Resilience of transfluthrin to oxidative attack by duplicated CYP6P9 variants known to confer pyrethroid resistance in the major malaria mosquito Anopheles funestus.

Resistance to common pyrethroids, such as deltamethrin and permethrin is widespread in the malaria mosquito Anopheles funestus and mainly conferred by upregulated cytochrome P450 monooxygenases (P450s). In the pyrethroid resistant laboratory strain An. funestus FUMOZ-R the duplicated genes CYP6P9a and CYP6P9b are highly upregulated and have been shown to metabolize various pyrethroids, including deltamethrin and permethrin.

Discovery of Rigidified α,β-Unsaturated Imines as New Resistance-breaking Insecticides for Malaria Vector Control.

During our continuous search for new resistance-breaking insecticides applicable to malaria vector control, a new class of α,β-unsaturated imines was identified by applying the principle of conformational rigidification as a powerful tool for compound optimisation. Herein we describe the successful synthesis of these compounds and their biological test results. Our lead compound 16 from this insecticidal class outperforms market standards, notably for the control of mosquito strains that exhibit either metabolic or target-site resistance to these established insecticides.

Flupyradifurone (Sivanto™) and its novel butenolide pharmacophore: Structural considerations.

Flupyradifurone (4-[(2,2-difluoroethyl)amino]-2(5H)-furanone), a member of the new class of butenolide insecticides, contains a novel bioactive scaffold as pharmacophore. It is very versatile in terms of application methods to a variety of crops, exhibits excellent and fast action against a broad spectrum of sucking pest insects including selected neonicotinoid resistant pest populations such as whiteflies and aphids expressing metabolic resistance mechanisms. As a partial agonist flupyradifurone reversibly binds to insect nicotinic acetylcholine receptors (nAChRs) and lacks metabolization by CYP6CM1, a cytochrome P450 over-expressed in cotton whiteflies resistant to imidacloprid and pymetrozine.

Flupyradifurone: a brief profile of a new butenolide insecticide.

Background: The development and commercialisation of new chemical classes of insecticides for efficient crop protection measures against destructive invertebrate pests is of utmost importance to overcome resistance issues and to secure sustainable crop yields. Flupyradifurone introduced here is the first representative of the novel butenolide class of insecticides active against various sucking pests and showing an excellent safety profile.

Results: The discovery of flupyradifurone was inspired by the butenolide scaffold in naturally occurring stemofoline.

Two pathogens and one disease: detection and identification of flea-borne Rickettsiae in areas endemic for murine typhus in California.

Results of an environmental assessment conducted in a newly emergent focus of murine typhus in southern California are described. Opossums, Didelphis virginiana Kerr, infested with cat fleas, Ctenocephalides felis Buché, in the suburban area were abundant. Animal and flea specimens were tested for the DNA of two flea-borne rickettsiae, Rickettsia typhi and Rickettsia felis.

Host (avian) biting preference of southern California Culex mosquitoes (Diptera: Culicidae).

The host preference of a vector mosquito species plays a significant role in determining human and animal risk of infection with mosquito-transmitted pathogens. Host preferences of common southern California Culex species for four bird species, American crow (Corvus brachyrhynchos), house sparrow (Passer domesticus), house finch (Carpodacus mexicanus), and mourning dove (Zenaida macroura), were examined by determining the proportion of each mosquito species that successfully engorged on each of the four bird species presented equally within a net trap to wild host-seeking mosquitoes. Bloodmeals in engorged mosquitoes captured within the net trap were identified to avian species by using a multiplex polymerase chain reaction assay targeting the cytochrome b gene sequence.

Insecticidal heterolignans--tubuline polymerization inhibitors with activity against chewing pests.

Starting from natural product podophyllotoxin 1 substituted heterolignans were identified with promising insecticidal in vivo activity. The impact of substitution in each segment of the core structure was investigated in a detailed SAR study, and variation of substituents in both aromatic moieties afforded derivatives 5 and 43 with broad insecticidal activity against lepidopteran and coleopteran species. In vitro measurements supported by modeling studies indicate that heterolignans 3-134 act as tubuline polymerization inhibitors interacting with the colchicine-binding site.

Alkaloids from stems and leaves of Stemona japonica and their insecticidal activities.

Five new alkaloids, 6beta-hydroxystemofoline (1), 16-hydroxystemofoline (2), neostemofoline (3), protostemodiol (4), and 13-demethoxy-11(S*),12(R*)-dihydroprotostemonine (5), along with 10 known alkaloids, were isolated from stems and leaves of Stemona japonica. Their structures were elucidated by 1D and 2D NMR and other spectroscopic studies. The insecticidal activity of the agonist 16-hydroxystemofoline (2) and antagonist 13-demethoxy-11(S*),12(R*)-dihydroprotostemonine (5) was demonstrated by electrophysiological in vitro tests on the insect nicotinic acetylcholine receptor and by in vivo screenings against relevant agricultural insect pests.

Acaricide resistance in northern fowl mite (Ornithonyssus sylviarum) populations on caged layer operations in Southern California.

Southern California caged layer operations were visited over 3 yr. Northern fowl mites from 26 field populations were tested for acaricide resistance using a capillary pipette and glass dish bioassay. One was a susceptible field population with no pesticide exposure for over 30 yr (reference site for resistance ratio calculation).

An automated feeding apparatus for in vitro maintenance of the human head louse, Pediculus capitis (Anoplura: Pediculidae).

An automated feeding apparatus was developed to maintain the human head louse (Pediculus capitis DeGeer) in vitro. With the use of valves and timers, banked human blood and saline from refrigerated reservoirs were pumped into and flushed out of the system every 7 d. During this rotational interval, bloodmeals were provided to head lice continuously and ad libitum through a stretched Nescofilm-silicone sandwich membrane.

Incidence of a new sex-ratio-distorting endosymbiotic bacterium among arthropods.

Many intracellular micro-organisms are now known to cause reproductive abnormalities and other phenomena in their hosts. The endosymbiont Wolbachia is the best known of these reproductive manipulators owing to its extremely high incidence among arthropods and the diverse host effects it has been implicated as causing. However, recent evidence suggests that another intracellular bacterium, a Cytophaga-like organism (CLO), may also induce several reproductive effects in its hosts.

Variation in the NS3/NS3A gene of bluetongue viruses contained in Culicoides sonorensis collected from a single site in southern California.

To determine the variability of the NS3/NS3A gene of field strains of BTV contained in Culicoides sonorensis collected from a single site in California (CA), the NS3/NS3A gene was directly amplified and sequenced from 22 pools of C. sonorensis and compared with those of previously characterized field isolates from CA, as well as to viruses that caused recent outbreaks of bluetongue disease in ruminants in CA. Phylogenetic analysis established that the NS3/NS3A gene of strains of BTV contained in C.

Failure of a permethrin treatment regime to protect cattle against bluetongue virus.

Holstein heifers in a confined feedlot setting on a southern California dairy were either sprayed individually along the ventral midline using 0.2% permethrin (250 ml/animal) (two pens) or were not treated (two pens). Treatments (n = 6 dates) were applied every 2 wk during the peak fall bluetongue virus transmission season (22 August-29 October).

Feeding and survival of Culicoides sonorensis on cattle treated with permethrin or pirimiphos-methyl.

The persistence of permethrin (5% a.i.) and pirimiphos-methyl (27% a.

Field morphological variation and laboratory hybridization of Culicoides variipennis sonorensis and C. v. occidentalis (Diptera:Ceratopogonidae) in southern California.

Two field populations of Culicoides variipennis (Coquillett) from southern California, C. v. occidentalis Wirth & Jones from the Salton Sea and C.

Lachnellins A, B, C, D, and naphthalene-1,3,8-triol, biologically active compounds from a Lachnellula species (ascomycetes).

In the course of our search for new biologically active metabolites, lachnellin A (1), a metabolite with high cytotoxic and antimicrobial activities, the structurally related lachnellins B, C and D (3, 4, 7), and naphthalene-1,3,8-triol (8), an inhibitor of malate synthase (EC 4.1.3.

Temperature Effects on Survival and Development of Heleidomermis magnapapula in the Laboratory.

The mermithid Heleidomermis magnapapula Poinar and Mullens, a parasite of the biting midge Culicoides variipennis (Coquillett), was exposed to constant temperatures in the laboratory. Survival of the free-living stages and development times of eggs and the parasitic phase were inversely related to temperature. Average preparasite longevity was 70, 46, 42, and 22 hours at 15.

Darlucins A and B, new isocyanide antibiotics from Sphaerellopsis filum (Darluca filum).

Two new xanthocillin type antibiotics, darlucin A (1) and B (2), were isolated from fermentations of Sphaerellopsis filum (Darluca filum). Their structures were established by spectroscopic methods. The darlucins are the first known compounds with a 1,2-diisocyanoalkene moiety.

Kuehneromycins A and B, two new biological active compounds from a Tasmanian Kuehneromyces sp. (Strophariaceae, Basidiomycetes).

In a search for new inhibitors of RNA-directed DNA-polymerases kuehneromycin A (1) was isolated from fermentations of a Tasmanian Kuehneromyces species. Its structure was elucidated by spectroscopic methods. Kuehneromycin A (1) is a non-competitive inhibitor of avian myeloblastosis virus (Ki 200 microM) and moloney murine leukemia virus (Ki 40 microM) reverse transcriptases.

Caloporoside, a new inhibitor of phospholipases C from Caloporus dichrous (Fr.) Ryv.

A new salicylic acid derivative, caloporoside, was isolated from fermentations of Caloporus dichrous. Its structure was elucidated by a combination of chemical and spectroscopic methods. Caloporoside exhibits weak antibacterial and antifungal activities and is a quite selective inhibitor of phospholipase C isolated from pig brain (Ki 12, 3 microM).

Hyphodontal, a new antifungal inhibitor of reverse transcriptases from Hyphodontia sp. (Corticiaceae, Basidiomycetes).

In a search for inhibitors of RNA-directed DNA polymerases a new isolactarane sesquiterpenoid, hyphodontal (1), was isolated from fermentations of a Canadian Hyphodontia species. Its structure was elucidated by spectroscopic methods. Hyphodontal strongly inhibits the growth of several yeasts and is a non-competitive inhibitor of avian myeloblastosis virus (Ki 346 microM) and Moloney murine leukemia virus (Ki 112 microM) reverse transcriptases.

The mniopetals, new inhibitors of reverse transcriptases from a Mniopetalum species (basidiomycetes). II. Structure elucidation.

The structures of six new drimance sesquiterpenoids, mniopetals A-F, were elucidated by a combination of chemical and spectroscopic methods. The mniopetals are inhibitors of RNA-directed DNA-polymerases.