Biophysics最新文献

This study aimed to investigate myoneural transmission in the presence of capsaicin, which acts as an integrator of pain stimuli and causes heat sensation. The effects of purines that participate in synaptic transmission, such as ATP and adenosine, in the presence of capsaicin were explored. When the neuromuscular preparation of frog was perfused with solution containing capsaicin, the inhibitory effects of both purines were significantly reduced. A reduction of the depressant effects of adenosine is associated with the inhibition of A₁ signaling, since the A_2A receptor agonist CGS21680 showed a pronounced potentiating effect in the presence of capsaicin, which was almost completely hidden in the control. Our findings suggest that the known neuroprotective effect of capsaicin is primarily due to elimination of inhibition by endogenous purines of the induced quantum output of the neurotransmitter.

The study of potential-dependent calcium channels sheds light on the formation of systems responsible for the coupling of sensors and actuators in a living cell. Based on data on the potential-sensitive calcium channel TCa_v3 (2063 amino acid residues) from Trichoplax adhaerens cells, homologues of 2090 amino acid residues in the scaffold of Trichoplax sp. H2 and an incomplete polypeptide with a length of 1510 amino acid residues in the scaffold of Trichoplax adhaerens are identified. The latter hypothetical protein is annotated as a Ca_v3 channel. An EEDD selective filter is found for all three proteins and the core structure of the calcium channel consisting of 24 transmembrane α-helices is reconstructed. Nevertheless, the studied proteins differ in cytoplasmic domains, which indicates a different specialization of Ca_v3 channels when conducting a signal into the cell. For example, part of the AID motif (alpha-interacting domain) and the adjacent potential sensor from the annotated channel have homology in 25 species of bony fish, and the corresponding region from other channels in 41 species of bony fish and in 4 species of snakes. Significantly, a highly conserved IIS1-S2 loop with the IEHHNQP sequence is found below the AID motif of bony fish, as in trichoplax; while a homologous IEHHEQP sequence is found in snakes, characterized by a negative glutamic acid residue, which is also present in the corresponding rat and human proteins. Based on the analysis of primary transcripts and mature polypeptides, a modular mechanism for the evolution of Ca_v3 channels is proposed by inserting and combining protein domains performing various regulatory functions.

Mitochondria are involved in diseases of various etiologies. The use of drugs aimed at improving the functional state of mitochondria may be a promising therapeutic approach to diseases of various etiologies. Astaxanthin is a keto-carotenoid (xanthophyll) of predominantly marine origin. It has both lipophilic and hydrophilic properties and can penetrate through the cell membrane, localizing in the mitochondria and preventing mitochondrial dysfunction. In this paper, the effect of astaxanthin on the functional state of rat brain mitochondria, changes in mitochondrial dynamics and mitophagy in isoproterenol-induced damage is studied. Under the action of astaxanthin, mitochondria are more resistant to the Ca²⁺-induced opening of a nonspecific pore and the activity of complexes I, IV, and V of the respiratory chain increases. Moreover, astaxanthin alters the level of markers of mitochondrial fission and fusion, as well as mitophagy in isoproterenol-induced mitochondrial dysfunction, which probably leads to an increase in the number of functional mitochondria of the rat brain and improved their condition. Astaxanthin can be considered as a mitochondria-directed agent in the therapy for pathological conditions associated with oxidative damage and mitochondrial dysfunction caused by heart failure. As a dietary supplement, astaxanthin has the potential for the antioxidant protection of cells in cardiovascular diseases.

A bulk segregant analysis (BSA) was used to analyze the F₂ population from crossing two flax varieties that differ in fusarium wilt resistance genes. The causative agent of this disease, the fungus Fusarium oxysporum f. sp. lini is one of the main pathogens of flax, causing huge economic damage to its global production. Sequencing of DNA pools of highly resistant and sensitive to fusarium wilt F₂ plants and their subsequent analysis identified two regions on chromosomes 9 and 13 that caused resistance to fusarium wilt. Candidate genes for subsequent analysis are selected by functional gene annotation and analysis of gene expression of QTL regions in the transcriptomic data obtained as a result of the infection of the fusarium-resistant Atalante variety. As a result of combining the two approaches, three genes are identified in each of the QTL regions, which, according to the published data, are involved in the plant’s response to infection and are differentially expressed in the transcriptome experiment.

It has been shown in a number of our studies that low-frequency (LF) oscillations in the functional parameters of the oxygen transport system are stable and synchronized with each other. The literature presents a large number of examples of LF oscillations of various functional indicators that are directly or indirectly related to energy metabolism. In parallel, for more than 40 years, artificially induced attenuated and constant spontaneous oscillations in the energization levels of mitochondria in the same LF range have been studied. The aim of this review is to consider a possible relationship between oscillations in the functional parameters of the oxygen transport system and the functional parameters of mitochondria in the very-low-frequency (VLF) range common to them (0.003–0.03 Hz). We believe that a common source for all these oscillations is the periodic dynamics of “energization” in mitochondria united in mitochondrial networks. The process of generating these oscillations proceeds in two phases. In the first phase, the inflow of Ca²⁺ into the mitochondria exceeds the outflow and enhances the activity of oxidative phosphorylation. In the second phase, the outflow of Ca²⁺ from the mitochondria prevails over the inflow and is accompanied by the inhibition of oxidative phosphorylation. The oscillations are of a constant spontaneous nature and are based on autocatalytic regulation based on the feedback principle. The inertia of the full cycle processes (first and second phases) lasting 1–3 min may be due to the capacity of the mitochondrial phosphate buffer. The mitochondrial networks of excitable tissues can be the structural basis for synchronizing oscillations at the tissue level. Synchronization at the body level between mitochondrial oscillations and oscillations in indicators related to energy metabolism can be carried out through a system of tunneling nanotubes.

Abstract

Hafnium is a promising element as contrast agent for diagnostic and therapeutic radiology. Currently there are no suitable hafnium drugs with renal excretion which can be used in radiology. In this work two new hafnium complexes with nitrilotriacetic acid (Hf-NTA) and 1,2-diaminocyclohexanetetraacetic acid (Hf-CDTA) were synthesized and studied for acute toxicity and biodistribution. Inorganic chemistry methods were used for Hf-NTA and Hf-CDTA synthesis. Acute toxicity was studied in female mice C57Bl/6. Median lethal dose (LD50) of Hf-CDTA was assessed as 408 ± 64 mg Hf/kg and of Hf-NTA less than 120 mg Hf/kg. Biodistribution and contrast properties studies of Hf-CDTA were performed in vivo using micro-CT in mice with transplanted subcutaneous mammary adenocarcinoma Ca755. CT imaging of mice intravenously injected with Hf-CDTA confirmed its renal excretion and contrast capability. CT imaging of tumor region with single intratumoral administration of Hf-CDTA showed promising hafnium concentration and retention in tumor for use in contrast-enhanced radiotherapy. Hf-CDTA showed acceptable toxicity and biodistribution in mice with subcutaneous tumors for biomedical application in radiology and radiotherapy. For diagnostic clinical application, the Hf-CDTA formulation must be improved to increase water solubility and decrease toxicity. Hf-NTA appeared to be unacceptably toxic for radiological application.

Based on a dynamic parameter of the cerebrospinal fluid (CSF) flow, an original formula for estimating the pathology of the spinal motion segments of the spine is given. The graphs that clearly demonstrate a change in pathology depending on the depth of traumatization are given. The data obtained will be useful to specialists in computed tomography and magnetic resonance imaging, who are currently describing the pathology itself in a simplified way.

The patterns of tumor induction and growth in mice under single irradiation ex vivo and in vivo of ascitic Ehrlich carcinoma (EAC) cells with a proton beam at doses of 30, 60, and 80 Gy are studied. It is shown that the frequency of tumor induction after the proton irradiation of EAC cells at a dose of 30 Gy under ex vivo irradiation was lower than after in vivo irradiation, and at doses of 60 Gy and 80 Gy, the number of tumors was the same. The temporal patterns of tumor occurrence in the ex vivo irradiation of EAC cells differed significantly from those after in vivo irradiation of the tumor: the time period during which the appearance of new tumors was recorded in the ex vivo groups was the same for all the studied doses, while when tumors were irradiated in vivo, this interval depended on the dose. The rate of tumor growth after the ex vivo and in vivo irradiation of cells does not depend on the dose, irradiation conditions, or time of their occurrence, but is significantly lower than in the control nonirradiated groups. The results obtained are of interest for understanding the mechanisms of potentially lethal damage to tumor cells, the role of the tumor microenvironment in inducing relapses, and ways to overcome them using the potential of proton therapy, as well as for developing biomedical models to find optimal targets for hadron cancer therapy.

A theoretical conformational analysis was performed to study the conformational possibilities for the casoxin C molecule (Tyr1–Ile2–Pro3–Ile4–Gln5–Tyr6–Val7–Leu8–Ser9–Arg10–OH). The potential function of the system was chosen as a sum of non-valence, electrostatic, and torsion interactions, and the energy of hydrogen bonds. The low-energy conformations of the casoxin C molecule were found, the values of dihedral angles of the main and side chains of the amino acid residues that make up the molecule were determined, and the energy of intra- and interresidual interactions was estimated. It has been shown that the spatial structure of the casoxin C molecule is represented by conformations of eight shapes of the peptide backbone. The results obtained can be used to elucidate the structural and structural-functional organization of casoxin molecules.

Abstract

It has been shown using experimental (electron paramagnetic resonance) and quantum chemical (density functional theory) research methods that the previously observed changes in the electron paramagnetic resonance spectrum of the semiquinone Tiron radical in seawater are due to its interaction with Mg²⁺ ions. The formation of a complex between Mg²⁺ and the Tiron radical is due to the electrostatic attraction of ions carrying large charges of the opposite sign (+2 and –3), on the one hand, and the ability of Mg²⁺ ions to bind effectively to bidentate oxygen-containing ligands, on the other hand. The formation of tight contact ion pairs leads to a redistribution of the electron and spin density in the Tiron radical, which can be judged by the observed changes in the electron paramagnetic resonance spectrum of this radical.