Three-dimensional structures of unligated uridine phosphorylase from Yersinia pseudotuberculosis at 1.4 Å resolution and its complex with an antibacterial drug

Uridine phosphorylases play an essential role in the cellular metabolism of some antibacterial agents. Acute infectious diseases (bubonic plague, yersiniosis, pseudotuberculosis, etc., caused by bacteria of the genus Yersinia) are treated using both sulfanilamide medicines and antibiotics, including trimethoprim. The action of an antibiotic on a bacterial cell is determined primarily by the character of its interactions with cellular components, including those which are not targets (for example, with pyrimidine phosphorylases). This type of interaction should be taken into account in designing drugs. The three-dimensional structure of uridine phosphorylase from the bacterium Yersinia pseudotuberculosis (YptUPh) with the free active site was determined for the first time by X-ray crystallography and refined at 1.40 Å resolution (DPI = 0.062 Å; IDPDB: 4OF4). The structure of the complex of Ypt UPh with the bacteriostatic drug trimethoprim was studied by molecular docking and molecular dynamics methods. The trimethoprim molecule was shown to be buffered by the enzyme Ypt UPh, resulting in a decrease in the efficiency of the treatment of infectious diseases caused by bacteria of the genus Yersinia with trimethoprim

Correlation of BOLD Signal with Linear and Nonlinear Patterns of EEG in Resting State EEG-Informed fMRI

Concurrent EEG and fMRI acquisitions in resting state showed a correlation between EEG power in various bands and spontaneous BOLD fluctuations. However, there is a lack of data on how changes in the complexity of brain dynamics derived from EEG reflect variations in the BOLD signal. The purpose of our study was to correlate both spectral patterns, as linear features of EEG rhythms, and nonlinear EEG dynamic complexity with neuronal activity obtained by fMRI. We examined the relationships between EEG patterns and brain activation obtained by simultaneous EEG-fMRI during the resting state condition in 25 healthy right-handed adult volunteers. Using EEG-derived regressors, we demonstrated a substantial correlation of BOLD signal changes with linear and nonlinear features of EEG. We found the most significant positive correlation of fMRI signal with delta spectral power. Beta and alpha spectral features had no reliable effect on BOLD fluctuation. However, dynamic changes of alpha peak frequency exhibited a significant association with BOLD signal increase in right-hemisphere areas. Additionally, EEG dynamic complexity as measured by the HFD of the 2–20 Hz EEG frequency range significantly correlated with the activation of cortical and subcortical limbic system areas. Our results indicate that both spectral features of EEG frequency bands and nonlinear dynamic properties of spontaneous EEG are strongly associated with fluctuations of the BOLD signal during the resting state condition