The effect of pesticides on the NADH-supported mitochondrial respiration of permeabilized potato mitochondria.

Pesticides can seriously affect the respiratory chain of the mitochondria of many crops, reducing the intensity of plant growth and its yield. Studying the effect of pesticides on the bioenergetic parameters of intact plant mitochondria is a promising approach for assessing their toxicity. In this study, we investigated the effect of some pesticides on isolated potato mitochondria, which used exogenous NADH as a substrate for respiration. We showed that succinate is the most preferred substrate for phosphorylating respiration of intact potato tubers mitochondria. Potato mitochondria poorly oxidize exogenous NADH, despite of the presence of external NADH dehydrogenases. Permeabilization of the mitochondrial membrane with alamethicin increased the availability of exogenous NADH to complex I. However, the pathway of electrons through complex I to complex IV makes intact potato mitochondria susceptible to a number of pesticides such as difenoconazole, fenazaquin, pyridaben and tolfenpyrad, which strongly inhibit the rate of mitochondrial respiration. However, these pesticides only slightly inhibited the rate of oxygen consumption during succinate-supported respiration. Dithianon, the inhibitor of Complex II, is the only pesticide which significantly increased the respiratory rate of NADH-supported respiration of permeabilized mitochondria of potato. Thus, it can be assumed that the alternative NADH dehydrogenases for electron flow represent a factor responsible for plant resistance to xenobiotics, such as mitochondria-targeted pesticides.

The connection between rs6265 polymorphism in the BDNF gene and successful mastering of the video-oculographic interface.

A video-oculographic interface is a system for controlling objects using eye movements. The video-oculographic interface differs from other brain-computer interfaces regarding its improved accuracy, simplicity, and ergonomics. Despite these advantages, all users are not equally successful in mastering these various devices. It has been suggested that the genetic characteristics of the operators may determine the efficiency of video-oculographic interface mastery. We recruited healthy users with rs6313, rs2030324, rs429358, rs10119, rs457062, rs4290270, and rs6265 polymorphisms and analyzed the relationships between these polymorphisms and values of success in video-oculographic interface mastery. We found that carriers of the G/G genotype of the rs6265 polymorphism (BDNF gene) demonstrated the best results in video-oculographic interface mastery. In contrast, carriers of the A/A genotype were characterized by large standard deviations in the average amplitude of eye movement and the range of eye movement negatively correlated with goal achievement. This can be explained through the fact that carriers of the A/A genotype demonstrate lower synaptic plasticity due to reduced expression of BDNF when compared to carriers of the G/G genotype. These results expand our understanding of the genetic predictors of successful video-oculographic interface management, which will help to optimize device management training for equipment operators and people with disabilities.

The effect of pesticides on the mtDNA integrity and bioenergetic properties of potato mitochondria.

Potato (Solanum tuberosum L.) is one of the most common crops in the world, and it is very susceptible to a wide range of pests such as insects and fungi. The use of pesticides often results in the suppression of seed germination and plant growth, in particular, due to their effect on the respiratory chain of mitochondria. There are numerous studies of the effect of pesticides on animal mitochondria, but their interference with the electron transport in plant mitochondria is not well documented. We present the data showing that a number of pesticides inhibit electron flow, and other pesticides uncouple the respiratory chain. Among the studied pesticides engaging the alternative pathways of electron transport, dithianon led to an increase in the rate of H2O2 production but did not cause a strong increase in the amount of mtDNA damage as compared to other pesticides. In general, the main negative effect of the studied pesticides is manifested in a decrease of membrane potential with the maintenance of the rate of oxygen consumption and a low rate of H2O2 production. The mtDNA damage is caused mainly by pesticides belonging to the pyrethroid class and remains minor as compared to its damage in animals. Our data indicate that the respiratory chain of plant mitochondria is more resistant to pesticides as compared to animal mitochondria due to the presence of the alternative pathways of electron transport.

Long-term mildronate treatment increased Proteobacteria level in gut microbiome, and caused behavioral deviations and transcriptome change in liver, heart and brain of healthy mice.

Mildronate is a cardiac and neuroprotective drug that is widely used in some countries. By inhibiting carnitine biosynthesis, mildronate impairs the fatty acids transport into mitochondria, thereby decreasing the ß-oxidation intensity. Since 2016, it has been prohibited by the World Anti-Doping Agency (WADA). However, the information on its safety and its influence on the athletes' health is scarce. There are no published studies on whether mildronate-induced long-term metabolism "rearrangement" may cause negative effects on high-metabolic-rate organs and on the whole organism. Here, we demonstrate that long-term mildronate treatment of healthy mice induced global metabolism change at the transcriptome level in liver, heart, and brain. Mildronate treatment also induced some behavioral changes such as anxiety-related behavior and diminished explorative behavior. We also found that mildronate induced a dysbiosis, as manifested by an increase in Proteobacteria level in gut microbiome. At the same time, the absence of a statistically significant increase in mouse strength and endurance procedures suggests that mildronate effect on productivity is negligible. The sum of our data suggests that long-term treatment of healthy mice with mildronate induces dysbiosis and behavioral deviations despite the effectiveness of mildronate for cardiac and neurological diseases. Thus, we suggest that long-term mildronate treatment is undesirable or at the very least should be accompanied by prebiotics treatments, but this issue should be studied further.

Connection between polymorphisms in HTR2A, TPH2, BDNF, TOMM40 genes and the successful mastering of human-computer interfaces.

The development of human-computer interfaces in different individuals occur with different efficiencies, this is due to the individual characteristics of the genotype determined by the single-nucleotide polymorphism (SNP) of a person. Here, we checked the connection between the success of the acquisition of the brain-computer, eye-tracking, electromyographic, and respiratory interfaces and SNP of the TOMM40, BDNF, HTR2A and TPH2 genes. Here, we show that the T-allele in rs6313 of the HTR2A gene is associated with an increase in the number of correctly submitted commands of the electromyographic and eye-tracking interfaces. This is probably due to the fact that, the T-allele carriers decrease expression of this serotonin receptor. The decreased expression of HTR2A may be a reason for an increase in the number of accurately submitted commands. It was shown that the TT genotype of rs4290270 polymorphism was associated with an increase in the accuracy of work with the myographic interface. In addition, the association of subjective interfaces work time with polymorphisms rs429358 and rs2030324 was noted. Thus, the genotypic characteristics of individuals can be a predictive sign for the degree of success of mastering human-computer interfaces, which can allow to expand the understanding of training the neural mechanisms when working with this class of devices.