Modification of cell vulnerability to oxidative stress by N-(3-oxododecanoyl)-L-homoserine-lactone, a quorum sensing molecule, in rat thymocytes

N-(3-oxododecanoyl)-L-homoserine-lactone (ODHL), a quorum sensing molecule, affects intracellular Zn2+ concentration ([Zn2+]i) and cellular levels of nonprotein thiols ([NPT]i) of rat thymic lymphocytes, both of which are assumed to affect cell vulnerability to oxidative stress. Therefore, it is interesting to examine the effects of ODHL on the cells under oxidative stress. ODHL augmented the cytotoxicity of H2O2, but not calcium ionophore A23187. ODHL potentiated the H2O2-induced elevation of [Zn2+]i, wherein, it greatly attenuated the H2O2-induced increase in intracellular Ca2+ concentration. ODHL did not affect [NPT]i in the presence of H2O2. Therefore, we conclude that the elevation of [Zn2+]i is involved in the ODHL-induced potentiation of H2O2 cytotoxicity. Our findings suggest that ODHL modifies cell vulnerability to oxidative stress in host cells

Ziram, a dithiocarbamate fungicide, exhibits pseudo-cytoprotective actions against oxidative stress in rat thymocytes : Possible environmental risks

Ziram, a dithiocarbamate fungicide, protects various vegetables and fruits against infections by fungus. Recently, there have been increasing anxieties about the risks in the use of dithiocarbamate fungicides. Our previous studies showed that Zn2+ was a determinant of Ziram cytotoxicity. In addition, Zn2+ is linked to H2O2 cytotoxicity. Therefore, in this study, we aimed to test the hypothesis that Ziram could augment the cytotoxicity of H2O2 by examining the changes induced by Ziram in some cellular parameters in rat thymic lymphocytes subjected to H2O2-induced oxidative stress using flow-cytometric methods with fluorescent dyes. Ziram significantly attenuated H2O2-induced cell death at sublethal concentrations. However, in the cells under oxidative stress elicited by H2O2, Ziram promoted the changing over from intact cells to living cells with exposed phosphatidylserine (PS) on plasma membranes, whereas it inhibited the transition from PS-exposed living cells to dead cells. Ziram significantly augmented H2O2 actions, including reduction of cellular glutathione levels and elevation of intracellular Zn2+ concentrations. Conversely, it attenuated H2O2-induced depolarization of mitochondrial membrane potential. Ziram at sublethal concentrations seems to exhibit promotive and suppressive actions on the process of cell death caused by H2O2. Ziram increased the number of living cells with exposed PS, a phenomenon characteristic of early stages of apoptosis. Thus, it is concluded that Ziram exhibits pseudo-cytoprotective actions against H2O2- induced oxidative stress

Cell death process induced by hydrogen peroxide is accelerated by clioquinol in rat thymocytes

We examined the effect of clioquinol on the process of cell death induced by hydrogen peroxide (H2O2) using a flow cytometric technique with propidium iodide and annexin V-FITC in order to see if clioquinol augments the toxicity caused by oxidative stress. Clioquinol (100 nM) alone did not change the process of spontaneous cell death. However, the agent accelerated the process of cell death induced by 300 μM H2O2. Result indicates that clioquinol augments the cytotoxicity induced by H2O2. Therefore, the use of clioquinol may be inadequate for the treatment of some diseases related to oxidative stress

Zinc is a determinant of the cytotoxicity of Ziram, a dithiocarbamate fungicide, in rat thymic lymphocytes : Possible environmental risk

Ziram, one of dithiocarbamate fungicides, is widely applied to agriculture because the agent protects various crops from fungal infections. Risks of dithiocarbamate biocide use are concerned. It was previously reported that Ziram increased the intracellular concentration of Zn2+. Therefore, we cytometrically studied the mechanism of Zn2+-dependent lethal actions of Ziram on rat lymphocytes under environmentally relevant Zn2+ levels. Membrane and cellular parameters of rat lymphocytes were estimated by flow-cytometric techniques with appropriate fluorescent probes. The Ziram-induced increase in cell lethality was completely attenuated by Zn2+ chelators. A significant raise of cell lethality was found on the simultaneous application of Ziram at a sublethal concentration and ZnCl2. The combination of Ziram and ZnCl2 increased the cellular superoxide anion content and decreased the cellular GSH content, which possibly caused the increase in cell lethality. The zinc concentrations under present experimental conditions were comparable to the environmentally relevant concentrations found in rivers. Therefore, the environmental level of zinc may be critical in estimating the toxicity of Ziram to wild animals

Spatial Evolution of Wave‐Particle Interaction Region Deduced From Flash‐Type Auroras and Chorus‐Ray Tracing

In-situ observations of spatial variations of the wave-particle interaction region require a large number of satellite probes. As an alternative, flash-type auroras, a kind of pulsating aurora, driven by discrete chorus elements, can be used to investigate the interaction region with a high spatial resolution. We estimated the spatial extent of wave-particle interaction region from ground-based observations of flash aurora at Gakona (62.39°N, 214.78°E), Alaska at subauroral latitudes, and found that the auroral expansion was predominantly to the low-latitude side. The spatial displacement is thought to be caused by the propagation effects of chorus waves in the magnetosphere. Using ray tracing analysis to take into account chorus wave propagation, we reconstructed the spatiotemporal evolution of the volume emission rate and confirmed that the predominant expansion is toward the lower-latitude side in the ionosphere. This study shows that chorus wave propagation in the magnetosphere gives new insight for characterizing the transverse size (across the geomagnetic field line) of wave-particle interaction regions. The calculated spatial scale of the column auroral emission shows a correlation with the magnetic latitude of the resonance region at magnetic latitudes within 10° of the equatorial plane of the magnetosphere. Our results suggest that the spatial scale of a flash aurora is indirectly related to the chorus amplitude because the latitudinal range of the wave-particle interaction is important for the growth of wave amplitude

Recent Results from LHD Experiment with Emphasis on Relation to Theory from Experimentalist’s View

he Large Helical Device (LHD) has been extending an operational regime of net-current free plasmas towardsthe fusion relevant condition with taking advantage of a net current-free heliotron concept and employing a superconducting coil system. Heating capability has exceeded 10 MW and the central ion and electron temperatureshave reached 7 and 10 keV, respectively. The maximum value of β and pulse length have been extended to 3.2% and 150 s, respectively. Many encouraging physical findings have been obtained. Topics from recent experiments, which should be emphasized from the aspect of theoretical approaches, are reviewed. Those are (1) Prominent features in the inward shifted configuration, i.e., mitigation of an ideal interchange mode in the configuration with magnetic hill, and confinement improvement due to suppression of both anomalous and neoclassical transport, (2) Demonstration ofbifurcation of radial electric field and associated formation of an internal transport barrier, and (3) Dynamics of magnetic islands and clarification of the role of separatrix

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection