Vol 12, No 3 (2018)

It has been revealed recently that the subterahertz/terahertz vibrational motions in enzymes and DNA immersed in aqueous solutions can be underdamped. Importantly, these motions are associated with coherent delocalized modes that control functional processes. Analogous propagating phonon-like modes have been found in free hydrated lipid bilayers. In the present work, subterahertz (frequencies of the order of tens and hundreds of gigahertz) longitudinal acoustic oscillations in a bilayer lipid membrane immersed in aqueous medium are investigated theoretically. We consider driven oscillations excited by tangential mechanical tensions at the bilayer surfaces and thermally induced phonon modes. The analysis is based on: (i) a generalized hydrodynamic model of two-dimensional lipid bilayer in aqueous medium; (ii) known estimates of frequencies and lifetimes of longitudinal acoustic phonons in free hydrated lipid bilayer and in water, which were obtained in the experiments on non-elastic X-ray scattering and the molecular dynamics simulations. We show that the membrane phonon-like excitations are underdamped for the typical values of the system parameters, and the contribution of aqueous medium to the membrane mode damping is small compared to the contribution of the lipid bilayer. The obtained results suggest the possibility of realization of thermally induced longitudinal membrane phonons in physiological conditions, as well as the possibility of resonance amplification of the impact of subnanosecond electric impulses and impulses of subterahertz electromagnetic radiation on membrane dynamics.

Synaptic proteins synucleins are found in pathologic aggregates in human brain during neurodegenerative diseases and in some tumors. Normal functions of these proteins in synapses are still unclear. In the present study, we used cDNA cloning to determine amino acid sequences of synucleins in the central nervous system of river lamprey (Lampetra fluviatilis), which is used as a model organism to study molecular mechanisms of synaptic transmission. Three genes are identified. High similarity in amino acid sequences as compared to other vertebrate species is revealed. The bioinformatic analysis predicts that the river lamprey synucleins relate to the group of gamma-synucleins. High homology with human alpha-synuclein is reported. The hydrophobic region required for the formation of alpha-synuclein amyloid fibers is also present in the river lamprey synucleins. The latter suggests that this region appeared at early stages of evolution. The obtained amino acid sequences of synucleins in the river lamprey brain will allow generating novel molecular tools for dissecting physiological functions of these proteins.

Giant neurons of the mollusc Lymnaea stagnalis contain heterogeneous population of nicotinic acetylcholine receptors (nAChRs) according to their relative sensitivity to antagonists. All these receptors are involved in the total response to acetylcholine (ACh). To evaluate activity of different pharmacological agents correctly it is necessary to know ionic selectivity of nAChRs which participate in transmembrane ionic current. In this work we studied the influence of ionic composition of the external and intracellular solutions on the current amplitude and current–voltage relation under the action of ACh or other nAChR agonists on the identified neurons of the left and right parietal ganglia of Lymnaea. After non-permeable cation N-methyl-D-glucamine was completely substituted for external Na⁺ ions there were no changes in the current characteristics. After a 10-fold decrease in Cl–concentration in the external solution there was a considerable shift of the current–voltage curve to the right, outward currents at the holding potential (V_h) up to 30 mV were not observed. On the contrary, a 10-fold decrease of Cl^– concentration in the intracellular solution led to a shift of the current–voltage curve to hyperpolarizing direction, the reversal potential shift was in the average –42 mV. When ACh and nicotinic agonists with higher selectivity towards vertebrate α7 neuronal nAChR type and one of the two subtypes of Lymnaea nAChRs were compared, no differences in changes of ionic current characteristics were found. Neurons with distinct relative fraction of one or another nAChR subtype reacted to Cl^– concentration change in the same way. Our results support earlier data on Cl^– mechanism of Lymnaea neuron responses to ACh and evidence identical ionic selectivity of the two nAChR subtypes in identified neurons tested.

Membrane TNFα (mTNFα) is expressed on many immune cell types and performs various biological functions. Dendritic cells (DC) of high-grade glioma patients exhibit impaired cytotoxic activity against TNFα-sensitive HEp-2 tumor cells. The mechanisms leading to the impairment of the TNFα- dependent tumoricidal activity of DC and the possibility of regulating the cytotoxic activity of DC mediated by the TNFα/TNF-R1 signaling pathway have been studied. The study was conducted on healthy donors and patients with newly diagnosed high-grade glioma. DC were generated by culturing the plastic-adherent peripheral blood mononuclear cell fraction in the presence of GM-CSF and interferon-α (IFN-DC). It was shown that the impairment of the cytotoxic activity of patient IFN-DC was associated with a low number of DC expressing mTNFα and a low level of TNFα mRNA expression in DC. IFN-DC of patients exhibited a tendency of high activity of the TNFα-converting enzyme (TACE), which accomplishes shedding of mTNFα from the cell membrane. An increased number of IFN-DC with mTNFα caused by TACE blocking enhanced cytotoxic activity of the patient’s IFN-DC against HEp-2 cells. It was established that exogenous interleukin-2 and extracellular DNA are up-regulators of the mTNFα expression on IFN-DC of the patients, but their effects are mediated by different mechanisms.

The dynamics of changes of spontaneous neuronal activity in primary hippocampal cell cultures developing on a multielectrode array (MEA) was studied using a multielectrode system. The intensification of bioelectrical activity, which depended on the duration of cultivation and stabilized by the second week in vitro, has been revealed. An increase in the concentration of glutamate (up to 2 μM) by addition into the incubation medium during the stabilization period resulted in a rapid and significant reorganization of the neuronal network activity pattern. On the other hand, inhibition and subsequent gradual recovery of the neuronal network activity immediately after the neurotransmitter addition at higher concentrations (50 or 100 μM) have been observed. At the same time, on some electrodes in the presence of high doses of glutamate (100 μM), a complete or partially irreversible suppression of the activity has been recorded. A significant reduction in spontaneous activity of the neuronal network, which was not accompanied by neuronal death, also occurred when copper ions (Cu²⁺) at a concentration of 10 μM were added into the incubation medium for 48 h. The obtained data demonstrate high biosensor sensitivity of the neuronal network cultured on the multielectrode array, which makes it possible to use it as an effective test system for studies of biologically active compounds.

“Our oldness is a disease that has to be treated like any other one,”—this statement formulated about a hundred years ago seems to be of current interest in the context of modern investigations. Recently, it has been established that accumulation of senescent cells in various organs and tissues is one of the main causes for the organismal aging, as well as for the progression of multiple age-related pathologies. On the one hand, this observation brings us one step closer to the desired goal—reversal or slowing down of aging. On the other hand, this raises a number of complicated questions: in what essentially lies the difference between senescent and normal cells and how they can be identified; whether senescent cells can be eliminated from the body and can this elimination stop/reverse aging; can such a targeted removal of senescent cells be accompanied by negative consequences, in particular, by an increase in the cancer incidence? This review summarizes the main features of senescent cells, surveys the existing approaches of targeted elimination of senescent cells in vivo, and highlights their advantages and disadvantages.