Sublethal Exposure Research Articles

Impact of the exposure of sublethal dose of mosquito coil on the development of insecticide resistance in Aedes aegypti (L.) (Diptera: Culicidae).

Mosquito coil is commonly used in many African households for protection against mosquito bites. The coil usually has semi-volatile pyrethroids as an active ingredient, which usually diffuse across open space, and the cloud either kills mosquitoes that are exposed, or mosquitoes can be exposed to sublethal doses of the insecticides. This study was conducted to assess the impact of sublethal doses of mosquito coil on the development of insecticide resistance in Aedes aegypti, a major vector for dengue fever and several other arboviral diseases. A laboratory colony of Ae. aegypti was exposed to sublethal doses of a meperfluthrin-based mosquito coil in a Peet-Grady chamber once per generation for 16 generations. The susceptibility of the exposed colony to a diagnostic dose of the mosquito coil as well as to three other insecticides was determined. Three different kdr mutations and five enzyme activities were evaluated in both the exposed and control colonies. After 16 generations of sublethal exposure to mosquito coils, the full diagnostic dose of the coil caused 68% mortality to the exposed colony compared to 100% mortality in the control colony. Mortality caused by deltamethrin (0.05%) was also significantly lower in the exposed colony. The frequency of 1016I kdr mutation as well as MFO and alpha esterase activities were higher in the exposed colony compared to the control colony. This study provides evidence of the development of pyrethroid resistance in an Ae. aegypti population due to sublethal exposure to mosquito coil for 16 generations. Given the large-scale use of mosquito coils in many African households, its role as a pyrethroid resistance selection source should be taken into consideration when designing resistance management strategies.

Can Bees Detect Perfluorooctane Sulfonate (PFOS)?

AbstractThe European honey bee (Apis mellifera) is an important crop pollinator threatened by multiple stressors, including exposure to contaminants. Perfluorooctane sulfonate (PFOS) is a persistent global contaminant that accumulates and biomagnifies in food chains and is detected in honey. Even sublethal exposure to PFOS is detrimental to bee health, but exposure routes are unclear and nothing is known about bee response (detection, avoidance, or attraction) to PFOS. Using Y‐mazes, we studied the response of individual bees to PFOS‐spiked sugar syrup at four concentrations, 0.02, 30, 61 and 103 µg L−1. Bee activity, choice behavior, and drink duration for unspiked and spiked sugar syrup was recorded for 10 min in the Y‐maze system. Most bees (≥80%) tasted and then drank the sugar syrup solutions, including the PFOS‐contaminated syrup. Only at 61 and 103 µg L−1 did bees significantly avoid drinking PFOS‐spiked syrup, and only when given a choice with unspiked syrup. When the choice of consuming unspiked syrup was removed, the bees drank PFOS‐spiked syrup at all the PFOS concentrations tested, and avoidance was not evident. Avoidance was not observed in any treatment at 0.02 or 30 µg L−1 PFOS, concentrations that are frequently reported in environmental waters in contaminated areas. These findings confirm that bees will access PFOS‐contaminated resources at concentrations detrimental to the colony health, and provide evidence of potential exposure pathways that may threaten crop pollination services and also human health via food chain transfer in PFOS‐contaminated areas. Environ Toxicol Chem 2024;00:1–10. © 2024 SETAC

De novo transcriptome analysis of Protohermes xanthodes Navás (Megaloptera: Corydalidae) reveling the effects of sublethal chlorpyrifos on the expression of cholinergic neuronal genes

The insect cholinergic neuron system is the target for various pesticides, including organophosphate, carbamate and neonicotinoid pesticides. In this study, we conducted a de novo transcriptome analysis on the aquatic insect Protohermes xanthodes and identified for the first time presenting sixteen genes encoding cholinergic neuronal proteins (PxanChaT, PxanVAChT, PxanmAChR, PxannAChRs, and PxanAChEs), which are candidates for acetylcholine synthesis, transport, reception and degradation in cholinergic synapse. FPKM analysis revealed that these genes are primarily expressed in head and nerve cord of P. xanthodes larvae, and some of them are also abundant in hindgut, malpighian tubules and tracheae. After exposed to different concentrations of sublethal chlorpyrifos (CPF), expression of these cholinergic neuronal genes are generally increased and then decreased with the increase of CPF concentration, except PxannAChRα9 which is increased in both 4.2 and 8.4 μg/L CPF groups. Short-term (96 h) CPF exposure resulted in significant up-regulation of PxanAChE1 expression in P. xanthodes larvae exposed to 0.42 and 4.2 μg/L CPF concentrations, while PxanAChE2 was up-regulated only in 0.42 μg/L CPF group. After long-term (14 d) CPF exposure, PxanAChE1 expression was down-regulated in 0.168 and 0.42 μg/L CPF groups. PxanAChE2 expression was dramatically decreased in all CPF groups. Moreover, acetylcholinesterase (AChE) activity was significantly decreased across all long-term CPF exposure groups. These results suggested that sublethal exposure to CPF can disrupt the expression of cholinergic neuronal genes in P. xanthodes larvae, and implied that long-term sublethal CPF exposure may cause toxic effects on P. xanthodes larvae by inhibiting AChE activity. Furthermore, identification of cholinergic neuronal genes in P. xanthodes provided candidate molecular markers for study the toxic effects of environmental pollutants on the neuron system of an aquatic predatory insect with ecological importance.

Recuperative Effects of Cinnamon (Cinnamomum zeylanicum) in Catla catla After Sub-Lethal Exposure to Lead.

This research was conducted to validate the beneficial effects of incorporating dietary cinnamon (Cinnamomum zeylanicum) powder (CzP) in alleviating lead (Pb) poisoning in fish. Healthy Catla catla individuals (16.36 ± 0.19g/fish) were distributed across 18 tanks in triplicate groups. The experimental groups were as follows: Control group: fish without supplementation or exposure to Pb; positive control group: fish without supplementation but exposed to 1mg/L Pb; 5g/kg CzP along with 1mg/L Pb exposure; 10g/kg CzP along with 1mg/L Pb exposure; 15g/kg CzP along with 1mg/L Pb exposure; and 20g/kg CzP along with 1mg/L Pb exposure. The trial continued for a period of 60days. Waterborne Pb had a deleterious effect on fish growth performance, body composition, blood profile, and digestive enzyme activity, along with elevated Pb accumulation in various tissues. Conversely, consumption of cinnamon effectively mitigated the toxic potential of Pb and enhanced fish longevity. Notably, 10g/kg CzP boosted growth, improved carcass quality, reversed blood indices, restored enzyme function in the gut, and mitigated Pb accumulation in tissues. In summary, the findings revealed that incorporating 10g/kg of CzP as a dietary supplement in C. catla aquaculture could effectively counteract heavy metal toxicity.

Effects of common co-occurring pesticides (a neonicotinoid and fungicide) on honey bee colony health in a semi-field study

Multiple stressors are linked to declines of insects and important pollinators, such as bees. Recently, interactive effects of multiple agrochemicals on bees have been highlighted, including fungicides, which increase toxicity of neonicotinoid insecticides. Here, we use a semi-field study across two seasons in controlled foraging tunnels to test the effects of a field application of a commercial fungicide product with two active ingredients (pyraclostrobin and metconazole) applied at label rates. We also examine its interactive effects with the neonicotinoid insecticide clothianidin, at a conservative field-realistic dose of 2.23 ppb, on 48 honey bee colonies. We found combined effects of pesticide exposure, including additive 2.93-fold increases in mortality, and an additional effect of increased infestation levels of the ectoparasitic mite, Varroa destructor. Pesticide treatments also reduced colony activity, reduced colony weight, and increased sugar consumption of whole colonies. These findings indicate that typical sublethal exposure levels to common, co-occurring agrochemicals in the field significantly affect the health of whole honey bee colonies, highlighting an unintended consequence of increasing pesticide applications.

Lethal and sublethal heat-exposure of bed bugs (Cimex lectularius L.) causes alarm pheromone emission and elicits a movement response in nearby recipients

Many gregarious insect species use aggregation and alarm pheromones. The bed bug, Cimex lectularius L., emits an alarm pheromone (AP), a 70/30 blend of (E)-2-hexenal and (E)-2-octenal, when threatened. Bed bugs avoid temperatures above 43 °C, which are lethal to bugs and used commercially as spatial heat treatments to manage infestations. However, the interaction of bed bug AP in heat avoidance has not been investigated. The goal of this research was to: 1) determine if bed bugs emit AP as an alarm response to heat exposure, and 2) quantify the behavioral responses of conspecifics to AP emitted by heat-exposed bed bugs. Using a selected ion flow tube mass spectrometer, we found that bed bugs responded to lethal and sublethal heat exposure by emitting AP. The Harlan laboratory population emitted more pheromone than a laboratory adapted field population from Florida (McCall). Harlan females emitted the most AP, followed by Harlan males, McCall females and males. In separate behavioral experiments, we showed that conspecifics (i.e., recipients) reacted to AP released by heat exposed bed bugs (i.e., emitters) by frantically moving within 50 mm and 100 mm test arenas. The Harlan recipients reacted to AP in 100 mm areas, whereas the McCall strain did not, indicating a short area of effectiveness of the AP. Synthetic AP components tested in behavioral experiments caused identical effects as the natural AP blend released by heat-exposed bed bugs.

Chronic sub-lethal exposure to clothianidin triggers organismal and sub-organismal-level health hazards in a non-target organism, Drosophila melanogaster

Neonicotinoids are extensively used systemic pesticides across the globe. These chemicals have gathered significant attention for their potential adverse impacts on non-target organisms. Clothianidin is a novel neonicotinoid pesticide, widely used to control sucking and chewing types of pests. In nature, various non-target organisms can be exposed to this chemical. Nonetheless, extensive investigations demonstrating the sub-lethal impacts of clothianidin on non-targets are limited. Hence, the present study aimed to unravel the chronic sub-lethal impacts (LC50 0.74 μg/mL) of clothianidin on a non-target organism, Drosophila melanogaster. The study parameters involved multiple tiers of life covering from organism level to the sub-cellular level. 1st instar larvae were exposed to the six sub-lethal concentrations viz. 0.05, 0.06, 0.07, 0.08, 0.09, and 0.1 μg/mL of clothianidin till their 3rd larval instar. Investigations involving organism level have revealed clothianidin-induced significant reduction in the developmental duration, life span, phototaxis, and physical activities of the treated individuals. Interestingly, the tested compound has also altered the compound eye morphology of treated flies. Study was extended to the tissue and cellular levels where reduced cell viability in gut, brain, and fat body was apparent. Additionally, increased ROS production, nuclear disorganization, and higher lipid deposition were evident in gut of treated larvae. Study was further extended to the sub-cellular level where chronic exposure to clothianidin up-regulated the major oxidative stress markers such as lipid peroxidation, protein carbonylation, HSP-70, SOD, catalase, GSH, and thioredoxin reductase. Furthermore, the activities of detoxifying enzymes such as CYP4501A1 and GST were also altered. Chronic exposure to clothianidin also favored DNA fragmentation in treated larvae. In essence, results of this multi-level study depict the ROS-mediated toxicity of clothianidin on a non-target organism, D. melanogaster.

Sublethal effect and detoxifying metabolism of metaflumizone and indoxacarb on the fall armyworm, Spodoptera frugiperda

The fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith) (Lepidoptera, Noctuidae), is a highly polyphagous invasive pest that damages various crops. Pesticide control is the most common and effective strategy to control FAW. In this study, we evaluated the toxicity of metaflumizone and indoxacarb against third-instar FAW larvae using the insecticide-incorporated artificial diet method under laboratory conditions. Both metaflumizone and indoxacarb exhibited substantial toxicity against FAW, with LC50 values of 2.43 and 14.66 mg/L at 72 h, respectively. The sublethal effects of metaflumizone and indoxacarb on parental and F1 generation FAW were investigated by exposing third-instar larvae to LC10 and LC30 concentrations of these insecticides. Sublethal exposure to these two insecticides significantly shortened adult longevity, extended pupal developmental times and led to reduced pupal weight, pupation rates, and adult fecundity in the treated parental generation and F1 generation at LC10 or LC30 concentrations, in comparison to the control group. The larval developmental times were shortened in the parental generation but prolonged in the F1 generation, after being treated with sublethal concentrations of metaflumizone. Furthermore, larvae exposed to LC10 or LC30 concentrations of indoxacarb exhibited elevated activity levels of cytochrome P450 monooxygenase and glutathione S-transferase, which coincides with the observed synergistic effect of piperonyl butoxide and diethyl maleate. In conclusion, the high toxicity and negative impact of metaflumizone and indoxacarb on FAW provided significant implications for the rational utilization of insecticides against this pest.

Dynamic alterations in physiological and biochemical indicators of Cirrhinus mrigala hatchlings: A sublethal exposure of triclosan

Triclosan (TCS), a biocide used in various day-to-day products, has been associated with several toxic effects in aquatic organisms. In the present study, biochemical and hematological alterations were evaluated after 14 d (sublethal) exposure of tap water (control), acetone (solvent control), 5, 10, 20, and 50 μg/L (environmentally relevant concentrations) TCS to the embryos/hatchlings of Cirrhinus mrigala, a major freshwater carp distributed in tropic and sub-tropical areas of Asia. A concentration-dependent increase in the content of urea and protein carbonyl, while a decrease in the total protein, glucose, cholesterol, triglycerides, uric acid, and bilirubin was observed after the exposure. Hematological analysis revealed a decrease in the total erythrocyte count, hemoglobin, and partial pressure of oxygen, while there was an increase in the total leucocyte count, carbon dioxide, and partial pressure of carbon dioxide and serum electrolytes. Comet assay demonstrates a concentration-dependent increase in tail length, tail moment, olive tail moment, and percent tail DNA. An amino acid analyzer showed a TCS-dose-dependent increase in various amino acids. Sodium dodecyl sulphate polyacrylamide gel electrophoresis analysis revealed different proteins ranging from 6.5 to 200 kDa, demonstrating TCS-induced upregulation. Fourier transform infrared spectra analysis exhibited a decline in peak area percents with an increase in the concentration of TCS in water. Curve fitting of amide I (1,700–1600 cm−1) showed a decline in α-helix and turns and an increase in β-sheets. Nuclear magnetic resonance study also revealed concentration-dependent alterations in the metabolites after 14 d exposure. TCS caused alterations in the biomolecules and heamatological parameters of fish, raising the possibility that small amounts of TCS may change the species richness in natural aquatic habitats. In addition, consuming TCS-contaminated fish may have detrimental effects on human health. Consequently, there is a need for the proper utilisation and disposal of this hazardous compound in legitimate quantities.

Small RNA-modulated anaerobic respiration allows bacteria to survive under antibiotic stress conditions.

Despite extensive knowledge of antibiotic-targeted bacterial cell death, deeper understanding of antibiotic tolerance mechanisms is necessary to combat multi-drug resistance in the global healthcare settings. Regulatory RNAs in bacteria control important cellular processes such as cell division, cellular respiration, metabolism, and virulence. Here, we investigated how exposing Escherichia coli to the moderately effective first-generation antibiotic cephalothin alters transcriptional and post-transcriptional dynamics. Bacteria switched from active aerobic respiration to anaerobic adaptation via an FnrS and Tp2 small RNA-mediated post-transcriptional regulatory circuit. From the early hours of antibiotic exposure, FnrS was involved in regulating reactive oxygen species levels, and delayed oxygen consumption in bacteria. We demonstrated that bacteria strive to maintain cellular homeostasis via sRNA-mediated sudden respiratory changes upon sublethal antibiotic exposure.

Toxic Impact of Sheathmar on Oreochromis mossambicus: A Comprehensive Biomarker Analysis.

This study assessed the toxicity of the Sheathmar pesticide on Oreochromis mossambicus. The 96-h median lethal concentration (LC50) was determined using probit analysis, with survivability assessed using general threshold survival models (GUTS). Over 45days, fish exposed to sublethal Sheathmar doses were studied for changes in growth, blood profiles, and liver enzymes. According to the findings, the LC50 values of Sheathmar for Oreochromis mossambicus at different time intervals were determined as follows: 3016.64µg/l at 24h, 2723.13µg/l at 48h, 2415.45µg/l at 72h, and 2154.87µg/l at 96h. The GUTS-SD model effectively predicted fish survivability after Sheathmar exposure. Sublethal exposure led to significant alterations in growth and hematological, biochemical, and stress enzyme parameters in Oreochromis mossambicus. Moreover, the correlation matrix, integrated biomarker response (IBR), and biomarker response index (BRI) highlighted significant impacts on multiple biomarkers in Oreochromis mossambicus. Thus, the results underscore the harmful effects of Sheathmar on Oreochromis mossambicus, indicating a need for further study and mitigation.

Mating behavior and responses to sublethal concentrations of imidacloprid in the predator Cyrtorhinus lividipennis.

Mating is an essential factor that governs the size of insect populations that reproduce sexually. The extensive application of insecticides has both lethal and sublethal effects on the physiology and mating behavior of insect natural enemies. The predatory bug Cyrtorhinus lividipennis is a natural enemy of planthopper and leafhopper populations in the rice ecosystem. Unfortunately, the effects of insecticides on the mating behavior of C. lividipennis are not well-understood. The mating behavior of C. livdipennis consisted of mounting, antennal touch and mating attempts, genital insertion, adjustment of posture, and separation of the mating pair. Approximately 82.5% of the C. lividipennis mating pairs displayed their first mating at 12-36 h postemergence. Mating activity occurred throughout a 24-h period, with peak activity at 12:00-14:00 h, and the mean duration of mating was 48.75 min. Sublethal exposure to imidacloprid increased mating latency. Compared with the controls, the duration of courtship, pre-mating and adjusting posture for males treated with imidacloprid were prolonged. The duration of mating for females treated with imidacloprid was prolonged relative to untreated controls. The fecundity and daily spawning capacity of females treated with imidacloprid were higher than the untreated controls. Our results provide insight into the mating process of C. lividipennis. Imidacloprid prolonged the duration of mating, which may explain the enhanced reproductive output in C. lividipennis females treated with imidacloprid. These findings will be useful in both rearing C. lividipennis and deploying this natural enemy in rice fields. © 2024 Society of Chemical Industry.

Sublethal acetamiprid exposure induces immunity, suppresses pathways linked to juvenile hormone synthesis in queens and affects cycle-related signaling in emerging bees

Acetamiprid is the only neonicotinoid registered in the European Union because the risks of neonicotinoids to honey bees and other pollinators are strictly regulated. Herein, we orally exposed honey bee colonies to sublethal concentrations of acetamiprid (20 μg/L) under isolated conditions. After one month of continuous exposure, the emerging bees and queens were collected and analyzed via high-throughput label-free quantitative proteomics using a data-independent acquisition strategy. Six and 34 significantly differentially expressed proteins (DEPs) were identified in the emerging bees and queens, respectively. Mrjp3 was the only DEP found in both sample types/castes, and its opposite regulation illustrated a differential response. The DEPs in the emerging bees (H/ACA RNP, Rap1GAP, Mrjp3, and JHE) suggested that sublethal exposure to acetamiprid affected cell cycle-related signaling, which may affect the life history of workers in the colony. The DEPs with increased levels in queens, such as Mrjps 1–4 and 6–7, hymenoptaecin, and apidaecin 22, indicated an activated immune response. Additionally, the level of farnesyl pyrophosphate synthase (FPPS), which is essential for the mevalonate pathway and juvenile hormone biosynthesis, was significantly decreased in queens. The impaired utilization of juvenile hormone in queens supported the identification of additional DEPs. Furthermore, the proteome changes suggested the existence of increased neonicotinoid detoxification by UDP-glucuronosyltransferase and increased amino acid metabolism. The results suggest that the continuous exposure of bee colonies to acetamiprid at low doses (nanograms per gram in feed) may pose a threat to the colonies. The different exposure routes and durations for the emerging bees and queens in our experiment must be considered, i.e., the emerging bees were exposed as larvae via feeding royal jelly and beebread provided by workers (nurse bees), whereas the queens were fed royal jelly throughout the experiment. The biological consequences of the proteomic changes resulting from sublethal/chronic exposure require future determination.

Study on the Impact of Brick-kiln Effluent on Histomorphology of Gill and Hepatopancreas of Channa punctata Bloch. with Reference to Mobilization of Thyroid Hormones

This study deals with the effect of sublethal exposure of brick kiln effluent on lipid and protein peroxides, Aspartate Transferase (AST), Alanine Transferase (ALT) and Alkaline Phosphatase (ALP) activities and mobilization of thyroid-stimulating and thyroid hormones in gill and hepatopancreas of Channa punctata Bloch., with supporting histochemical investigations in these tissues. Acclimatized adult fishes of either sexes of three groups were reared separately in three aquaria. Aquarium-I comprised the normal control group, and the other two aquariums, i.e. Aquarium-II and Aquarium-III, comprised experimental groups of fishes exposed to 20ppm/L and 30ppm/L of brick kiln effluents, respectively. Before these, the LC50 value of the Fish for brick kiln effluent was evaluated as 55±0.50 ppm/L for 28 days. Increased lipid and protein peroxides, decreased transaminase activities with hypothyroidic conditions were observed both in gills and hepatopancreas on treatment. Significant alternations of these biochemical parameters were recorded, with some drastic changes in the histo-architecture regarding treatment issues. Gills showed hypertrophy with fusion and curving of gill lamellae. Spiked secondary gill lamellae were also observed to have several degenerative features. Decreasing hepatocytes and vacuolation at several places were recorded in hepatopancreas with necrosis of the tissues and patchy degeneration.

Mitochondrial DNA Damage in Earthworms: A Hazard Associated with Sublethal Systemic Pesticide Exposures

Mitochondrial DNA Damage in Earthworms: A Hazard Associated with Sublethal Systemic Pesticide Exposures

Effects of sublethal fipronil exposure on cross-generational functional responses and gene expression in Binodoxys communis.

The effective systemic insecticide fipronil is widely used on a variety of crops and in public spaces to control insect pests. Binodoxys communis (Gahan) (Hymenoptera: Braconidae) is the dominant natural enemy of Aphis gossypii Glover (Homoptera: Aphididae), an important cotton pest, and has good efficiency in inhibiting aphid populations. The direct effects of environmental residues of sublethal fipronil doses on adult B. communis have not previously been reported. This study therefore aimed to evaluate the side effects and transcriptomic impacts of sublethal fipronil doses on B. communis. The results showed that exposure to the LC10 dose of fipronil significantly reduced the survival rate and parasitism rate of the F0 generation, but did not affect these indicators in the F1 generation. The LC25 dose did not affect the survival or parasitic rates of the F0 generation, but did significantly reduce the survival rate of F1 generation parasitoids. These results indicated that sublethal doses of fipronil affected B. communis population growth. Transcriptome analysis showed that differentially expressed genes (DEGs) in B. communis at 1h after treatment were primarily enriched in pathways associated with fatty acid elongation, biosynthesis of fatty acids, and fatty acid metabolism. DEGs at 3days after treatment were mainly enriched in ribosomal functions, glycolysis/gluconeogenesis, and tyrosine metabolism. Six DEGs (PY, ELOVL, VLCOAR, MRJP1, ELOVL AAEL008004-like, and RPL13) were selected for validation with real-time fluorescent quantitative PCR. This is the first report of sublethal, trans-generational, and transcriptomic side effects of fipronil on the dominant parasitoid of A. gossypii. The results of this study show that adaptation of parasitoids to high concentrations of pesticides may be at the expense of their offspring. These findings broaden our overall understanding of the intergenerational adjustments used by insects to respond to pesticide stress and call for risk assessments of the long-term impacts and intergenerational effects of other pesticides.

Forskolin rescues hypoxia-induced cognitive dysfunction in zebrafish with potential involvement of O-GlcNAc cycling regulation

Repeated sublethal hypoxia exposure induces brain inflammation and affects the initiation and progression of cognitive dysfunction. Experiments from the current study showed that hypoxic exposure downregulates PKA/CREB signaling, which is restored by forskolin (FSK), an adenylate cyclase activator, in both Neuro2a (N2a) cells and zebrafish brain. FSK significantly protected N2a cells from hypoxia-induced cell death and neurite shrinkage. Intraperitoneal administration of FSK for 5 days on zebrafish additionally led to significant recovery from hypoxia-induced social interaction impairment and learning and memory (L/M) deficit. FSK suppressed hypoxia-induced neuroinflammation, as indicated by the observed decrease in NF-κB activation and GFAP expression. We further investigated the potential effect of FSK on O-GlcNAcylation changes induced by hypoxia. Intriguingly FSK induced marked upregulation of the protein level of O-GlcNAc transferase catalyzing addition of the GlcNAc group to target proteins, accompanied by elevated O-GlcNAcylation of nucleocytoplasmic proteins. The hypoxia-induced O-GlcNAcylation decrease in the brain of zebrafish was considerably restored following FSK treatment. Based on the collective results, we propose that FSK rescues hypoxia-induced cognitive dysfunction, potentially through regulation of HBP/O-GlcNAc cycling.

Proteotranscriptomic analyses of the midgut and Malpighian tubules after a sublethal concentration of Cry1Ab exposure on Spodoptera litura.

Cry1Ab has emerged as a bio-insecticide to control Spodoptera litura (Lepidoptera: Noctuidae). However, the sublethal effects of Cry1Ab on the physiological changes and molecular level of S. litura have not been well documented. Our aims in this study were to assess the sublethal effect of Cry1Ab on S. litura, including midgut and Malpighian tubules as targets. After sublethal Cry1Ab exposure, distinct histological alterations were mainly observed in the midgut. Furthermore, the results of comparative RNA sequencing and tandem mass tag-based proteomics showed that, in the midgut, most differential expression genes (DEGs) were up-regulated and significantly enriched in the serine protease activity pathway, and up-regulated differential expression proteins (DEPs) were mainly associated with the oxidative phosphorylation pathway, whereas the down-regulated involved in the ribosome pathways. In the Malpighian tubules, DEGs and DEPs were significantly enriched in the ribosome pathway. We proposed that ribosome may act as a universal target in energy metabolism with other pathways via the results of protein-protein interaction analysis. Further, by verification of the mRNA expression of some Cry protein receptor and detoxification genes after Cry1Ab treatment, it was suggested that the ribosomal proteins (RPs) possibly participate in influencing the Bt-resistance of S. litura larvae under sublethal Cry1Ab exposure. Under sublethal Cry1Ab exposure, the midgut of S. litura was damaged, and the proteotranscriptomic analysis elucidated that Cry1Ab disrupted the energy homeostasis of larvae. Furthermore, we emphasized the potential role of ribosomes in sublethal Cry1Ab exposure. © 2024 Society of Chemical Industry.

Abstract C065: Base excision repair pathway regulates transcription-replication conflicts in pancreatic ductal adenocarcinoma

Abstract Oncogenic mutations (such as in KRAS) can dysregulate transcription and replication leading to transcription conflicts (TRCs). Unresolved TRCs can cause lethal DNA damage. Here, we sought to investigate the causal role of oncogenic mutations in regulating TRCs in pancreatic ductal adenocarcinoma (PDAC). Further, we characterize the adaptive pathways that mitigate TRCs for PDAC survival. Human PDAC demonstrated 30-120-fold higher levels of TRC genomic signature compared to breast, colon and lung cancer (p<0.001). Gene expression analysis demonstrated high levels of known TRC resolution factors in human tumors compared to normal tissues. TRCs as measured by RNAPII-PCNA proximity ligation assay were significantly enriched in human PDAC cells (Panc-1, BxPC3, MiaPaca2) compared to immortalized normal HPNE cells (p<0.001). Similarly transcriptomic complexes were enriched in nascent DNA immunoprecipitates from Panc1 cells but not HPNE cells. Ectopic expression of oncogenic KRAS(G12D) in human pancreatic ductal epithelial (HPNE) cells enhanced TRCs, and TRC-related DNA:RNA hybrids (R-loops). Inhibition of KRAS or downstream effectors abrogated TRCs in Panc1 and MiaPaca2 cells. An siRNA screen identified several factors in the base-excision repair (BER) pathway as regulators of TRCs. Sub-lethal exposure to hydrogen peroxide enhanced TRCs, whereas N-acetyl cysteine abrogated TRCs. These findings were validated by a pharmacologic approach using inhibitors of APE1 endonuclease in BER pathway (Methoxyamine and CRT). Mechanistic studies revealed that BER pathway inhibition severely altered RNA polymerase II dynamics at nascent DNA; causing RNAPII trapping and contributing to enhanced TRCs. The ensuing DNA damage activated Chk2-ATR pathway but not Chk1-ATM pathway. Co-treatment with ATR inhibitor (VX970, 10-80nM) and BER inhibitor (methoxyamine, 6-12mM) at clinically relevant doses, synergistically enhanced DNA damage and reduced clonogenic survival in PDAC cells. The study uncovers a novel role of BER pathway defects and oxidative DNA damage in promoting TRCs. Our studies provide mechanistic insights into the regulation of TRCs in PDAC which has implications for genome instability and therapy in PDAC. Citation Format: Fan Meng, Anup K. Singh, Tiane Li, Marc Attiyeh, Fatemeh Kohram, Terence Williams, Yilun Liu, Mustafa Raoof. Base excision repair pathway regulates transcription-replication conflicts in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C065.

Temperature effects on the hormetic response of Myzus persicae after sublethal exposure to insecticides

Studies on insecticide-induced stimulatory effects in pest insects have become of utmost importance due to their potential implications in pest management. Temperature influences the physiology and biology of ectothermic organisms like pest insects. It can also affect the toxicity and relative efficacy of insecticides that are used in agricultural fields. However, the impact of temperature on the insect stimulatory responses after exposure to mild insecticide-induced stresses has frequently been overlooked. Here, we investigated how different temperature levels (15; 20; 25; 28 °C) can modulate the toxicity of two synthetic insecticides chlorpyrifos (organophosphate) and deltamethrin pyrethroid); and subsequently how temperature impacts the survival and reproduction of the green peach aphid Myzus persicae exposed to sublethal concentrations of the two insecticides. Our findings indicated temperature-dependent effects of the two chemicals on mortality, longevity, and the number of nymphs produced by the aphids after lethal and sublethal exposures. In fact, besides the high toxicity induced by temperature at lower concentrations, the change’s magnitude and occurrence of stimulatory responses varied between temperatures and depended on the sublethal concentrations faced by the aphid females. Temperature increase from 15 to 28 °C increased chlorpyrifos and deltamethrin toxicity 4 and fivefold. Sublethal exposure of aphids extended the longevities for individuals treated with chlorpyrifos at 15 (all sublethal concentrations) and 25 °C (LC15 and LC20) and with deltamethrin at 20 (LC1) and 28 °C (LC20). Additionally, the total number of nymphs produced during the females' lifespan was increased after sublethal exposure to chlorpyrifos at 15 °C (LC1, LC5, and LC20) and at 20 °C (LC10) and to deltamethrin at 20 °C (LC1), 25 °C (LC5 and LC10) and 28 °C (LC1, LC5, and LC20). Our results reinforce the importance of a shift from studies focusing on the stimulatory effects of single stresses to studies investigating the effects of stressors’ combinations on insect hormetic response.