Biology subjects

Lee, M.-C.

Publications and source records attributed to Lee, M.-C..

5 recordsLinked to original sources

bioRxiv2024

Insecticide resistance and its intensity in urban Anopheles arabiensis in Kisumu City, Western Kenya: Implications for malaria control in urban areas

BackgroundThe rise of insecticide resistance poses a growing challenge to the effectiveness of vector control tools, particularly in rural areas. However, the urban setting has received comparatively less focus despite its significance in attracting rural to urban migration. Unplanned urbanization, often overlooked, exacerbates insecticide resistance as Anopheles mosquitoes adapt to the polluted environments of rapidly expanding cities. This study aimed to assess the insecticide susceptibility status of malaria vectors and identify potential underlying mechanisms across three distinct ecological settings characterized by differing levels of urbanization in Kisumu County, Kenya. MethodsField-derived An. gambiae (s.l.) larvae collected from a long stretch of urban-to-rural continuum were phenotyped as either resistant or susceptible to six different insecticides using the World Health Organization (WHO) susceptibility test. Polymerase chain reaction (PCR) techniques were used to identify the species of the An. gambiae complex and screened for mutations at voltage-gated sodium channels (Vgsc-1014F, Vgsc-1014S, Vgsc-1575Y) and acetylcholinesterase Ace1-119S. Metabolic enzymes activities (non-specific {beta}-esterases and monooxygenases) were evaluated in mosquitoes not exposed to insecticides using microplate assays. Additionally, during larval sampling, a retrospective questionnaire survey was conducted to determine pesticide usage by the local inhabitants. ResultsAnopheles arabiensis dominated in urban (96.2%) and peri-urban (96.8%) areas, while An. gambiae (s.s.) was abundant in rural settings (82.7%). Urban mosquito populations showed high resistance intensity to deltamethrin (Mortality rate: 85.2% at 10x) and suspected resistance to Pirimiphos-methyl and bendiocarb while peri-urban and rural populations exhibited moderate resistance intensity to deltamethrin (mortality rate >98% at 10x). Preexposure of mosquitoes to a synergist piperonyl butoxide (PBO) significantly increased mortality rates: from 40.7% to 88.5% in urban, 51.9% to 90.3% in peri-urban, and 55.4% to 87.6% in rural populations for deltamethrin, and from 41.4% to 78.8% in urban, 43.7% to 90.7% in peri-urban, and 35% to 84.2% in rural populations for permethrin. In contrast, 100% mortality to chlorfenapyr and clothianidin was observed in all the populations tested. The prevalence of L1014F mutation was notably higher in urban An. arabiensis (0.22) unlike the peri-urban (0.11) and rural (0.14) populations while the L1014S mutation was more prevalent in rural An. gambiae (0.93). Additionally, urban An. arabiensis exhibited elevated levels of mixed function oxidases (0.8/mg protein) and non-specific esterases (2.12/mg protein) compared to peri-urban (0.57/mg protein and 1.5/mg protein, respectively) and rural populations (0.6/mg protein and 1.8/mg protein, respectively). Pyrethroids, apart from their use in public health through LLINs, were being highly used for agricultural purposes across all ecological settings (urban 38%, peri-urban 36% and rural 37%) followed by amidine group, with organophosphates, neonicotinoids and carbamates being of secondary importance. ConclusionThese findings show high resistance of An. arabiensis to insecticides commonly used for vector control, linked with increased levels of detoxification enzymes. The observed intensity of resistance underscores the pressing issue of insecticide resistance in urban areas, potentially compromising the effectiveness of vector control measures, especially pyrethroid-treated LLINs. Given the species unique behavior and ecology compared to An. gambiae, tailored vector control strategies are needed to address this concern in urban settings.

ecology↗

bioRxiv2023

Can motional dynamics account for the cytotoxicity of beta amyloid oligomers?

The underlying biophysical principle governing the cytotoxicity of the oligomeric aggregates of {beta}-amyloid (A{beta}) peptides has long been an enigma. Here we show that the size of A{beta}40 oligomers can be actively controlled by incubating the peptides in reverse micelles. Our approach allowed for the first time a detailed comparison of the structures and dynamics of two A{beta}40 oligomers of different size, viz., 10 and 23 nm, by solid-state NMR. From the chemical shift data, we infer that the conformation of the residues from K16 to K28 are different between the 10-nm and 23-nm oligomers. We find that the 10-nm oligomers are more cytotoxic, and the molecular motions of their charged residues are more dynamic. Interestingly, the residue A21 exhibits an unusually high structural rigidity. Our data raise the interesting possibility that the cytotoxicity of A{beta}40 oligomers could also be correlated to the motional dynamics of the charged residues.

biophysics↗

bioRxiv2022

Mapping potential malaria vector larval habitats for larval source management: Introduction to multi-model ensembling approaches

Mosquito larval source management (LSM) is a viable supplement to the currently implemented first-line malaria control tools for use under certain conditions for malaria control and elimination. Implementation of larval source management requires a carefully designed strategy and effective planning. Identification and mapping of larval sources is a prerequisite. Ensemble modeling is increasingly used for prediction modeling, but it lacks standard procedures. We proposed a detailed framework to predict potential malaria vector larval habitats using ensemble modeling, which includes selection of models, ensembling method and predictors; evaluation of variable importance; prediction of potential larval habitats; and assessment of prediction uncertainty. The models were built and validated based on multi-site, multi-year field observations and climatic/environmental variables. Model performance was tested using independent multi-site, multi-year field observations. Overall, we found that the ensembled model predicted larval habitats with about 20% more accuracy than the average of the individual models ensembled. Key larval habitat predictors were elevation, geomorphon class, and precipitation 2 months prior. Mapped distributions of potential malaria vector larval habitats showed different prediction errors in different ecological settings. This is the first study to provide a detailed framework for the process of multi-model ensemble modeling. Mapping of potential habitats will be helpful in LSM planning. Authors summaryMosquito larval source management (LSM) is a viable supplement to the currently implemented first-line malaria control tools. Implementation of LSM requires a carefully designed strategy and effective planning. Identification and mapping of larval sources is a prerequisite. Ensemble modeling is increasingly used for prediction modeling, but it lacks standard procedures. We proposed a detailed framework for such a process, including selection of models, ensembling methods and predictors; evaluation of variable importance; and assessment of prediction uncertainty. We used predictions of potential malaria vector larval habitats as an example to demonstrate how the procedure works, specifically, we used multi-site multi-year field observations to build and validate the model, and model performance was further tested using independent multi-site multi-year field observations - this training-validation-testing is often missing from previous studies. The proposed ensemble modeling procedure provides a framework for similar biological studies.

ecology↗

bioRxiv2021

Azithromycin Plus Zinc Sulfate Rapidly and Synergistically Suppresses IκBα-Mediated In Vitro Human Airway Cell ACE2 Expression for SARS-CoV-2 Entry

Large-scale efforts have been persistently undertaken for medical prophylaxis and treatment of COVID-19 disasters worldwide. A variety of novel viral spike protein-targeted vaccine preparations have recently been clinically distributed based on accelerated approval. We revisited the early but inconclusive clinical interest in the combination of azithromycin and zinc sulfate repurposing with safety advantages. In vitro proof of concept was provided for rapid and synergistic suppression of ACE2 expression following treatments in human airway cells, Calu-3 and H322M. The two representative ACE2-expressing human airway cells indicate the upper and lower respiratory tracts. Prophylactic and early therapeutic roles of azithromycin combined with zinc are proposed for virus cellular entry prevention potential bridging to effective antibody production.

molecular biology↗

bioRxiv2020

Plasmodium falciparum increases its investment in gametocytes in the wet season in asymptomatic individuals

In many regions, malaria transmission is seasonal, but it is not well understood whether P. falciparum modulates its investment in transmission in response to seasonal vector abundance. In two sites in western Kenya (Chulaimbo and Homa Bay), we sampled 1116 asymptomatic individuals in the wet season, when vectors are abundant, and 1743 in the dry season. We screened for P. falciparum by qPCR, and gametocytes by pfs25 RT-qPCR. Parasite prevalence in Chulaimbo and Homa Bay was 27.1% and 9.4% in the dry season, and 48.2% and 7.8% in the wet season respectively. Mean parasite densities did not differ between seasons (P=0.562). A contrasting pattern of gametocyte carriage was observed. In the wet season, fewer infections harbored gametocytes (22.3% vs. 33.8%, P=0.009), but densities were 3-fold higher (P<0.001). Thus, in the wet season, among gametocyte positive individuals, higher proportion of all parasites were gametocytes, reflecting an increased investment in transmission.

microbiology↗