Andrey A. Grinevich

The immune response to peptides derived from SARS‐CoV‐2 S and M proteins and their effects on NADPH oxidase‐dependent generation of reactive species were explored. Peptides were selected based on B‐cell epitope predictions, and their fusions with glutathione S‐transferase were obtained. Such fusions containing fragments of the receptor binding domain (RBD) were recognized by IgG antibodies developed in COVID‐19 patients with efficiency comparable to full‐length RBD. The S673‐713 peptide containing the furin cleavage site demonstrated the highest reactivity in samples from patients with mild COVID‐19, suggesting a potential role in protective immune responses. Peptides with a high antibody recognition contained multiple protease cleavage sites, indicating a possible role for S protein processing in SARS‐CoV‐2 immunogenicity. Their effects on the generation of reactive species in blood and isolated neutrophils were investigated. Functionally, selected peptides (S672‐875, S592‐647, and S357‐380) modulated the opsonized zymosan induced response in blood, whereas S673‐713, S673‐713 P681H, and M105‐117 showed weaker effects. In isolated neutrophils, peptides containing fragments of RBD (S434‐483) or the S1/S2 cleavage site (S673‐713) enhanced phagocytosis‐dependent, formyl peptide receptor (FPR)‐mediated and PMA‐induced production of reactive species. In contrast, the P681H mutation both decreased antibody recognition of S673‐713 and removed or significantly reduced functional effects on blood neutrophils, suggesting a potential mechanism contributing to viral spread and immune evasion. These findings provide insight into how viral peptide fragments modulate innate immune responses via formyl peptide receptors and contribute to mechanisms of viral recognition.

Changes in the cardiovascular system are systemic during aging. The aim of this work is to describe systemic patterns of changes in heart rate variability (HRV) parameters during aging in healthy subjects. HRV data of 73 healthy subjects aged 11–76 years from the PhysioNet database were used, which were divided into three groups: young (11–17 years old), middle-aged (24–55 years old), and elderly (56–76 years old). Using the Hilbert–Huang method and wavelet analysis, spectral curves of empirical HRV modes were obtained, for which the maxima and their corresponding frequencies were determined. Nine modes were identified. A twofold decrease in the autonomic control modes and, to a lesser extent, in the very-low-frequency modes (0.002–0.04 Hz) was found in the elderly compared to the young. Very-low-frequency HRV oscillations (<0.001 Hz) did not change with age. The results obtained may serve as a basis for physiological interpretation of HRV regulation processes and may be useful in the development of controlled anti-aging therapy.

The aim of the study was to reveal the patterns of the age-related dynamics of the frequency-dependent regulation of heart rate variability (HRV) based on the analysis of Holter ECG recordings from healthy subjects of four age groups: neonates, one-year-old infants, adolescents, and adults. A wide spectral composition of HRV is shown, consisting of nine Hilbert–Huang modes in the frequency range from 0.0001 to 2 Hz. A decrease in the central frequencies of all modes is shown in the postnatal period with a plateau in adolescence. A rapid progression of systemic humoral regulation of HRV, characterized by a consolidated increase in the amplitudes of the corresponding modes with a plateau in adolescence, is demonstrated. The dome-shaped character of age-related changes in amplitude of modes associated with autonomic control with a maximum in adolescence is shown. The results obtained quantitatively demonstrate age-related consolidated changes in HRV parameters from neonates to adulthood.

The dynamics of the pulse wave (PW) associated with the PW transit time variability (PWTTV) determines the peripheral pulse rate variability, which is used as a surrogate for heart rate variability (HRV). The aim of the work is to analyze the frequency-dependent dynamics of PWTTV and to identify the possible frequency-phase modulation of PW velocity oscillations on the transit from the heart to the soft tissues of the distal parts of the upper extremities. RR-interval recordings and synchronous records of photoplethysmograms of 12 conditionally healthy subjects from the PhysioNet open database were used in this work. Using the Hilbert–Huang transform 3 spectral components of PWTTV and HRV were identified. It was shown that the amplitudes of PWTTV oscillations were many times (up to 8.4 times) smaller than the amplitudes of HRV, and the peaks of PWTTV spectral components were shifted towards higher frequencies than those of HRV. Functional relations between PWTTV and HRV, which can determine the phase modulation of periodic changes in the PW propagation velocity, were revealed.

A comprehensive spectral analysis of heart rate variability and skin perfusion of the extremities in patients with type 2 diabetes mellitus in response to local heating and identification of significant predictors of pathophysiological changes in the cardiovascular system has been carried out. Electrocardiogram and skin perfusion on the forearm and foot were measured by laser Doppler flowmetry at rest and under local heating in healthy individuals and diabetic patients. The signals of laser Doppler flowmetry and heart rate variability (according to electrocardiographic data) were subjected to wavelet analysis. Receiver operating characteristic analysis was used to evaluate significant predictors. It was found that in patients, compared with healthy individuals, there was (1) a decrease in the reserve of cutaneous blood flow on the foot under heating, (2) a decrease in the amplitudes of heart rate oscillations at rest and under heating, (3) an increase in the amplitudes of oscillations of laser Doppler flowmetry signals on the forearm in respiratory intervals and cardiac intervals at rest and under heating, and (4) a decrease in the amplitudes of oscillations of laser Doppler flowmetry signals on the foot in the myogenic interval at rest and in the cardiac interval under heating. The parameters of the cardiovascular system (the energy of heart rate variability in the low frequency interval and oscillations of laser Doppler flowmetry signals on the forearm in respiratory interval, which can serve as markers for early diagnosis of microvascular disorders) with high discriminatory power to distinguish patients and healthy individuals in response to local heating were revealed.

Analysis of heart rate variability (HRV) is widely used for noninvasive assessment of the state of the regulation systems of the heart. The aim of this study was to evaluate the capabilities of the Hilbert–Huang method for calculating spectral parameters of HRV in comparison with the commonly used Fourier analysis. Fourier analysis allows estimation of averaged spectral amplitudes and power of HRV oscillations in fixed frequency intervals, which are associated with the activity of sympathetic, parasympathetic, and humoral regulation systems. Using the Hilbert–Huang method, we revealed four spectral components, described by Gaussian functions, in which HRV oscillations are concentrated, and showed the absence of fixed boundaries between them. The obtained energy quantitative characteristics of the spectral components of heart rhythm oscillations can serve as the basis for diagnostic methods of heart rhythm regulation, supplementing the commonly used ones.

Peripheral blood flow analysis is used for noninvasive assessment of the cardiovascular system. The aim was to investigate the possibility of applying Hilbert–Huang spectral analysis (HH) to localize the mechanisms of nonlinear regulation of blood perfusion dynamics in the soft tissues of distal areas of the hands in human. In 9 healthy subjects, synchronous recording of photoplethysmograms (PPG) from the index fingers of the hands was performed. Using a band-pass filter, a cardiac signal was extracted from the PPG, which was separated into the carrier and modulating components. The latter was subjected to decomposition into empirical modes by HH method. Five modes were detected, for which the coherence between the hands was evaluated. The frequencies of the modes fell within the conventional frequency intervals of skin blood flow oscillations, and the coherence was 0.6. A decreased depth of modulation in the left hand compared to the right hand was shown. The results indicate a central origin of the nonlinear regulation of the dynamics of tissue blood perfusion in the hands.

In this study we used the kink solutions of the nonlinear sine-Gordon equation to apply methods of mathematical modeling to investigate the dynamics of the transcription bubble in the pPF1 plasmid. Based on the calculated energy profile for the pPF1 plasmid and its modified versions, it was shown that the minimum potential energy of the kink formation or transcription bubble nucleation corresponds to the region between the genes of the Egfp and mCherry proteins. The insertion of homogeneous sequences into the region between Egfp and mCherry showed that the kink is more likely to be activated in polyT or polyC compared to polyA or polyG, which indicates the dependence of nucleation of the transcription bubble on the molecular weight of base pairs. For insertions into the region between Egfp and mCherry of small fragments of the native sequence of Escherichia coli, the model identifies the DNA strands with the highest probability of nucleation of the transcription bubble and, accordingly, determines the direction (towards the Egfp or mCherry gene) of transcription, indicating a link between the direction of transcription and the energy profile of the plasmid.

—The phase relationships between heart rate variability, respiration, forearm skin blood flow oscillations (according to laser Doppler flowmetry), and finger-pad tissue blood volume oscillations (according to photoplethysmography) were analyzed in relatively healthy volunteers at rest. The degree of synchronization between phases of analyzed signals was estimated based on the value of the phase wavelet coherence function. A significant phase synchronization was detected between forearm skin blood flow oscillations and finger-pad tissue blood volume oscillations in the low frequency region (0.0095–0.1 Hz) and at the frequency of heart rate of ~ 1 Hz. At a respiration rate of ~0.3 Hz, differences were detected in the phase synchronization of peripheral hemodynamic oscillations (blood volume and blood flow) with both heart rate variability and respiration. For finger-pad tissue blood volume oscillations, a high phase synchronization with both heart rate variability and respiratory rate was observed; for forearm blood flow oscillations, low phase synchronization occurred in both cases.