Vector Group Ltd.

Abstract: Pyrethroids are commonly used as mosquito adulticides and evolution of resistance to these compounds is a major threat to public health. 'Knockdown resistance' to pyrethroids (kdr) is frequently caused by nonsynonymous mutations in the voltage-gated sodium channel transmembrane protein (para) that reduce pyrethroid binding. Early detection of kdr is critical to the development of resistance management strategies in mosquitoes including Aedes aegypti, the most prevalent vector of dengue and yellow fever viruses. Brengues et al. described seven novel mutations in hydrophobic segment 6 of domain II of para in Ae. aegypti. Assays on larvae from strains bearing these mutations indicated reduced nerve sensitivity to permethrin inhibition. Two of these occurred in codons Iso1011 and Val1016 in exons 20 and 21 respectively. A transition in the third position of Iso1011 encoded a Met1011 replacement and a transversion in the second position of Val1016 encoded a Gly1016 replacement. We have screened this same region in 1318 mosquitoes in 32 additional strains; 30 from throughout Latin America. While the Gly1016 allele was never detected in Latin America, we found two new mutations in these same codons. A transition in the first position of codon 1011 encodes a Val replacement while a transition in the first position of codon 1016 encodes an Iso replacement. We developed PCR assays for these four mutations that can be read either on an agarose gel or as a melting curve. Selection experiments, one with deltamethrin on a field strain from Santiago de Cuba and another with permethrin on a strain from Isla Mujeres, Mexico rapidly increased the frequency of the Iso1016 allele. Bioassays of F(3) offspring arising from permethrin susceptible Val1016 homozygous parents and permethrin resistant Iso1016 homozygous parents show that Iso1016 segregates as a recessive allele in conferring kdr. Analysis of segregation between alleles at the 1011 and 1016 codons in the F(3) showed a high rate of recombination even though the two codons are only separated by a ~250 bp intron. The tools and information presented provide a means for early detection and characterization of kdr that is critical to the development of strategies for resistance management.

Abstract: Alleles subject to strong, recent positive selection will be swept toward fixation together with contiguous sections of the genome. Whether the genomic signatures of such selection will be readily detectable in outbred wild populations is unclear. In this study, we employ haplotype diversity analysis to examine evidence for selective sweeps around knockdown resistance (kdr) mutations associated with resistance to dichlorodiphenyltrichloroethane and pyrethroid insecticides in the mosquito Anopheles gambiae. Both kdr mutations have significantly lower haplotype diversity than the wild-type (nonresistant) allele, with kdr L1014F showing the most pronounced footprint of selection. We complement these data with a time series of collections showing that the L1014F allele has increased in frequency from 0.05 to 0.54 in 5 years, consistent with a maximum likelihood–fitted selection coefficient of 0.16 and a dominance coefficient of 0.25. Our data show that strong, recent positive selective events, such as those caused by insecticide resistance, can be identified in wild insect populations.

Abstract: Experimental test results are used to determine the performance that can be achieved from a multibeam antenna array, with fixed-beam azimuths, relative to a traditional dual-diversity three-sector antenna configuration. The performance tradeoffs between the hysterisis level, switching time, and gain improvement for a multibeam antenna are also examined. The multibeam antenna uses selection combining to switch the signals from the two strongest directional beams to the base station's main and diversity receivers. To assess the impact of beamwidth on overall system performance, the following two multibeam antennas were tested: a 12-beam 30/spl deg/ beamwidth array and a 24-beam 15/spl deg/ beamwidth array. Both multibeam antennas were field-tested in typical cellular base station sites located in heavy urban and light urban environments. Altogether, the system performance is evaluated by investigating three fundamental aspects of multibeam antenna behavior. First, the relative powers of the signals measured in each directional beam of the multibeam antenna are characterized. Then, beam separation statistics for the strongest two signals are examined. Gain improvements achievable with a multibeam antenna compared to the traditional sector configuration are determined in the second phase of the analysis. Results indicate that in excess of 5 dB of gain enhancement can be achieved with a 24-beam base station antenna in a cellular mobile radio environment. Finally, the effects of hysterisis level and switching time are characterized based on gain reductions relative to a reference case with no hysterisis and a 0.5-s switching decision time. Useful approximations are developed for the gain effects associated with varying hysterisis levels and switching times. The resulting design curves and empirical rules allow engineers to quantify multibeam antenna performance while making appropriate tradeoffs for parameter selection.