Comparison of the calcium signaling alterations in GABA-ergic medium spiny neurons produced from iPSCs of different origins.

Disease models based on induced pluripotent stem cells (iPSCs) are in high demand because of their physiological adequacy and well-reproducibility of the pathological phenotype. Nowadays, the most common approach to generate iPSCs is the reprogramming of somatic cells using vectors based on lentivirus or Sendai virus. We have previously shown impairments of calcium signaling including store-operated calcium entry in Huntington's disease-specific iPSCs-based GABA-ergic medium spiny neurons. However, different approaches for iPSCs generation make it difficult to compare the models since the mechanism of reprogramming may influence the electrophysiological properties of the terminally differentiated neurons. Here, we have studied the features of calcium homeostasis in GABA-ergic medium spiny neurons differentiated from iPSCs obtained from fibroblasts of the same donor using different methods. Our data demonstrated that there were no significant differences neither in calcium influx through the store-operated channels, nor in the levels of proteins activating this type of calcium entry in neurons differentiated from iPSCs generated with lenti- and Sendai viruses-based approaches. We also found no differences in voltage-gated calcium entry for these neurons. Thus, we clearly showed that various methods of cell reprogramming result in similar deregulations in neuronal calcium signaling which substantiates the ability to combine the experimental data on functional studies of ion channels in models based on iPSCs obtained by different methods and expands the prospects for the use of biobanking.

The Mystery of EVP4593: Perspectives of the Quinazoline-Derived Compound in the Treatment of Huntington's Disease and Other Human Pathologies.

Quinazoline derivatives have various pharmacological activities and are widely used in clinical practice. Here, we reviewed the proposed mechanisms of the physiological activity of the quinazoline derivative EVP4593 and perspectives for its clinical implication. We summarized the accumulated data about EVP4593 and focused on its activities in different models of Huntington's disease (HD), including patient-specific iPSCs-based neurons. To make a deeper insight into its neuroprotective role in HD treatment, we discussed the ability of EVP4593 to modulate calcium signaling and reduce the level of the huntingtin protein. Moreover, we described possible protective effects of EVP4593 in other pathologies, such as oncology, cardiovascular diseases and parasite invasion. We hope that comprehensive analyses of the molecular mechanisms of EVP4593 activity will allow for the expansion of the scope of the EVP4593 application.

What Differences Exist in Professional Ice Hockey Performance Using Virtual Reality (VR) Technology between Professional Hockey Players and Freestyle Wrestlers? (a Pilot Study).

There is little research on the study of specific characteristics that contribute to the faster adaptation of athletes during the transition from one sport to another. We used virtual reality (VR) to study the differences between professional ice hockey players and other sport professionals (freestyle wrestlers), who were novices in hockey in terms of motor responses and efficiency performance, on different levels of difficulty. In the VR environment, four levels of difficulty (four blocks) were simulated, depended on the speed of the puck and the distance to it (Bl1-60-80 km/h and 18 m; Bl2-60-100 km/h, distances 12 and 18 m; Bl3-speeds up to 170 km/h and 6, 12, and 18 m; Bl4-the pucks are presented in a series of two (in sequence with a 1 s interval)). The results of the study showed that the hockey professionals proved to have more stable movement patterns of the knee and hip joints. They also made fewer head movements as a response to stimuli during all runs (0.66 vs. 1.25, p = 0.043). Thus, working out on these parameters can contribute to the faster adaptation of wrestlers in developing professional ice hockey skills.