The mode of action of different organochlorine pesticides families in mammalians.

Organochlorine pesticides (OCPs) show differences in their chemical structure, mechanism of toxicity, and target organisms. However, OCPs also have some common characteristics such as high persistence in the environment, bioaccumulation, and toxicity which lead to health issues. Nowadays, the toxicity of OCPs is well known, but we still do not know all the specific molecular mechanisms leading to their toxicity in mammalians. Therefore, this review aims to collect data about the mode of action of various classes of OCPs, highlighting their differences and common behavioural reactions in the human and animal body. To discuss the OCPs molecular pathways and fate in different systems of the body, three organochlorine insecticides were selected (Dichlorodiphenyltrichloroethane, Hexachlorocyclohexane and Chlordecone), regarding to their widespread use, with consequent effects on the ecosystem and human health. Their common biological responses at the molecular scale and their different interactions in human and animal bodies were highlighted and presented.

Self-assembled mesoporous silica decorated with biogenic carbon dot nanospheres hybrid nanomaterial for efficient removal of aqueous Methoxy-DDT via a Short-Bed Adsorption column technique.

Methoxy-DDT is an organochlorine pesticide extensively used in agricultural practices as a DDT substitute. Methoxy-DDT has been found and quantified in several investigations in groundwater, drinking water, sediment, and various biota. Therefore, designing efficient and cost-effective adsorbents for removing methoxy-DDT is vital. In this work, we embedded Ficus benghalensis L. derived carbon dots (CDs) in mesoporous silica (MS) to fabricate MS-CDs nanohybrid material. MS-CDs nanohybrid exhibited remarkable selectivity and removal efficiency towards methoxy-DDT, outperforming other endocrine disruptors. Parameters for industrial-scale fixed-bed adsorption columns, such as bed capacity, length, and breakthrough times, were analyzed. The kinetic study revealed that pseudo-second-order (PSO) adsorption and isotherm analysis confirmed the Langmuir model as the best fit. Small bed adsorption (SBA) column analysis was carried out using spiked Yamuna river water, and the breakthrough curves were demonstrated by varying MS-CDs bed height. The maximum adsorption capacity obtained for methoxy-DDT was 17.16 mg/g at breakthrough and 49.98 mg/g at exhaustion. The adsorbent showed 86.53% removal efficiency in the 5th cycle, demonstrating good reusability. These results indicate that the developed material MS-CDs-based organic sphere is an effective adsorbent for aqueous methoxy-DDT adsorption and can be applied to wastewater treatment.

Screening, characterization and optimization of potential dichlorodiphenyl trichloroethane (DDT) degrading fungi.

Dichlorodiphenyltrichloroethane is an organo-chlorine insecticide used for malaria and agricultural pest control, but it is the most persistent pollutant, endangering both human and environmental health. The primary aim of the research is to screen, characterize, and assess putative fungi that degrade DDT for mycoremediation. Samples of soil and wastewater were gathered from Addis Ababa, Koka, and Ziway. Fungi were isolated and purified using potato dextrose media. Matrix-Assisted Laser Desorption, Ionization, and Flight Duration The technique of mass spectrometry was employed to identify fungi. It was found that the finally selected isolate, AS1, was Aspergillus niger. Based on growth factor optimization at DDT concentrations (0, 3500, and 7000 ppm), temperatures (25, 30, and 35 °C), and pH levels (4, 7, and 10), the potential DDT-tolerant fungal isolates were investigated. A Box-Behnken experimental design was used to analyze and optimize fungal biomass and sporulation. The highest biomass (0.981 ± 0.22 g) and spore count (5.60 ± 0.32 log/mL) of A. niger were found through optimization assessment, and this fungus was chosen as a potential DDT-degrader. For DDT degradation investigations by A. niger in DDT-amended liquid media, gas chromatograph-electron capture detector technology was employed. DDT and its main metabolites, DDE and DDD, were eliminated from both media to the tune of 96-99 % at initial DDT concentrations of 1750, 3500, 5250, and 7000 ppm. In conclusion, it is a promising candidate for detoxifying and/or removing DDT and its breakdown products from contaminated environments.

Organochlorine pesticides in Ethiopian waters: Implications for environmental and human health.

Despite the global ban on organochlorine pesticides (OCPs) since the 1970s, their use continues in many developing countries, including Ethiopia, primarily due to the lack of viable alternatives and weak regulations. Nonetheless, the extent of contamination and the resulting environmental and health consequences in these countries remain inadequately understood. To address these knowledge gaps, we conducted a comprehensive analysis of reported concentrations (n=398) of OCPs (n=30) in distinct yet interconnected water matrices: water, sediment, and biota in Ethiopia. Our analysis revealed a notable geographical bias, with higher concentrations found in sediments (0.074-1161.2 µg/kg), followed by biota (0.024-1003 µg/kg) and water (0.001-1.85 µg/L). Moreover, DDTs, endosulfan, and hexachlorohexenes (HCHs) were among the most frequently detected OCPs in higher concentrations in Ethiopian waters. The DDT metabolite p,p'-DDE was commonly observed across all three matrices, with concentrations in water birds reaching levels up to 57 and 143,286 times higher than those found in sediment and water, respectively. The findings showed a substantial potential for DDTs and endosulfan to accumulate and biomagnify in Ethiopian waters. Furthermore, it was revealed that the consumption of fish contaminated with DDTs posed both non-carcinogenic and carcinogenic risks while drinking water did not pose significant risks in this regard. Importantly, the issue of OCPs in Ethiopia assumes even greater significance as their concentrations were found to be eight times higher than those of currently used pesticides (CUPs) in Ethiopian waters. Consequently, given the ongoing concerns about OCPs in Ethiopia, there is a need for ongoing monitoring, implementation of sustainable mitigation measures, and strengthening of OCP management systems in the country, as well as in other developing countries with similar settings and practices.

Characterization of the ddt1 Mutant in Rice and Its Impact on Plant Height Reduction and Water Use Efficiency.

Rice (Oryza sativa L.), a fundamental global staple, nourishes over half of the world's population. The identification of the ddt1 mutant in rice through EMS mutagenesis of the indica cultivar Shuhui527 revealed a dwarf phenotype, characterized by reduced plant height, smaller grain size, and decreased grain weight. Detailed phenotypic analysis and map-based cloning pinpointed the mutation to a single-base transversion in the LOC_Os03g04680 gene, encoding a cytochrome P450 enzyme, which results in a premature termination of the protein. Functional complementation tests confirmed LOC_Os03g04680 as the DDT1 gene responsible for the observed phenotype. We further demonstrated that the ddt1 mutation leads to significant alterations in gibberellic acid (GA) metabolism and signal transduction, evidenced by the differential expression of key GA-related genes such as OsGA20OX2, OsGA20OX3, and SLR1. The mutant also displayed enhanced drought tolerance, as indicated by higher survival rates, reduced water loss, and rapid stomatal closure under drought conditions. This increased drought resistance was linked to the mutant's improved antioxidant capacity, with elevated activities of antioxidant enzymes and higher expression levels of related genes. Our findings suggest that DDT1 plays a crucial role in regulating both plant height and drought stress responses. The potential for using gene editing of DDT1 to mitigate the dwarf phenotype while retaining improved drought resistance offers promising avenues for rice improvement.

Prognostic and therapeutic insights into MIF, DDT, and CD74 in melanoma.

Macrophage Migration Inhibitory Factor (MIF) and its homolog D-dopachrome Tautomerase (DDT) have been implicated as drivers of tumor progression across a variety of cancers. Recent evidence suggests MIF as a therapeutic target in immune checkpoint inhibition (ICI) resistant melanomas, however clinical evidence of MIF and particularly of DDT remain limited. This retrospective study analyzed 97 patients treated at Yale for melanoma between 2002-2020. Bulk-RNA sequencing of patient tumor samples from the Skin Cancer SPORE Biorepository was used to evaluate for differential gene expression of MIF, DDT, CD74, and selected inflammatory markers, and gene expression was correlated with patient survival outcomes. Our findings revealed a strong correlation between MIF and DDT levels, with no statistically significant difference across common melanoma mutations and subtypes. Improved survival was associated with lower MIF and DDT levels and higher CD74:MIF and CD74:DDT levels. High CD74:DDT and CD74:MIF levels were also associated with enrichment of infiltrating inflammatory cell markers. These data suggest DDT as a novel target in immune therapy. Dual MIF and DDT blockade may provide synergistic responses in patients with melanoma, irrespective of common mutations, and may overcome ICI resistance. These markers may also provide prognostic value for further biomarker development.

The synthesis of 1,2,3-triazoles as binders of D-dopachrome tautomerase (D-DT) for the development of dual-targeting inhibitors.

Despite recent advances in the treatment of cancer, the issue of therapy resistance remains one of the most significant challenges in the field. In this context, signaling molecules, such as cytokines have emerged as promising targets for drug discovery. Examples of cytokines include macrophage migration inhibitory factor (MIF) and its closely related analogue D-dopachrome tautomerase (D-DT). In this study we aim to develop a new chemical class of D-DT binders and subsequently create a dual-targeted inhibitor that can potentially trigger D-DT degradation via the Proteolysis Targeting Chimera (PROTAC) technology. Here we describe the synthesis of a novel library of 1,2,3-triazoles targeting D-DT. The most potent derivative 19c (IC50 of 0.5 ± 0.04 µM with high selectivity toward D-DT) was attached to a cereblon (CRBN) ligand through aliphatic amides, which were synthesized by a remarkably convenient and effective solvent-free reaction. Enzyme inhibition experiments led to the discovery of the compound 10d, which exhibited moderate inhibitory potency (IC50 of 5.9 ± 0.7 µM), but unfortunately demonstrated no activity in D-DT degradation experiments. In conclusion, this study offers valuable insight into the SAR of D-DT inhibition, paving the way for the development of novel molecules as tools to study D-DT functions in tumor proliferation and, ultimately, new therapeutics for cancer treatment.

Development of simplified probabilistic models for predicting phytoextraction timeframes of soil contaminants: demonstration at the DDX-contaminated Kolleberga tree nursery in Sweden.

Phytoextraction, utilizing plants to remove soil contaminants, is a promising approach for environmental remediation but its application is often limited due to the long time requirements. This study aims to develop simplified and user-friendly probabilistic models to estimate the time required for phytoextraction of contaminants while considering uncertainties. More specifically we: i) developed probabilistic models for time estimation, ii) applied these models using site-specific data from a field experiment testing pumpkin (Cucurbita pepo ssp. pepo cv. Howden) for phytoextraction of DDT and its metabolites (ΣDDX), iii) compared timeframes derived from site-specific data with literature-derived estimates, and iv) investigated model sensitivity and uncertainties through various modelling scenarios. The models indicate that phytoextraction with pumpkin to reduce the initial total concentration of ΣDDX in the soil (10 mg/kg dw) to acceptable levels (1 mg/kg dw) at the test site is infeasible within a reasonable timeframe, with time estimates ranging from 48-123 years based on literature data or 3 570-9 120 years with site-specific data using the linear or first-order exponential model, respectively. Our results suggest that phytoextraction may only be feasible at lower initial ΣDDX concentrations (< 5 mg/kg dw) for soil polishing and that alternative phytomanagement strategies should be considered for this test site to manage the bioavailable fraction of DDX in the soil. The simplified modes presented can be useful tools in the communication with site owners and stakeholders about time approximations for planning phytoextraction interventions, thereby improving the decision basis for phytomanagement of contaminated sites.

Comprehensive investigation of the mutagenic potential of six pesticides classified by IARC as probably carcinogenic to humans.

Pesticides are significant environmental pollutants, and many of them possess mutagenic potential, which is closely linked to carcinogenesis. Here we tested the mutagenicity of all six pesticides classified probably carcinogenic (Group 2A) by the International Agency of Research on Cancer: 4,4'-DDT, captafol, dieldrin, diazinon, glyphosate and malathion. Whole genome sequencing of TK6 human lymphoblastoid cell clones following 30-day exposure at subtoxic concentrations revealed a clear mutagenic effect of treatment with captafol or malathion when added at 200 nM or 100 µM initial concentrations, respectively. Each pesticide induced a specific base substitution mutational signature: captafol increased C to A mutations primarily, while malathion induced mostly C to T mutations. 4,4'-DDT, dieldrin, diazinon and glyphosate were not mutagenic. Whereas captafol induced chromosomal instability, H2A.X phosphorylation and cell cycle arrest in G2/M phase, all indicating DNA damage, malathion did not induce DNA damage markers or cell cycle alterations despite its mutagenic effect. Hypersensitivity of REV1 and XPA mutant DT40 chicken cell lines suggests that captafol induces DNA adducts that are bypassed by translesion DNA synthesis and are targets for nucleotide excision repair. The experimentally identified mutational signatures of captafol and malathion could shed light on the mechanism of action of these compounds. The signatures are potentially suitable for detecting past exposure in tumour samples, but the reanalysis of large cancer genome databases did not reveal any evidence of captafol or malathion exposure.

Waste barrel contamination and macrobenthic communities in the San Pedro Basin DDT dumpsite.

Industrial waste barrels were discarded from 1947 to 1961 at a DDT dumpsite in the San Pedro Basin (SPB) in southern California, USA at ~890 m. The barrels were studied for effects on sediment concentrations of DDX, PCBs, PAHs and sediment properties, and on benthic macrofaunal assemblages, including metazoan meiofaunal taxa >0.3 mm. DDX concentration was highest in the 2-6 cm fraction of the 10-cm deep cores studied but exhibited no correlation with macrofaunal density, composition or diversity. Macrofaunal diversity was lowest and distinct in sediments within discolored halos surrounding the barrels. Low macrobenthos density and diversity, high dominance by Entoprocta, and numerical prevalence of large nematodes may result from the very low oxygen concentrations in bottom waters (< 4.4 µM). There is potential for macrofauna to remobilize DDX into the water column and ultimately the food web in the SPB.

Normative values for tests of central auditory processing disorder in children aged from 6 to 12 years old.

INTRODUCTION: Central auditory processing disorders (CAPD) can significantly affect the daily functioning of a child, and the first step in determining whether rehabilitation procedures are required is a proper diagnosis. Different guidelines for making diagnoses have been published in the literature, and in various centers normative values for psychoacoustic tests of CAPD have been used internally. The material presented in this paper is based on more than 1000 children and is the largest collection so far published. The aim of this study is to present normative values for tests assessing CAPD in children aged 6 to 12 years, divided by age at last birthday. METHOD: We tested 1037 children aged 6 to 12 years who were attending primary schools and kindergartens. The criteria for inclusion were a normal audiogram, intellectually normal, no developmental problems, and no difficulties in auditory processing. To evaluate auditory processing all children were given three tests on the Senses Examination Platform: the Frequency Pattern Test (FPT), Duration Pattern Test (DPT), and Dichotic Digit Test (DDT). RESULTS: The results from 1,037 children allowed us to determine normative values for FPT, DPT, and DDT in seven different age groups (6 through to 12 years). We developed a newapproach, based on quantile-based norms, to determine normative values in each group. Three categories - average, below-average, and above-average - allow for a broader but more realistic interpretation than those used previously. We compare our results with published standards. CONCLUSIONS: Our study is the largest normative database published to date for CAPD testing, setting a standard for each child by age in years. We used the Senses Examination Platform, a universal tool, to unify standards for the classification of CAPD. Our study can serve as a basis for the development of a Polish model for the diagnosis of CAPD.

Metabolic Resistance and Not Voltage-Gated Sodium Channel Gene Mutation Is Associated with Pyrethroid Resistance of Aedes albopictus (Skuse, 1894) from Cambodia.

(1) Background: In Cambodia, Aedes albopictus is an important vector of the dengue virus. Vector control using insecticides is a major strategy implemented in managing mosquito-borne diseases. Resistance, however, threatens to undermine the use of insecticides. In this study, we present the levels of insecticide resistance of Ae. albopictus in Cambodia and the mechanisms involved. (2) Methods: Two Ae. albopictus populations were collected from the capital, Phnom Penh city, and from rural Pailin province. Adults were tested with diagnostic doses of malathion (0.8%), deltamethrin (0.03%), permethrin (0.25%), and DDT (4%) using WHO tube assays. Synergist assays using piperonyl butoxide (PBO) were implemented before the pyrethroid assays to detect the potential involvement of metabolic resistance mechanisms. Adult female mosquitoes collected from Phnom Penh and Pailin were tested for voltage-gated sodium channel (VGSC) kdr (knockdown resistance) mutations commonly found in Aedes sp.-resistant populations throughout Asia (S989P, V1016G, and F1534C), as well as for other mutations (V410L, L982W, A1007G, I1011M, T1520I, and D1763Y). (3) Results: The two populations showed resistance against all the insecticides tested (<90% mortality). The use of PBO (an inhibitor of P450s) strongly restored the efficacy of deltamethrin and permethrin against the two resistant populations. Sequences of regions of the vgsc gene showed a lack of kdr mutations known to be associated with pyrethroid resistance. However, four novel non-synonymous mutations (L412P/S, C983S, Q1554STOP, and R1718L) and twenty-nine synonymous mutations were detected. It remains to be determined whether these mutations contribute to pyrethroid resistance. (4) Conclusions: Pyrethroid resistance is occurring in two Ae. albopictus populations originating from urban and rural areas of Cambodia. The resistance is likely due to metabolic resistance specifically involving P450s monooxygenases. The levels of resistance against different insecticide classes are a cause for concern in Cambodia. Alternative tools and insecticides for controlling dengue vectors should be used to minimize disease prevalence in the country.

Macrophage Migration Inhibitory Factor (MIF) and D-Dopachrome Tautomerase (DDT): Pathways to Tumorigenesis and Therapeutic Opportunities.

Discovered as inflammatory cytokines, MIF and DDT exhibit widespread expression and have emerged as critical mediators in the response to infection, inflammation, and more recently, in cancer. In this comprehensive review, we provide details on their structures, binding partners, regulatory mechanisms, and roles in cancer. We also elaborate on their significant impact in driving tumorigenesis across various cancer types, supported by extensive in vitro, in vivo, bioinformatic, and clinical studies. To date, only a limited number of clinical trials have explored MIF as a therapeutic target in cancer patients, and DDT has not been evaluated. The ongoing pursuit of optimal strategies for targeting MIF and DDT highlights their potential as promising antitumor candidates. Dual inhibition of MIF and DDT may allow for the most effective suppression of canonical and non-canonical signaling pathways, warranting further investigations and clinical exploration.

Effects of DDT and DDE on placental cholinergic receptors.

The placental cholinergic system; known as an important factor in intracellular metabolic activities, regulation of placental vascular tone, placental development, and neurotransmission; can be affected by persistent organic pesticides, particularly organochlorine pesticides(OCPs), which can influence various epigenetic regulations and molecular pathways. Although OCPs are legally prohibited, trace amounts of the persistent dichlorodiphenyltrichloroethane(DDT) are still found in the environment, making prenatal exposure inevitable. In this study, the effects of 2,4'-DDT and 4,4'-DDT; and its breakdown product 4,4'-DDE in the environment on placental cholinergic system were evaluated with regards to cholinergic genes. 40 human placentas were screened, where 42,50% (17 samples) were found to be positive for the tested compounds. Average concentrations were 10.44 µg/kg; 15.07 µg/kg and 189,42 µg/kg for 4,4'-DDE; 2,4'-DDT and 4,4'-DDT respectively. RNA-Seq results revealed 2396 differentially expressed genes in positive samples; while an increase in CHRM1,CHRNA1,CHRNG and CHRNA2 genes at 1.28, 1.49, 1.59 and 0.4 fold change were found(p<0028). The increase for CHRM1 was also confirmed in tissue samples with immunohistochemistry. In vitro assays using HTR8/SVneo cells; revealed an increase in mRNA expression of CHRM1, CHRM3 and CHRN1 in DDT and DDE treated groups; which was also confirmed through western blot assays. An increase in the expression of CHRM1,CHRNA1, CHRNG(p<0001) and CHRNA2(p<0,05) were found from the OCPs exposed and non exposed groups.The present study reveals that intrauterine exposure to DDT affects the placental cholinergic system mainly through increased expression of muscarinic receptors. This increase in receptor expression is expected to enhance the sensitivity of the placental cholinergic system to acetylcholine.

Reproductive toxicity of DDT in the Japanese medaka fish model: Revisiting the impacts of DDT+ on female reproductive health.

The organochlorine pesticide dichlorodiphenyltrichloroethane (DDT) is an endocrine-disrupting compound (EDC) that has been banned by most countries for decades. However, it continues to be detected in nearly all humans and wildlife due to its biological and environmental persistence. The ovarian dysgenesis syndrome hypothesis speculates that exposure to EDCs during sensitive developmental windows such as early gonadal differentiation lead to reproductive disorders later in life. Yet, mechanisms by which DDT affects developing gonads remain unclear due to the inherent challenge of getting developmental exposure data from adults presenting with reproductive disease. The Japanese medaka (Oryzias latipes) is a valuable fish model for sex-specific toxicological studies due to its chromosomal sex determination, external embryonic development, short generation time, and extensively mapped genome. It is well documented that medaka exposed to DDT and its metabolites and byproducts (herein referred to as DDT+) at different developmental time points experience permanent alterations in gonadal morphology, reproductive success, and molecular and hormonal signaling. However, the overwhelming majority of studies focus primarily on functional and morphological outcomes in males and females and have rarely investigated long-term transcriptional or molecular effects. This review summarizes previous experimental findings and the state of our knowledge concerning toxic effects DDT + on reproductive development, fertility, and health in the valuable medaka model. It also identifies gaps in knowledge, emphasizing a need for more focus on molecular mechanisms of ovarian endocrine disruption using enhanced molecular tools that have become increasingly available over the past few decades. Furthermore, DDT forms a myriad of over 45 metabolites and transformation products in biota and the environment, very few of which have been evaluated for environmental abundance or health effects. This reinforces the demand for high throughput and economical in vivo models for predictive toxicology screening, and the Japanese medaka is uniquely positioned to meet this need.

DDT contamination in water resources of some African countries and its impact on water quality and human health.

Dichlorodiphenyltrichloroethane (DDT) usage has been prohibited in developed nations since 1972 but is exempted for use in indoor residual spraying (IRS) in developing countries, including African countries, for malaria control. There have been no previous reviews on DDT residues in water resources in Africa. The study aimed to provide a review of available research investigating the levels of DDT residues in water sources in Africa and to assess the consequent human health risks. A scoping review of published studies in Africa was conducted through a systematic electronic search using PubMed, Web of Science, EBSCO HOST, and Scopus. A total of 24 articles were eligible and reviewed. Concentrations of DDT ranged from non-detectable levels to 81.2 µg/L. In 35% of the studies, DDT concentrations surpassed the World Health Organization (WHO) drinking water guideline of 1 µg/L in the sampled water sources. The highest DDT concentrations were found in South Africa (81.2 µg/L) and Egypt (5.62 µg/L). DDT residues were detected throughout the year in African water systems, but levels were found to be higher during the wet season. Moreover, water from taps, rivers, reservoirs, estuaries, wells, and boreholes containing DDT residues was used as drinking water. Seven studies conducted health risk assessments, with two studies identifying cancer risk values surpassing permissible thresholds in water sampled from sources designated for potable use. Non-carcinogenic health risks in the studies fell below a hazard quotient of 1. Consequently, discernible evidence of risks to human health surfaced, given that the concentration of DDT residues surpassed either the WHO drinking water guidelines or the permissible limits for cancer risk in sampled drinking sources within African water systems. Therefore, alternative methods for malaria vector control should be investigated and applied.

Systematic investigation of organochlorine pesticides and polychlorinated biphenyls blood levels in Greek children from the Rhea birth cohort suggests historical exposure to DDT and through diet to DDE.

The blood levels of organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) have been thoroughly investigated in Greek children from the Rhea birth cohort study. This investigation aimed to assess exposure levels, explore their possible relationship with children's age and sex, and indicate potential sources of exposure. Exposure patterns and common sources of PCBs and OCPs were analyzed using bivariate and multivariate statistics. A total of 947 blood samples from study participants were analyzed for OCP and PCB exposure, with 375 samples collected at 4 years old, 239 at 6.5 years old, and 333 at 11 years old. Elevated levels of DDE were observed in 6.5-year-old children compared to corresponding levels in other European countries. Higher levels of DDE were found in 4-year-old children, with the lowest concentrations in the 11-year-old group. The DDT/DDE ratio was consistently less than 1 among all the examined subjects. These results indicate exposure to DDT and DDE both in utero and through breastfeeding and dietary intake. For the entire cohort population, the highest concentration was determined for PCB 28, followed by PCBs 138, 153, and 180. The sum of the six indicator PCBs implied low exposure levels for the majority of the cohort population. Spearman correlations revealed strong associations between PCBs and OCPs, while principal component analysis identified two different groupings of exposure. DDE exhibited a correlation with a series of PCBs (153, 156, 163, 180), indicating a combined OCP-PCB source, and an anticorrelation with others (52, 28, 101), implying a separate and competing source.

Back on top: Resuspended by dredging and other environmental disturbances, organochlorine compounds may affect the health of a dolphin population in a tropical estuary, Sepetiba Bay.

Organochlorine compounds (OCs) are persistent organic pollutants linked to damaging the immune and endocrine systems, leading to a greater susceptibility to infectious diseases at high concentrations. Sepetiba Bay, in the Southeastern Brazilian coast, historically presents anthropogenic activities and environmental contamination that could negatively impact resident populations. In this context, this study aimed to investigate the temporal trends in the accumulation of organochlorine compounds over a 12-year database in the Guiana dolphins' (Sotalia guianensis) resident population from Sepetiba Bay, including individuals collected before, during, and after an unusual mortality event triggered by morbillivirus (n = 85). The influence of biological parameters was also evaluated. The OCs concentrations in the blubber ranged from 0.98 to 739 µg/g of ΣPCB; 0.08-130 µg/g of ΣDDT; <0.002-4.56 µg/g of mirex; <0.002-1.84 µg/g of ΣHCH and <0.001-0.16 µg/g of HCB in lipid weight. Increased temporal trends were found for OCs in Guiana dolphins coinciding with periods of large events of dredging in the region. In this way, our findings suggest that the constant high OCs concentrations throughout the years in this Guiana dolphin population are a result of the constant environmental disturbance in the area, such as dredging. These elevated OCs levels, e.g., ΣPCB concentrations found above the known thresholds, may impair the response of the immune system during outbreak periods, which could lead the population to a progressive decline.

Non-Coding RNAs Potentially Involved in Pyrethroid Resistance of Anopheles funestus Population in Western Kenya.

Backgrounds: The resurgence of Anopheles funestus, a dominant vector of human malaria in western Kenya was partly attributed to insecticide resistance. However, evidence on the molecular basis of pyrethroid resistance in western Kenya is limited. Noncoding RNAs (ncRNAs) form a vast class of RNAs that do not code for proteins and are ubiquitous in the insect genome. Here, we demonstrated that multiple ncRNAs could play a potential role in An. funestusresistance to pyrethroid in western Kenya. Materials and Methods: Anopheles funestus mosquitoes were sampled by aspiration methods in Bungoma, Teso, Siaya, Port Victoria and Kombewa in western Kenya. The F1 progenies were exposed to deltamethrin (0.05%), permethrin (0.75%), DDT (4%) and pirimiphos-methyl (0.25%) following WHO test guidelines. A synergist assay using piperonyl butoxide (PBO) (4%) was conducted to determine cytochrome P450s' role in pyrethroid resistance. RNA-seq was conducted on a combined pool of specimens that were resistant and unexposed, and the results were compared with those of the FANG susceptible strain. This approach aimed to uncover the molecular mechanisms underlying pyrethroid resistance. Results: Pyrethroid resistance was observed in all the sites with an average mortality rate of 57.6%. Port Victoria had the highest level of resistance to permethrin (MR=53%) and deltamethrin (MR=11%) pyrethroids. Teso had the lowest level of resistance to permethrin (MR=70%) and deltamethrin (MR=87%). Resistance to DDT was observed only in Kombewa (MR=89%) and Port Victoria (MR=85%). A full susceptibility to P-methyl (0.25%) was observed in all the sites. PBO synergist assay revealed high susceptibility (>98%) to the pyrethroids in all the sites except for Port Victoria (MR=96%, n=100). Whole transcriptomic analysis showed that most of the gene families associated with pyrethroid resistance comprised non-coding RNAs (67%), followed by imipenemase (10%), cytochrome P450s (6%), cuticular proteins (5%), olfactory proteins (4%), glutathione S-transferases (3%), UDP-glycosyltransferases (2%), ATP-binding cassettes (2%) and carboxylesterases(1%). Conclusions: This study unveils the molecular basis of insecticide resistance in An. funestus in western Kenya, highlighting for the first time the potential role of non-coding RNAs in pyrethroid resistance. Targeting non-coding RNAs for intervention development could help in insecticide resistance management.

Identification of putative promoter elements for epsilon glutathione s-transferases genes associated with resistance to DDT in the malaria vector mosquito anopheles arabiensis.

The purpose of this study was to identify the putative regulatory elements in the promoter region of An. arabiensis strains which differed in susceptibility to DDT and compare with those identified in its sibling An. gambaie. Basal expression level of Epsilon class GSTs (Glutathione S - transferases) GSTe1 gene was 0.512 - 0.658 (95% CI) and GSTe2 0.672 - 1.204 (95% CI) in adults of DDT resistant KGB compared to 0.031 - 0.04 (95% CI) and 0.148 - 0.199 (95% CI) respectively in susceptible MAT strains of An. arabiensis. Induced mean expression of GSTe2 in larvae exposed to DDT for one hour was 0.901 - 1.172 (95% CI) in KGB and 0.475 - 0.724 (95% CI) in MAT strain. In present work, strain specific primers were used to amplify and sequenced the promoter regions of GSTe1 and GSTe2 in the KGB, MAT and field specimens. Computational analysis revealed presence of classical arthropod initiator sequence TCAGT and putative core promoter elements, GC, CAAT, TATA boxes. A typical TATA box was identified at 35 bp upstream Transcription Start Site (TSS) in GSTe1 but was absent in GSTe2. Several binding sites for regulatory elements downstream and multiple polymorphic sites were identified between strains. The role of these regulatory elements in transcription of these genes has not been determined. However, on comparison the 2 bp adenosine indel (insertion/deletion) which was essential in driving the promoter activity in An. gambiae was identified only DDT resistant KGB strain.