Cerny, F. | Search bioRxiv

bioRxiv2023

All-night spectral and microstate EEG analysis in patients with Recurrent Isolated Sleep Paralysis (RISP)

The pathophysiology of recurrent isolated sleep paralysis (RISP) has yet to be fully clarified. Very little research has been performed on electroencephalographic (EEG) signatures outside RISP episodes. This study aimed to investigate whether sleep is disturbed even without the occurrence of a RISP episode and in a stage different than conventional REM sleep. 17 RISP patients and 17 control subjects underwent two consecutive full-night video-polysomnography recordings. Spectral analysis was performed on all sleep stages in the delta, theta, and alpha band. EEG microstate (MS) analysis was performed on the NREM 3 phase due to the overall high correlation of subject template maps with canonical templates. Spectral analysis showed a significantly higher power of theta band activity in REM and NREM 2 sleep stages in RISP patients. The observed rise was also apparent in other sleep stages. Conversely, alpha power showed a downward trend in RISP patients deep sleep. MS maps similar to canonical topographies were obtained indicating the preservation of prototypical EEG generators in RISP patients. RISP patients showed significant differences in the temporal dynamics of MS, expressed by different transitions between MS C and D and between MS A and B. Both spectral analysis and MS characteristics showed abnormalities in the sleep of non-episodic RISP subjects. Our findings suggest that in order to understand the neurobiological background of RISP, there is a need to extend the analyses beyond REM-related processes and highlight the value of EEG microstate dynamics as promising functional biomarkers of RISP. Significance StatementWe focused on tracking electrophysiological traces of RISP (a REM parasomnia) beyond REM sleep of subjects clinically diagnosed with RISP outside of RISP episodes. We observed a rise of theta band activity in NREM 2 sleep of RISP patients. This may point to a larger dysregulation of sleep mechanism making the person more prone to sudden awakenings in the upcoming REM sleep. Theta band differences were further observed in REM sleep. We additionally utilized the EEG MS methodology on deep sleep to investigate differences in dominant brain topographies. Though dominant brain topographies are consistent with canonical MS, RISP patients show significantly different transitioning between sleep-related topographies suggesting a difference in their sleep regulation mechanisms.

neuroscience↗

bioRxiv2022

Continuous B- to A- Transition in Protein-DNA Binding - How Well Is It Described by Current AMBER Force Fields?

When DNA interacts with a protein, its structure often undergoes significant conformational adaptation. Perhaps the most common is the transition from canonical B-DNA towards the A-DNA form, which is not a two-state, but rather a continuous transition. The A- and B-forms differ mainly in sugar pucker P (north/south) and glycosidic torsion {chi} (high-anti/anti). The combination of A-like P and B-like {chi} (and vice versa) represents the nature of the intermediate states lying between the pure A- and B- forms. In this work, we study how the A/B equilibrium and in particular the A/B intermediate states, which are known to be over-represented at protein-DNA interfaces, are modeled by current AMBER force fields. Eight protein-DNA complexes and their naked (unbound) DNAs were simulated with OL15 and bsc1 force fields as well as an experimental combination OL15{chi}OL3. We found that while the geometries of the A-like intermediate states in the molecular dynamics (MD) simulations agree well with the native X-ray geometries found in the protein-DNA complexes, their populations (stabilities) are significantly underestimated. Different force fields predict different propensities for A-like states growing in the order OL15 < bsc1 < OL15{chi}OL3, but the overall populations of the A-like form are too low in all of them. Interestingly, the force fields seem to predict the correct sequence-dependent A-form propensity, as they predict larger populations of the A-like form in naked (unbound) DNA in those steps that acquire A-like conformations in protein-DNA complexes. The instability of A-like geometries in current force fields may significantly alter the geometry of the simulated protein-DNA complex, destabilize the binding motif, and reduce the binding energy, suggesting that refinement is needed to improve description of protein-DNA interactions in AMBER force fields.

biophysics↗