Studies of clomazone mode of action

Intact spinach chloroplasts were used to determine if clomazone, 5-OH clomazone, and/or 5-keto clomazone inhibited the chloroplastic isoprenoid pathway. When isopentenyl pyrophosphate was used as a precursor, neither clomazone nor the clomazone metabolites (5-OH clomazone and 5-keto clomazone) inhibited the formation of products separated by HPLC in the organic phase. However, when pyruvate, a substrate for the first committed step of the pathway, was used as a precursor, both 5-keto clomazone and fosmidomycin reduced the formation of a non-polar product and increased the formation of a polar product in the organic phase. Only 5-keto clomazone, not 5-OH clomazone or clomazone, inhibited the formation of an additional product other than fosmidomycin in the aqueous phase from pyruvate incorporation. In an in vitro assay, 5-keto clomazone inhibited DXP synthase, the enzyme catalyzing the first committed step of the chloroplastic isoprenoid pathway. Therefore, our studies show that neither clomazone nor 5-OH clomazone inhibits the chloroplastic isoprenoid pathway, only 5-keto clomazone does.     

Distribution of Megastigmus aculeatus (Hymenoptera: Torymidae) and the levels of seed predation of Rosa multiflora (Rosaceae)

Rosa multiflora Thunb. (Rosaceae), an invasive plant that currently infests millions of hectares in the eastern half of the USA, was planted initially in the 1940s as a “living fence”, cover for game animals and for erosion control. The larvae of Megastigmus aculeatus var. nigroflavus Hoffmeyer (Hymenoptera: Torymidae) feed on the developing R. multiflora seeds and have the potential to reduce the seed output of R. multiflora. Rosehips were collected from 49 sites across eastern and southern Iowa, USA, to determine the presence and distribution of M. aculeatus, the larvae of which were found in 266 of the 979 (27%) rosehips that were dissected and at 31 of the 49 sites (63%) that were sampled. The levels of M. aculeatus infestation over 2–3 years were determined at three selected sites and it was documented that more seeds were aborted than were viable or contained wasp larvae. A negative relationship was observed between the numbers of both the aborted and the viable seeds and the probability of a rosehip being attacked by M. aculeatus, indicating that M. aculeatus females are not preferentially selecting rosehips with higher numbers of viable or aborted seeds for oviposition. There is a significant reduction in both the viable seeds and the aborted seeds in hips that have been attacked by M. aculeatus. Detailed knowledge of R. multiflora demography is necessary to determine the level of seed predation that is required to reduce the recruitment of new individuals into the population.     

Argentine ant control around homes: efficacy of treatments and urban runoff

ABSTRACT

Pest management professionals in California receive more customer complaints about Argentine ants than for any other urban ant pest. Fipronil, applied as a 30 × 30 cm band around the house foundation, has become the preferred treatment used to control these ants. Unfortunately, fipronil is now showing up in urban waterways at levels that are toxic to aquatic invertebrates. Our recent studies are aimed at mitigating insecticide runoff while still controlling the ant infestations. A high priority is preventing fipronil runoff from the driveway to the street, where it can flow into drains and from there to urban waterways. In this paper, two related studies address these issues. Not treating driveways with fipronil reduced by two to three orders of magnitude its runoff when compared with earlier studies. However, not treating the driveway can reduce efficacy of treatments. Granular bifenthrin, indoxacarb, botanicals, and a thiamethoxam ant bait were tested as supplemental treatments. The gel bait showed the best result as a supplement, but only after 8 weeks. We have reduced fipronil runoff while maintaining efficacy of the ant treatments.     

Therapeutic Potential of Marine Peptides in Prostate Cancer: Mechanistic Insights

Prostate cancer (PCa) is the leading cause of cancer death in men, and its treatment is commonly associated with severe adverse effects. Thus, new treatment modalities are required. In this context, natural compounds have been widely explored for their anti-PCa properties. Aquatic organisms contain numerous potential medications. Anticancer peptides are less toxic to normal cells and provide an efficacious treatment approach via multiple mechanisms, including altered cell viability, apoptosis, cell migration/invasion, suppression of angiogenesis and microtubule balance disturbances. This review sheds light on marine peptides as efficacious and safe therapeutic agents for PCa.     

Conus regius-Derived Conotoxins: Novel Therapeutic Opportunities from a Marine Organism

Conus regius is a marine venomous mollusk of the Conus genus that captures its prey by injecting a rich cocktail of bioactive disulfide bond rich peptides called conotoxins. These peptides selectively target a broad range of ion channels, membrane receptors, transporters, and enzymes, making them valuable pharmacological tools and potential drug leads. C. regius-derived conotoxins are particularly attractive due to their marked potency and selectivity against specific nicotinic acetylcholine receptor subtypes, whose signalling is involved in pain, cognitive disorders, drug addiction, and cancer. However, the species-specific differences in sensitivity and the low stability and bioavailability of these conotoxins limit their clinical development as novel therapeutic agents for these disorders. Here, we give an overview of the main pharmacological features of the C. regius-derived conotoxins described so far, focusing on the molecular mechanisms underlying their potential therapeutic effects. Additionally, we describe adoptable chemical engineering solutions to improve their pharmacological properties for future potential clinical translation.     

Ultra‐long‐acting recombinant insulin for the treatment of diabetes mellitus in dogs

BackgroundFor the treatment of diabetes mellitus (DM) in dogs, novel insulins with decreased injection frequency while maintaining safety and efficacy are desirable. Insulin fused with immunoglobulin‐fragment‐crystallizable (Fc) has an ultra‐long plasma half‐life because it recycles through cells, protected from proteolysis.HypothesisGlycemic control can be achieved in diabetic dogs with a recombinant fusion protein of a synthetic insulin and canine Fc (AKS‐218d) administered subcutaneously once‐weekly.AnimalsFive client‐owned dogs with naturally occurring DM.MethodsProspective clinical trial in dogs with DM that were recruited from the UC Davis Veterinary Teaching Hospital and local veterinary clinics. Dogs previously controlled using intermediate‐acting insulin q12h were transitioned to once‐weekly injections of a preliminary construct identified as AKS‐218d. The dose of AKS‐218d was titrated weekly for 8 weeks based on clinical response and continuous interstitial glucose monitoring. Clinical signs, body weight, serum fructosamine concentrations, and mean interstitial glucose concentrations (IG) over the preceding week were compared between baseline (before AKS‐218d) and during the last week of treatment. Data were compared using nonparametric paired tests.ResultsOnce‐weekly AKS‐218d, compared to baseline twice‐daily insulin therapy, resulted in no significant changes in clinical signs, median (range) body weight (+0.4 kg [−0.5‐1.1]; P = .6), fructosamine concentration (−75 mmol/L [−215 to +126]; P = .4), or mean IG (+81 mg/dL [−282 to +144]; P = .8). No adverse reactions were reported.ConclusionControl of clinical signs, body weight, and maintenance of glycemia was achieved with this once‐weekly novel insulin construct in 4 of 5 dogs.