Integrating biological and chemical controls in decision making: European corn borer (Lepidoptera: Crambidae) control in sweet corn as an example

As growers switch to transgenic crops and selective insecticides that are less toxic to natural enemies, natural enemies can become more important in agricultural pest management. Current decision-making guides are generally based on pest abundance and do not address pest and natural enemy toxicity differences among insecticides or the impact of natural enemies on pest survival. A refined approach to making pest management decisions is to include the impact of natural enemies and insecticides, thereby better integrating biological and chemical control. The result of this integration is a dynamic threshold that varies for each product and the level of biological control expected. To demonstrate the significance of conserved biological control in commercial production, a decision-making guide was developed that evaluates control options for European corn borer, Ostrinia nubilalis (Hübner) (Lepidoptera: Crambidae), in sweet corn, Zea mays L., where the primary natural enemies are generalist predators. Management options are lambda-cyhalothrin (broad-spectrum insecticide), spinosad (selective insecticide), Trichogramma ostriniae (Peng and Chen) (Hymenoptera: Trichogrammatidae) (parasitoid), and Bacillus thuringiensis (Bt) sweet corn (transgenic variety). The key factors influencing thresholds for all treatments are the intended market, predator populations, and the presence of alternative foods for the predators. Treatment cost is the primary factor separating the threshold for each treatment within a common scenario, with the lowest cost treatment having the lowest pest threshold. However, when the impact of a treatment on natural enemies is projected over the 3-wk control period, the impact of the treatment on predators becomes the key factor in determining the threshold, so the lowest thresholds are for broad-spectrum treatments, whereas selective products can have thresholds > 6 times higher by the third week. This decision guide can serve as a framework to help focus future integrated pest management research and to aid in the selection of pest management tools.     

Pregnancy increases myometrial artery myogenic tone via NOS- or COX-independent mechanisms

Myogenic tone (MT) is a primary modulator of blood flow in the resistance vasculature of the brain, kidney, skeletal muscle, and perhaps in other high-flow organs such as the pregnant uterus. MT is known to be regulated by endothelium-derived factors, including products of the nitric oxide synthase (NOS) and/or the cyclooxygenase (COX) pathways. We asked whether pregnancy influenced MT in myometrial arteries (MA), and if so, whether such an effect could be attributed to alterations in NOS and/or COX. MA (200-300 μm internal diameter, 2-3 mm length) were isolated from 10 nonpregnant and 12 pregnant women undergoing elective hysterectomy or cesarean section, respectively. In the absence of NOS and/or COX inhibition, pregnancy was associated with increased MT in endothelium-intact MA compared with MA from nonpregnant women (P < 0.01). The increase in MT was not due to increased Ca(2+) entry via voltage-dependent channels since both groups of MA exhibited similar levels of constriction when exposed to 50 mM KCl. NOS inhibition (N(ω)-nitro-l-arginine methyl ester, l-NAME) or combined NOS/COX inhibition (l-NAME/indomethacin) increased MT in MA from pregnant women (P = 0.001 and P = 0.042, respectively) but was without effect in arteries from nonpregnant women. Indomethacin alone was without effect on MT in MA from either nonpregnant or pregnant women. We concluded that MT increases in MA during human pregnancy and that this effect was partially opposed by enhanced NOS activity.     

Effect of insecticides and Plutella xylostella (Lepidoptera: Plutellidae) genotype on a predator and parasitoid and implications for the evolution of insecticide resistance

In the laboratory and in cages in the greenhouse, we evaluated the toxicity of two insecticides (lambda-cyhalothrin and spinosad) on the parasitoid, Diadegma insulare (Cresson), and the predator, Coleomegilla maculate (DeGeer), both natural enemies of the diamondback moth, Plutella xylostella (L.). Lambda-cyhalothrin was very toxic to both natural enemies. Spinosad was less toxic to C. maculata adults and larvae, and slightly toxic to D. insulare. Both natural enemies suppressed P. xylostella populations in cages with 80% spinosad-treated and 20% nontreated plants; such suppression was not seen when lambda-cyhalothrin was used. Using broccoli, Brassica oleracea L. variety italica, a common host for P. xylostella, we also studied direct and indirect effects of both natural enemies in the presence and absence of the two insecticides and to different P. xylostella genotypes: resistant to the insecticide, susceptible, or heterozygous. Neither natural enemy could distinguish host genotype if P. xylostella were feeding on nontreated plants. They could also not distinguish between larvae feeding on spinosad-treated plants and nontreated plants, but D. insulare could distinguish between larvae feeding on lambda-cyhalothrin treated and nontreated plants. Our studies suggest that lambda-cyhalothrin has direct toxicity to these two natural enemies, can affect their host foraging and acceptance of P. xylostella and consequently would not be compatible in conserving these natural enemies in a program for suppression of P. xylostella. In contrast, our studies suggest that treatment with spinosad has much less effect on these natural enemies and would allow them to help suppress populations of P. xylostella. These findings are discussed in relation to the evolution of insecticide resistance and suppression of the pest populations.     

Increasing serum half-life and extending cholesterol lowering in vivo by engineering antibody with pH-sensitive binding to PCSK9

Target-mediated clearance and high antigen load can hamper the efficacy and dosage of many antibodies. We show for the first time that the mouse, cynomolgus, and human cross-reactive, antagonistic anti-proprotein convertase substilisin kexin type 9 (PCSK9) antibodies J10 and the affinity-matured and humanized J16 exhibit target-mediated clearance, resulting in dose-dependent pharmacokinetic profiles. These antibodies prevent the degradation of low density lipoprotein receptor, thus lowering serum levels of LDL-cholesterol and potently reducing serum cholesterol in mice, and selectively reduce LDL-cholesterol in cynomolgus monkeys. In order to increase the pharmacokinetic and efficacy of this promising therapeutic for hypercholesterolemia, we engineered pH-sensitive binding to mouse, cynomolgus, and human PCSK9 into J16, resulting in J17. This antibody shows prolonged half-life and increased duration of cholesterol lowering in two species in vivo by binding to endogenous PCSK9 in mice and cynomolgus monkeys, respectively. The proposed mechanism of this pH-sensitive antibody is that it binds with high affinity to PCSK9 in the plasma at pH 7.4, whereas the antibody-antigen complex dissociates at the endosomal pH of 5.5-6.0 in order to escape from target-mediated degradation. Additionally, this enables the antibody to bind to another PCSK9 and therefore increase the antigen-binding cycles. Furthermore, we show that this effect is dependent on the neonatal Fc receptor, which rescues the dissociated antibody in the endosome from degradation. Engineered pH-sensitive antibodies may enable less frequent or lower dosing of antibodies hampered by target-mediated clearance and high antigen load.     

A spatial analytical approach for selecting reintroduction sites for burbot in English rivers

1. Availability of suitable habitat is a prerequisite for species reintroduction success, and to ensure population persistence, investigations of a species’ habitat utilisation throughout its life history should be conducted as part of a feasibility study. 2. Habitat utilisation models for burbot, Lota lota, developed using data from field studies conducted in France and Germany and information from the literature were used to assess the feasibility of reintroducing burbot into rivers of its former native range in eastern England. 3. Per cent tree roots, aquatic vegetation and flow types were important predictors of adult burbot abundance. Furthermore, the habitat utilisation models were supplemented with information from the literature, which suggested that off‐channel habitat such as wetlands and backwaters is important for spawning and nursery stages. 4. An assessment of the habitat availability in the rivers of the burbot’s former native range using variables related to spawning and nursery and adult life stages showed that although adult habitat was widely distributed, the availability of spawning and nursery habitat was less abundant, potentially limiting successful reestablishment. 5. Potential suitable habitat was concentrated in the central and southern areas of the species’ former English distribution. Overall, rivers of the burbot’s former range potentially afford suitable habitat to sustain a reintroduced population. However, sites should be preferentially selected on the basis of having appropriate spawning and nursery areas.     

Reproductive Schedules in Southern Bluefin Tuna: Are Current Assumptions Appropriate?

Southern bluefin tuna (SBT) appear to comprise a single stock that is assumed to be both mixed across its distribution and having reproductive adults that are obligate, annual spawners. The putative annual migration cycle of mature SBT consists of dispersed foraging at temperate latitudes with migration to a single spawning ground in the tropical eastern Indian Ocean. Spawning migrations have been assumed to target two peaks in spawning activity; one in September-October and a second in February-March. SBT of sizes comparable to that of individuals observed on the spawning ground were satellite tagged in the Tasman Sea region (2003-2008) and demonstrated both migrations to the spawning grounds and residency in the Tasman Sea region throughout the whole year. All individuals undertaking apparent spawning migrations timed their movements to coincide with the second recognised spawning peak or even later. These observations suggest that SBT may demonstrate substantial flexibility in the scheduling of reproductive events and may even not spawn annually as currently assumed. Further, the population on the spawning grounds may be temporally structured in association with foraging regions. These findings provide new perspectives on bluefin population and spatial dynamics and warrant further investigation and consideration of reproductive schedules in this species.     

Dispersed oil disrupts microbial pathways in pelagic food webs

Most of the studies of microbial processes in response to the Deepwater Horizon oil spill focused on the deep water plume, and not on the surface communities. The effects of the crude oil and the application of dispersants on the coastal microbial food web in the northern Gulf of Mexico have not been well characterized even though these regions support much of the fisheries production in the Gulf. A mesocosm experiment was carried out to determine how the microbial community off the coast of Alabama may have responded to the influx of surface oil and dispersants. While the addition of glucose or oil alone resulted in an increase in the biomass of ciliates, suggesting transfer of carbon to higher trophic levels was likely; a different effect was seen in the presence of dispersant. The addition of dispersant or dispersed oil resulted in an increase in the biomass of heterotrophic prokaryotes, but a significant inhibition of ciliates, suggesting a reduction in grazing and decrease in transfer of carbon to higher trophic levels. Similar patterns were observed in two separate experiments with different starting nutrient regimes and microbial communities suggesting that the addition of dispersant and dispersed oil to the northern Gulf of Mexico waters in 2010 may have reduced the flow of carbon to higher trophic levels, leading to a decrease in the production of zooplankton and fish on the Alabama shelf.     

Synthesis, SAR, and preliminary mechanistic evaluation of novel antiproliferative N⁶,5'-bis-ureido- and 5'-carbamoyl-N⁶-ureidoadenosine derivatives

We have developed efficient methods for the preparation of N(6),5'-bis-ureidoadenosine derivatives and their 5'-carbamoyl-N(6)-ureido congeners. Treatment of 5'-azido-5'-deoxy-N(6)-(N-alkyl or -arylurea)adenosine derivatives (6a-d) with H(2)/Pd-C or Ph(3)P/H(2)O, followed by N-methyl-p-nitrophenylcarbamate gave N(6),5'-bis-ureido products 7a-d in 49-78% yield. Analogous derivatives in the 5'-carbamoyl-N(6)-ureido series were prepared by treatment of 2',3'-bis-O-TBS-adenosine (11) with N-methyl-p-nitrophenylcarbamate followed by acylation with appropriate isocyanates which gave 13a-d in 45-69% yield. A more versatile route for obtaining potentially vast libraries of compounds from both series was achieved by treatment of 5'-N-methylureido- or 5'-N-methylcarbamoyladenosine derivatives with ethylchlorformate to give N(6)-ethoxycarbonyl derivatives (9 and 14) in 55-63% yields, respectively. Simple heating of 9 or 14 in the presence of primary alkyl- or arylamines gave the corresponding N(6),5'-bis-ureido- or 5'-carbamoyl-N(6)-ureidoadenosine derivatives in good yields (33-72% and 39-83%; 10a-e and 15a-e, respectively). Significant antiproliferative activities (IC(50)≈4-10 μg/mL) were observed for a majority of the N(6),5'-bis-ureido derivatives, whereas the 5'-carbamoyl-N(6)-ureido derivatives were generally less active (IC(50) >100 μg/mL). A 2',3'-O-desilylated derivative (5'-amino-5'-deoxy-5'-N-methylureido-N(6)-(N-phenylcarbamoyl)adenosine, 16) was shown to inhibit binding of 16 of 441 protein kinases to immobilized ATP-binding site ligands by 30-40% in a competitive binding assay at 10 μM. Compound 16 was also shown to bind to bone morphogenetic protein receptor 1b (BMPR1b) with a Kd=11.5 ± 0.7 μM.     

A comparative analysis of carbon dioxide displacement rates for euthanasia of the ferret

Though carbon dioxide asphyxiation is a common method of euthanasia for laboratory animals, species-specific guidelines have not been established for this procedure in the domestic ferret (Mustela putorius furo). The authors investigated the efficacy and stress effects of carbon dioxide euthanasia in 24 ferrets that had participated in previous experimental protocols. They euthanized ferrets by placing them in cages that were either prefilled with carbon dioxide or gradually filled at a displacement rate of 10%, 20% or 50% of the cage volume per min. Blinded observers subjectively evaluated ferret distress. Prefilling the cage or filling it at a rate of 50% volume per min resulted in less time to recumbency and to last breath than did filling the cage at a slower displacement rate. Slower carbon dioxide displacement rates also caused an increase in ferret blood glucose concentrations, which may indicate distress. Overall, observers found that prefilling the euthanasia cage caused the least stress to ferrets.