Quantitative Evaluation of the Environmental Impact Quotient (EIQ) for Comparing Herbicides

Various indicators of pesticide environmental risk have been proposed, and one of the most widely known and used is the environmental impact quotient (EIQ). The EIQ has been criticized by others in the past, but it continues to be used regularly in the weed science literature. The EIQ is typically considered an improvement over simply comparing the amount of herbicides applied by weight. Herbicides are treated differently compared to other pesticide groups when calculating the EIQ, and therefore, it is important to understand how different risk factors affect the EIQ for herbicides. The purpose of this work was to evaluate the suitability of the EIQ as an environmental indicator for herbicides. Simulation analysis was conducted to quantify relative sensitivity of the EIQ to changes in risk factors, and actual herbicide EIQ values were used to quantify the impact of herbicide application rate on the EIQ Field Use Rating. Herbicide use rate was highly correlated with the EIQ Field Use Rating (Spearman’s rho >0.96, P-value <0.001) for two herbicide datasets. Two important risk factors for herbicides, leaching and surface runoff potential, are included in the EIQ calculation but explain less than 1% of total variation in the EIQ. Plant surface half-life was the risk factor with the greatest relative influence on herbicide EIQ, explaining 26 to 28% of the total variation in EIQ for actual and simulated EIQ values, respectively. For herbicides, the plant surface half-life risk factor is assigned values without any supporting quantitative data, and can result in EIQ estimates that are contrary to quantitative risk estimates for some herbicides. In its current form, the EIQ is a poor measure of herbicide environmental impact.     

Isomeric lipid signatures reveal compartmentalized fatty acid metabolism in cancer

The cellular energy and biomass demands of cancer drive a complex dynamic between uptake of extracellular FAs and their de novo synthesis. Given that oxidation of de novo synthesized FAs for energy would result in net-energy loss, there is an implication that FAs from these two sources must have distinct metabolic fates; however, hitherto, all FAs have been considered part of a common pool. To probe potential metabolic partitioning of cellular FAs, cancer cells were supplemented with stable isotope-labeled FAs. Structural analysis of the resulting glycerophospholipids revealed that labeled FAs from uptake were largely incorporated to canonical (sn-) positions on the glycerol backbone. Surprisingly, labeled FA uptake also disrupted canonical isomer patterns of the unlabeled lipidome and induced repartitioning of n-3 and n-6 PUFAs into glycerophospholipid classes. These structural changes support the existence of differences in the metabolic fates of FAs derived from uptake or de novo sources and demonstrate unique signaling and remodeling behaviors usually hidden from conventional lipidomics.     

Filamin structure,function and mechanics: are altered filamin-mediated force responses associated with human disease?

The cytoskeleton framework is essential not only for cell structure and stability but also for dynamic processes such as cell migration, division and differentiation. The F-actin cytoskeleton is mechanically stabilised and regulated by various actin-binding proteins, one family of which are the filamins that cross-link F-actin into networks that greatly alter the elastic properties of the cytoskeleton. Filamins also interact with cell membrane-associated extracellular matrix receptors and intracellular signalling proteins providing a potential mechanism for cells to sense their external environment by linking these signalling systems. The stiffness of the external matrix to which cells are attached is an important environmental variable for cellular behaviour. In order for a cell to probe matrix stiffness, a mechanosensing mechanism functioning via alteration of protein structure and/or binding events in response to external tension is required. Current structural, mechanical, biochemical and human disease-associated evidence suggests filamins are good candidates for a role in mechanosensing.     

1-Alkyl-3-amino-5-aryl-1H-[1,2,4]triazoles: novel synthesis via cyclization of N-acyl-S-methylisothioureas with alkylhydrazines and their potent corticotropin-releasing factor-1 (CRF(1)) receptor antagonist activities.

Cyclizations of alkylhydrazines with N-acyl-S-methylisothioureas, readily synthesized from acyl chlorides, sodium thioisocyanate, dialkylamines then methyl iodide in a one-pot reaction, gave 1-alkyl-3-dialkylamino-5-phenyltriazoles 7 as major products. The regioisomers were assigned through the use of NOE NMR experiments. While bearing a N-bis(cyclopropyl)methyl-N-propylamino group, this series of compounds shows very good binding affinity on the human CRF₁ receptor. Among them, 1-methyl-3-[N-bis(cyclopropyl)methyl-N-propylamino]-5-(2,4-dichlorophenyl)-1H-[1,2,4]triazole 7a had the best binding affinity for the CRF₁ receptor (K_i=9 nM).     

Screening of Drug Metabolizing Enzymes for the Ginsenoside Compound K In Vitro: An Efficient Anti-Cancer Substance Originating from Panax Ginseng

Ginsenoside compound K (CK), a rare ginsenoside originating from Panax Ginseng, has been found to possess unique pharmacological activities specifically as anti-cancers. However, the role of cytochrome P450s (CYPs) in the metabolism of CK is unclear. In this study, we screened the CYPs for the metabolism of CK in vitro using human liver microsomes (HLMs) or human recombinant CYPs. The results showed that CK inhibited the enzyme activities of CYP2C9 and CYP3A4 in the HLMs. The K_m and V_max values of CK were 84.20±21.92 μM and 0.28±0.04 nmol/mg protein/min, respectively, for the HLMs; 34.63±10.48 μM and 0.45±0.05 nmol/nmol P450/min, respectively, for CYP2C9; and 27.03±5.04 μM and 0.68±0.04 nmol/nmol P450/min, respectively, for CYP3A4. The IC₅₀ values were 16.00 μM and 9.83 μM, and K_i values were 14.92 μM and 11.42μM for CYP2C9 and CYP3A4, respectively. Other human CYP isoforms, including CYP1A2, CYP2A6, CYP2D6, CYP2E1, and CYP2C19, showed minimal or no effect on CK metabolism. The results suggested that CK was a substrate and also inhibitors for both CYP2C9 and CYP3A4. Patients using CK in combination with therapeutic drugs that are substrates of CYP2C9 and CYP3A4 for different reasons should be careful, although the inhibiting potency of CK is much poorer than that of enzyme-specific inhibitors.     

Application of a bioinformatics training delivery method for reaching dispersed and distant trainees

Many initiatives have addressed the global need to upskill biologists in bioinformatics tools and techniques. Australia is not unique in its requirement for such training, but due to its large size and relatively small and geographically dispersed population, Australia faces specific challenges. A combined training approach was implemented by the authors to overcome these challenges. The “hybrid” method combines guidance from experienced trainers with the benefits of both webinar-style delivery and concurrent face-to-face hands-on practical exercises in classrooms. Since 2017, the hybrid method has been used to conduct 9 hands-on bioinformatics training sessions at international scale in which over 800 researchers have been trained in diverse topics on a range of software platforms. The method has become a key tool to ensure scalable and more equitable delivery of short-course bioinformatics training across Australia and can be easily adapted to other locations, topics, or settings.