The paper reports the results of the study on the influence of weak low-frequency magnetic fields on human vision. In particular, it determines the primary magnetic fields frequency ranges that cause magnetobiological reactions, i. e., individual contraction of oculomotorius muscles. The magnitude of magnetic fields did not exceed 300 μT, which makes it possible to classify such fields as safe for human health according to the current legislation. Exposure of eye motoneurons to an external alternating magnetic field causes reactions on the part of specific oculomotorius muscles that are identical to their reactions under natural motoneuron control. Neurons located at other hierarchical levels show more complex reactions in which several oculomotorius muscles take part. The study found that the frequency of oculomotorius muscles ranges from 40 to 85 Hz. Each neuron can be characterized by its 'frequency range' of external magnetic control. Hence, the knowledge of frequency ranges for all neurons of a particular control system not only allows the possibility of external control of such a system, but also the possibility of its diagnosis by means of external noninvasive examination. The conducted research is another contribution into weak fields magnetobiology. It aims to create alternative noninvasive technologies for practical medicine.
The Earth’s magnetic field is subject to continuous changes. It has also been shown to induce effect on the vital activities of all living organisms. These factors make the study of magneto-biological effects important and highly relevant. From the biological point of view, weak magnetic fields, especially weak static magnetic fields, are among the most poorly understood, however, they have a noticeable effect on living organisms, including humans. The use of such fields is on the rise, which requires a comprehensive understanding of mechanisms behind their effect on living things. The article investigates the effect of weak static magnetic fields amplified and weakened relative to the Earth’s magnetic field on cellular tissue regeneration. It has been shown that one of the main cellular processes—proliferation—increases when the cells are exposed to enhanced or depressed static magnetic fields. The greatest effect of such exposure is observed in mesodermal tissue, i. e., the myocardium, vessels, and muscles. The effect of tissue-specific oligopeptides on cellular proliferation is comparable to that of static magnetic fields: the stimulation of cellular regeneration occurs primarily in the myocardium, muscles, and vessels. A special focus is given to the therapeutic potential of weak magnetic fields and their interaction with clinical drugs in various pathologies.
Kynurenine products of tryptophan metabolism are modifiers of the nervous activity and oxidative processes in mammals and invertebrates. 3-Hydroxykynurenine (3HOK) in moderate concentrations is a lipid peroxidation inhibitor. However, its accumulation and oxidative auto-dimerization lead to oxidative stress development manifested in age-related neurodegenerative diseases (NDD) and neurological disorders provoked by acute stress. Different forms of stress, the mostly studied being heat shock response, rely on functioning of heat shock proteins of the Hsp70 superfamily. Since kynurenines are called "kids of stress," we performed computational estimation of affinity of 3HOK and other kynurenines binding to predicted ATP site of Drosophila melanogaster Hsp cognate 71 protein (Dhsp71) using AutoDock Vina. The binding energy of 3HOK dimer is - 9.4 kcal/mol; its orientation within the active site is close to that of ATP. This might be a new mechanism of producing a competitive inhibitor of Hsp70 chaperones that decreases organism ability to adapt to heat shock. We also showed that the Drosophila cardinal (cd(1)) mutant with 3HOK excess, serving as a model for Huntington's disease (HD), manifests severe defects of short-term memory after heat shock applied either in adults or at the prepupal stage.
M. E. Lobashev and V. B. Savvateev’s research laid the foundation for studying the relationship between neuroplasticity and reaction to extreme conditions. Common mechanisms underlying adaptive reactions and learning have been proven to exist. Hypoxia is one of the most common damaging factors in various adverse external and internal effects. Severe forms of hypoxia suppress neuroplasticity and cause learning and memory disorders. Chromatin remodelling and expression of genes involved in memory formation and learning may require double-stranded DNA breaks because they accompany intense matrix processes in neurogenesis and serve as indicators of physiological neuronal activity. Stimulation of regulatory cascades involved in learning has an impact on adaptive response formation. For instance, metabolites of the kynurenine pathway of tryptophan metabolism affect the synaptic plasticity processes that regulate memory formation and learning. This article studies the effect of hypoxia on the state of chromosomal apparatus in Drosophila cd mutant (accumulation of 3-hydroxykynurenine). We discover interlinear differences in the frequency of double-stranded DNA breaks following exposure to hypoxia in mutant cd and wild-type CS strain. Obtained data are discussed in terms of the relationship between neuroplasticity processes, circadian rhythm regulation, and mechanisms for adapting to extreme conditions.
В последние годы активно исследуются механизмы воздействия на биологические объекты техногенных источников электромагнитных излучений и изменений естественного электромагнитного фона окружающей среды (ослабление, усиление). Важными индикаторами неблагоприятного влияния неионизирующих электромагнитных излучений являются изменения элементов врожденного поведения и когнитивных функций. При этом роль наследственно обусловленных характеристик нервной системы в определении чувствительности/устойчивости к колебаниям электромагнитных полей практически не изучалась. Цель работы заключалась в исследовании влияния излучения УВЧ-диапазона стандартного Wi-Fi-роутера и ослабленных экранированием внешних магнитных и электрических полей на врожденное поведение, отражающее ориентировочно-исследовательскую активность и эмоциональность животных в тесте «открытое поле», и когнитивные функции (сохранение условного рефлекса пассивного избегания) у самцов крыс двух селектированных линий ВП и НП (с высоким и низким порогами возбудимости нервной системы, низковозбудимые и высоковозбудимые, соответственно), а также крыс контрольной линии Вистар. Показано негативное влияние на врожденное поведение и память крыс двух линий с различными порогами возбудимости нервной системы ослабленных внешних электрических и магнитных полей, а также ЭМИ УВЧ-диапазона. Крысы с высокой возбудимостью нервной системы оказались более чувствительными к изменениям магнитного и электрического фона, электромагнитным излучениям по сравнению с низковозбудимыми животными.
Прогресс в области информационных технологий, средств глобальной беспроводной связи приводит к изменениям в естественном электромагнитном фоне Земли и экологической безопасности живых организмов. Представляется актуальным исследовать влияние техногенных и естественных электромагнитных полей c использованием модельных биологических объектов, включая медоносную пчелу, особо чувствительную к действию электромагнитных излучений (ЭМИ) в связи с врожденной необходимостью их использования в естественной среде обитания. Разрабатываемые системы защиты от ЭМИ за счет изменения характеристик излучения могут также вызывать специфические магнитобиологические реакции живых систем. В настоящей работе на медоносной пчеле (Apis mellifera L.) изучено влияние на врожденные и когнитивные компоненты поведения устройств — резонаторов ЭМИ, действующих изолированно и вкупе с Wi-Fi-роутером, а также изменений (ослабления/усиления) магнитного поля в месте проведения эксперимента относительно магнитного поля Земли. Показано угнетающее действие на процессы формирования памяти всех изучаемых факторов, кроме усиленного магнитного поля (стимулирующее воздействие). При этом наиболее глубокие изменения в процессы формирования памяти вносит изменение магнитных полей. Как ослабление, так и усиление магнитного поля значительно ингибирует долговременную память. Наблюдаемые изменения в процессах формирования памяти неизбежно отразятся на летной пищедобывательной активности и в целом на продуктивности семей медоносных пчел.
Сhromosomal machinery of highly excited animals with low threshold of the nervous system excitability (LT strain) is more susceptible to the damaging effect of high frequency EMR compared against the animals with high threshold of the nervous system excitability (HT strain). High nervous system excitability determines greater decrease in chromosome aberrations level in the presence of additional reflecting elements Aires Defender Pro resonators under UHF-waves of standard Wi-Fi router. It is shown that the genotype of animals and the functional state of their nervous system affect susceptibility to the UHF EMR and the action of resonators.
We used molecular dynamics to find the average path of the A-domainH→Bconformational transition in protein kinase A I α . We obtained thirteen productive trajectories and processed them sequentially using factor and cross-correlation analyses. The conformational transition is presented as partly deterministic sequence of six events. Event B representsH→Btransition of the phosphate binding cassette. Main participants of this event form electrostatic switch cAMP(O6)–A202(N-H)–G199(C=O). Through this switch, cAMP transmits information about its binding to hydrophobic switch L203–Y229 and thus triggers conformational transition of A-domain. Events C and D consist in N3A-motif displacement towards phosphate binding cassette and B/C-helix rotation. Event E involves an increase in interaction energy between Y229 and β -subdomain. Taken together, events B, E, and D correspond to the hinge movement towards β -barrel. Transition of B/C-helix turn (a.a. 229–234) from α -form to π -form accounts for event F. Event G implies that π -helical turn is replaced by kink. Emerging in the resulting conformation, electrostatic interaction R241–E200 facilitates kink formation. The obtained data on the mechanism of cAMP-dependent activation of PKA I α may contribute to new approaches to designing pharmaceuticals based on cAMP analogs.
Kynurenines, the main products of tryptophan catabolism, possess both prooxidant and anioxidant effects. Having multiple neuroactive properties, kynurenines are implicated in the development of neurological and cognitive disorders, such as Alzheimer's, Parkinson's, and Huntington's diseases. Autoxidation of 3-hydroxykynurenine (3HOK) and its derivatives, 3-hydroxyanthranilic acid (3HAA) and xanthommatin (XAN), leads to the hyperproduction of reactive oxygen species (ROS) which damage cell structures. At the same time, 3HOK and 3HAA have been shown to be powerful ROS scavengers. Their ability to quench free radicals is believed to result from the presence of the aromatic hydroxyl group which is able to easily abstract an electron and H-atom. In this study, the redox properties for kynurenines and several natural and synthetic antioxidants have been calculated at different levels of density functional theory in the gas phase and water solution. Hydroxyl bond dissociation enthalpy (BDE) and ionization potential (IP) for 3HOK and 3HAA appear to be lower than for xanthurenic acid (XAA), several phenolic antioxidants, and ascorbic acid. BDE and IP for the compounds with aromatic hydroxyl group are lower than for their precursors without hydroxyl group. The reaction rate for H donation to *O-atom of phenoxyl radical (Ph-O*) and methyl peroxy radical (Met-OO*) decreases in the following rankings: 3HOK ~ 3HAA > XAAOXO > XAAENOL. The enthalpy absolute value for Met-OO* addition to the aromatic ring of the antioxidant radical increases in the following rankings: 3HAA* < 3HOK* < XAAOXO* < XAAENOL*. Thus, the high free radical scavenging activity of 3HAA and 3HOK can be explained by the easiness of H-atom abstraction and transfer to O-atom of the free radical, rather than by Met-OO* addition to the kynurenine radical.
We studied the effect produced on the development and functional activity of skeletal muscle cells from newborn Wistar rats in primary culture by weak static magnetic fields (WSMF; 60-400 µT) with a high capacity of penetrating the biological media. To reduce the impact of external magnetic fields, cells were cultured at 37 °C in a multilayered shielding chamber with the attenuation coefficient equal to 160. WSMF inside the chamber was created by a circular permanent magnet. We found that the application of WSMF with the magnetic field strength only a few times that of the geomagnetic field can accelerate the development of skeletal muscle cells, resulting in the formation of multinuclear hypertrophied myotubes. WSMF was shown to induce 1.5- to 3.5-fold rise in the concentration of intracellular calcium [Ca(2+)]i due to the release of Ca(2+) from the sarcoplasmic reticulum (SR) through ryanodine receptors (RyR), which increases in the maturation of myotubes. We also found that fully differentiated myotubes at late stages of development were less sensitive to WSMF, manifesting a gradual decrease in the frequency of contractions. However, myotubes at the stage when electromechanical coupling was forming dramatically reduced the frequency of contractions during the first minutes of their exposure to WSMF.
Using the combination of molecular dynamics (MD) simulations and geometric clustering we analyzed the role of arginine at 209 position in the transition of protein kinase A Iα (PKA Iα) regulatory subunit A-domain from H- to B-conformation and stabilization of the latter. The mechanism underlying the role of the residue at position 209 in the realization of B-conformation includes: (1) possibility to bind the ligand tightly (if transition happens in the presence of cAMP), (2) capability to hold β2β3-loop in the correct conformation, (3) tendency of residue at 209 position to stabilize B-conformation in the absence and in presence of the ligand. In terms of the effect produced on transition of A-domain from H- to B-conformation in the presence of cAMP, mutational substitutions for R209 can be arranged in the following order: Glu(Gly)>Lys>Ile. In the absence of cAMP the order is different Lys>Gly>Glu>Ile. Thus, our results allow us to presume that the role of arginine at 209 position can be important though not crucial.
Stacking interaction is known to play an important role in protein folding, enzyme-substrate and ligand-receptor complex formation. It has been shown to make a contribution into the aromatic antagonists binding with glutamate ionotropic receptors (iGluRs), in particular, the complex of NMDA receptor NR1 subunit with the kynurenic acid (KYNA) derivatives. The specificity of KYNA binding to the glutamate receptors subtypes might partially result from the differences in stacking interaction. We have calculated the optimal geometry and binding energy of KYNA dimers with the four types of aromatic amino acid residues in Rattus and Drosophila ionotropic iGluR subunits. All ab initio quantum chemical calculations were performed taking into account electron correlations at MP2 and MP4 perturbation theory levels. We have also investigated the potential energy surfaces (PES) of stacking and hydrogen bonds (HBs) within the receptor binding site and calculated the free energy of the ligand-receptor complex formation. The energy of stacking interaction depends both on the size of aromatic moieties and the electrostatic effects. The distribution of charges was shown to determine the geometry of polar aromatic ring dimers. Presumably, stacking interaction is important at the first stage of ligand binding when HBs are weak. The freedom of ligand movements and rotation within receptor site provides the precise tuning of the HBs pattern, while the incorrect stacking binding prohibits the ligand-receptor complex formation.
Using modified CNDO/2 calculations on small silica fragments, allowing for structure relaxation, the authors have estimated the formation energy of a pair of oppositely charged dangling bonds in vitreous silica to be 3-4 eV.