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G3 (Bethesda, Md.) Dec 2022Animals exhibit phenotypic plasticity through the interaction of genes with the environment, and little is known about the genetic factors that change synaptic function...
Animals exhibit phenotypic plasticity through the interaction of genes with the environment, and little is known about the genetic factors that change synaptic function at different developmental stages. Here, we investigated the genetic determinants of how animal's sensitivity to drugs that alter synaptic activity is regulated at a specific developmental stage using the free-living nematode Caenorhabditis elegans. C. elegans enters the stress-resistant dauer larval stage under harsh conditions. Although dauer is known to have reduced permeability and increased resistance to most known exogenous chemicals, we discovered that dauer is hypersensitive to a cholinesterase inhibitor, aldicarb. To investigate genes regulating dauer-specific acetylcholine transduction, we first screened for aldicarb-resistant mutations in dauer and then performed a secondary screen to rule out aldicarb-resistant mutations that also affect adults. We isolated 2 different mutations of a single gene called cyp-34A4 or dach-1 encoding a cytochrome P450. In the nondauer stages, dach-1 is mainly expressed in the intestine, but its expression is robustly increased in the epidermis of dauers. By tissue-specific rescue experiments, we found that dach-1 modulates aldicarb sensitivity in a cell nonautonomous manner. In addition, dach-1 plays pleiotropic functions in dauers by regulating quiescence and surviving heat shock and hyperosmolar stress. Our study reveals novel functions of the cytochrome P450 in synaptic and physiological changes during the developmental plasticity.
Topics: Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Larva; Aldicarb; Alleles; Cytochrome P-450 Enzyme System
PubMed: 36194018
DOI: 10.1093/g3journal/jkac266 -
Frontiers in Nutrition 2022The common carbamate insecticide aldicarb is considered one of the most acutely toxic pesticides. Herein, rational design was used to synthesize two haptens with spacers...
The common carbamate insecticide aldicarb is considered one of the most acutely toxic pesticides. Herein, rational design was used to synthesize two haptens with spacers of different carbon chain lengths. The haptens were then used to immunize mice. The antibodies obtained were evaluated systematically, and a colloidal gold immunochromatographic strip was developed based on an anti-aldicarb monoclonal antibody. The 50% inhibition concentration and linear range of anti-aldicarb monoclonal antibody immunized with Hapten 1 were 0.432 ng/mL and 0.106-1.757 ng/mL, respectively. The cross-reactivities for analogs of aldicarb were all <1%. The limit of detection of the colloidal gold immunochromatographic strip was 30 μg/kg, and the average recoveries of aldicarb ranged from 80.4 to 110.5% in spiked samples. In the analysis of spiked samples, the test strip could accurately identify positive samples detected by the instrumental method in the GB 23200.112-2018 standard but produced some false positives for negative samples. This assay provides a rapid and accurate preliminary screening method for the determination of aldicarb in agricultural products and environments.
PubMed: 36082035
DOI: 10.3389/fnut.2022.976284 -
MicroPublication Biology 2022Atropine has been used as an established anticonvulsant treatment for nerve agent intoxication. Atropine reduces electroshock recovery time among aldicarb-exposed...
Atropine has been used as an established anticonvulsant treatment for nerve agent intoxication. Atropine reduces electroshock recovery time among aldicarb-exposed wild-type .
PubMed: 36017190
DOI: 10.17912/micropub.biology.000621 -
Aquatic Toxicology (Amsterdam,... Aug 2022Originally designed as a general alternative to acute fish toxicity testing (AFT), the fish embryo toxicity test (FET) has become subject to concerns with respect to...
Originally designed as a general alternative to acute fish toxicity testing (AFT), the fish embryo toxicity test (FET) has become subject to concerns with respect to neurotoxic substances. Whereas oxygen uptake in the fish embryo primarily occurs via diffusion across the skin, juvenile and adult fish rely on active ventilation of the gills. As a consequence, substances including, e.g., neurotoxicants which prevent appropriate ventilation of gills ("respiratory failure syndrome") might lead to suffocation in juvenile and adult fish, but not in skin-breathing embryos. To investigate if this respiratory failure syndrome might play a role for the higher sensitivity of juvenile and adult fish to neurotoxicants, a modified acute toxicity test using post-embryonic, early gill-breathing life-stages of zebrafish was developed with chlorpyrifos, permethrin, lindane, aldicarb, ziram and aniline as test substances. Additionally, a comparative study into bioaccumulation of lipophilic substances with log > 3.5 and swimbladder deflation as potential side effects of the respiratory failure syndrome was performed with 4 d old skin-breathing and 12 d old gill-breathing zebrafish. With respect to acute toxicity, post-embryonic 12 d larvae proved to be more sensitive than both embryos (FET) and adult zebrafish (AFT) to all test substances except for permethrin. Accumulation of chlorpyrifos, lindane and permethrin was 1.3- to 5-fold higher in 4 d old than in 12 d old zebrafish, suggesting that (intermediate) storage of substances in the yolk might reduce bioavailability and prevent metabolization, which could be a further reason for lower toxicity in 4 d than in 12 d old zebrafish. Whereas ziram and aniline showed no significant effect on the swimbladder, zebrafish exposed to chlorpyrifos, lindane and permethrin showed significantly deflated swimbladders in 12 d old larvae; in the case of aldicarb, there was a significant hyperinflation in 4 d old larvae. Swimbladder deflation in post-embryonic 12 d zebrafish larvae might be hypothesized as a reason for a lack of internal oxygen supplies during the respiratory failure syndrome, whereas in 4 d old embryos cholinergic hyperinflation of the swimbladder dominates over other effects. Regarding acute lethality, the study provides further evidence that the switch from transcutaneous to branchial respiration in post-embryonic zebrafish life-stages might be the reason for the higher sensitivity of juvenile and adult fish to neurotoxic substances.
Topics: Aldicarb; Aniline Compounds; Animals; Chlorpyrifos; Embryo, Nonmammalian; Gills; Hexachlorocyclohexane; Larva; Oxygen; Permethrin; Respiration; Respiratory Insufficiency; Toxicity Tests, Acute; Water Pollutants, Chemical; Zebrafish; Ziram
PubMed: 35863251
DOI: 10.1016/j.aquatox.2022.106240 -
American Journal of Human Genetics Aug 2022PPFIBP1 encodes for the liprin-β1 protein, which has been shown to play a role in neuronal outgrowth and synapse formation in Drosophila melanogaster. By exome and...
PPFIBP1 encodes for the liprin-β1 protein, which has been shown to play a role in neuronal outgrowth and synapse formation in Drosophila melanogaster. By exome and genome sequencing, we detected nine ultra-rare homozygous loss-of-function variants in 16 individuals from 12 unrelated families. The individuals presented with moderate to profound developmental delay, often refractory early-onset epilepsy, and progressive microcephaly. Further common clinical findings included muscular hyper- and hypotonia, spasticity, failure to thrive and short stature, feeding difficulties, impaired vision, and congenital heart defects. Neuroimaging revealed abnormalities of brain morphology with leukoencephalopathy, ventriculomegaly, cortical abnormalities, and intracranial periventricular calcifications as major features. In a fetus with intracranial calcifications, we identified a rare homozygous missense variant that by structural analysis was predicted to disturb the topology of the SAM domain region that is essential for protein-protein interaction. For further insight into the effects of PPFIBP1 loss of function, we performed automated behavioral phenotyping of a Caenorhabditis elegans PPFIBP1/hlb-1 knockout model, which revealed defects in spontaneous and light-induced behavior and confirmed resistance to the acetylcholinesterase inhibitor aldicarb, suggesting a defect in the neuronal presynaptic zone. In conclusion, we establish bi-allelic loss-of-function variants in PPFIBP1 as a cause of an autosomal recessive severe neurodevelopmental disorder with early-onset epilepsy, microcephaly, and periventricular calcifications.
Topics: Acetylcholinesterase; Animals; Drosophila melanogaster; Epilepsy; Loss of Heterozygosity; Microcephaly; Nervous System Malformations; Neurodevelopmental Disorders; Pedigree
PubMed: 35830857
DOI: 10.1016/j.ajhg.2022.06.008 -
Toxicology Research Jun 2022Aldicarb, a carbamate pesticide banned in France since 2008, represents a persistent risk of human poisoning. There is no up-to-date picture of aldicarb intentional...
Aldicarb, a carbamate pesticide banned in France since 2008, represents a persistent risk of human poisoning. There is no up-to-date picture of aldicarb intentional poisonings associated to detailed diagnosis and clinical management of cases to evaluate the effect of its ban on intoxication risk reduction, including suicide. This retrospective epidemiological study describes cases of suicidal intoxication from the Hauts-de-France region between 2012 and 2021 and illustrates this situation through one analytically documented case. 60 cases were collected, mostly presenting a pathognomonic symptomatology. Thirty-five victims presented a muscarinic syndrome (58.3%), 14 a nicotinic syndrome (23.3%), and 37 a central nervous system impairment (61.7%). Hospitalization was necessary for 44 cases (73.3%), with 2 fatal evolutions. Diagnosis was based on the blood cholinesterase activities. Among the 25 cases with toxicology results, 45.8% presented a moderate decrease of acetylcholinesterase activity, whereas 87.5% presented a strong decrease of butyrylcholinesterase activity. Blood or urine detection of aldicarb and its metabolites may be considered in therapeutic management, although their quantification is unlikely to change the emergency medical care. Our study updates epidemiology of aldicarb poisoning at a regional level, highlighting a persisting health threatening situation with banned pesticides. More than 65% of national cases occurred in this agricultural area, aldicarb remaining available from storage of previously purchased products. Robust evidence is presented that acute poisoning is an ongoing major global public health challenge. There is a need for continued international efforts in risk reduction, knowledge, and information strategies.
PubMed: 35782643
DOI: 10.1093/toxres/tfac031 -
Chemical Research in Toxicology Jun 2022Oxime-type carbamate pesticides having an oxime moiety such as aldicarb, butocarboxim, methomyl, oxamyl, and thiofanox are widely used and have been detected in many...
Oxime-type carbamate pesticides having an oxime moiety such as aldicarb, butocarboxim, methomyl, oxamyl, and thiofanox are widely used and have been detected in many fatal cases of accidental exposure or suicide. In forensic toxicology, the accurate determination of blood pesticide concentration is obligatory to prove death by oxime-type carbamate pesticide poisoning. However, the fatal pesticide concentration in blood at autopsy differs from that at the time of death. In this study, we found that oxime-type carbamate pesticides were decomposed by Hb in a temperature-dependent fashion. The mechanism underlying methomyl, aldicarb, oxamyl, and thiofanox decomposition involves the formation of adducts with the amino acids in Hb. With regard to butocarboxim, its decomposition involves the oxidation of the free form and the formation of adducts with the amino acids in Hb. The mass spectra obtained by liquid chromatography quadrupole time-of-flight mass spectrometry revealed that carbamylated amino acid adducts such as W-adduct and V-adduct were formed in Hb solution incubated with methomyl, aldicarb, oxamyl, and thiofanox, whereas alkylated amino acid adducts such as W-adduct were formed in Hb solution incubated with butocarboxim. These results indicate that aldicarb, butocarboxim, methomyl, oxamyl, and thiofanox are post-mortem changed by Hb.
Topics: Aldicarb; Amino Acids; Autopsy; Carbamates; Cholinesterase Inhibitors; Hemoglobins; Humans; Methomyl; Oximes; Pesticides
PubMed: 35559618
DOI: 10.1021/acs.chemrestox.2c00092 -
Environmental Technology Sep 2023This work is interested in studying the removal of 27 harmful pollutants from drinking water in the Rosetta branch of the River Nile by advanced treatment processes...
This work is interested in studying the removal of 27 harmful pollutants from drinking water in the Rosetta branch of the River Nile by advanced treatment processes (i.e. photo-catalysis under natural conditions and normal pH of surface water). The concentration levels of the selected pesticides (11 compounds) in raw water by the spiking method ranged from 1.57-0.40 µg/L, while the concentration of pharmaceuticals (10 compounds) ranged from 41.56-5.95 µg/L and the herbicides (6 compounds) in the range of 1.89-1.37 µg/L. For this purpose, TiO-Hombikat/alumina (T/A) was prepared by a two-step method; sonication followed by the hydrothermal method. Cu/TiO-Hombikat/alumina was prepared hydrothermally (H-Cu/T/Al) and by the wet impregnation method (Ma-Cu/T/Al). The prepared materials were characterized by XRD and SEM. The use of advanced treatment could successfully remove selected pollutants. In the case of pharmaceutical residues, the prepared catalysts showed a powerful efficiency in the complete removal of sulfamethazine, while only (T/A) and (H-Cu/T/Al) showed such an efficiency in the complete removal of diclofenac sodium. On the other hand, lower efficiencies were observed with caffeine (17.99% (T/A) and 24.05% (H-Cu/T/Al)). In the case of pesticides, a high removal of pendimethalin (93.77%) using (H-Cu/T/Al) and 86.03% by using (Mb-Cu/T/Al), whereas lower efficiencies were observed for T/A toward the degradation of aldicarb (15.6%) (l) and H-Cu/T/Al (26.07%). In the case of herbicides, the catalysts showed no more than 57% efficiency in the removal of these pollutants.
Topics: Herbicides; Pesticides; Drinking Water; Pharmaceutical Preparations; Water Pollutants, Chemical; Catalysis
PubMed: 35410576
DOI: 10.1080/09593330.2022.2064234 -
Frontiers in Bioengineering and... 2021In this study, was grown on municipal biosolids (BS) as the substrate to produce laccase for the removal of pesticides (fungicides, herbicides, and insecticides) from...
In this study, was grown on municipal biosolids (BS) as the substrate to produce laccase for the removal of pesticides (fungicides, herbicides, and insecticides) from wastewater. Among the various types of BS tested, sterilized biosolids were the most promising substrate for laccase production by with a maximal laccase activity (162.1 ± 21.1 U/g dry substrate), followed by hygenized biosolids (96.7 ± 17.6 U/g dry substrate), unsterilized biosolids (UBS) (31.9 ± 1.2 U/g dry substrate), and alkali-treated biosolids (8.2 ± 0.4 U/g dry substrate). The ultrasound-assisted extraction of this enzyme from fermented UBS was carried out with 0.1 M phosphate buffer at pH 7.0, which increased the enzyme activity of the crude extract by 30%. To test the catalytic potential of the biocatalyst in real matrices, 1 U/ml of recovered crude laccase extract was applied for 24 h for the removal of 29 pesticides (nine fungicides, 10 herbicides, and 10 insecticides) either separately or as a mixture from spiked biologically treated wastewater effluent. When treated with crude enzyme extract, high-priority herbicides metolachlor and atrazine were completely removed, while 93%-97% of the insecticides aldicarb, spinosad, and azinphos-methyl and up to 91% of kresoxim-methyl were removed. Promising results were obtained with BS-derived crude enzyme extract exhibiting improved pesticides removal, which may be due to the mediator effect resulting from the catalytic transformation of other molecules in the cocktail. The results demonstrated a promising integrated bioprocess for the removal of pesticides in wastewater using crude laccase obtained from BS.
PubMed: 35223809
DOI: 10.3389/fbioe.2021.770435 -
Plant Disease Aug 2022Meta-analysis was used to compare yield protection and nematode suppression provided by two seed-applied and two soil-applied nematicides against and on cotton across... (Meta-Analysis)
Meta-Analysis
Meta-analysis was used to compare yield protection and nematode suppression provided by two seed-applied and two soil-applied nematicides against and on cotton across 3 years and several trial locations in the U.S. Cotton Belt. Nematicides consisted of thiodicarb- and fluopyram-treated seed, aldicarb and fluopyram applied in furrow, and combinations of the seed treatments and soil-applied fluopyram. The nematicides had no effect on nematode reproduction or root infection but had a significant impact on seed cotton yield response ([Formula: see text]), with an average increase of 176 and 197 kg/ha relative to the nontreated control in and infested fields, respectively. However, because of significant variation in yield protection and nematode suppression by nematicides, five or six moderator variables (cultivar resistance [ only], nematode infestation level, nematicide treatment, application method, trial location, and growing season) were used depending on nematode species. In -infested fields, greater yield protection was observed with nematicides applied in furrow and with seed-applied + in-furrow than with solo seed-applied nematicide applications. Most notable of these in-furrow nematicides were aldicarb and fluopyram (>131 g/ha) with or without a seed-applied nematicide compared with thiodicarb. In -infested fields, moderator variables provided no further explanation of the variation in yield response produced by nematicides. Furthermore, moderator variables provided little explanation of the variation in nematode suppression by nematicides in and -infested fields. The limited explanation by the moderator variables on the field efficacy of nematicides in and -infested fields demonstrates the difficulty of managing these pathogens with nonfumigant nematicides across the U.S. Cotton Belt.
Topics: Aldicarb; Animals; Antinematodal Agents; Benzamides; Gossypium; Pyridines; Seeds; Soil; Tylenchoidea; United States
PubMed: 34978874
DOI: 10.1094/PDIS-07-21-1529-RE