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Cancer continues to be one of the leading causes of death worldwide, and conventional cancer therapies such as chemotherapy, radiation therapy, and surgery have limitations. RNA therapy and cancer vaccines hold considerable promise as an alternative to conventional therapies for their ability to enable personalized therapy with improved efficacy and reduced side effects. The principal approach of cancer vaccines is to induce a specific immune response against cancer cells. However, a major challenge in cancer immunotherapy is to predict which patients will respond to treatment and to monitor the efficacy of the vaccine during treatment. Theragnostics, an integration of diagnostic and therapeutic capabilities into a single hybrid platform system, has the potential to address these challenges by enabling real-time monitoring of treatment response while allowing endogenously controlled personalized treatment adjustments. In this article, we review the current state-of-the-art in theragnostics for cancer vaccines and RNA therapy, including imaging agents, biomarkers, and other diagnostic tools relevant to cancer, and their application in cancer therapy development and personalization. We also discuss the opportunities and challenges for further development and clinical translation of theragnostics in cancer vaccines., Competing Interests: Author OS was employed by Genterra JSC. Author AG-E was employed by ABTECH Scientific, Inc. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Sergeeva, Luo and Guiseppi-Elie.)

The COVID-19 pandemic has shown the urgent need for new treatments for coronavirus infections. Nucleoside analogs were successfully used to inhibit replication of some viruses through the incorporation into the growing DNA or RNA chain. However, the replicative machinery of coronaviruses contains nsp14, a non-structural protein with a 3'→5'-exonuclease activity that removes misincorporated and modified nucleotides from the 3' end of the growing RNA chain. Here, we studied the efficiency of hydrolysis of RNA containing various modifications in the 3'-terminal region by SARS-CoV-2 nsp14 exonuclease and its complex with the auxiliary protein nsp10. Single-stranded RNA was a preferable substrate compared to double-stranded RNA, which is consistent with the model of transfer of the substrate strand to the exonuclease active site, which was proposed on the basis of structural analysis. Modifications of the phosphodiester bond between the penultimate and last nucleotides had the greatest effect on nsp14 activity., (© 2023. Pleiades Publishing, Ltd.)

Nanomedicine has revolutionized the available treatment options during the last decade, but poor selectivity of targeted drug delivery and release is still poses a challenge. In this study, doxorubicin (DOX) and magnetite nanoparticles were encapsulated by freezing-induced loading, coated with polymeric shell bearing two bi-layers of polyarginine/dextran sulphate and finally modified with HER2-specific DARPin proteins. We demonstrated that the enhanced cellular uptake of these nanocarriers predominantly occurs by SKOV-3 (HER2+) cells, in comparison to CHO (HER2-) cells, together with the controlled DOX release using low intensity focused ultrasound (LIFU). In addition, a good ability of DARPin+ capsules to accumulate in the tumor and the possibility of combination therapy with LIFU were demonstrated. A relatively high sensitivity of the obtained nanocarriers to LIFU and their preferential interactions with mitochondria in cancer cells make these carriers promising candidates for cancer treatment, including novel approaches to overcome drug resistance., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Dysregulation of RNA splicing causes many diseases and disorders. Several therapeutic approaches have been developed to correct aberrant alternative splicing events for the treatment of cancers and hereditary diseases, including gene therapy and redirecting splicing, using small molecules or splice switching oligonucleotides (SSO). Significant advances in the chemistry and pharmacology of nucleic acid have led to the development of clinically approved SSO drugs for the treatment of spinal muscular dystrophy and Duchenne muscular dystrophy (DMD). In this review, we discuss the mechanisms of SSO action with emphasis on "less common" approaches to modulate alternative splicing, including bipartite and bifunctional SSO, oligonucleotide decoys for splice factors and SSO-mediated mRNA degradation via AS-NMD and NGD pathways. We briefly discuss the current progress and future perspectives of SSO therapy for rare and ultrarare diseases.

DDX3 RNA helicase is involved in many processes of RNA metabolism in eukaryotic cells. Many studies of DDX3 have shown that it is also involved in the translation initiation process, both cap-dependent and IRES-dependent. However, the specificity of the secondary structure of mRNA 5'-UTRs, which require DDX3 RNA helicase for effective translation, has not yet been determined. We performed a bioinformatic analysis of the 5'-UTR secondary structures in the pool of DDX3-dependent mRNAs in silico and predicted that the length of 5'-UTRs for such mRNAs is less than the average for the genome and that there are also characteristic hairpin structures in the region of the first 50 nucleotides from the 5'-end of the mRNA., (© 2021. Pleiades Publishing, Ltd.)

A series of 2'-deoxy and novel 2'- O -methyl and 2'- O -(2-methoxyethyl) (2'-MOE) oligonucleotides with internucleotide methanesulfonyl (mesyl, μ) or 1-butanesulfonyl (busyl, β) phosphoramidate groups has been synthesized for evaluation as potential splice-switching oligonucleotides. Evaluation of their splice-switching activity in spinal muscular atrophy patient-derived fibroblasts revealed no significant difference in splice-switching efficacy between 2'-MOE mesyl oligonucleotide and the corresponding phosphorothioate (nusinersen). Yet, a survival study with model neonatal mice has shown the antisense 2'-MOE mesyl oligonucleotide to be inferior to nusinersen at the highest dose of 40 mg/kg. A reason for their lower activity in vivo as ascertained by cellular uptake study by fluorescent confocal microscopy in HEK293 cell line could possibly be ascribed to compromised endosomal release and/or nuclear uptake of the 2'-OMe or 2'-MOE μ- and β-oligonucleotides compared to their phosphorothioate analog.

Development of multimodal systems for therapy and diagnosis of neoplastic diseases is an unmet need in oncology. The possibility of simultaneous diagnostics, monitoring, and therapy of various diseases allows expanding the applicability of modern systems for drug delivery. We have developed hybrid particles based on biocompatible polymers containing magnetic nanoparticles (MNPs), photoacoustic (MNPs), fluorescent (Cy5 or Cy7 dyes), and therapeutic components (doxorubicin). To achieve high loading efficiency of MNP and Dox to nanostructured carriers, we utilized a novel freezing-induced loading technique. To reduce the systemic toxicity of antitumor drugs and increase their therapeutic efficacy, we can use targeted delivery followed by the remote control of drug release using high intensity-focused ultrasound (HIFU). Loading of MNPs allowed performing magnetic targeting of the carriers and enhanced optoacoustic signal after controlled destruction of the shell and release of therapeutics as well as MRI imaging. The raster scanning optoacoustic mesoscopy (PA, RSOM), MRI, and fluorescent tomography (FT) confirmed the ultrasound-induced release of doxorubicin from capsules: in vitro (in tubes and pieces of meat) and in vivo (after delivery to the liver). Disruption of capsules results in a significant increase of doxorubicin and Cy7 fluorescence initially quenched by magnetite nanoparticles that can be used for real-time monitoring of drug release in vivo. In addition, we explicitly studied cytotoxicity, intracellular localization, and biodistribution of these particles. Elaborated drug delivery carriers have a good perspective for simultaneous imaging and focal therapy of different cancer types, including liver cancer., (Copyright © 2021. Published by Elsevier B.V.)

Introduction: Women and men experience sleep differently and the difference in intrinsic desire for sleep might underlie some of the observed male-female differences. The objective of this cross-sectional questionnaire study of university students was to determine male-female differences in self-reported sleepiness and sleep-wake patterns., Methods: Five questionnaires were completed by 1650 students at four Russian universities., Results: Compared to male students, female students reported a lower subjective sleep quality score, had a higher morning sleepability score and lower nighttime and daytime wakeability scores. They more often reported excessive daytime sleepiness and expected to be sleepier at any time of the day with the largest male-female difference around the times of sleep onset and offset. On free days, they reported a longer sleep duration and an earlier sleep onset. Free-weekday difference was larger for sleep duration and smaller for sleep onset. Such male-female differences showed similarity to the differences observed in university and high school students from different countries around the globe. There was no significant male-female difference in weekly averaged sleep duration, weekday sleep duration, hours slept, midpoint of sleep on free days, free-weekday difference in sleep offset, social jetlag, and morningness-eveningness score. Therefore, when studies rely on these self-reports, the most salient male-female differences might not be immediately evident., Conclusions: It seems that the intrinsic desire for longer sleep duration might contribute to a higher susceptibility of female students to weekday sleep loss. Among these students, negative effects of reduced sleep duration might be more common and more detrimental., (Copyright © 2021 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.)

The state of the art in optical biosensing is focused on reaching high sensitivity at a single wavelength by using any type of optical resonance. This common strategy, however, disregards the promising possibility of simultaneous measurements of a bioanalyte's refractive index over a broadband spectral domain. Here, we address this issue by introducing the approach of in-fibre multispectral optical sensing (IMOS). The operating principle relies on detecting changes in the transmission of a hollow-core microstructured optical fibre when a bioanalyte is streamed through it via liquid cells. IMOS offers a unique opportunity to measure the refractive index at 42 wavelengths, with a sensitivity up to ~3000 nm per refractive index unit (RIU) and a figure of merit reaching 99 RIU -1 in the visible and near-infra-red spectral ranges. We apply this technique to determine the concentration and refractive index dispersion for bovine serum albumin and show that the accuracy meets clinical needs., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) 2020.)

The efficacy of fluorescent hybridization assays is often limited by the low signal-to-background ratio of the probes that can be partially overcome by sophisticated signal amplification methods. Deep understanding of the mechanisms of fluorescence quenching and energy transfer in complex DNA probes and the choice of optimal donor/acceptor pairs along with rational design can significantly enhance the performance of DNA probes. Here, we proposed and studied novel Förster resonance energy transfer (FRET) dual DNA probes with the excimer-forming pyrene pair as a donor and sulfo-Cy3 dye as an acceptor, which demonstrated remarkable 75-fold enhancement of sulfo-Cy3 fluorescence upon target capturing. Stokes shift up to 220 nm minimizes fluorescence crosstalk. Time-correlated single-photon counting revealed two excited states of pyrene excimer wherein only one is directly involved in the resonance energy transfer to sulfo-Cy3. Optimized DNA probes demonstrated high sensitivity with excellent signal-to-background ratio, which were applied for visualization of 18S rRNA by fluorescent in situ hybridization in HEK-293T cells.

Poly(rC)-binding protein 2 (PCBP2, hnRNP E2) is one of the most abundant RNA-binding proteins in mammalian cells. In humans, it exists in seven isoforms, which are assumed to play similar roles in cells. The protein is shown to bind 3'-untranslated regions (3'-UTRs) of many mRNAs and regulate their translation and/or stability, but nothing is known about the functional consequences of PCBP2 binding to 5'-UTRs. Here we show that the PCBP2 isoform f interacts with the 5'-UTRs of mRNAs encoding eIF4G2 (a translation initiation factor with a yet unknown mechanism of action, also known as DAP5) and Cyclin I, and inhibits their translation in vitro and in cultured cells, while the PCBP2 isoform e only affects Cyclin I translation. Furthermore, eIF4G2 participates in a cap-dependent translation of the PCBP2 mRNA. Thus, PCBP2 and eIF4G2 seem to regulate one another's expression via a novel type of feedback loop formed by the translation initiation factor and the RNA-binding protein., (© 2019 Smirnova et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.)

Long noncoding RNAs (lncRNA) play important roles in the regulation of transcription, splicing, translation, and other processes in the cell. Human and mouse lncRNA (DEANR1 and LL35/Falcor, respectively) located in the genomic environment in close proximity to the Foxa2 transcription factor were discovered earlier. In this work, tissue-specific expression of LL35/Falcor lncRNA has been shown in mouse liver and lungs. The use of antisense oligonucleotides allowed us to achieve LL35/Falcor lncRNA downregulation by 90%. As a result, the level of Foxa2 mRNA and protein dropped, which confirms the involvement of LL35/Falcor lncRNA in the regulation of transcription factor Foxa2. We have shown a decrease in the expression of LL35 lncRNA in liver fibrosis, which correlates with the previously published data for mRNA Foxa2. Thus, lncRNA LL35 regulates Foxa2 expression in the liver not only in normal conditions, but also during development of fibrosis, which allows one to consider lncRNA a biomarker of this pathological process., (Copyright ® 2019 National Research University Higher School of Economics.)

Williams-Beuren syndrome is a genetic disorder characterized by physiological and mental abnormalities, and is caused by hemizygous deletion of several genes in chromosome 7. One of the removed genes encodes the WBSCR27 protein. Bioinformatic analysis of the sequence of WBSCR27 indicates that it belongs to the family of SAM-dependent methyltransferases. However, exact cellular functions of this protein or phenotypic consequences of its deficiency are still unknown. Here we report nearly complete 1 H, 15 N, and 13 C chemical shifts assignments of the 26 kDa WBSCR27 protein from Mus musculus in complex with the cofactor S-adenosyl-L-methionine (SAM). Analysis of the assigned chemical shifts allowed us to characterize the protein's secondary structure and backbone dynamics. The topology of the protein's fold confirms the assumption that the WBSCR27 protein belongs to the family of class I methyltransferases.

Proteins containing the NIF3 domain are highly conserved and are found in bacteria, eukaryotes, and archaea. YbgI is an Escherichia coli protein whose gene is conserved among bacteria. The structure of YbgI is known; however, the function of this protein in cells remains obscure. Our studies of E. coli cells with deleted ybgI gene suggest that YbgI is involved in formation of the bacterial cell wall.

Asialoglycoprotein receptor (ASGP-R) is a promising biological target for drug delivery into hepatoma cells. Nevertheless, there are only few examples of small-molecule conjugates of ASGP-R selective ligand equipped by a therapeutic agent for the treatment of hepatocellular carcinoma (HCC). In the present work, we describe a convenient and versatile synthetic approach to novel mono- and multivalent drug-conjugates containing N-acetyl-2-deoxy-2-aminogalactopyranose and anticancer drug - paclitaxel (PTX). Several molecules have demonstrated high affinity towards ASGP-R and good stability under physiological conditions, significant in vitro anticancer activity comparable to PTX, as well as good internalization via ASGP-R-mediated endocytosis. Therefore, the conjugates with the highest potency can be regarded as a promising therapeutic option against HCC., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

By means of EEG analysis the functional state of subjects with high and low levels of anxiety was studied in different periods preceding a cognitive task - a visual expression recognition. Several conditions were investigated: background/eyes closed; background/eyes opened; listening the instruction for the cognitive task; operative rest (time lapse between listening the instruction and the beginning of the task), as well as short intervals immediately preceding the exposition of target stimuli (stage of preparation) - pairs of faces pictures with identical or different emotional expressions. At all these pre-task stages high-anxiety subjects exhibited much lower amplitude values in alpha and theta bands (as compared with low-anxiety subjects). The most prominent differences were revealed in the phases of instruction listening and operative rest. These data could provide more precise electrophysiological markers of anxiety level in conditions preceeding cognitive task performance.

Psychoemotional stress is one of the leading cardiovascular risk factors. The aim of this study was to explore manifestations of arterial hypertension (AH) in young men employed in the stress associatedfield works. Material and methods. A total of 68 young men, exposed to job stress (JS) of different severity during 1 to 5 years were surveyed. The control group was formed of persons whose daily work was unrelated to operational activities. The study included ambulatory monitoring (AM) blood pressure (BP) on different days of the week, comparing the results of the office and DMBP determination and assessment of resistance to a variety of diagnostic loads. Results. The study revealed an increase of AMBP indicators during the working day and their normalization at weekend. The comparison of the results of office and ambulatory determination of BP demonstrated that different forms of stressful AH (stable, isolated office and latent) occurred significantly more often than in the control group. These changes almost completely disappeared at weekends. The tolerance ofpsychoemotional testing was much worse than that of traditional exercises. It is proposed to more extensively use AMBP during regular medical examinations of young men exposed to JS in order to establish a timely differential diagnosis of various forms of stressful hypertension.

In this review we discuss features of mRNA synthesis and modifications used to minimize immune response and prolong efficiency of the translation process in vivo. Considerable attention is given to the use of liposomes and nanoparticles containing lipids and polymers for the mRNA delivery. Finally we briefly discuss mRNAs which are currently in the clinical trials for cancer immunotherapy, vaccination against infectious diseases, and replacement therapy.

N6-methyladenosine (m(6)A) is ubiquitously present in the RNA of living organisms from Escherichia coli to humans. Methyltransferases that catalyze adenosine methylation are drastically different in specificity from modification of single residues in bacterial ribosomal or transfer RNA to modification of thousands of residues spread among eukaryotic mRNA. Interactions that are formed by m(6)A residues range from RNA-RNA tertiary contacts to RNA-protein recognition. Consequences of the modification loss might vary from nearly negligible to complete reprogramming of regulatory pathways and lethality. In this review, we summarized current knowledge on enzymes that introduce m(6)A modification, ways to detect m(6)A presence in RNA and the functional role of this modification everywhere it is present, from bacteria to humans., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

A ribosome is a ribonucleoprotein that performs the synthesis of proteins. Ribosomal RNA of all organisms includes a number of modified nucleotides, such as base or ribose methylated and pseudouridines. Methylated nucleotides are highly conserved in bacteria and some even universally. In this review we discuss available data on a set of modification sites in the most studied bacteria, Escherichia coli. While most rRNA modification enzymes are known for this organism, the function of the modified nucleotides is rarely identified., (Copyright © 2014 Elsevier B.V. and Société française de biochimie et biologie Moléculaire (SFBBM). All rights reserved.)

Propranolol and atenolol were used to examine the role of the adrenergic system in the genesis of slow HR variations (waves) in rabbits, the animals characterized by pronounced sympathetic influences. The control experiments were performed with physiological solution and long-term records in intact rabbits. The harmonic (spectrum) analysis was performed with fast Fourier transform. The adrenoblockers produced no decrease in the power of slow waves. The study did not found the sympathetic genesis of slow variations in rabbit HR.

Ribosome is a macromolecular complex, which is responsible for protein biosynthesis. Two bacterial ribosomal subunits contain more than 4000 RNA nucleotides and 50 proteins. Ribosome assembly is a complicated multi-step process, vitally important for cell. In this review we summarised present-day conceptions about the mechanism of the bacterial ribosome assembly in the cell and in vitro model systems. Some details of the assembly of this machinery are still-unknown.

The functional centers of the ribosome in all organisms contain ribosomal RNA (rRNA) modifications, which are introduced by specialized enzymes and come at an energy cost for the cell. Surprisingly, none of the modifications tested so far was essential for growth and hence the functional role of modifications is largely unknown. Here, we show that the methyl groups of nucleosides m(2)G966 and m(5)C967 of 16S rRNA in Escherichia coli are important for bacterial fitness. In vitro analysis of all phases of translation suggests that the m(2)G966/m(5)C967 modifications are dispensable for elongation, termination and ribosome recycling. Rather, the modifications modulate the early stages of initiation by stabilizing the binding of fMet-tRNA(fMet) to the 30S pre-initiation complex prior to start-codon recognition. We propose that the m(2)G966 and m(5)C967 modifications help shaping the bacterial proteome, most likely by fine-tuning the rates that determine the fate of a given messenger RNA (mRNA) at early checkpoints of mRNA selection.

Modification of ribosomal RNA is ubiquitous among living organisms. Its functional role is well established for only a limited number of modified nucleotides. There are examples of rRNA modification involvement in the gene expression regulation in the cell. There is a need for large data set analysis in the search for potential functional partners for rRNA modification. In this study, we extracted phylogenetic profile, genome neighbourhood, co-expression and phenotype profile and co-purification data regarding Escherichia coli rRNA modification enzymes from public databases. Results were visualized as graphs using Cytoscape and analysed. Majority linked genes/proteins belong to translation apparatus. Among co-purification partners of rRNA modification enzymes are several candidates for experimental validation. Phylogenetic profiling revealed links of pseudouridine synthetases with RF2, RsmH with translation factors IF2, RF1 and LepA and RlmM with RdgC. Genome neighbourhood connections revealed several putative functionally linked genes, e.g. rlmH with genes coding for cell wall biosynthetic proteins and others. Comparative analysis of expression profiles (Gene Expression Omnibus) revealed two main associations, a group of genes expressed during fast growth and association of rrmJ with heat shock genes. This study might be used as a roadmap for further experimental verification of predicted functional interactions.

Ribosomal RNA modification is accomplished by a variety of enzymes acting on all stages of ribosome assembly. Among rRNA methyltransferases of Escherichia coli, RsmD deserves special attention. Despite its minimalistic domain architecture, it is able to recognize a single target nucleotide G966 of the 16S rRNA. RsmD acts late in the assembly process and is able to modify a completely assembled 30S subunit. Here, we show that it possesses superior binding properties toward the unmodified 30S subunit but is unable to bind a 30S subunit modified at G966. RsmD is unusual in its ability to withstand multiple amino acid substitutions of the active site. Such efficiency of RsmD may be useful to complete the modification of a 30S subunit ahead of the 30S subunit's involvement in translation.

In this work we describe methodology for studying the role of bacterial ribosome modification in the regulation of gene expression. Ribosomal components modification influences translation efficiencies of certain mRNAs. Proteome analysis allows us to identify cellular protein composition change caused by ribosome modification gene knockout. Particular stage of gene expression responsible for certain protein concentration change could be found using reporter constructs. After identification of mRNA species, whose translation is influenced by ribosome modification we can determine exact mRNA region responsible for the observed changes. The developed methodology can be applied for studying other translational control mechanisms.

The relationship between chronotropic and inotropic components of cardiac reflexes were studied in cats using intravenous blood injections, occlusion of the abdominal aorta, pressing on eyeballs (Aschner maneuver), and occlusion of the carotid arteries. Inotropic reactions were characterized by the contractility index DPxHR/MSAP. Different reflexes were shown to be characterized by different ratio of chronotropic and inotropic components, in addition, heart rate and contractility were often altered in opposite directions.

Were studied the effects of atropine and beta-adrenoblockers on the power of very low (<0.25 Hz), low (0.25-0.70 Hz), and high frequency (0.7-1.8 Hz) waves of the heart rhythm in wakeful rats. Atropine reduced the power of all waves in 100% cases. Propranolol on average decreased the power of very low frequency waves and increased the power of low and high frequency waves, although opposite effects were observed in many cases. Atenolol produced similar effects. Some animals demonstrated spontaneous moderation of respiratory rate to a level corresponding to low-frequency oscillations of the heart rhythm accompanied by elevation of the relative power of low frequency waves. Inconsistency of the effects of beta-adrenoblockers in rats can be related to variability of sympathetic tone and spontaneous deceleration of respiration with the corresponding changes of low frequency waves. Augmentation of the high frequency waves during application of beta-adrenoblockers is not related to their action on CNS.

The relationship between dromotropic and chronotropic components of various cardiac reflexes was studied in cats. Intravenous infusion of blood was mainly accompanied by unidirectional negative chronotropic and dromotropic effects, but the dynamics of these effects was different. Clumping of the carotid arteries in most animals induced unidirectional negative chronotropic and dromotropic effects. Their dynamics was also different and differed from that observed during intravenous blood infusion. Pulsatile increase in blood pressure in the carotid artery was accompanied by a unidirectional negative effect in the majority of animals. The opposite chronotropic and dromotropic effects with similar temporal dynamics were revealed in 1/3 animals. The ratio of positive and negative effects was similar during clumping of the abdominal aorta (1/3 unidirectional, 1/3 opposite, and 1/3 isolated chronotropic and dromotropic effects). Aschner test was characterized by the prevalence of isolated chronotropic effect (negative effect in the majority of animals; positive effect in 1/3 animals). Hence, different cardiac reflexes are characterized by different ratio between chronotropic and dromotropic components.

Effects of pentobarbital on spectral characteristics and phase ratios of wave oscillations of the cardiac contraction period (RR interval) and time of atrioventricular conduction (AV interval) were studied in experiments of cats. Pentobarbital moderately reduced the mean values of both intervals and significantly reduced their standard deviations and spectral powers in all frequency bands (high-frequency, low-frequency, and very low-frequency). Pentobarbital treatment led to deceleration of breathing, the frequency range of respiratory oscillations of RR and AV intervals shifted in some cases from high to low frequencies; evaluation of spectral power in the intermittent band corresponding to respiration frequency (instead of standard fixed high-frequency band) showed that pentobarbital suppressed the respiratory oscillations in these bands. Pentobarbital induced inversion of phase ratio between respiratory oscillations of RR and AV intervals: oscillations of both intervals before pentobarbital coincided by phase, while after pentobarbital injection they were in antiphase. The mechanisms of the latter phenomenon deserve further investigation.

The coordinated nervous influences on HR and atrioventricular conduction velocity (chronodromotropic coordination) were examined in wakeful cats. The wave structure and reflex reactions of RR and atrioventricular (AV) intervals to stress noise stimulation were studied under normal conditions and during the action of blockers of peripheral receptors in ANS. Variations of both intervals had similar wave structure (power spectrum) and similar reactions to noise stimulus. Atropine pronouncedly decreased all components of the spectra in the high, low, and very low frequency ranges. It eliminated the reactions of both intervals to noise stimulation. In RR intervals, the high-frequency spectrum component decreased more strongly than the low-frequency ones. By contrast, in AV intervals atropine most greatly decreased the very-low-spectrum component, while the high frequency was decreased less of all. Propranolol produced no effect on the response to noise. It did not decrease components of the wave structure in both intervals, except for the very-low-frequency peak of AV interval. The nervous chronotropic and dromotropic influences were largely coordinated, although they were not obligatorily parallel.

The effects of atropine and beta-adrenoceptor blockers on mean HR, wave structure of the cardiac rhythm, and chronotropic reaction to noise stress were examined in cats. Atropine (0.5 mg/kg) increased the mean HR and significantly decreased the spectrum power of HF, LF, and VLF oscillations. The decrease in HF power was most pronounced, which enhanced LF/HF ratio. Propranolol (0.5 mg/kg) decreased the mean HR and slightly increased the power of HF, LF, and VLF oscillations. Atenolol (2 mg/kg) exerted similar but more pronounced effects. beta-Adrenoceptor blockers increased HF power to a greater extent than LF and VLF power, which led to a decrease in LF/HF ratio. Atropine markedly decreased the chronotropic reaction to stress. beta-Adrenoceptor blockers produced no effect on the amplitude of this reaction, but accelerated restoration of initial HR. It is established that the changes in power spectrum of HR and the phase reflex reactions in cats are mediated by parasympathetic influences; the sympathetic system is involved only in the control of mean HR, probably in response to the level of animal activity. The changes in LF/HF ratio during blockade of sympathetic and parasympathetic systems are caused by opposite influences of these systems on HF oscillations, but not by hypothetic "sympathetic" and "parasympathetic" nature of LF and HF oscillations of the heart rhythm.

The relationships between dromotropic and chronotropic components of five reflexes were studied in rabbits: intravenous and intraarterial blood injections, occlusion of the carotid arteries, Aschner maneuver, and stimulation of depressors. All these stimuli reduced heart rate (except carotid artery occlusion, which induced approximately equal number of tachi- and bradycardic responses). The former three stimuli also reduced atrioventricular (AV) conduction velocity, the changes in these two parameters were proportional. Changes in heart rate induced by Aschner maneuver were more pronounced than changes in AV conduction. Stimulation of depressor induced co-directed shifts in these parameters during the first seconds, but then AV conduction increased, while heart rate remained decreased; bradycardia and AV acceleration persisted for long time after termination of stimulation. Our findings attest to independent regulation of heart rate and AV conduction velocity and to the absence of a strict relationship between these two parameters.