Mixed Type of Malignant Mesothelioma in an Aged Male ICR Mouse

Multiple whitish nodules in the thoracic cavity at the site of the thymus were observed in a 101-week-old male ICR mouse. In a histopathological examination, the neoplastic cells were predominantly fusiform in shape and proliferated in sarcomatoid growth patterns. Some neoplastic cells showed epithelial growth patterns, such as the ductal structures. Mitotic figures were frequently seen, and small necrotic foci and invasion to adjacent thoracic organs were noted. In Alcian blue staining, bluish materials were observed between fusiform-shaped cells and in some of the lumens of the ductal structures. In immunohistochemistry, both fusiform-shaped and ductal structure-forming cells were positive for vimentin and weakly positive to positive for cytokeratin. Based on the aforementioned findings, the thoracic nodules were diagnosed as a mixed type of malignant mesothelioma. This case was thought to be rare because of the very low occurrence of spontaneous mesothelioma in mice

Ethylene Glycol Monomethyl Ether–Induced Toxicity Is Mediated through the Inhibition of Flavoprotein Dehydrogenase Enzyme Family

Ethylene glycol monomethyl ether (EGME) is a widely used industrial solvent known to cause adverse effects to human and other mammals. Organs with high metabolism and rapid cell division, such as testes, are especially sensitive to its actions. In order to gain mechanistic understanding of EGME-induced toxicity, an untargeted metabolomic analysis was performed in rats. Male rats were administrated with EGME at 30 and 100 mg/kg/day. At days 1, 4, and 14, serum, urine, liver, and testes were collected for analysis. Testicular injury was observed at day 14 of the 100 mg/kg/day group only. Nearly 1900 metabolites across the four matrices were profiled using liquid chromatography-mass spectrometry/mass spectrometry and gas chromatography-mass spectrometry. Statistical analysis indicated that the most significant metabolic perturbations initiated from the early time points by EGME were the inhibition of choline oxidation, branched-chain amino acid catabolism, and fatty acid β-oxidation pathways, leading to the accumulation of sarcosine, dimethylglycine, and various carnitine- and glycine-conjugated metabolites. Pathway mapping of these altered metabolites revealed that all the disrupted steps were catalyzed by enzymes in the primary flavoprotein dehydrogenase family, suggesting that inhibition of flavoprotein dehydrogenase–catalyzed reactions may represent the mode of action for EGME-induced toxicity. Similar urinary and serum metabolite signatures are known to be the hallmarks of multiple acyl-coenzyme A dehydrogenase deficiency in humans, a genetic disorder because of defects in primary flavoprotein dehydrogenase reactions. We postulate that disruption of key biochemical pathways utilizing flavoprotein dehydrogenases in conjugation with downstream metabolic perturbations collectively result in the EGME-induced tissue damage

Practical Application of Toxicogenomics for Profiling Toxicant-Induced Biological Perturbations

A systems-level understanding of molecular perturbations is crucial for evaluating chemical-induced toxicity risks appropriately, and for this purpose comprehensive gene expression analysis or toxicogenomics investigation is highly advantageous. The recent accumulation of toxicity-associated gene sets (toxicogenomic biomarkers), enrichment in public or commercial large-scale microarray database and availability of open-source software resources facilitate our utilization of the toxicogenomic data. However, toxicologists, who are usually not experts in computational sciences, tend to be overwhelmed by the gigantic amount of data. In this paper we present practical applications of toxicogenomics by utilizing biomarker gene sets and a simple scoring method by which overall gene set-level expression changes can be evaluated efficiently. Results from the gene set-level analysis are not only an easy interpretation of toxicological significance compared with individual gene-level profiling, but also are thought to be suitable for cross-platform or cross-institutional toxicogenomics data analysis. Enrichment in toxicogenomics databases, refinements of biomarker gene sets and scoring algorithms and the development of user-friendly integrative software will lead to better evaluation of toxicant-elicited biological perturbations

On-chip in vitro cell-network pre-clinical cardiac toxicity using spatiotemporal human cardiomyocyte measurement on a chip

To overcome the limitations and misjudgments of conventional prediction of arrhythmic cardiotoxicity, we have developed an on-chip in vitro predictive cardiotoxicity assay using cardiomyocytes derived from human stem cells employing a constructive spatiotemporal two step measurement of fluctuation (short-term variability; STV) of cells repolarization and cell-to-cell conduction time, representing two origins of lethal arrhythmia. Temporal STV of field potential duration (FPD) showed a potential to predict the risks of lethal arrhythmia originated from repolarization dispersion for false negative compounds, which was not correctly predicted by conventional measurements using animal cells, even for non-QT prolonging clinical positive compounds. Spatial STV of conduction time delay also unveiled the proarrhythmic risk of asynchronous propagation in cell networks, whose risk cannot be correctly predicted by single-cell-based measurements, indicating the importance of the spatiotemporal fluctuation viewpoint of in vitro cell networks for precise prediction of lethal arrhythmia reaching clinical assessment such as thorough QT assay

Changes in the quality of democracy from 1970 to 2020

Bakalaura darba nosaukums ir “Demokrātijas kvalitātes izmaiņas no 1970.gada līdz 2020.gadam”. Izvirzītais pētnieciskais jautājums ir: kādi apstākļi rada izmaiņas valsts demokrātiskās kvalitātes līmenī? Darba mērķis ir analizēt demokrātijas kvalitātes līmeņa izmaiņas septiņās valstīs laika posmā no 1970.gada līdz 2020.gadam. Darba teorētiskajā pamatā ir Roberta Dāla darbs “Polyarchy” un Semuela Hantingtona “Trešais vilnis”. Darba gadījuma pētniecība balstās uz Freedom House veikto apskatu par atbilstošo valsti un tās padziļinātu vēstures apskatu. Kopumā, tiek apskatītas sešas Eiropas valstis un Amerikas Savienotās valstis, kas sniegs informāciju par demokrātijas kvalitāti un mainošajiem apstākļiem. Darba rezultātā tiek noskaidrots, ka demokrātijas kvalitāti ietekmē sabiedrības pieredze ar demokrātisku sistēmu, terorisma draudi, konstitūcija un sabiedrības mainošie uzskati.The name of this paper is “Changes in the quality of democracy from 1970 to 2020”. The paper raises a research question: what circumstances cause change in a state’s level of democratic quality? The aim of this paper is to analyze the changes in the quality of democracy within seven countries between 1970 and 2020. The theoretical basis of this work formed from Robert Dahl’s work “Polyarchy” and Samuel Huntington’s work “The Third Wave”. The paper uses the case study method to inspect each country’s political history and Freedom House to attach a reliable score to its relative situation. The paper draws the conclusion that countries with long term democratic experience have less problems with threats to its systems or faster recoveries from a sudden stop of its democracy system, terrorism affects the quality of democracy and so does a state’s constitution. Changes in views are also a factor of change in the quality of democracy