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BMC Genomics Jul 2024Indoor residual spraying (IRS) and insecticide-treated nets (ITNs) are the main methods used to control mosquito populations for malaria prevention. The efficacy of...
Indoor residual spraying (IRS) and insecticide-treated nets (ITNs) are the main methods used to control mosquito populations for malaria prevention. The efficacy of these strategies is threatened by the spread of insecticide resistance (IR), limiting the success of malaria control. Studies of the genetic evolution leading to insecticide resistance could enable the identification of molecular markers that can be used for IR surveillance and an improved understanding of the molecular mechanisms associated with IR. This study used a weighted gene co-expression network analysis (WGCNA) algorithm, a systems biology approach, to identify genes with similar co-expression patterns (modules) and hub genes that are potential molecular markers for insecticide resistance surveillance in Kenya and Benin. A total of 20 and 26 gene co-expression modules were identified via average linkage hierarchical clustering from Anopheles arabiensis and An. gambiae, respectively, and hub genes (highly connected genes) were identified within each module. Three specific genes stood out: serine protease, E3 ubiquitin-protein ligase, and cuticular proteins, which were top hub genes in both species and could serve as potential markers and targets for monitoring IR in these malaria vectors. In addition to the identified markers, we explored molecular mechanisms using enrichment maps that revealed a complex process involving multiple steps, from odorant binding and neuronal signaling to cellular responses, immune modulation, cellular metabolism, and gene regulation. Incorporation of these dynamics into the development of new insecticides and the tracking of insecticide resistance could improve the sustainable and cost-effective deployment of interventions.
Topics: Anopheles; Animals; Insecticide Resistance; Pyrethrins; Systems Biology; Insecticides; Gene Regulatory Networks; Organophosphates; Mosquito Vectors; Kenya; Gene Expression Profiling
PubMed: 38961324
DOI: 10.1186/s12864-024-10572-z -
Zhonghua Yu Fang Yi Xue Za Zhi [Chinese... Jun 2024To explore the impact of whole blood organophosphate esters (OPEs) flame retardant exposure on thyroid function-related hormones in healthy older adults. In this panel...
To explore the impact of whole blood organophosphate esters (OPEs) flame retardant exposure on thyroid function-related hormones in healthy older adults. In this panel study, five repeated population-based epidemiological surveys and biological sample collection were conducted from September 2018 to January 2019, with 76 healthy older adults aged 60-69 years in the Dianliu Community of Jinan, Shandong Province. Information on the sociodemographic characteristics, diet, and health status of the respondents was systematically gathered through questionnaires and physical examinations. Fasting venous blood was collected to determine the levels of OPEs, thyroid-stimulating hormone (TSH), triiodothyronine (T), and thyroxine (T). A linear mixed-effects model was used to analyze the impact of OPEs exposure on thyroid function-related hormones in healthy older adults. Each of the 76 subjects participated in at least two follow-up visits, resulting in a total of 350 person visits. The age of the study participants was (65.07±2.76) years, with 38 participants of both sexes. A total of eight OPEs were included with a detection rate exceeding 50%, and the (, ) for ∑OPEs was 3.85 (2.33, 5.74) ng/ml, with alkyl-OPEs being the major type of OPEs with an (, ) of 1.27 (0.64, 2.50) ng/ml. The (, ) for TSH, T, and T was 3.74 (2.55, 5.69) μIU/ml, 1.32 (1.10, 1.60) ng/ml, and 45.04 (36.96, 53.27) ng/ml, respectively. Linear mixed-effects model showed that TSH was significantly decreased by 9.93% (95%:-15.17%, -4.36%) and 11.14% (95%:-15.94%, -6.06%) in older adults for each quartile level increase in TnBP and TEHP exposures, respectively. Gender-stratified analysis indicated that TEHP exposure was negatively associated with TSH levels in male older adults, whereas a decrease in TSH levels among female older adults was associated with TnBP exposure. Exposure to whole blood OPEs is associated with decreased TSH levels among healthy older adults, with notable gender differences.
Topics: Humans; Flame Retardants; Aged; Middle Aged; Thyrotropin; Esters; Thyroxine; Organophosphates; Triiodothyronine; Environmental Exposure; Thyroid Hormones; Male; Female; Surveys and Questionnaires; Thyroid Gland
PubMed: 38955732
DOI: 10.3760/cma.j.cn112150-20240217-00126 -
Journal of Photochemistry and... Jun 2024This research aimed to develop natural plant systems to serve as biological sentinels for the detection of organophosphate pesticides in the environment. The working...
This research aimed to develop natural plant systems to serve as biological sentinels for the detection of organophosphate pesticides in the environment. The working hypothesis was that the presence of the pesticide in the environment caused changes in the content of pigments and in the photosynthetic functioning of the plant, which could be evaluated non-destructively through the analysis of reflected light and emitted fluorescence. The objective of the research was to furnish in vivo indicators derived from spectroscopic parameters, serving as early alert signals for the presence of organophosphates in the environment. In this context, the effects of two pesticides, Chlorpyrifos and Dimethoate, on the spectroscopic properties of aquatic plants (Vallisneria nana and Spathyfillum wallisii) were studied. Chlorophyll-a variable fluorescence allowed monitoring both pesticides' presence before any damage was observed at the naked eye, with the analysis of the fast transient (OJIP curve) proving more responsive than Kautsky kinetics, steady-state fluorescence, or reflectance measurements. Pesticides produced a decrease in the maximum quantum yield of PSII photochemistry, in the proportion of PSII photochemical deexcitation relative to PSII non photochemical decay and in the probability that trapped excitons moved electrons into the photosynthetic transport chain beyond Q. Additionally, an increase in the proportion of absorbed energy being dissipated as heat rather than being utilized in the photosynthetic process, was notorious. The pesticides induced a higher deactivation of chlorophyll excited states by photophysical pathways (including fluorescence) with a decrease in the quantum yields of photosystem II and heat dissipation by non-photochemical quenching. The investigated aquatic plants served as sentinels for the presence of pesticides in the environment, with the alert signal starting within the first milliseconds of electronic transport in the photosynthetic chain. Organophosphates damage animals' central nervous systems similarly to certain compounds found in chemical weapons, thus raising the possibility that sentinel plants could potentially signal the presence of such weapons.
PubMed: 38955078
DOI: 10.1016/j.jphotobiol.2024.112965 -
Zhongguo Xue Xi Chong Bing Fang Zhi Za... May 2024The insecticide resistance is becoming increasingly severe in malaria vectors and has become one of the most important threats to global malaria elimination. Currently,...
The insecticide resistance is becoming increasingly severe in malaria vectors and has become one of the most important threats to global malaria elimination. Currently, malaria vectors not only have developed high resistance to conventional insecticides, including organochlorine, organophosphates, carbamates, and pyrethroids, but also have been resistant to recently used neonicotinoids and pyrrole insecticides. This article describes the current status of global insecticide resistance in malaria vectors and global insecticide resistance management strategies, analyzes the possible major challenges in the insecticide resistance management, and proposes the response actions, so as to provide insights into global insecticide resistance management and contributions to global malaria elimination.
Topics: Animals; Humans; Insect Vectors; Insecticide Resistance; Insecticides; Malaria; Mosquito Vectors
PubMed: 38952309
DOI: 10.16250/j.32.1374.2024088 -
Journal of Biochemical and Molecular... Jul 2024The treatment of organophosphate (OP) anticholinesterases currently lacks an effective oxime reactivator of OP-inhibited acetylcholinesterase (AChE) which can penetrate...
The treatment of organophosphate (OP) anticholinesterases currently lacks an effective oxime reactivator of OP-inhibited acetylcholinesterase (AChE) which can penetrate the blood-brain barrier (BBB). Our laboratories have synthesized novel substituted phenoxyalkyl pyridinium oximes and tested them for their ability to promote survival of rats challenged with lethal doses of nerve agent surrogates. These previous studies demonstrated the ability of some of these oximes to promote 24-h survival to rats challenged with a lethal level of highly relevant surrogates for sarin and VX. The reactivation of OP-inhibited AChE in peripheral tissues was likely to be a major contributor to their efficacy in survival of lethal OP challenges. In the present study, twenty of these novel oximes were screened in vitro for reactivation ability for AChE in rat skeletal muscle and serum using two nerve agent surrogates: phthalimidyl isopropyl methylphosphonate (PIMP, a sarin surrogate) and 4-nitrophenyl ethyl methylphosphonate (NEMP, a VX surrogate). The oximes demonstrated a range of 23%-102% reactivation of AChE in vitro across both tissue types. Some of the novel oximes tested in the present study demonstrated the ability to more effectively reactivate AChE in serum than the currently approved oxime, 2-PAM. Therefore, some of these novel oximes have the potential to reverse AChE inhibition in peripheral target tissues and contribute to survival efficacy.
Topics: Animals; Oximes; Rats; Acetylcholinesterase; Muscle, Skeletal; Cholinesterase Inhibitors; Organophosphates; Male; Cholinesterase Reactivators; Pyridinium Compounds; Rats, Sprague-Dawley
PubMed: 38952032
DOI: 10.1002/jbt.23750 -
Small (Weinheim An Der Bergstrasse,... Jul 2024Solution Gated Graphene Field-Effect Transistors (SGGT) are eagerly anticipated as an amplification platform for fabricating advanced ultra-sensitive sensors, allowing...
Solution Gated Graphene Field-Effect Transistors (SGGT) are eagerly anticipated as an amplification platform for fabricating advanced ultra-sensitive sensors, allowing significant modulation of the drain current with minimal gate voltage. However, few studies have focused on light-matter interplay gating control for SGGT. Herein, this challenge is addressed by creating an innovative photoelectrochemical solution-gated graphene field-effect transistor (PEC-SGGT) functionalized with enzyme cascade reactions (ECR) for Organophosphorus (OPs) detection. The ECR system, consisting of acetylcholinesterase (AChE) and CuBTC nanomimetic enzymes, selectively recognizes OPs and forms o-phenylenediamine (oPD) oligomers sediment on the PEC electrode, with layer thickness related to the OPs concentration, demonstrating time-integrated amplification. Under light stimulation, the additional photovoltage generated on the PEC gate electrode is influenced by the oPD oligomers sediment layer, creating a differentiated voltage distribution along the gate path. PEC-SGGT, inherently equipped with built-in amplification circuits, sensitively captures gate voltage changes and delivers output with an impressive thousandfold current gain. The seamless integration of these three amplification modes in this advanced sensor allows a good linear range and highly sensitive detection of OPs, with a detection limit as low as 0.05 pm. This work provides a proof-of-concept for the feasibility of light-assisted functionalized gate-controlled PEC-SGGT for small molecule detection.
PubMed: 38949408
DOI: 10.1002/smll.202402655 -
Methods in Enzymology 2024Prenyltransferases are terpene synthases that combine 5-carbon precursor molecules into linear isoprenoids of varying length that serve as substrates for terpene...
Prenyltransferases are terpene synthases that combine 5-carbon precursor molecules into linear isoprenoids of varying length that serve as substrates for terpene cyclases, enzymes that catalyze fascinating cyclization reactions to form diverse terpene natural products. Terpenes and their derivatives comprise the largest class of natural products and have myriad functions in nature and diverse commercial uses. An emerging class of bifunctional terpene synthases contains both prenyltransferase and cyclase domains connected by a disordered linker in a single polypeptide chain. Fusicoccadiene synthase from Phomopsis amygdali (PaFS) is one of the most well-characterized members of this subclass and serves as a model system for the exploration of structure-function relationships. PaFS has been structurally characterized using a variety of biophysical techniques. The enzyme oligomerizes to form a stable core of six or eight prenyltransferase domains that produce a 20-carbon linear isoprenoid, geranylgeranyl diphosphate (GGPP), which then transits to the cyclase domains for the generation of fusicoccadiene. Cyclase domains are in dynamic equilibrium between randomly splayed-out and prenyltransferase-associated positions; cluster channeling is implicated for GGPP transit from the prenyltransferase core to the cyclase domains. In this chapter, we outline the methods we are developing to interrogate the nature of cluster channeling in PaFS, including enzyme activity and product analysis assays, approaches for engineering the linker segment connecting the prenyltransferase and cyclase domains, and structural analysis by cryo-EM.
Topics: Alkyl and Aryl Transferases; Dimethylallyltranstransferase; Diterpenes; Enzyme Assays; Polyisoprenyl Phosphates; Cyclization
PubMed: 38942517
DOI: 10.1016/bs.mie.2023.11.003 -
International Journal of Molecular... Jun 2024Chlorpyrifos (CPF) is a widely used organophosphate insecticide, though its excessive use causes environmental contamination, raising concerns about its adverse effects...
Chlorpyrifos (CPF) is a widely used organophosphate insecticide, though its excessive use causes environmental contamination, raising concerns about its adverse effects on human health. In this regard, stands out as a promising candidate for counteracting chemical 'contaminant' toxicity thanks to its therapeutic properties. Therefore, our study aimed to investigate the potential of an ethanolic extract (UDE) to mitigate chlorpyrifos-induced toxicity. Eight compounds in the ethanolic extract have been identified, most of which present significant potential as antioxidant, anti-inflammatory, and neuroprotective agents. Chlorpyrifos exposure altered hatching rates, increased the incidence of teratogenic effects, and upregulated the expression of brain-derived neurotrophic factor (Bdnf) in zebrafish larvae telencephalon. On the other hand, demonstrated a preventive effect against CPF-induced teratogenicity, which is expressed by a lower morphological deformity rate. Moreover, the UDE showed a rather protective effect, maintaining the physiological condition of the telencephalon. Additionally, CPF altered the locomotor behavior of larvae, which was characterized by irregular swimming and increased activity. This defective behavioral pattern was slightly attenuated by the UDE. Our findings suggest that the UDE possesses significant protective properties against CPF-induced toxicity, probably conferred by its natural antioxidant and anti-inflammatory contents. Still, further research is needed to elucidate the recruited mechanisms and implicated pathways on UDE's protective effects.
Topics: Animals; Zebrafish; Chlorpyrifos; Plant Extracts; Larva; Urtica dioica; Antioxidants; Insecticides; Telencephalon
PubMed: 38928336
DOI: 10.3390/ijms25126631 -
International Journal of Molecular... Jun 2024and , bacterial degraders of the herbicide glyphosate, were found to induce phosphonatase (phosphonoacetaldehyde hydrolase, EC 3.11.1.1) when grown on minimal media...
and , bacterial degraders of the herbicide glyphosate, were found to induce phosphonatase (phosphonoacetaldehyde hydrolase, EC 3.11.1.1) when grown on minimal media with glyphosate as the sole source of phosphorus. The phosphonatases of the strains were purified to an electrophoretically homogeneous state and characterized. The enzymes differed in their kinetic characteristics and some other parameters from the previously described phosphonatases. The phosphonatase of was first revealed to separate into two stable forms, which had similar kinetic characteristics but interacted differently with affinity and ion-exchange resins. The genomes of the investigated bacteria were sequenced. The phosphonatase genes were identified, and their context was determined: the bacteria were shown to have gene clusters, which, besides the phosphonatase operon, included genes for LysR-type transcription activator (substrate sensor) and putative iron-containing oxygenase PhnHD homologous to monooxygenases PhnY and TmpB of marine organophosphonate degraders. Genes of 2-aminoethylphosphonate aminotransferase (PhnW, EC 2.6.1.37) were absent in the achromobacterial phosphonatase operons; instead, we revealed the presence of genes encoding the putative flavin oxidase HpnW. In silico simulation showed 1-hydroxy-2-aminoethylphosphonate to be the most likely substrate of the new monooxygenase, and a number of glycine derivatives structurally similar to glyphosate to be substrates of flavin oxidase.
Topics: Glyphosate; Glycine; Achromobacter; Operon; Soil Microbiology; Bacterial Proteins; Herbicides; Multigene Family; Kinetics; Gene Expression Regulation, Bacterial
PubMed: 38928116
DOI: 10.3390/ijms25126409 -
Environmental Health : a Global Access... Jun 2024The prevalence of metabolic syndrome (MetS) in American adults increased from 37.6% in the 2011-12 period to 41.8% in 2017-2018. Environmental exposure, particularly to...
BACKGROUND
The prevalence of metabolic syndrome (MetS) in American adults increased from 37.6% in the 2011-12 period to 41.8% in 2017-2018. Environmental exposure, particularly to common compounds such as glyphosate, has drawn increasing attention as a potential risk factor.
METHODS
We employed three cycles of data (2013-2018) from the National Health and Nutrition Examination Survey (NHANES) in a cross-sectional study to examine potential associations between urine glyphosate measurements and MetS incidence. We first created a MetS score using exploratory factor analysis (EFA) of the International Diabetes Federation (IDF) criteria for MetS, with data drawn from the 2013-2018 NHANES cycles, and validated this score independently on an additional associated metric, the albumin-to-creatinine (ACR) ratio. The score was validated via a machine learning approach in predicting the ACR score via binary classification and then used in multivariable regression to test the association between quartile-categorized glyphosate exposure and the MetS score.
RESULTS
In adjusted multivariable regressions, regressions between quartile-categorized glyphosate exposure and MetS score showed a significant inverted U-shaped or saturating dose‒response profile, often with the largest effect for exposures in quartile 3. Exploration of potential effect modification by sex, race, and age category revealed significant differences by race and age, with older people (aged > 65 years) and non-Hispanic African American participants showing larger effect sizes for all exposure quartiles.
CONCLUSIONS
We found that urinary glyphosate concentration is significantly associated with a statistical score designed to predict MetS status and that dose-response coefficient is nonlinear, with advanced age and non-Hispanic African American, Mexican American and other Hispanic participants exhibiting greater effect sizes.
Topics: Glyphosate; Humans; Glycine; Cross-Sectional Studies; Male; Female; Middle Aged; Adult; Nutrition Surveys; Herbicides; Aged; Metabolic Syndrome; United States; Environmental Exposure; Young Adult; Risk Factors; Environmental Pollutants
PubMed: 38926689
DOI: 10.1186/s12940-024-01098-8