3,401 research outputs found
The role of Ruditapes philippinarum glutathione transferases in the metabolism of microcystin-LR
No full textNo abstracts are to be cited without prior reference to the author. Glutathione transferases (GSTs) are phase II enzymes involved in the microcystin (MC) induced detoxication processes. In this study we analyze and compare the metabolism of MC-LR by the cytosolic GSTs from gills and hepatopancreas of Ruditapes philippinarum. Cytosolic GSTs were purified by glutathione (GSH)–agarose affinity chromatography from exposed and non-exposed bivalves to MC-LR (100 µg/L) representing the inducible and constitutive (Basal) GST fractions, respectively. For each mixture, we examined the in vitro cytosolic GST inhibition efficiency of the conjugation of CDNB to GSH by MC-LR and characterize the inhibition mechanism. Results support the important role of GST enzymes in detoxification of MCs in bivalve mollusk
Transcriptional responses of glutathione transferase genes in Ruditapes philippinarum exposed to microcystin-LR
No full textNo abstracts are to be cited without prior reference to the author. Microcystins (MCs) are potent hepatotoxins produced by bloom-forming species of toxic cyanobacteria. Among these, MC-LR is the most commonly found and toxic variant. Bivalves, due to their benthic and sedentary mode of life, are one of the most threatened organisms by these environmental stressors. Glutathione transferases (GSTs) play a major role in cellular defense against MCs toxicity. The aim of this study was to compare the relative changes of gene expression of the different GSTs isoforms in mollusc bivalves exposed to MCs. The time-dependent changes of relative transcription abundance of several GST isoforms in parallel with enzymatic activity of total GST were investigated in gills and hepatopancreas of Ruditapes philippinarum exposed to dissolved MC-LR. The relative changes of gene expression and enzyme activity were analyzed by quantitative real-time PCR and colorimetric assays respectively. We found that MC-LR could affect the transcriptional activities of these detoxification enzymes in gills and hepatopancreas of the tested bivalves. Most GST isoforms showed differential response profiles depending on the concentrations of MC-LR and exposure times for clams. These results highlight the important role of GSTs in counteracting the potential deleterious effects induced by MCs in bivalve
The LR does not exist
No full textMore than 40 years ago, De Finetti warned that probability is a misleading misconception when regarded as objectively existing exterior to the mind. According to De Finetti, probabilities are necessarily subjective, and quantify our belief in the truth of events in the real world. Given evidence of a shared feature of a trace and an accused, we apply this framework to assign an evidential value to this correspondence. Dividing 1 by the objectively existing proportion of the population sharing that feature would give that evidential value − expressed as a likelihood ratio (LR) − only if that proportion were known. As in practice the proportion can only be estimated, this leads some to project their sampling uncertainty − or precision − associated with the estimated proportion onto the likelihood ratio, and to report an interval. Limited data should limit our LR however, because as we will demonstrate the LR is given by what we know about the proportion rather than by the unknown proportion itself. Encapsulating all uncertainty − including sampling uncertainty of the proportion − our LR reflects how much information we have retrieved from the feature regarding the trace's origin, based on our present knowledge. Not an interval but a number represents this amount of information, equal to the logarithm of the LR. As long as we know how to interpret the evidence with a well-defined probabilistic model, we know what our evidence is worth
Fast removal of cyanobacterial toxin microcystin-LR by a low-cytotoxic microgel-Fe(III) complex
No full textEutrophication has become a serious environmental threat throughout the world. In particular, the presence of cyanobacteria toxins, especially microcystins (MCs), has become a severe problem. Inhibition of Microcystis growth in water resources is the most effective way to reduce MCs, but it is a long-term investment. In the present study, a microgel-Fe(III) complex was developed for the fast removal of MC-LR. The microgel-Fe(III) characteristics and the MC-LR removal dynamics in Milli-Q water and natural water were evaluated. The removal efficiency negatively correlated to the initial MC-LR concentration and pH value (2.0-11.5), but the kinetics was not significantly influenced. The presence of natural organic matter (NOM) in water slightly reduced MC-LR removal using microgel-Fe(III). In addition, microgel-Fe(III) removed 98.99% of MC-LR in 12 min, while for activated carbon, it took 15-24 h to reach equilibrium. Furthermore, methanol was found to regenerate the microgel-Fe(III) after MC-LR removal for at least five regeneration cycles. Finally, the microgel-Fe(III) material was made into a membrane so that MCs could be removed by filtration. Therefore, microgel-Fe(III) is an effective technology and has a great potential in removing MC-LR from drinking water resources. (C) 2011 Elsevier Ltd. All rights reserved.Eutrophication has become a serious environmental threat throughout the world. In particular, the presence of cyanobacteria toxins, especially microcystins (MCs), has become a severe problem. Inhibition of Microcystis growth in water resources is the most effective way to reduce MCs, but it is a long-term investment. In the present study, a microgel-Fe(III) complex was developed for the fast removal of MC-LR. The microgel-Fe(III) characteristics and the MC-LR removal dynamics in Milli-Q water and natural water were evaluated. The removal efficiency negatively correlated to the initial MC-LR concentration and pH value (2.0-11.5), but the kinetics was not significantly influenced. The presence of natural organic matter (NOM) in water slightly reduced MC-LR removal using microgel-Fe(III). In addition, microgel-Fe(III) removed 98.99% of MC-LR in 12 min, while for activated carbon, it took 15-24 h to reach equilibrium. Furthermore, methanol was found to regenerate the microgel-Fe(III) after MC-LR removal for at least five regeneration cycles. Finally, the microgel-Fe(III) material was made into a membrane so that MCs could be removed by filtration. Therefore, microgel-Fe(III) is an effective technology and has a great potential in removing MC-LR from drinking water resources. (C) 2011 Elsevier Ltd. All rights reserved
Response paper to “The likelihood of encapsulating all uncertainty”: The relevance of additional information for the LR
No full textIn this response paper, part of the Virtual Special Issue on “Measuring and Reporting the Precision of Forensic Likelihood Ratios”, we further develop our position on likelihood ratios which we described previously in Berger et al. (2016) “The LR does not exist”. Our exposition is inspired by an example given in Martire et al. (2016) “On the likelihood of encapsulating all uncertainty”, where the consequences of obtaining additional information on the LR were discussed. In their example, two experts use the same data in a different way, and the LRs of these experts change differently when new data are taken into account. Using this example as a starting point we will demonstrate that the probability distribution for the frequency of the characteristic observed in trace and reference material can be used to predict how much an LR will change when new data become available. This distribution can thus be useful for such a sensitivity analysis, and address the question of whether to obtain additional data or not. But it does not change the answer to the original question of how to update one's prior odds based on the evidence, and it does not represent an uncertainty on the likelihood ratio based on the current data
Incremental Scannerless Generalized LR Parsing
No full textThe Scannerless Generalized LR (SGLR) parsing algorithm supports the development of composed languages seamlessly but does not support incremental parsing. The Incremental Generalized LR (IGLR) parsing algorithm, on the other hand, does not support the seamless composition of languages. This thesis presents the Incremental Scannerless Generalized LR (ISGLR) parsing algorithm and investigates the effects of combining the SGLR and IGLR parsing algorithms. While the algorithmic differences are orthogonal, the fact that scannerless parsing relies on non-deterministic parsing for disambiguation has a negative impact on incrementality. Nonetheless, we show that the ISGLR parsing algorithm performs better than the batch SGLR parsing algorithm in typical scenarios. On average, the ISGLR parser can reuse 99% of a previous parse result. When parsing from scratch, the ISGLR parser has a 24% run time overhead compared to the SGLR parser, but when parsing incrementally for changes that are smaller than 1% of the input size on average, it has a 9× speedup.Successor of https://doi.org/10.1145/3359061.3361085Computer Scienc
TOXIC EFFECTS OF MICROCYSTIN-LR ON MICE ERYTHROCYTES in vitro
No full textHaematological abnormalities have been verified in patients intoxicated by microcystins (MCs) in haemodialysis unit in Caruaru, Brazil, and 60 patients died. In our previous studies, obvious anemia has been determined in rabbit after in vivo exposure to microcystins. As to the cause of the anemia, except for hematopoiesis obstacles, we hypothesized that microcystins result in erythrocyte destruction. In the present study, Kunming mice erythrocytes in vitro were incubated with 1, 10, 100 and 1000 nM microcystin-LR at 37 degrees C. Lipid peroxidation, haemolysis, cell morphology, antioxidative response and some biochemical biomarkers were measured. The results showed that the level of lipid peroxidation significantly increased in microcystin-LR treatment groups. The level of glutathione and activities of glutathione peroxidase, glutathione-S-transferase and superoxide dismutase were significantly increased after incubation with microcystin-LR at 12, 24 and 48 h. Also, significant decreases in activities of acetylcholinesterase, Na+-K+-ATPase and Ca2+-Mg2+-ATPase were observed. Obvious increases of haemolysis were determined in 10, 100 and 1000 nM groups from 12 to 48 h. Additionally, abnormal erythrocytes with bleb-bing and notched cell membrane were observed in both 100 and 1000 nM groups. It is presumed that microcystin-LR triggers lipid peroxidation of erythrocytes and oxidative stress destroys the structure of cell membrane, leading to alterations of antioxidative enzymes and biochemical indicators. Our results demonstrate that in vitro exposure to microcystin-LR resulted in damage of mice erythrocytes.Haematological abnormalities have been verified in patients intoxicated by microcystins (MCs) in haemodialysis unit in Caruaru, Brazil, and 60 patients died. In our previous studies, obvious anemia has been determined in rabbit after in vivo exposure to microcystins. As to the cause of the anemia, except for hematopoiesis obstacles, we hypothesized that microcystins result in erythrocyte destruction. In the present study, Kunming mice erythrocytes in vitro were incubated with 1, 10, 100 and 1000 nM microcystin-LR at 37 degrees C. Lipid peroxidation, haemolysis, cell morphology, antioxidative response and some biochemical biomarkers were measured. The results showed that the level of lipid peroxidation significantly increased in microcystin-LR treatment groups. The level of glutathione and activities of glutathione peroxidase, glutathione-S-transferase and superoxide dismutase were significantly increased after incubation with microcystin-LR at 12, 24 and 48 h. Also, significant decreases in activities of acetylcholinesterase, Na+-K+-ATPase and Ca2+-Mg2+-ATPase were observed. Obvious increases of haemolysis were determined in 10, 100 and 1000 nM groups from 12 to 48 h. Additionally, abnormal erythrocytes with bleb-bing and notched cell membrane were observed in both 100 and 1000 nM groups. It is presumed that microcystin-LR triggers lipid peroxidation of erythrocytes and oxidative stress destroys the structure of cell membrane, leading to alterations of antioxidative enzymes and biochemical indicators. Our results demonstrate that in vitro exposure to microcystin-LR resulted in damage of mice erythrocytes
Construction Methods of LR Parsers
No full textThis paper presents five different LR parser generators and an error recovery method which is derived directly from the LR parser. The parsers presented include the original LR (1) parser defined by Knuth. The SLR(1) and LALR(1) parsers defined by DeRemer, and the weak and strong compatible LR parsers presented by Pager. All five parsers have been implemented by the author using two programs. Furthermore, the implementation of the SLR (1) parser generator includes an error recovery method and produces an SLR(1) parser with error recovery built in
Microcystin-LR stabilizes c-myc protein by inhibiting protein phosphatase 2A in HEK293 cells
No full textMicrocystin-LR is the most toxic and the most frequently encountered toxin produced by the cyanobacteria in the contaminated aquatic environment. Previous studies have demonstrated that Microcystin-LR is a potential carcinogen for animals and humans, and the International Agency for Research on Cancer has classified Microcystin-LR as a possible human carcinogen. However, the precise molecular mechanisms of Microcystin-LR-induced carcinogenesis remain a mystery. C-myc is a proto-oncogene, abnormal expression of which contributes to the tumor development. Although several studies have demonstrated that Microcystin-LR could induce c-myc expression at the transcriptional level, the exact connection between Microcystin-LR toxicity and c-myc response remains unclear. In this study, we showed that the c-myc protein increased in HEK293 cells after exposure to Microcystin-LR. Coexpression of protein phosphatase 2A and two stable c-myc protein point mutants (either c-myc(T58A) or c-myc(562A)) showed that Microcystin-LR increased c-myc protein level mainly through inhibiting protein phosphatase 2A activity which altered the phosphorylation status of serine 62 on c-myc. In addition, we also showed that Microcystin-LR could increase c-myc promoter activity as revealed by luciferase reporter assay. And the TATA box for P1 promoter of c-myc might be involved. Our results suggested that Microcystin-LR can stimulate c-myc transcription and stabilize c-myc protein, which might contribute to hepatic tumorigenesis in animals and humans. (C) 2014 Elsevier Ireland Ltd. All rights reserved.Microcystin-LR is the most toxic and the most frequently encountered toxin produced by the cyanobacteria in the contaminated aquatic environment. Previous studies have demonstrated that Microcystin-LR is a potential carcinogen for animals and humans, and the International Agency for Research on Cancer has classified Microcystin-LR as a possible human carcinogen. However, the precise molecular mechanisms of Microcystin-LR-induced carcinogenesis remain a mystery. C-myc is a proto-oncogene, abnormal expression of which contributes to the tumor development. Although several studies have demonstrated that Microcystin-LR could induce c-myc expression at the transcriptional level, the exact connection between Microcystin-LR toxicity and c-myc response remains unclear. In this study, we showed that the c-myc protein increased in HEK293 cells after exposure to Microcystin-LR. Coexpression of protein phosphatase 2A and two stable c-myc protein point mutants (either c-myc(T58A) or c-myc(562A)) showed that Microcystin-LR increased c-myc protein level mainly through inhibiting protein phosphatase 2A activity which altered the phosphorylation status of serine 62 on c-myc. In addition, we also showed that Microcystin-LR could increase c-myc promoter activity as revealed by luciferase reporter assay. And the TATA box for P1 promoter of c-myc might be involved. Our results suggested that Microcystin-LR can stimulate c-myc transcription and stabilize c-myc protein, which might contribute to hepatic tumorigenesis in animals and humans. (C) 2014 Elsevier Ireland Ltd. All rights reserved
Sulforaphane prevents microcystin-LR-induced oxidative damage and apoptosis in BALB/c mice
No full textMicrocystins (MCs), the products of blooming algae Microcystis, are waterborne environmental toxins that have been implicated in the development of liver cancer, necrosis, and even fatal intrahepatic bleeding. Alternative protective approaches in addition to complete removal of MCs in drinking water are urgently needed. In our previous work, we found that sulforaphane (SFN) protects against microcystin-LR (MC-LR)-induced cytotoxicity by activating the NF-E2-related factor 2 (Nrf2)-mediated defensive response in human hepatoma (HepG2) and NIH 3T3 cells. The purpose of this study was to investigate and confirm efficacy the SFN-induced multi-mechanistic defense system against MC-induced hepatotoxicity in an animal model. We report that SFN protected against MC-LR-induced liver damage and animal death at a nontoxic and physiologically relevant dose in BALB/c mice. The protection by SFN included activities of anti-cytochrome P450 induction, anti-oxidation, anti-inflammation, and anti-apoptosis. Our results suggest that SFN may protect mice against MC-induced hepatotoxicity. This raises the possibility of a similar protective effect in human populations, particularly in developing countries where freshwaters are polluted by blooming algae. (C) 2011 Elsevier Inc. All rights reserved
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