotoxic potential. These findings should alleviate the some of public concerns regarding depleted uranium as an etiologic agent of neurodegenerative conditions associated with Gulf War Syndrome.
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Wilson RK, Metzstein MM, Ainscough R, Waterston RH, Coulson AR, Craxton M, Thomas K, Dear S, Qiu L, Staden R, Berks M, Halloran N, Thierry-Mieg J, Hillier L, Sulston JE, Du Z, Durbin RM, Hawkins TL, Green P
[
Nature,
1992]
The long-term goal of this project is the elucidation of the complete sequence of the Caenorhabditis elegans genome. During the first year methods have been developed and a strategy implemented that is amenable to large-scale sequencing. The three cosmids sequenced in this initial phase are surprisingly rich in genes, many of which have mammalian homologues.AD - MRC Laboratory of Molecular Biology, Cambridge, UK.FAU - Sulston, JAU - Sulston JFAU - Du, ZAU - Du ZFAU - Thomas, KAU - Thomas KFAU - Wilson, RAU - Wilson RFAU - Hillier, LAU - Hillier LFAU - Staden, RAU - Staden RFAU - Halloran, NAU - Halloran NFAU - Green, PAU - Green PFAU - Thierry-Mieg, JAU - Thierry-Mieg JFAU - Qiu, LAU - Qiu LAU - et al.LA - engPT - Journal ArticleCY - ENGLANDTA - NatureJID - 0410462RN - 0 (Cosmids)SB - IM
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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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[
BMC Cell Biol,
2007]
ABSTRACT: BACKGROUND: Protein aggregation is a hallmark of several neurodegenerative diseases including Huntington''s disease and Parkinson''s disease. Proteins containing long, homopolymeric stretches of glutamine are especially prone to form aggregates. It has long been known that the small protein modifier, ubiquitin, localizes to these aggregates. In this report, nematode and cell culture models for polyglutamine aggregation are used to investigate the role of the ubiquitin pathway in protein aggregation. RESULTS: Ubiquitin conjugating enzymes (Ubc''s) were identified that affect polyglutamine aggregates in C. elegans. Specifically, RNAi knockdown of
ubc-2 or
ubc-22 causes a significant increase in the size of aggregates as well as a reduction in aggregate number. In contrast, RNAi of
ubc-1,
ubc-13, or
uev-1 leads to a reduction of aggregate size and eliminates ubiquitin and proteasome localization to aggregates. In cultured human cells, shRNA knockdown of human homologs of these Ubc''s (Ube2A, UbcH5b, and E2-25K) causes similar effects indicating a conserved role for ubiquitination in polyglutamine protein aggregation. CONCLUSIONS: Results of knockdown of different Ubc enzymes indicate that at least two different and opposing ubiquitination events occur during polyglutamine aggregation. The loss of ubiquitin localization after
ubc-1,
ubc-13, or
uev-1 knockdown suggests that these enzymes might be directly involved in ubiquitination of aggregating proteins.
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[
Mycologia,
1972]
The hyphomycete Asteromyces cruciatus F. & Mme Moreau was described without a Latin diagnosis or a designated type. The taxon was validated by Hennebert. The known distribution of this monotypic genus has been limited. F. and Mme Moreau found the fungus in sand dunes at Point du Siege (under Psamma sp.) and between Franceville and Le Home (under Agropyrum sp.) on the Normandy coast of France. Brown found A. cruciatus in open sand in the intertidal zone at Studland, Dorset and Sandwich, Kent, England; and Nicot found it in sand dunes and beach samples at Malo-les-Bains on the North Sea coast of France.
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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.
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[
Nat Commun,
2021]
R-bodies are long, extendable protein polymers formed in the cytoplasm of some bacteria; they are best known for their role in killing of paramecia by bacterial endosymbionts. Pseudomonas aeruginosa PA14, an opportunistic pathogen of diverse hosts, contains genes (referred to as the reb cluster) with potential to confer production of R-bodies and that have been implicated in virulence. Here, we show that products of the PA14 reb cluster associate with R-bodies and control stochastic expression of R-body structural genes.PA14 expresses reb genes during colonization of plant and nematode hosts, and R-body production is required for full virulence in nematodes. Analyses of nematode ribosome content and immune response indicate that P. aeruginosa R-bodies act via a mechanism involving ribosome cleavage and translational inhibition. Our observations provide insight into the biology of R-body production and its consequences during P. aeruginosa infection.
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[
Dev Biol,
2024]
While the nervous system of bilaterian animals is mainly left-right (L-R) symmetric at the anatomical level, some molecular and functional L-R asymmetries exist. However, the extent of these molecular asymmetries and their functional consequences remain poorly characterized. C. elegans allows to study L-R asymmetries in the nervous system with single-neuron resolution. We have previously shown that a neural bHLH transcription factor, HLH-16/Olig, is L-R asymmetrically expressed in the AIY neuron lineage and regulates AIY axon projections in a L-R asymmetric manner. Here, by combining a candidate approach and single-cell RNA sequencing data analysis, we identify the ephrin protein EFN-2 and the Flamingo protein FMI-1 as downstream targets of HLH-16 that are L-R asymmetrically expressed in the AIY lineage. We show that EFN-2 and FMI-1 collaborate in the L-R asymmetric regulation of axonal growth. EFN-2 may act via a non-canonical receptor of the L1CAM family, SAX-7. Our study reveals novel molecular L-R asymmetries in the C. elegans nervous system and their functional consequences.