Advancements in Mass Rearing the Air Potato Beetle Lilioceris cheni

The air potato beetle, Lilioceris cheni Gressitt and Kimoto (Coleoptera:Chrysomelidae), is a successful biological control agent of the air potato vine, Dioscorea bulbifera L. (Dioscoreales: Dioscoreaceae), in the southern United States. Lilioceris cheni is currently being mass-reared by the Florida Department of Agriculture and Consumer Services Division of Plant Industry (FDACS-DPI) for biological control releases and research. The facility rears and releases over 50,000 adult beetles annually at approximately 1000 different locations. In addition to data on beetle production and distribution, studies on alternative larval and adult diets are described. Adults fed bulbils as the sole food source had reduced life spans compared with beetles given fresh air potato leaves. Adults survived without air potato leaves or bulbils for several days to two weeks depending on availability of leaves at emergence. Larvae did not survive on a modified artificial Colorado potato beetle diet containing fresh air potato vine leaves. Adults survived while consuming artificial diet but ceased oviposition. They, however, resumed egg laying less than one week after being returned to a diet of fresh air potato vine leaves.

Determination of Oxaliplatin by a UHPLC-MS/MS Method: Application to Pharmacokinetics and Tongue Tissue Distribution Studies in Rats

Oxaliplatin (OXP), a third-generation platinum-based chemotherapy drug, was often indirectly analyzed via total platinum by an ICP-MS because it was difficult to directly quantify using an LC-MS/MS method, due to its instability, bad column separability and severe MS signal inhibition. Here, we developed and validated a specific, sensitive and reproducible LC-MS/MS method for the quantification of OXP itself in rat plasma and tongue tissue on a SCIEX 4000 QTRAP® MS/MS system equipped with a Phenomenex Lux 5u Cellulose-1 column (250 × 4.6 mm, 5 μm). This method was validated at the lower limit of detection (LOD) and the lower limit of quantitation (LLOQ) of 5 ng/mL and 10 ng/mL, with linearity of 10–5000 ng/mL (r2 > 0.99) and 10–2500 ng/mL (r2 > 0.99), in rat plasma and tongue homogenates, respectively. The intra- and inter-day precision (CV%) and accuracy (RE%) were within 15% for LLOQ, low-, medium- and high-quality control samples. The mean extraction recoveries were around 50% and 80% for plasma and tongue homogenates, respectively. This assay was successfully applied to pharmacokinetics study following intravenous administration of OXP, as well as tongue tissue distribution after 1 h and 4 h of a novel oral mucosal patch application.

A Use of Tritium-Labeled Peat Fulvic Acids and Polyphenolic Derivatives for Designing Pharmacokinetic Experiments on Mice

Natural products (e.g., polyphenols) have been used as biologically active compounds for centuries. Still, the mechanisms of biological activity of these multicomponent systems are poorly understood due to a lack of appropriate experimental techniques. The method of tritium thermal bombardment allows for non-selective labeling and tracking of all components of complex natural systems. In this study, we applied it to label two well-characterized polyphenolic compounds, peat fulvic acid (FA-Vi18) and oxidized lignin derivative (BP-Cx-1), of predominantly hydrophilic and hydrophobic character, respectively. The identity of the labeled samples was confirmed using size exclusion chromatography. Using ultra-high resolution Fourier transform ion cyclotron resonance mass spectrometry (FT ICR MS), key differences in the molecular composition of BP-Cx-1 and FA-Vi18 were revealed. The labeled samples ([3H]-FA-Vi18 (10 mg/kg) and [3H]-BP-Cx-1 (100 mg/kg)) were administered to female BALB/c mice intravenously (i.v.) and orally. The label distribution was assessed in blood, liver, kidneys, brain, spleen, thymus, ovaries, and heart using liquid scintillation counting. Tritium label was found in all organs studied at different concentrations. For the fulvic acid sample, the largest accumulation was observed in the kidney (Cmax 28.5 mg/kg and 5.6 mg/kg, respectively) for both routes. The organs of preferential accumulation of the lignin derivative were the liver (Cmax accounted for 396.7 and 16.13 mg/kg for i.v. and p.o. routes, respectively) and kidney (Cmax accounted for 343.3 and 17.73 mg/kg for i.v. and p.o. routes, respectively). Our results demonstrate that using the tritium labeling technique enabled successful pharmacokinetic studies on polyphenolic drugs with very different molecular compositions. It proved to be efficient for tissue distribution studies. It was also shown that the dosage of the polyphenolic drug might be lower than 10 mg/kg due to the sensitivity of the 3H detection technique.

Prediction Modeling of Household’s Preparedness of Natural Hazards Mitigation

Natural disasters are showing an increase in the magnitude, frequency, and geographic distribution. Studies have shown that individuals’ self-sufficiency, which largely depends on household preparedness, is very important for hazard mitigation in at least the first 72 hours following a disaster. However, for factors that influence a household’s disaster preparedness, though there are many studies trying to identify from different aspects, we still lack an integrative analysis on how these factors contribute to a household’s preparation. This paper aims to build a classification model to predict whether a household has prepared for a potential disaster based on their personal characteristics and the environment they located. We collect data from the Federal Emergency Management Agency’s National Household Survey in 2018 and train four classification models - logistic regression, decision trees, support vector machines, and multi-layer perceptron classifier models- to predict the impact of personal characteristics and the environment they located on household prepare for the potential natural disaster. Results show that the multi-layer perceptron classifier model outperforms others with the highest scoring on both recall (0.8531) and f1 measure (0.7386). In addition, feature selection results also show that among other factors, a household’s accessibility to disaster-related information is the most critical factor that impacts household disaster preparation. Though there is still room for further parameter optimization, the model gives a clue that we could support disaster management by gathering publicly accessible data.

Prediction modeling of Household’s Preparedness of Natural Hazards Mitigation

Natural disasters are showing an increase in the magnitude, frequency, and geographic distribution. Studies have shown that individuals’ self-sufficiency, which largely depends on household preparedness, is very important for hazard mitigation in at least the first 72 hours following a disaster. However, for factors that influence a household’s disaster preparedness, though there are many studies trying to identify from different aspects, we still lack an integrative analysis on how these factors contribute to a household’s preparation. This paper aims to build a classification model to predict whether a household has prepared for a potential disaster based on their personal characteristics and the environment they located. We collect data from the Federal Emergency Management Agency’s National Household Survey in 2018 and train four classification models - logistic regression, decision trees, support vector machines, and multi-layer perceptron classifier models- to predict the impact of personal characteristics and the environment they located on household prepare for the potential natural disaster. Results show that the multi-layer perceptron classifier model outperforms others with the highest scoring on both recall (0.8531) and f1 measure (0.8531). In addition, feature selection results also show that among other factors, a household’s accessibility to disaster-related information is the most critical factor that impacts household disaster preparation. Though there is still room for further parameter optimization, the model gives a clue that we could support disaster management by gathering publicly accessible data.

Single Cell Center of Mass for the Analysis of BMP Receptor Heterodimers Distributions

At the plasma membrane, transmembrane receptors are at the interface between cells and their environment. They allow sensing and transduction of chemical and mechanical extracellular signals. The spatial distribution of receptors and the specific recruitment of receptor subunits to the cell membrane is crucial for the regulation of signaling and cell behavior. However, it is challenging to define what regulates such spatial patterns for receptor localization, as cell shapes are extremely diverse when cells are maintained in standard culture conditions. Bone morphogenetic protein receptors (BMPRs) are serine-threonine kinases, which build heteromeric complexes of BMPRI and II. These are especially interesting targets for receptor distribution studies, since the signaling pathways triggered by BMPR-complexes depends on their dimerization mode. They might exist as preformed complexes, or assemble upon binding of BMP, triggering cell signaling which leads to differentiation or migration. In this work we analyzed BMPR receptor distributions in single cells grown on micropatterns, which allow not only to control cell shape, but also the distribution of intracellular organelles and protein assemblies. We developed a script called ComRed (Center Of Mass Receptor Distribution), which uses center of mass calculations to analyze the shift and spread of receptor distributions according to the different cell shapes. ComRed was tested by simulating changes in experimental data showing that shift and spread of distributions can be reliably detected. Our ComRed-based analysis of BMPR-complexes indicates that receptor distribution depends on cell polarization. The absence of a coordinated internalization after addition of BMP suggests that a rapid and continual recycling of BMPRs might occur. Receptor complexes formation and localization in cells induced by BMP might yield insights into the local regulation of different signaling pathways.

Pharmacokinetics and brain distribution studies of 6-hydroxykynurenic acid and its structural modified compounds

Objectives 6-Hydroxykynurenic acid (6-HKA) is an organic acid component in extracts of Ginkgo biloba leaves and acts as a major contributor to neurorestorative effects, while its oral bioavailability was low. Therefore, using prodrug method to improve the bioavailability and brain content of 6-HKA is significant. Methods Three structural modified compounds of 6-HKA were synthesized, and ultra performance liquid chromatography-tandem mass spectrometry methods for quantification of these structural modified compounds in rat plasma and rat brain homogenate were established and comprehensively validated. The methods were effectively applied to investigate the effects of structural modification on apparent permeability coefficients in cells, the pharmacokinetics and the brain distribution in rats. Key findings The results illustrated that esterification can greatly improve the apparent permeability coefficient and bioavailability of 6-HKA. Comparing with direct oral administration of 6-HKA, the bioavailability of isopropyl ester was greatly improved (from 3.96 ± 1.45% to 41.8 ± 15.3%), and the contents of 6-HKA in rat brains (49.7 ± 9.2 ng/g brain) were significantly higher after oral administration. Conclusions The bioavailability and the brain content of 6-HKA can be improved by the prodrug method. Among three structural modified compounds, isopropyl-esterified 6-HKA was the most promising treatment.

A Semi Rigid Novel Hydroxamate AMPED-Based Ligand for 89Zr PET Imaging

In this work, we designed, developed, characterized, and investigated a new chelator and its bifunctional derivative for 89Zr labeling and PET-imaging. In a preliminary study, we synthesized two hexadentate chelators named AAZTHAS and AAZTHAG, based on the seven-membered heterocycle AMPED (6-amino-6-methylperhydro-1,4-diazepine) with the aim to increase the rigidity of the 89Zr complex by using N-methyl-N-(hydroxy)succinamide or N-methyl-N-(hydroxy)glutaramide pendant arms attached to the cyclic structure. N-methylhydroxamate groups are the donor groups chosen to efficiently coordinate 89Zr. After in vitro stability tests, we selected the chelator with longer arms, AAZTHAG, as the best complexing agent for 89Zr presenting a stability of 86.4 ± 5.5% in human serum (HS) for at least 72 h. Small animal PET/CT static scans acquired at different time points (up to 24 h) and ex vivo organ distribution studies were then carried out in healthy nude mice (n = 3) to investigate the stability and biodistribution in vivo of this new 89Zr-based complex. High stability in vivo, with low accumulation of free 89Zr in bones and kidneys, was measured. Furthermore, an activated ester functionalized version of AAZTHAG was synthesized to allow the conjugation with biomolecules such as antibodies. The bifunctional chelator was then conjugated to the human anti-HER2 monoclonal antibody Trastuzumab (Tz) as a proof of principle test of conjugation to biologically active molecules. The final 89Zr labeled compound was characterized via radio-HPLC and SDS-PAGE followed by autoradiography, and its stability in different solutions was assessed for at least 4 days.