Structure-dependent relative toxic potencies of selected pyrrolizidine alkaloids

Pyrrolizidine alkaloids are naturally occurring secondary plant metabolites mainly found in plant families of Asteraceae, Boraginaceae, and Fabaceae. Chemically, PAs consist of a pyrrolizidine core bearing hydroxyl groups, the so-called necine base, and mono- or dicarboxylic necine acids bound to the pyrrolizidine core via ester linkages. 1,2-unsaturated PAs are hepatotoxic, genotoxic, and carcinogenic due to the highly reactive pyrrolic metabolites formed by cytochrome P450 monooxygenases (CYPs) primarily in the liver. The presence of PAs as frequent contaminants in the wide variety of food and feed products would be a concern for public health. Due to the inadequate data, the risk assessment of PAs was mainly approached using the two most toxic potent congeners, i.e., lasiocarpine and riddelliine. However, the toxic potencies of individual PA congeners differentiated widely between the congeners probably related to their structural features. The risk of PA-containing products is indeed overestimated, and a comprehensive risk assessment should take these differences into account. After analyzing the data of many PAs, Merz and Schrenk derived interim Relative Potency (iREP) factors to present the differences in their toxicity between the sub-groups concerning their structural features. But since this concept was derived from an inadequate database, it was found that the relative toxicity of individual congeners cannot be entirely reliably evaluated. My work aimed to achieve more comprehensive congener-specific in vitro toxicological data and estimate the structure-related characteristics for refining this concept. For this purpose, ten congeners, lasiocarpine, monocrotaline, retrorsine, senecionine, seneciphylline, echimidine, europine, heliotrine, indicine, and lycopsamine, were determined in a series of in vitro test systems with different endpoints to quantify their cytotoxicity, genotoxicity, and mutagenicity. Cytotoxicity was assessed using the Alamar blue assay. A clear structure dependence could be demonstrated in primary rat hepatocytes and HepG2 (CYP3A4) cells. On the contrary, in HepG2 cells, none of the selected PAs exhibited cytotoxic effects, probably due to the lack of CYPs. The role of CYP450 enzymes in metabolic activation was further confirmed using an inhibition assay and the activity of CYP450 enzymes was measured by a kinetic assay analyzing 7-benzyloxyresorufin-O-dealkylation (BROD). Furthermore, utilizing a glutathione-reductase-DTNB recycling assay indicated that glutathione might not play a critical role in PA-induced cytotoxicity. A micronucleus test was used for determining the PA-induced clastogenic genotoxicity. All selected PA congeners exhibited a concentration-dependent manner in the HepG2 (CYP3A4) cells. The relative potencies of PA congeners estimated from Alamar blue assay and micronucleus assay are generally consistent with the following ranking: lasiocarpine > senecionine > seneciphylline ≥ retrorsine > heliotrine (?) echimidine ≥ europine ≈ indicine ≈ lycopsamine ≈ monocrotaline. Compared to the iREP reported by Merz and Schrenk, monocrotaline exhibited considerably lower toxic potency. However, echimidine was more toxic than expected. On the other hand, mutagenicity was measured in Ames fluctuation assay with Salmonella typhimurium strains TA98 and TA100. None of the selected PA congeners up to 300 µM showed mutagenic effects despite metabolic activation with S9-mix

Coherent output of photons from coupled superconducting transmission line resonators controlled by charge qubits

We study the coherent control of microwave photons propagating in a superconducting waveguide consisting of coupled transmission line resonators, each of which is connected to a tunable charge qubit. While these coupled line resonators form an artificial photonic crystal with an engineered photonic band structure, the charge qubits collectively behave as spin waves in the low excitation limit, which modify the band-gap structure to slow and stop the microwave propagation. The conceptual exploration here suggests an electromagnetically controlled quantum device based on the on-chip circuit QED for the coherent manipulation of photons, such as the dynamic creation of laser-like output from the waveguide by pumping the artificial atoms for population inversion.Comment: 8 pages, 3 figure

Flat bands and Z2 topological phases in a non-Abelian kagome lattice

We introduce a non-Abelian kagome lattice model that has both time-reversal and inversion symmetries and study the flat band physics and topological phases of this model. Due to the coexistence of both time-reversal and inversion symmetries, the energy bands consist of three doubly degenerate bands whose energy and conditions for the presence of flat bands could be obtained analytically, allowing us to tune the flat band with respect to the other two dispersive bands from the top to the middle and then to the bottom of the three bands. We further study the gapped phases of the model and show that they belong to the same phase as the band gaps only close at discrete points of the parameter space, making any two gapped phases adiabatically connected to each other without closing the band gap. Using the Pfaffian approach based on the time-reversal symmetry and parity characterization from the inversion symmetry, we calculate the bulk topological invariants and demonstrate that the unique gapped phases belong to the Z2 quantum spin Hall phase, which is further confirmed by the edge state calculation

Effect of Peer assessment on Project Performance of Students at Different Learning Levels

Peer assessment has been increasingly integrated in educational settings as a strategy to foster student learning. Yet little has been studied about how students at different learning levels may benefit from peer assessment. This study examined how peer assessment and students’ learning levels influenced students’ project performance by using a two-way factorial design. One hundred and thirty teacher education students participated in this quasi-experimental study. When working on a technology-integrated lesson plan project, the experimental group completed an online peer assessment process while the control group followed the traditional discussion method. Students’ learning levels were measured and divided into low-, average- and high-achieving according to the quality of their draft lesson plans. Data analysis suggested that the impact of peer assessment on students’ lesson plan project seemed to vary according to students’ learning levels. While low- and average-achieving students showed significantly improved performance right after the integration of a peer assessment model, the model seemed to have had less impact on the performance of high-achieving students. Significance, implications and limitations of findings are discussed