Molecular Ecology of Pyrethroid Knockdown Resistance in Culex pipiens pallens Mosquitoes

Pyrethroid insecticides have been extensively used in China and worldwide for public health pest control. Accurate resistance monitoring is essential to guide the rational use of insecticides and resistance management. Here we examined the nucleotide diversity of the para-sodium channel gene, which confers knockdown resistance (kdr) in Culex pipiens pallens mosquitoes in China. The sequence analysis of the para-sodium channel gene identified L1014F and L1014S mutations. We developed and validated allele-specific PCR and the real-time TaqMan methods for resistance diagnosis. The real-time TaqMan method is more superior to the allele-specific PCR method as evidenced by higher amplification rate and better sensitivity and specificity. Significant positive correlation between kdr allele frequency and bioassay-based resistance phenotype demonstrates that the frequency of L1014F and L1014S mutations in the kdr gene can be used as a molecular marker for deltamethrin resistance monitoring in natural Cx. pipiens pallens populations in the East China region. The laboratory selection experiment found that L1014F mutation frequency, but not L1014S mutation, responded to deltamethrin selection, suggesting that the L1014F mutation is the key mutation conferring resistance to deltamethrin. High L1014F mutation frequency detected in six populations of Cx. pipens pallens suggests high prevalence of pyrethroid resistance in Eastern China, calling for further surveys to map the resistance in China and for investigating alternative mosquito control strategies

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

Insecticide Resistance Status and Mechanisms of Anopheles sinensis (Diptera: Culicidae) in Wenzhou, an Important Coastal Port City in China

Although scaled-up interventions and effective control efforts have drastically reduced malaria morbidity and mortality, malaria remains a serious threat to public health worldwide. Anopheles sinensis Wiedemann 1828 is a historically important vector of Plasmodium vivax (Haemosporida: Plasmodiidae) malaria in China. Insecticide resistance has become a major obstacle to vector-borne disease control. However, little is known about the insecticide resistance of An. sinensis in Wenzhou, an important coastal port city in Zhejiang province, China. The aim of this study was to examine insecticide resistance and mechanisms in An. sinensis field mosquito populations. Evidence of multiple insecticide resistance was found in An. sinensis adult female populations. Medium to high frequencies of target site kdr together with fixed ace-1 mutations was detected in both the Ruian and Yongjia populations. Both populations showed an association between kdr L1014 mutation and resistance phenotype when tested against deltamethrin and DDT. Significantly different metabolic enzyme activities were found between the susceptible laboratory strain and field-collected mosquitoes from both Ruian and Yongjia. Both field collected An. sinensis populations exhibited significantly higher P450 enzyme activity compared with the laboratory strain, while the field-collected resistant mosquitoes exhibited various GST and COE enzyme activities. These results indicate multiple resistance mechanisms in An. sinensis field populations. Effective implementation of insecticide resistance management strategies is urgently needed. The data collected in this study will be valuable for modeling insecticide resistance spread and vector-control interventions

Insecticide Resistance Status and Mechanisms of \u3cem\u3eAnopheles sinensis \u3c/em\u3e (Diptera: Culicidae) in Wenzhou, an Important Coastal Port City in China

Although scaled-up interventions and effective control efforts have drastically reduced malaria morbidity and mortality, malaria remains a serious threat to public health worldwide. Anopheles sinensis Wiedemann 1828 is a historically important vector of Plasmodium vivax (Haemosporida: Plasmodiidae) malaria in China. Insecticide resistance has become a major obstacle to vector-borne disease control. However, little is known about the insecticide resistance of An. sinensis in Wenzhou, an important coastal port city in Zhejiang province, China. The aim of this study was to examine insecticide resistance and mechanisms in An. sinensis field mosquito populations. Evidence of multiple insecticide resistance was found in An. sinensis adult female populations. Medium to high frequencies of target site kdr together with fixed ace-1 mutations was detected in both the Ruian and Yongjia populations. Both populations showed an association between kdr L1014 mutation and resistance phenotype when tested against deltamethrin and DDT. Significantly different metabolic enzyme activities were found between the susceptible laboratory strain and field-collected mosquitoes from both Ruian and Yongjia. Both field collected An. sinensis populations exhibited significantly higher P450 enzyme activity compared with the laboratory strain, while the field-collected resistant mosquitoes exhibited various GST and COE enzyme activities. These results indicate multiple resistance mechanisms in An. sinensis field populations. Effective implementation of insecticide resistance management strategies is urgently needed. The data collected in this study will be valuable for modeling insecticide resistance spread and vector-control interventions

Molecular Ecology of Pyrethroid Knockdown Resistance in Culex pipiens pallens Mosquitoes

Pyrethroid insecticides have been extensively used in China and worldwide for public health pest control. Accurate resistance monitoring is essential to guide the rational use of insecticides and resistance management. Here we examined the nucleotide diversity of the para-sodium channel gene, which confers knockdown resistance (kdr) in Culex pipiens pallens mosquitoes in China. The sequence analysis of the para-sodium channel gene identified L1014F and L1014S mutations. We developed and validated allele-specific PCR and the real-time TaqMan methods for resistance diagnosis. The real-time TaqMan method is more superior to the allele-specific PCR method as evidenced by higher amplification rate and better sensitivity and specificity. Significant positive correlation between kdr allele frequency and bioassay-based resistance phenotype demonstrates that the frequency of L1014F and L1014S mutations in the kdr gene can be used as a molecular marker for deltamethrin resistance monitoring in natural Cx. pipiens pallens populations in the East China region. The laboratory selection experiment found that L1014F mutation frequency, but not L1014S mutation, responded to deltamethrin selection, suggesting that the L1014F mutation is the key mutation conferring resistance to deltamethrin. High L1014F mutation frequency detected in six populations of Cx. pipens pallens suggests high prevalence of pyrethroid resistance in Eastern China, calling for further surveys to map the resistance in China and for investigating alternative mosquito control strategies

<i>Culex pipiens pallens</i> mosquito mortality rate in standard WHO deltamethrin resistance bioassay.

<p><i>Culex pipiens pallens</i> mosquito mortality rate in standard WHO deltamethrin resistance bioassay.</p

Frequencies (in percentage) of <i>kdr</i> alleles in relation to mosquito survival phenotype determined by the deltamethrin susceptibility bioassay in six <i>Culex pipiens pallens</i> populations from China.

<p>Frequencies (in percentage) of <i>kdr</i> alleles in relation to mosquito survival phenotype determined by the deltamethrin susceptibility bioassay in six <i>Culex pipiens pallens</i> populations from China.</p

Dynamics of <i>kdr</i> allele frequency in response to deltamethrin selection.

<p><b>A</b>: wildtype L1014 allele frequency was significantly decreased under deltamethrin selection, but significantly increased in the absence of selection; <b>B</b>: L1014F allele frequency was significantly increased under selection, but significantly decreased when no insecticide selection pressure was available; and <b>C</b>: L1014S allele frequency was decreased regardless of deltamethrin selection.</p