Random Effects in Magnetobiology and a Way to Summarize Them.

In magnetobiology, it is difficult to reproduce the nonspecific (not associated with specialized receptors) biological effects of weak magnetic fields. This means that some important characteristic of the data may be missed in standard statistical processing, where the set of measurements to be averaged belongs to the same population so that the contribution of fluctuations decreases according to the Central Limit Theorem. It has been shown that a series of measurements of a nonspecific magnetic effect contains not only the usual scatter of data around the mean but also a significant random component in the mean itself. This random component indicates that measurements belong to different statistical populations, which requires special processing. This component, otherwise called heterogeneity, is an additional characteristic that is typically overlooked, and which reduces reproducibility. The current method for studying and summarizing highly heterogeneous data is the random-effect meta-analysis of absolute values, i.e., of magnitudes, rather than the values themselves. However, this estimator-the average of absolute values-has a significant positive bias when it comes to the small effects that are characteristic of magnetobiology. To solve this problem, an improved estimator based on the folded normal distribution that gives several times less bias is proposed. We used this improved estimator to analyze the nonspecific effect of the hypomagnetic field in the Stroop test in 40 subjects and found a statistically significant meta-effect with a standardized average of magnitudes of about 0.1. It has been shown that the proposed approach can also be applied to a single study. © 2021 Bioelectromagnetics Society.

Unfolding and Aggregation of Lysozyme under the Combined Action of Dithiothreitol and Guanidine Hydrochloride: Optical Studies.

Using a number of optical techniques (interferometry, dynamic light scattering, and spectroscopy), denaturation of hen egg white lysozyme (HEWL) by treatment with a combination of dithiothreitol (DTT) and guanidine hydrochloride (GdnHCl) has been investigated. The denaturing solutions were selected so that protein denaturation occurred with aggregation (Tris-HCl pH = 8.0, 50 mM, DTT 30 mM) or without aggregation (Tris-HCl pH = 8.0, 50 mM, DTT 30 mM, GdnHCl 6 M) and can be evaluated after 60 min of treatment. It has been found that denatured by solution with 6 M GdnHCl lysozyme completely loses its enzymatic activity after 30 min and the size of the protein molecule increases by 1.5 times, from 3.8 nm to 5.7 nm. Denaturation without of GdnHCl led to aggregation with preserving about 50% of its enzymatic activity. Denaturation of HEWL was examined using interferometry. Previously, it has been shown that protein denaturation that occurs without subsequent aggregation leads to an increase in the refractive index (Δn ~ 4.5 × 10-5). This is most likely due to variations in the HEWL-solvent interface area. By applying modern optical techniques conjointly, it has been possible to obtain information on the nature of time-dependent changes that occur inside a protein and its hydration shell as it undergoes denaturation.

A physical mechanism of magnetoreception: Extension and analysis.

Proposed is a general physical mechanism of magnetoreception of weak magnetic fields (MFs). The mechanism is based on classical precessional dynamics of a magnetic moment in a thermally disturbed environment and includes a minimum of necessary parameters-the gyromagnetic ratio, thermal relaxation time, and rate of downstream events generated by changes in the state of the magnetic moment. The mechanism imposes general restrictions on the probability of initial biophysical magnetic transduction event before the involvement of specific biophysical and biochemical mechanisms-i.e., regardless of the nature of an MF target and the subsequent cascade of events. It is shown that biological effects of weak MFs have, in certain cases, nonlinear and frequency selective properties. The observation of these characteristics provides information not only on the target's gyromagnetic ratio, but also on the parameters of its interaction with the immediate environment. This enables one to develop experimental strategies for identifying the biophysical mechanisms of magnetoreception including the specific case of effects of a near-zero MF exposure. The mechanism is universally applicable to magnetic moments of different nature, in particular, of electron and proton orbital motion and of spins. Experimental exposure conditions are derived which would lead to validation of the proposed mechanism. Bioelectromagnetics. 38:41-52, 2017. © 2016 Wiley Periodicals, Inc.

Statistical Amplification of the Effects of Weak Magnetic Fields in Cellular Translation.

We assume that the enzymatic processes of recognition of amino acids and their addition to the synthesized molecule in cellular translation include the formation of intermediate pairs of radicals with spin-correlated electrons. The mathematical model presented describes the changes in the probability of incorrectly synthesized molecules in response to a change in the external weak magnetic field. A relatively high chance of errors has been shown to arise from the statistical enhancement of the low probability of local incorporation errors. This statistical mechanism does not require a long thermal relaxation time of electron spins of about 1 µs-a conjecture often used to match theoretical models of magnetoreception with experiments. The statistical mechanism allows for experimental verification by testing the usual Radical Pair Mechanism properties. In addition, this mechanism localizes the site where magnetic effects originate, the ribosome, which makes it possible to verify it by biochemical methods. This mechanism predicts a random nature of the nonspecific effects caused by weak and hypomagnetic fields and agrees with the diversity of biological responses to a weak magnetic field.

Theoretical Concepts in Magnetobiology after 40 Years of Research.

This review contains information on the development of magnetic biology, one of the multidisciplinary areas of biophysics. The main historical facts are presented and the general observed properties of magnetobiological phenomena are listed. The unavoidable presence of nonspecific magnetobiological effects in the everyday life of a person and society is shown. Particular attention is paid to the formation of theoretical concepts in magnetobiology and the state of the art in this area of research. Some details are provided on the molecular mechanisms of the nonspecific action of a magnetic field on organisms. The prospects of magnetobiology for the near and distant future are discussed.

Investigation of Aggregation and Disaggregation of Self-Assembling Nano-Sized Clusters Consisting of Individual Iron Oxide Nanoparticles upon Interaction with HEWL Protein Molecules.

In this paper, iron oxide nanoparticles coated with trisodium citrate were obtained. Nanoparticles self-assembling stable clusters were ~10 and 50-80 nm in size, consisting of NPs 3 nm in size. The stability was controlled by using multi-angle dynamic light scattering and the zeta potential, which was -32 ± 2 mV. Clusters from TSC-IONPs can be destroyed when interacting with a hen egg-white lysozyme. After the destruction of the nanoparticles and proteins, aggregates are formed quickly, within 5-10 min. Their sizes depend on the concentration of the lysozyme and nanoparticles and can reach micron sizes. It is shown that individual protein molecules can be isolated from the formed aggregates under shaking. Such aggregation was observed by several methods: multi-angle dynamic light scattering, optical absorption, fluorescence spectroscopy, TEM, and optical microscopy. It is important to note that the concentrations of NPs at which the protein aggregation took place were also toxic to cells. There was a sharp decrease in the survival of mouse fibroblasts (Fe concentration ~75-100 µM), while the ratio of apoptotic to all dead cells increased. Additionally, at low concentrations of NPs, an increase in cell size was observed.

A limit in the dynamic increase in the accuracy of group migration.

Many migratory animals regularly travel thousands of kilometers, exactly finding their seasonal destinations. The nature of this ability is still not fully understood. The aggregation of animals in groups and their socially coordinated movement is considered a way to eliminate navigational errors. Orientation accuracy of a group may be significantly higher as the errors caused by a variety of casual factors are averaged due to social interactions. This idea, called the "many wrongs principle," has been confirmed both in behavioral experiments and numerical simulations. However, little is known about the dependence of this effect on the number N of individuals. Until now, there were no analytical models considering this effect and its limitations. In this article, a stochastic dynamic model of group navigation is presented in terms of the course deviation angle and its variance. The N-dependence of the variance of deviations is found. The variance first decreases with N, however the decrease then slows down thus showing disagreement with the "many wrongs principle." This can be interpreted as meaning that the growth in the accuracy of migration due to the aggregation of individuals into groups is limited. The limit depends on the individual sensitivity of the animal compass, the power of the herd instinct, and the level of random noise.

Rotations of macromolecules affect nonspecific biological responses to magnetic fields.

We have previously proposed that there are at least two initial molecular transduction mechanisms needed to explain specific and nonspecific biological effects of weak magnetic fields. For the specific effect associated with animal magnetic navigation, the radical pair mechanism is the leading hypothesis; it associates the specialised magnetic sense with the radical pairs located in the eye retina. In contrast to the magnetic sense, nonspecific effects occur through the interaction of magnetic fields with magnetic moments dispersed over the organism. However, it is unlikely that the radical pair mechanism can explain such nonspecific phenomena. In order to explain these, we further develop our physical model for the case of magnetic moments residing in rotating molecules. It is shown that, in some conditions, the precession of the magnetic moments that reside on rotating molecules can be slowed relative to the immediate biophysical structures. In terms of quantum mechanics this corresponds to the mixing of the quantum levels of magnetic moments. Hence this mechanism is called the Level Mixing Mechanism, or the LMM. The results obtained are magnetic field-dependences that are in good agreement with known experiments where biological effects arise in response to the reversal of the magnetic field vector.

Biological effects of the hypomagnetic field: An analytical review of experiments and theories.

During interplanetary flights in the near future, a human organism will be exposed to prolonged periods of a hypomagnetic field that is 10,000 times weaker than that of Earth's. Attenuation of the geomagnetic field occurs in buildings with steel walls and in buildings with steel reinforcement. It cannot be ruled out also that a zero magnetic field might be interesting in biomedical studies and therapy. Further research in the area of hypomagnetic field effects, as shown in this article, is capable of shedding light on a fundamental problem in biophysics-the problem of primary magnetoreception. This review contains, currently, the most extensive bibliography on the biological effects of hypomagnetic field. This includes both a review of known experimental results and the putative mechanisms of magnetoreception and their explanatory power with respect to the hypomagnetic field effects. We show that the measured correlations of the HMF effect with HMF magnitude and inhomogeneity and type and duration of exposure are statistically absent. This suggests that there is no general biophysical MF target similar for different organisms. This also suggests that magnetoreception is not necessarily associated with evolutionary developed specific magnetoreceptors in migrating animals and magnetotactic bacteria. Independently, there is nonspecific magnetoreception that is common for all organisms, manifests itself in very different biological observables as mostly random reactions, and is a result of MF interaction with magnetic moments at a physical level-moments that are present everywhere in macromolecules and proteins and can sometimes transfer the magnetic signal at the level of downstream biochemical events. The corresponding universal mechanism of magnetoreception that has been given further theoretical analysis allows one to determine the parameters of magnetic moments involved in magnetoreception-their gyromagnetic ratio and thermal relaxation time-and so to better understand the nature of MF targets in organisms.