Search bioRxiv⌕ Search

bioRxiv · 10.1101/2021.12.22.473821

Control effectiveness of APL formulation against dengue- and Zika-transmitting Aedes mosquitoes in Gia Lai province, Vietnam

Abstract

BackgroundDengue fever and Zika are two of the Aedes-borne diseases. Despite being widely used, synthetic mosquitocides become abortive for the mosquito control due to growing resistance and environmental pollution. In Gia Lai province (dengue-endemic area), a huge amount of cashew nut shell waste with roughly 100,000 tons/year has been disposed of into the environment, potentiating a high risk of pollution. Methodology/Principal findingsTo utilize it, anacardic acid was extracted and combined it with ethanol extract of the local lime peel, which contains limonene, to generate APL formulation. APL robustly exhibited inhibition of egg hatching, larvicidal effect, and repellent effect against female mosquitoes from oviposition sites in the laboratory and field. The results showed that, at a dose of 12.5 ppm, the APL formulation after 24 hours of treatment demonstrated oviposition deterrence against Ae. aegypti (43.6%) and Ae. albopictus (59.6%); inhibited egg hatching of Ae. aegypti (49.6%) and Ae. albopictus (59.6%); caused larval lethality in Ae. aegypti (LC50 = 9.5 ppm, LC90 = 21 ppm) and Ae. albopictus (LC50 = 7.6 ppm, LC90 = 18 ppm). Under natural field conditions, it showed a 100% reduction in larval density after 48 and 72 hours of the APL treatment at a tested concentration of 120 mg a.i./m2 and maintained a mortality rate of 100% in the next 14 days. Conclusions/SignificanceThe APL formulation is promisingly to become an environmentally friendly and highly effective biological product for future management programs of dengue and Zika-transmitting vectors. Here offer prospects in controlling critical illnesses transmitted by several mosquito species in dengue-endemic areas. Author summaryThe use of synthetic insecticide to control the dengue and Zika vector population has contributed to drug resistance and caused negative impacts on the environment. The plant-based insecticide should be beneficial for mosquito management in the current situation. Gia Lai province in Vietnam is a dengue-endemic area. A large amount of cashew nut shell waste gets discarded in the area every year, which imposes an increased risk of pollution. The authors took advantage of this by extracting anacardic acid to combine with ethanol extract of local lime peel (containing limonene) to produce APL formulation. This formulation demonstrated potential activities and efficiency in controlling mosquitoes transmitting disease. In the laboratory condition, at a low dose of 12.5 ppm, APL showed activities in inhibiting egg hatching, larviciding, and repelling female Aedes aegypti and Aedes albopictus. In the field condition, APL at a dose of 120 mg a.i./m2 thoroughly reduced the dengue larval density after two days of contact, and this effect lasted to the next 14 days. APL is a promising and environmentally friendly larvicidal product that is highly effective in controlling dengue and Zika vectors and can play as an alternative measure for vector-borne dengue in the locality.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Hue, P. T. K., Vien, L. T., Nga, D. M., Truong, L. V., Ha, H., Khoa, P. T., Nhung, L. T., Hieu, H. V., Sy, L. D., Trung, T. N., Quang, T. T. D. T. U. D. H. D. T., Loc, T. V.. 2021-12-24. Control effectiveness of APL formulation against dengue- and Zika-transmitting Aedes mosquitoes in Gia Lai province, Vietnam. https://doi.org/10.1101/2021.12.22.473821

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Hierarchical cysteine oxidation controls reversible amyloid formation in an ankyrin repeat protein

The formation of amyloids, including functional amyloids, is observed for an increasing number of proteins but the molecular mechanisms that control this structural transition remain poorly understood. Here we report that the kinase inhibitor protein P18 (drP18) from Danio rerio (zebrafish), which contains two cysteine residues, undergoes a complex and hierarchical redox switch that strictly governs reversible amyloid formation. We identify cysteine 50 (C50) acting as a regulatory residue. Upon oxidation, C50 forms an intramolecular disulfide bond with the executioner cysteine 128 (C128), thereby blocking it. C50 can become S-glutathionylated, and upon oxidation, C128 then forms intermolecular disulfides that lead to rapid transition into amyloid fibrils. S-glutathionylation of C50 therefore enables amyloid formation of drP18 and the outcome is oxidant-dependent with diamide, hydrogen peroxide, peroxymonocarbonate and hypothiocyanous acid each leading to amyloid assembly with distinct kinetics and morphologies. These amyloids are fully reversible, where disulfide reduction is leading to disassembly. Whereas monomeric drP18 inhibits CDK4-mediated retinoblastoma phosphorylation, the amyloid conformation abolishes this inhibition, and reduction restores both structure and function. Expression of drP18 in zebrafish embryos yields Congo red-positive, oxidation-dependent aggregates in vivo. Together, our findings show that a regulatory cysteine controls an executioner cysteine to induce reversible, functional amyloid formation, revealing that proteins can encode sophisticated mechanisms to control amyloid assembly.

biochemistry↗

Snapshots from the Catalytic Landscape of Chalcone Isomerase

Chalcone isomerase (CHI) catalyzes the cyclization of 3-ring scaffolds of flavonoids, a class of plant-based natural products important for nutrition and disease prevention. A persistent question has been whether the enzyme uses dynamics to facilitate conformational rearrangements of substrates within the active site. To help resolve this question, CHI was crystallized with phloretin, a flexible substrate analogue that cannot undergo cyclization. The crystal structure possesses eight protein molecules per asymmetric unit, revealing different active site conformations that accommodate different bound conformers of phloretin. Together, the structural snapshots depict a series of coordinated, dynamic chemical interactions that lower barriers to substrate rearrangements approaching bond formation. Differential scanning fluorimetry combined with mutational analysis and enzyme kinetics further confirm that phloretin binds to the enzyme active site and that it acts as a competitive inhibitor of CHI. Together these findings answer outstanding questions about the flexibility and dynamics of CHI catalysis, information that may be useful for future biosynthetic design and enzyme engineering goals. Overall, this work supports a catalytic model in which the CHI enzyme operates as a dynamic ensemble of structures necessary to facilitate catalytic substrate rearrangements.

biochemistry↗

Structures of pUG-fold RNA bound to DNMT1 reveal a mechanism for RNA-mediated epigenetic regulation

Many chromatin-associated proteins have been found to bind RNA as a means of epigenetic regulation. Specifically, DNA methyltransferase 1 (DNMT1), which maintains cytosine methylation at CpG dinucleotides, is inhibited by RNA at transcribed DNA loci in cells. However, the mechanisms by which RNA binds DNMT1 and inhibits its activity remain unknown. Here, we determine a series of cryogenic electron microscopy (cryo-EM) structures of human DNMT1 bound to pUG-fold RNA, a non-canonical G-quadruplex previously observed to inhibit activity, revealing two distinct RNA-binding modes. The pUG-fold RNA binds the surface of DNMT1 in its autoinhibited conformation across a positively charged surface between the methyltransferase domain and the CXXC domain, and it binds directly in the active site of an open DNMT1 conformation. RNA binding is sterically incompatible with substrate DNA engagement in both states. Our 2.5 [A] structure captures the intricate network of hydrogen bonds and electrostatic interactions between amino acids in the methyltransferase domain and the tetrad layers of pUG-fold RNA. Metadynamics molecular dynamics simulations provide an orthogonal view of the conformational landscape of DNMT1, revealing the two distinct RNA-binding modes. Furthermore, our analysis of published DNMT1 RIP-seq and eCLIP-seq data confirms that DNMT1-interacting RNAs in cells exhibit a strong propensity to form non-canonical G-quadruplex RNA structures. Collectively, our study provides the first structural basis for pUG-fold RNA recognition by a protein and illustrates how cryo-EM and AI-based methods for protein and RNA structure prediction synergize to inform the mechanism of RNA-mediated regulation of DNMT1.

biochemistry↗