-
Food Chemistry Mar 2021A simple, sensitive and rapid fluorometric system has been developed for the detection of aldicarb (ALD) based on inner filter effect (IFE) of gold nanoparticles (AuNPs)...
A simple, sensitive and rapid fluorometric system has been developed for the detection of aldicarb (ALD) based on inner filter effect (IFE) of gold nanoparticles (AuNPs) on fluorescence (FL) intensity of carbon quantum dots (CQDs). Addition of CQDs into AuNPs, gets them aggregated due to electrostatic interaction resulting in quenching the FL intensity of CQDs. With addition of ALD into AuNPs, an intercalated layer was formed between them through Au-N and Au-S bond which reduced IFE of AuNPs. Hence, CQDs FL intensity recovered along with ALD concentration varying between 3.8 and 76 µg L with lower detection limit of 3.02 µg L. The spiked real samples study in fruits, vegetables and soft drinks revealed that this sensing platform was repeatable and effective for real samples. The validation of proposed method indicates that the ALD sensor is promising and adaptable for everyday on spot environment and food safety monitoring.
Topics: Aldicarb; Carbon; Fluorescence; Food Analysis; Food Contamination; Fruit; Gold; Intercalating Agents; Metal Nanoparticles; Quantum Dots; Reproducibility of Results; Spectrometry, Fluorescence; Vegetables
PubMed: 33002825
DOI: 10.1016/j.foodchem.2020.127835 -
Protein and Peptide Letters 2021Aldicarb is a carbamate pesticide commercially used in potato crop production. Once it enters human body, it interacts with diverse proteins and other substances.
BACKGROUND
Aldicarb is a carbamate pesticide commercially used in potato crop production. Once it enters human body, it interacts with diverse proteins and other substances.
OBJECTIVE
Aldicarb is toxic to human health and it is also a cholinesterase inhibitor, which prevents the breakdown of acetylcholine in synapse. Human alpha-2-macroglobulin (α2M), is a large tetrameric glycoprotein of 720 kDa with antiproteinase activity, found abundantly in plasma.
METHODS
In the present study, the interaction of aldicarb with alpha-2-macroglobulin was explored utilizing various spectroscopic techniques and molecular docking studies.
RESULTS
UV-vis and fluorescence spectroscopy suggests the formation of a complex between aldicarb and α2M apparent by increased absorbance and decreased fluorescence with static quenching mode. CD spectroscopy indicates a slight change in the structure of alpha-2-macroglobulin. Docking studies confirm the interaction of aldicarb with Pro- 1391, Leu-1392, Lys-1393, Val-1396, Lys- 1397, Thr-1408, Glu-1409, Val-1410, Asp-282 and Glu-281 in the receptor binding domain at the C-terminal of the alpha 2 macroglobulin.
DISCUSSION
In this work, aldicarb is shown to bind with alpha 2-macroglobulin at receptor binding domain which is the binding site for various extracellular and intracellular ligand too. Also, affecting the functional activity of the protein may lead to further physiological consequences.
CONCLUSION
It is possible that aldicarb binds and compromises antiproteinase activity of α2M and binding properties by inducing changes in the secondary structure of the protein.
Topics: Aldicarb; Humans; Molecular Docking Simulation; Pesticides; Pregnancy-Associated alpha 2-Macroglobulins; Spectrometry, Fluorescence
PubMed: 32957873
DOI: 10.2174/0929866527666200921165834 -
The Science of the Total Environment Jan 2021Long Island, New York, has a mix of urban/suburban to agricultural/horticultural land use and nearly 3 million residents that rely on a sole-source aquifer for drinking...
Long Island, New York, has a mix of urban/suburban to agricultural/horticultural land use and nearly 3 million residents that rely on a sole-source aquifer for drinking water. The analysis of shallow groundwater (<40 m below land surface) collected from 54 monitoring wells across Long Island detected 53 pesticides or pesticide degradates. Maximum concentrations for individual pesticides or pesticide degradates ranged from 3 to 368,000 ng/L. The highest concentrations and most frequent pesticide detections occurred in samples collected from the pesticide management (PM) network, set in an agricultural/horticultural area in eastern Long Island with coordinated pesticide management by state and local agencies. The other two networks (Suffolk and Nassau/Queens) were set in suburban and urban areas, respectively, and had less frequent detections and lower pesticide concentrations than the PM network. Pesticide detections and concentration patterns (herbicide, insecticide, or fungicide) differed among the three networks revealing broad differences in land use. The predominance of fungicides metalaxyl, 1H-1,2,4-triazole (propiconazole/myclobutanil degradate), and 4-hydroxychlorothalonil (HCTL, chlorothalonil degradate) in samples from the PM network reflects their intensive use in agricultural settings. Total fungicide concentrations in the PM network ranged from <10 to >300,000 ng/L. The widespread detection of imidacloprid and triazine herbicides, simazine and atrazine, reveal a mixture of current and past use pesticides across the Long Island region. Low concentrations (<200 ng/L) of the triazines in the Suffolk and Nassau/Queens networks may reflect a change in land use and application. Acetanilide herbicides and aldicarb have been discontinued for 20 and 40 years, respectively, yet the concentrations of their degradates were among the highest observed in this study. Acetanilide (total concentrations up to 10,000 ng/L) and aldicarb degradates (up to 270 ng/L) are present in the PM network at much lower concentrations than previous Long Island studies and reflect changes in agricultural practices and pesticide management.
PubMed: 32892047
DOI: 10.1016/j.scitotenv.2020.141895 -
Journal of Neurochemistry Sep 2021Acetylcholine is an abundant neurotransmitter in all animals. Effects of acetylcholine are excitatory, inhibitory, or modulatory depending on the receptor and cell type....
Acetylcholine is an abundant neurotransmitter in all animals. Effects of acetylcholine are excitatory, inhibitory, or modulatory depending on the receptor and cell type. Research using the nematode C. elegans has made ground-breaking contributions to the mechanistic understanding of cholinergic transmission. Powerful genetic screens for behavioral mutants or for responses to pharmacological reagents identified the core cellular machinery for synaptic transmission. Pharmacological reagents that perturb acetylcholine-mediated processes led to the discovery and also uncovered the composition and regulators of acetylcholine-activated channels and receptors. From a combination of electrophysiological and molecular cellular studies, we have gained a profound understanding of cholinergic signaling at the levels of synapses, neural circuits, and animal behaviors. This review will begin with a historical overview, then cover in-depth current knowledge on acetylcholine-activated ionotropic receptors, mechanisms regulating their functional expression and their functions in regulating locomotion.
Topics: Acetylcholine; Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Cholinergic Agents; Humans; Ion Channel Gating; Locomotion; Muscle Contraction; Receptors, Cholinergic; Synaptic Transmission
PubMed: 32869293
DOI: 10.1111/jnc.15164 -
Journal of Hazardous Materials Feb 2021The cehA gene is the earliest reported and most widely found carbaryl hydrolase gene. CehA detoxifies carbaryl and other carbamate pesticides via de-esterification....
The cehA gene is the earliest reported and most widely found carbaryl hydrolase gene. CehA detoxifies carbaryl and other carbamate pesticides via de-esterification. Currently, there is no systematic research available on substrate preference or the mechanism of CehA action in different hosts. In this study, we found that CehA from different hosts is highly conserved, with more than 99% amino acid sequence similarity, and that transposable elements exist in both the upstream and downstream regions of cehA. By introducing point mutations into the cehA gene of Sphingobium sp. CFD-1, we obtained and heterologously expressed all reported CehA(CehAS) encoding genes. Assays to determine enzymatic properties and substrate profiles of CehAS showed that each CehA has a significant substrate preference for different carbamate insecticides. Specifically, CehA152Phe/Leu determines the catalytic preference for bicyclic carbamate substrates (carbofuran, carbaryl), while CehA494Thr/Ala and 570Thr/Ile determine the preference for monocyclic carbamate substrates (isoprocarb, propoxur) and linear carbamate substrates (oxamyl, aldicarb), respectively. Considering the existence of transposable elements in the flanking regions of cehA, we speculate that the cehA hosts may have acquired the hydrolysis ability, as well as substrate preference for carbamate pesticides, through horizontal gene transfer and genetic copying errors.
Topics: Carbaryl; Carbofuran; Carboxylic Ester Hydrolases; Insecticides
PubMed: 32835992
DOI: 10.1016/j.jhazmat.2020.123677 -
Annals of the New York Academy of... Nov 2020Aldicarb, a carbamate pesticide, is an acetylcholinesterase inhibitor, with oral median lethal dose (LD ) estimates in rats ranging from 0.46 to 0.93 mg/kg. A...
Aldicarb, a carbamate pesticide, is an acetylcholinesterase inhibitor, with oral median lethal dose (LD ) estimates in rats ranging from 0.46 to 0.93 mg/kg. A three-phase approach was used to comprehensively assess aldicarb as an oral-ingestion hazard. First, the solubility of aldicarb in popular consumer beverages (bottled water, apple juice, and 2% milk) was assessed. Lethality was then assessed by administering aldicarb in bottled water via gavage. A probit model was fit to 24-h survival data and predicted a median lethal dose of 0.83 mg/kg (95% CI: 0.54-1.45 mg/kg; slope: 4.50). Finally, organoleptic properties (e.g., taste, smell, and texture) were assessed by allowing rats to voluntarily consume 3.0 mL of the above beverages as well as liquid eggs adulterated with aldicarb at various concentrations. This organoleptic assessment determined that aldicarb was readily consumed at lethal and supralethal doses. Overt toxic signs presented within 5 min post-ingestion, and all rats died within 20 min after consuming the highest concentration (0.542 mg/mL), regardless of amount consumed. Because rats have more developed chemoreceptive capabilities than humans, these results suggest that aldicarb may be consumed in toxic or even lethal concentrations by humans in a variety of beverages or foods.
Topics: Aldicarb; Animals; Cholinesterase Inhibitors; Humans; Insecticides; Lethal Dose 50; Male; Models, Biological; Rats; Rats, Sprague-Dawley
PubMed: 32761625
DOI: 10.1111/nyas.14448 -
Neurotoxicology and Teratology 2020Neuroactive chemicals are frequently detected in the environment. At sufficiently high concentrations or within mixtures, they could provoke neurotoxic effects and...
Neuroactive chemicals are frequently detected in the environment. At sufficiently high concentrations or within mixtures, they could provoke neurotoxic effects and neurological diseases to organisms and humans. Fast identification of such neuroactive compounds in the environment could help in hazard assessment and risk mitigation. Behavior change is considered as an important endpoint and might be directly or indirectly connected to a neuroactive mode of action. For a fast evaluation of environmental samples and pure substances, we optimized the measurement of a behavioral endpoint in zebrafish embryos - the spontaneous tail coiling (STC). Evaluation of results is automated via the use of a workflow established with the KNIME® software. Analysis duration and developmental stage were optimized to 1 min and 25 ± 1 hpf respectively during measurement. Exposing the embryos in a group of 10 or 20 and acclimatizing for 30 min at room temperature proved to be reliable. The optimized method was used to investigate neurotoxic effects of 18 substances with different modes of action (MoA). The STC test accurately detected the effect of 8 out of 11 neuroactive substances (chlorpyrifos, chlorpyrifos-oxon, diazinon, paraoxon-methyl, abamectin, carbamazepine, propafenone and diazepam). Aldicarb and nicotine showed subtle effects which were considered to be conditional and imidacloprid showed no effect. For substances with unknown neuroactive MoA, 3 substances did not provoke any effect on the STC (pyraclostrobin, diuron and daunorubicin-hydrochloride) while 4 other substances provoked an increased STC (hexaconazole, aniline, dimethyl-sulfoxide and 3,4-dichloroaniline). Such unexpected effects indicate possible neuroactive side effects or unknown mechanisms of action that impact on the STC. In conclusion, the optimized STC parameters and the automated analysis in KNIME® indicate opportunities for the harmonization of the STC test and further development for prospective and diagnostic testing.
Topics: Animals; Embryo, Mammalian; Embryo, Nonmammalian; Neurotoxicity Syndromes; Paraoxon; Prospective Studies; Water Pollutants, Chemical; Workflow; Zebrafish
PubMed: 32730898
DOI: 10.1016/j.ntt.2020.106918 -
Molecular and Cellular Neurosciences Sep 2020Multiple C2 and Transmembrane Domain Proteins (MCTPs) are putative calcium sensors. Proteins that contain C2 domains play essential roles in membrane trafficking and...
Multiple C2 and Transmembrane Domain Proteins (MCTPs) are putative calcium sensors. Proteins that contain C2 domains play essential roles in membrane trafficking and exocytosis; however, MCTPs functions in neurotransmitter release are not known. Here we report that in C. elegans mctp-1 is under the control of two promoters - one active in the nervous system and the second in the spermatheca. We generated and characterized a loss of function amt1 mutant and compared it to a previously published loss of function mutant (av112). Loss of mctp-1 function causes defects in egg-laying, crawling velocity, and thrashing rates. Both amt1 and av112 mutants are hyposensitive to the acetylcholinesterase blocker aldicarb, suggesting that MCTP-1 may play a role in synaptic vesicle release.
Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Calcium; Exocytosis; Membrane Proteins; Neurotransmitter Agents; Synaptic Transmission; Synaptic Vesicles
PubMed: 32650044
DOI: 10.1016/j.mcn.2020.103528 -
Experimental Gerontology Sep 2020The ailments related to a malfunction in cholinergic functioning currently employ the use of inhibitors for acetylcholinesterase (AChE) and N-methyl-d-aspartate (NMDA)...
The ailments related to a malfunction in cholinergic functioning currently employ the use of inhibitors for acetylcholinesterase (AChE) and N-methyl-d-aspartate (NMDA) receptors. The present study was designed to elucidate the potential of swertiamarin (SW), a secoiridoidal glycoside isolated from Enicostemma littorale in curtailing the cholinergic dysfunction. Using Caenorhabditis elegans as a model, SW was found to enhance neurotransmission by modulating AChE and nicotinic acetylcholine receptor (nAChR) activity; being orchestrated through up-regulation of unc-17 and unc-50. SW exhibited AChE inhibition both in vivo and cell-free system. The in silico molecular docking of SW and human AChE (hAChE) displayed good binding energy of -6.02. Interestingly, the increase in aldicarb and levamisole sensitivity post SW treatment was curtailed to a significant level in daf-16 and skn-1 mutants. SW raised the level of the endogenous antioxidant enzymes through up-regulation of sod-3 and gst-4 that act downstream to DAF-16 and SKN-1, imparting protection against neurodegeneration. The outcome of our study displays SW as a potential natural molecule for the amelioration of cholinergic dysfunction. Moreover, the study also indicates that SW elicits antioxidant response via up-modulation of daf-16 possibly through unc-17 upregulation. Further research on SW pertaining to the underlying mechanism and potential is expected to significantly advance the current understanding and design of possible ameliorative or near ameliorative regimens for cholinergic dysfunction.
Topics: Acetylcholinesterase; Animals; Glycosides; Humans; Iridoid Glucosides; Molecular Docking Simulation; Pyrones; Receptors, Nicotinic
PubMed: 32590127
DOI: 10.1016/j.exger.2020.111010 -
PLoS Genetics Jun 2020Ion channels are present at specific levels within subcellular compartments of excitable cells. The regulation of ion channel trafficking and targeting is an effective...
Ion channels are present at specific levels within subcellular compartments of excitable cells. The regulation of ion channel trafficking and targeting is an effective way to control cell excitability. The BK channel is a calcium-activated potassium channel that serves as a negative feedback mechanism at presynaptic axon terminals and sites of muscle excitation. The C. elegans BK channel ortholog, SLO-1, requires an endoplasmic reticulum (ER) membrane protein for efficient anterograde transport to these locations. Here, we found that, in the absence of this ER membrane protein, SLO-1 channels that are seemingly normally folded and expressed at physiological levels undergo SEL-11/HRD1-mediated ER-associated degradation (ERAD). This SLO-1 degradation is also indirectly regulated by a SKN-1A/NRF1-mediated transcriptional mechanism that controls proteasome levels. Therefore, our data indicate that SLO-1 channel density is regulated by the competitive balance between the efficiency of ER trafficking machinery and the capacity of ERAD.
Topics: Aldicarb; Animals; Animals, Genetically Modified; Caenorhabditis elegans; Caenorhabditis elegans Proteins; DNA-Binding Proteins; Endoplasmic Reticulum; Endoplasmic Reticulum-Associated Degradation; Excitation Contraction Coupling; Feedback, Physiological; Large-Conductance Calcium-Activated Potassium Channels; Membrane Proteins; Muscles; Presynaptic Terminals; Proteasome Endopeptidase Complex; Protein Isoforms; Transcription Factors; Ubiquitin-Protein Ligases
PubMed: 32502151
DOI: 10.1371/journal.pgen.1008829