scholarly journals Transcriptomic response of Anopheles gambiae sensu stricto mosquito larvae to Curry tree (Murraya koenigii) phytochemicals

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Clarence M. Mang’era ◽  
Fathiya M. Khamis ◽  
Erick O. Awuoche ◽  
Ahmed Hassanali ◽  
Fidelis Levi Odhiambo Ombura ◽  
...  
Keyword(s):  
Immune Response ◽  
Anopheles Gambiae ◽  
Growth And Development ◽  
Leaf Extract ◽  
Expression Profiles ◽  
Sensu Stricto ◽  
Mosquito Larvae ◽  
Insect Vector ◽  
Murraya Koenigii ◽  
Transcriptomic Response

Abstract Background Insect growth regulators (IGRs) can control insect vector populations by disrupting growth and development in juvenile stages of the vectors. We previously identified and described the curry tree (Murraya koenigii (L.) Spreng) phytochemical leaf extract composition (neplanocin A, 3-(1-naphthyl)-l-alanine, lumiflavine, terezine C, agelaspongin and murrayazolinol), which disrupted growth and development in Anopheles gambiae sensu stricto mosquito larvae by inducing morphogenetic abnormalities, reducing locomotion and delaying pupation in the mosquito. Here, we attempted to establish the transcriptional process in the larvae that underpins these phenotypes in the mosquito. Methods We first exposed third-fourth instar larvae of the mosquito to the leaf extract and consequently the inherent phytochemicals (and corresponding non-exposed controls) in two independent biological replicates. We collected the larvae for our experiments sampled 24 h before peak pupation, which was 7 and 18 days post-exposure for controls and exposed larvae, respectively. The differences in duration to peak pupation were due to extract-induced growth delay in the larvae. The two study groups (exposed vs control) were consequently not age-matched. We then sequentially (i) isolated RNA (whole larvae) from each replicate treatment, (ii) sequenced the RNA on Illumina HiSeq platform, (iii) performed differential bioinformatics analyses between libraries (exposed vs control) and (iv) independently validated the transcriptome expression profiles through RT-qPCR. Results Our analyses revealed significant induction of transcripts predominantly associated with hard cuticular proteins, juvenile hormone esterases, immunity and detoxification in the larvae samples exposed to the extract relative to the non-exposed control samples. Our analysis also revealed alteration of pathways functionally associated with putrescine metabolism and structural constituents of the cuticle in the extract-exposed larvae relative to the non-exposed control, putatively linked to the exoskeleton and immune response in the larvae. The extract-exposed larvae also appeared to have suppressed pathways functionally associated with molting, cell division and growth in the larvae. However, given the age mismatch between the extract-exposed and non-exposed larvae, we can attribute the modulation of innate immune, detoxification, cuticular and associated transcripts and pathways we observed to effects of age differences among the larvae samples (exposed vs control) and to exposures of the larvae to the extract. Conclusions The exposure treatment appears to disrupt cuticular development, immune response and oxidative stress pathways in Anopheles gambiae s.s larvae. These pathways can potentially be targeted in development of more efficacious curry tree phytochemical-based IGRs against An. gambiae s.s mosquito larvae.

scholarly journals The effect of coexistence between larvae of Anopheles gambiae and Culex quinquefasciatus on larvicidal efficacy of Bacillus thuringiensis var. israelensis

2021 ◽  
Vol 3 (1) ◽  
pp. 77-85
Author(s):  
Yahya A. Derua ◽  
Eliningaya J. Kweka ◽  
William N. Kisinza ◽  
Guiyun Yan ◽  
Andrew K. Githeko ◽  
...  
Keyword(s):  
Bacillus Thuringiensis ◽  
Anopheles Gambiae ◽  
Culex Quinquefasciatus ◽  
Significant Variation ◽  
General Trend ◽  
Sensu Stricto ◽  
Probit Analysis ◽  
Mosquito Larvae ◽  
Breeding Habitats ◽  
Larval Bioassay

Background: The efficacy of Bacillus thuringiensis var. israelensis (Bti) is affected by several factors including the species of the mosquito. Mosquito larvae of different species are found to coexist in larval breeding habitats. This study evaluated whether the coexistence between Anopheles gambiae and Culex quinquefasciatus affect the larvicidal activity of Bti. Methods: Two parallel larval bioassay experiments were conducted to test A. gambiae sensu stricto (s.s) and C. quinquefasciatus larvae susceptibility to Bti. They were followed by three parallel bioassays in which A. gambiae s.s and C. quinquefasciatus larvae were mixed in different proportions such that the earlier species contributed three quarters, half and a quarter of the larvae in each testing cup respectively. In each bioassay, six Bti concentrations were tested in four replicates and repeated on three different days. Larvae mortality was scored 24 hours after application of Bti and subjected to Probit analysis. Results: C. quinquefasciatus was significantly more susceptible to Bti than A. gambiae s.s at both lethal concentration values (LC50 and LC95). In coexisting scenario, LC50 of Bti was significantly lower when the proportion of C. quinquefasciatus exceeded 50%. No significant variation in susceptibility to Bti was observed at LC95 in any proportion of coexistence between the two species. Conclusion: The findings show that larvae of C. quinquefasciatus were significantly more susceptible to Bti than those of A. gambiae s.s. Moreover, when larvae of the two species coexisted, there was a general trend of increase in sensitivity to Bti with higher proportion of C. quinquefasciatus. Although this increase in sensitivity of coexisting larvae to Bti is worth noting, our findings suggest that it will not impact larval control where A. gambiae s.s and C. quinquefasciatus coexist.

scholarly journals Short-term metabolic resistance inductive effect of different agrochemical groups on Anopheles gambiae mosquitoes

2021 ◽  
Vol 6 ◽  
pp. 147
Author(s):  
Christabelle G. Sadia ◽  
France-Paraudie A. Kouadio ◽  
Behi K. Fodjo ◽  
Sebastien K. Oyou ◽  
Adepo-Gourene A. Beatrice ◽  
...  
Keyword(s):  
Anopheles Gambiae ◽  
Inductive Effect ◽  
Expression Profiles ◽  
Short Exposure ◽  
Mosquito Larvae ◽  
Metabolic Resistance ◽  
Pesticide Mixture ◽  
Agricultural Pesticides ◽  
Time Required ◽  
The Impact

Background: In order to assess the impact of the different groups of agricultural pesticides used in Côte d'Ivoire on the increase of mosquitoes resistance to insecticides, the expression profiles of 7 P450 cytochromes and one GSTE2 of Anopheles gambiae involved in mosquito resistance to insecticides were studied. The goal of this study was to determine the effect of short exposure of mosquito larvae to different groups of agricultural pesticides on mosquito resistance. Methods: Three groups of pesticides were selected: (i) agricultural insecticide solutions, (ii) non-insecticide pesticide solutions (a mixture of herbicides and fungicides), and (iii) a mixture of the first two. A fourth non-pesticide solution was used as a control. Four groups of each stage 2 larvae (strain Kisumu, male and female) were exposed to 20% concentrated solution for 24 hours. Susceptibility tests for dichlorodiphenyltrichloroethane (DDT) and Deltamethrin were carried out on adults aged 2-5 days. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was performed to quantify the expression of eight metabolic genes involved in mosquito resistance to insecticides.  Results: Susceptibility to DDT showed a similar increase in the time required to knock down 50% of mosquitoes (kdt50) in l colonies exposed to insecticides and non-insecticides compared to the control colony. As for deltamethrin, kdt50 was higher in the colonies exposed to insecticides and the pesticide mixture compared to the colony exposed to non-insecticides. Of all the genes studied in all colonies, except for CYP6P1 induced only in the colony consisting of the pesticide mixture, no genes were induced. Conclusions: This study confirmed that induction is influenced by the duration, the concentration of the solution and the type of xenobiotic used as an inducer. The overexpression of CYP6P1 confirmed the inductive effect that a short exposure of mosquito larvae to agricultural pesticides could have.

scholarly journals Short-term metabolic resistance inductive effect of different agrochemical groups on Anopheles gambiae mosquitoes

2021 ◽  
Vol 6 ◽  
pp. 147
Author(s):  
Christabelle G. Sadia ◽  
France-Paraudie A. Kouadio ◽  
Behi K. Fodjo ◽  
Sebastien K. Oyou ◽  
Adepo-Gourene A. Beatrice ◽  
...  
Keyword(s):  
Anopheles Gambiae ◽  
Inductive Effect ◽  
Expression Profiles ◽  
Short Exposure ◽  
Mosquito Larvae ◽  
Metabolic Resistance ◽  
Pesticide Mixture ◽  
Agricultural Pesticides ◽  
Time Required ◽  
The Impact

Background: In order to assess the impact of the different groups of agricultural pesticides used in Côte d'Ivoire on the increase of mosquitoes resistance to insecticides, the expression profiles of 7 P450 cytochromes and one GSTE2 of Anopheles gambiae involved in mosquito resistance to insecticides were studied. The goal of this study was to determine the effect of short exposure of mosquito larvae to different groups of agricultural pesticides on mosquito resistance. Methods: Three groups of pesticides were selected: (i) agricultural insecticide solutions, (ii) none-insecticide pesticide solutions (a mixture of herbicides and fungicides), and (iii) a mixture of the first two. A fourth non-pesticide solution was used as a control. Four groups of each stage 2 larvae (strain Kisumu, male and female) were exposed to 20% concentrated solution for 24 hours. Susceptibility tests for dichlorodiphenyltrichloroethane (DDT) and Deltamethrin were carried out on adults aged 2-5 days. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was performed to quantify the expression of eight metabolic genes involved in mosquito resistance to insecticides.  Results: Susceptibility to DDT showed a similar increase in the time required to knock down 50% of mosquitoes (kdt50) in l colonies exposed to insecticides and none-insecticides compared to the control colony. As for deltamethrin, kdt50 was higher in the colonies exposed to insecticides and the pesticide mixture compared to the colony exposed to none-insecticides. Of all the genes studied in all colonies, except for CYP6P1 induced only in the colony consisting of the pesticide mixture, no genes were induced. Conclusions: This study confirmed that induction is influenced by the duration, the concentration of the solution and the type of xenobiotic used as an inducer. The overexpression of CYP6P1 confirmed the inductive effect that a short exposure of mosquito larvae to agricultural pesticides could have.

scholarly journals Modulation of the Immune Response by Deferasirox in Myelodysplastic Syndrome Patients

2021 ◽  
Vol 14 (1) ◽  
pp. 41
Author(s):  
Hana Votavova ◽  
Zuzana Urbanova ◽  
David Kundrat ◽  
Michaela Dostalova Merkerova ◽  
Martin Vostry ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Blood Cell ◽  
Myelodysplastic Syndrome ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Adaptive Immune Response ◽  
Gene Expression Profiles ◽  
Iron Chelator ◽  
Multiple Cancer

Deferasirox (DFX) is an oral iron chelator used to reduce iron overload (IO) caused by frequent blood cell transfusions in anemic myelodysplastic syndrome (MDS) patients. To study the molecular mechanisms by which DFX improves outcome in MDS, we analyzed the global gene expression in untreated MDS patients and those who were given DFX treatment. The gene expression profiles of bone marrow CD34+ cells were assessed by whole-genome microarrays. Initially, differentially expressed genes (DEGs) were determined between patients with normal ferritin levels and those with IO to address the effect of excessive iron on cellular pathways. These DEGs were annotated to Gene Ontology terms associated with cell cycle, apoptosis, adaptive immune response and protein folding and were enriched in cancer-related pathways. The deregulation of multiple cancer pathways in iron-overloaded patients suggests that IO is a cofactor favoring the progression of MDS. The DEGs between patients with IO and those treated with DFX were involved predominantly in biological processes related to the immune response and inflammation. These data indicate DFX modulates the immune response mainly via neutrophil-related genes. Suppression of negative regulators of blood cell differentiation essential for cell maturation and upregulation of heme metabolism observed in DFX-treated patients may contribute to the hematopoietic improvement.

scholarly journals Laboratory and microcosm experiments reveal contrasted adaptive responses to ammonia and water mineralisation in aquatic stages of the sibling species Anopheles gambiae (sensu stricto) and Anopheles coluzzii

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Nwamaka Oluchukwu Akpodiete ◽  
Frédéric Tripet
Keyword(s):  
West Africa ◽  
Anopheles Gambiae ◽  
Emerging Adults ◽  
Sibling Species ◽  
Adult Emergence ◽  
Ecological Speciation ◽  
Sensu Stricto ◽  
Rice Fields ◽  
Anopheles Coluzzii ◽  
Phenotypic Quality

Abstract Background The sibling species of the malaria mosquito, Anopheles gambiae (sensu stricto) and Anopheles coluzzii co-exist in many parts of West Africa and are thought to have recently diverged through a process of ecological speciation with gene flow. Divergent larval ecological adaptations, resulting in Genotype-by-Environment (G × E) interactions, have been proposed as important drivers of speciation in these species. In West Africa, An. coluzzii tends to be associated with permanent man-made larval habitats such as irrigated rice fields, which are typically more eutrophic and mineral and ammonia-rich than the temporary rain pools exploited by An. gambiae (s.s.) Methods To highlight G × E interactions at the larval stage and their possible role in ecological speciation of these species, we first investigated the effect of exposure to ammonium hydroxide and water mineralisation on larval developmental success. Mosquito larvae were exposed to two water sources and increasing ammonia concentrations in small containers until adult emergence. In a second experiment, larval developmental success was compared across two contrasted microcosms to highlight G × E interactions under conditions such as those found in the natural environment. Results The first experiment revealed significant G × E interactions in developmental success and phenotypic quality for both species in response to increasing ammonia concentrations and water mineralisation. The An. coluzzii strain outperformed the An. gambiae (s.s.) strain under limited conditions that were closer to more eutrophic habitats. The second experiment revealed divergent crisscrossing reaction norms in the developmental success of the sibling species in the two contrasted larval environments. As expected, An. coluzzii had higher emergence rates in the rice paddy environment with emerging adults of superior phenotypic quality compared to An. gambiae (s.s.), and vice versa, in the rain puddle environment. Conclusions Evidence for such G × E interactions lends support to the hypothesis that divergent larval adaptations to the environmental conditions found in man-made habitats such as rice fields in An. coluzzii may have been an important driver of its ecological speciation.

scholarly journals Response patterns in adventitial layer of Echinococcus granulosus sensu stricto cysts from naturally infected cattle and sheep

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Christian Hidalgo ◽  
Caroll Stoore ◽  
María Soledad Baquedano ◽  
Ismael Pereira ◽  
Carmen Franco ◽  
...  
Keyword(s):  
Immune Response ◽  
Echinococcus Granulosus ◽  
Cystic Echinococcosis ◽  
Direct Contact ◽  
Sensu Stricto ◽  
Response Patterns ◽  
Granulomatous Reaction ◽  
Adventitial Layer ◽  
Laminated Layer ◽  
Cattle And Sheep

AbstractCystic echinococcosis is a zoonotic disease caused by the metacestode of Echinococcus granulosus sensu lato. The disease is characterized by the development of cystic structures inside viscera of the intermediate host, mainly liver and lungs. These cysts are formed by three layers: germinal, laminated, and adventitial layer, the latter being the local host immune response. Metacestodes that develop protoscoleces, the infective stage to the definitive host, are termed fertile, whereas cysts that do not produce protoscoleces are termed non-fertile. Sheep usually harbor fertile cysts while cattle usually harbor non-fertile cysts. Adventitial layers with fibrotic resolution are associated to fertile cysts, whereas a granulomatous reaction is associated with non-fertile cysts. The aim of this study was to analyze cellular distribution in the adventitial layer of fertile and non-fertile E. granulosus sensu stricto cysts found in liver and lungs of cattle and sheep. A total of 418 cysts were analyzed, 203 from cattle (8 fertile and 195 non-fertile) and 215 from sheep (64 fertile and 151 non-fertile). Fertile cysts from cattle showed mixed patterns of response, with fibrotic resolution and presence of granulomatous response in direct contact with the laminated layer, while sheep fertile cysts always displayed fibrotic resolution next to the laminated layer. Cattle non-fertile cysts display a granulomatous reaction in direct contact with the laminated layer, whereas sheep non-fertile cysts display a granulomatous reaction, but in direct contact with the fibrotic resolution. This shows that cattle and sheep cystic echinococcosis cysts have distinct local immune response patterns, which are associated to metacestode fertility.

scholarly journals Identification and validation of a miRNA-related expression signature for tumor mutational burden in colorectal cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lijun Xu ◽  
Qing Zheng
Keyword(s):  
Colorectal Cancer ◽  
Immune Response ◽  
Validation Cohort ◽  
Expression Profiles ◽  
Functional Enrichment ◽  
Immune Checkpoints ◽  
Positive Correlation ◽  
Expression Signature ◽  
Mutational Burden ◽  
Tumor Mutational Burden

Abstract Background Tumor mutational burden (TMB) is a promising predictor, which could stratify colorectal cancer (CRC) patients based on the response to immune checkpoint inhibitors (ICIs). MicroRNAs (miRNAs) act as the key regulators of anti-cancer immune response. However, the relationship between TMB and miRNA expression profiles is not elucidated in CRC. Methods Differentially expressed miRNAs (DE miRNAs) between the TMBhigh group and the TMBlow group were identified for the CRC cohort of the TCGA database. In the training cohort, a miRNA-related expression signature for predicting TMB level was developed by the least absolute shrinkage and selection operator (LASSO) method and tested with reference to its discrimination, calibration, and decision curve analysis (DCA) in the validation cohort. Functional enrichment analysis of these TMB-related miRNAs was performed. The correlation between this miRNA-related expression signature and three immune checkpoints was analyzed. Results Twenty-one out of 43 DE miRNAs were identified as TMB-related miRNAs, which were used to develop a miRNA-related expression signature. This TMB-related miRNA signature demonstrated great discrimination (AUCtest set = 0.970), satisfactory calibration (P > 0.05), and clinical utility in the validation cohort. Functional enrichment results revealed that these TMB-related miRNAs were mainly involved in biological processes associated with immune response and signaling pathways related with cancer. This miRNA-related expression signature showed a median positive correlation with PD-L1 (R = 0.47, P < 0.05) and CTLA4 (R = 0.39, P < 0.05) and a low positive correlation with PD-1 (R = 0.16, P < 0.05). Conclusion This study presents a miRNA-related expression signature which could stratify CRC patients with different TMB levels.

scholarly journals Single blinded semi-field evaluation of MAÏA® topical repellent ointment compared to unformulated 20% DEET against Anopheles gambiae, Anopheles arabiensis and Aedes aegypti in Tanzania

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Emmanuel Mbuba ◽  
Olukayode G. Odufuwa ◽  
Frank C. Tenywa ◽  
Rose Philipo ◽  
Mgeni M. Tambwe ◽  
...  
Keyword(s):  
Aedes Aegypti ◽  
Anopheles Gambiae ◽  
Anopheles Arabiensis ◽  
Protective Efficacy ◽  
Latin Square ◽  
Field Evaluation ◽  
Sensu Stricto ◽  
Lower Limbs ◽  
Complete Protection ◽  
Regular User

Abstract Background N,N-Diethyl-3-methylbenzamide (DEET) topical mosquito repellents are effective personal protection tools. However, DEET-based repellents tend to have low consumer acceptability because they are cosmetically unappealing. More attractive formulations are needed to encourage regular user compliance. This study evaluated the protective efficacy and protection duration of a new topical repellent ointment containing 15% DEET, MAÏA® compared to 20% DEET in ethanol using malaria and dengue mosquito vectors in Bagamoyo Tanzania. Methods Fully balanced 3 × 3 Latin square design studies were conducted in large semi-field chambers using laboratory strains of Anopheles gambiae sensu stricto, Anopheles arabiensis and Aedes aegypti. Human volunteers applied either MAÏA® ointment, 20% DEET or ethanol to their lower limbs 6 h before the start of tests. Approximately 100 mosquitoes per strain per replicate were released inside each chamber, with 25 mosquitoes released at regular intervals during the collection period to maintain adequate biting pressure throughout the test. Volunteers recaptured mosquitoes landing on their lower limbs for 6 h over a period of 6 to 12-h post-application of repellents. Data analysis was conducted using mixed-effects logistic regression. Results The protective efficacy of MAÏA® and 20% DEET was not statistically different for each of the mosquito strains: 95.9% vs. 97.4% against An. gambiae (OR = 1.53 [95% CI 0.93–2.51] p = 0.091); 96.8% vs 97.2% against An. arabiensis (OR = 1.08 [95% CI 0.66–1.77] p = 0.757); 93.1% vs 94.6% against Ae. aegypti (OR = 0.76 [95% CI 0.20–2.80] p = 0.675). Average complete protection time (CPT) in minutes of MAÏA® and that of DEET was similar for each of the mosquito strains: 571.6 min (95% CI 558.3–584.8) vs 575.0 min (95% CI 562.1–587.9) against An. gambiae; 585.6 min (95% CI 571.4–599.8) vs 580.9 min (95% CI 571.1–590.7) against An. arabiensis; 444.1 min (95% CI 401.8–486.5) vs 436.9 min (95% CI 405.2–468.5) against Ae. aegypti. Conclusions MAÏA® repellent ointment provides complete protection for 9 h against both An. gambiae and An. arabiensis, and 7 h against Ae. aegypti similar to 20% DEET (in ethanol). MAÏA® repellent ointment can be recommended as a tool for prevention against outdoor biting mosquitoes in tropical locations where the majority of the people spend an ample time outdoor before going to bed.

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