Photochemical Metal-Free synthesis and biological Assessment of isocryptolepine analogues targeting estrogen receptor Alpha in breast cancer cells.

The aim of this study was to develop a new series of isocryptolepines and evaluate their antiproliferative and antiestrogenic activities on cancer cells. A series of isocryptolepine derivatives were synthesized using developed one-pot photochemical, metal-free protocol, employing readily available 2-arylindoles as starting compounds. The resulting isocryptolepines demonstrated (sub)micromolar inhibitory activity against selected breast cancer cell lines.

Chaos-hyperchaos transition in three identical quorum-sensing mean-field coupled ring oscillators.

We investigate the dynamics of three identical three-dimensional ring synthetic genetic oscillators (repressilators) located in different cells and indirectly globally coupled by quorum sensing whereby it is meant that a mechanism in which special signal molecules are produced that, after the fast diffusion mixing and partial dilution in the environment, activate the expression of a target gene, which is different from the gene responsible for their production. Even at low coupling strengths, quorum sensing stimulates the formation of a stable limit cycle, known in the literature as a rotating wave (all variables have identical waveforms shifted by one third of the period), which, at higher coupling strengths, converts to complex tori. Further torus evolution is traced up to its destruction to chaos and the appearance of hyperchaos.

Emergence of multistability and strongly asymmetric collective modes in two quorum sensing coupled identical ring oscillators.

The simplest ring oscillator is made from three strongly nonlinear elements repressing each other unidirectionally, resulting in the emergence of a limit cycle. A popular implementation of this scheme uses repressor genes in bacteria, creating the synthetic genetic oscillator known as the Repressilator. We consider the main collective modes produced when two identical Repressilators are mean-field-coupled via the quorum-sensing mechanism.

Evolution of quasiperiodicity in quorum-sensing coupled identical repressilators.

The dynamics of three three-dimensional repressilators globally coupled by a quorum sensing mechanism was numerically studied. This number (three) of coupled repressilators is sufficient to obtain such a set of self-consistent oscillation frequencies of signal molecules in the mean field that results in the appearance of self-organized quasiperiodicity and its complex evolution over wide areas of model parameters. Numerically analyzing the invariant curves as a function of coupling strength, we observed torus doubling, three torus arising via quasiperiodic Hopf bifurcation, the emergence of resonant cycles, and secondary Neimark-Sacker bifurcation.

[The experimental evaluation of the protective effect of the extract of the cyclodextrin-containing phytotherapeutic composition on the development of osteoporosis].

Objective: The relevance of the problem considered in the present communication arises to-day from the widespread prevalence of osteoporosis (OP), the rather low effectiveness of the methods currently available for the treatment of this condition, and iatrogenic effects of its medication therapy. The great diversity of phytotherapeutic modalities of traditional medicine are is only poorly supported by the results of the scientific studies results; moreover, most of them are coming from the foreign literature publications.

Aim:  The objective of the present study was to evaluate the influence of the phytotherapeutic preparation (Phytocost) having cyclodextrin in its composition on the restoration of the cartilaginous and bony tissues based on the experimental research with the use of the OP experimental model.

Flexible dynamics of two quorum-sensing coupled repressilators.

Genetic oscillators play important roles in cell life regulation. The regulatory efficiency usually depends strongly on the emergence of stable collective dynamic modes, which requires designing the interactions between genetic networks. We investigate the dynamics of two identical synthetic genetic repressilators coupled by an additional plasmid which implements quorum sensing (QS) in each network thereby supporting global coupling.

[New phytotherapeutic composition for restoring bone and cartilage. Experimental study].

Presents a new import-substituting the composition of the powder mixture 60 medicinal plants and dead bees. In prednisolonbuy models of osteoporosis have shown dose-dependent regenerative effects bone and cartilage of the hip joints of mice. Unwanted side effects when taking composition was observed.

[The effect of low frequency electrical stimulation on bone tissue regeneration].

The study was performed on 30 male rats of Wistar line (weight 330-360 g, age 3.5 months).In an experimental model of damage to the femur bone in the hip joint studied the effect of low frequency electrical stimulation of the damaged area on the rate of regeneration of bone.

FLUORESCENT MICROSCOPY IDENTIFICATION OF THE EXPRESSION OF a2 AND b1 NA +/K+-ATPase, a1S (L-TYPE), ÑÀ2+-CHANNEL, SERCA 1/2/3 CA2+-ATPase SUBUNITS AT FAST AND SLOW MUSCLES IN THE HYPOGRAVITY MODELING EXPERIMENTS IN RATS.

The experiments of modeling hypogravity using fluorescent microscopy have shown a decrease of expression of b1 of Na +/K+-ATPase and Ca2+-ATPase subunits and the increase in the insensitivity of synthesis of a1S subunit of the L-type Ca2+-channel of the plasmatic membrane, whereas the synthesis of a2 subunit of Na+/K+-ATPase does not change. In «fast» muscle only observed similar for «slow» muscle decrease in the expression of b1 subunit without changing other parameters were studied. However, the decrease in fluorescence b1 subunit due to spread of data was not statistically significant.

[Influence of modeling of gravitational unloading on the postsynaptic acetylcholine receptor organization and acetylcholinesterase activity in neuromuscular synapses of rat fast and slow muscles].

Using immunofluorescent techniques, we have revealed that, after 35 days of rats hindlimb unloading, neuromuscular synapses of fast and slow muscles show enhanced fluorescence intensity and decreased area of fluorescent staining of acetylcholine receptors; increased fluorescent intensity and area of fluorescent staining for acetylcholinesterase. The ratio of the number of postsynaptic acetylcholine receptors and the amount of acetylcholinesterase changed as well as their spatial position in relation to each other. These rearrangements correspond to electrophysiological data on the reduction of the amplitude of the miniature endplate currents in both muscles.

Multi-stable dynamics of the non-adiabatic repressilator.

The assumption of the fast binding of transcription factors (TFs) to promoters is a typical point in studies of synthetic genetic circuits functioning in bacteria. Although the assumption is effective for simplifying the models, it becomes questionable in the light of in vivo measurements of the times TF spends searching for its cognate DNA sites. We investigated the dynamics of the full idealized model of the paradigmatic genetic oscillator, the repressilator, using deterministic mathematical modelling and stochastic simulations.

The role of chloride ions in the maintenance of resting membrane potential in rat fast and slow muscles during hypogravity modeling.

Antiorthostatic hindlimb suspension reduces resting membrane potential of rat fast and slow muscles within 7 days. Changes in Na+/K+ pump activity and shifts of the equilibrium potential for chloride ions are the main mechanism of the changes in the resting potential of muscle fibers. The latter is presumably associated with increased intracellular ion current due to activation of the second active Na+, K+, 2Cl- symport.

[A model of primary open-angle glaucoma: manifestations and outcomes].

Objective: To determine the expected duration of the disease and the age of the patients with different stages ofprimary open-angle glaucoma complicated by pseudoexfoliation syndrome (PES) and/or patients with pseudoexfoliation glaucoma (PEG).

Methods: The study protocol included data from 120 patients (50 males (41.7%), 70 females (58.

Impaired electro-genesis in skeletal muscle fibers of transgenic Alzheimer mice.

Alzheimer's disease (AD) is characterized by memory decline, but is often associated with non-cognitive symptoms, including muscular dysfunction. In the majority of cases these motor disturbances are seen when other neuro-degenerative disorders such as Parkinson's disease overlap dementia, however these can also be directly related to AD itself. Although the patho-mechanism remains largely unclear, β-amyloid peptide (βAP) is thought to be a key role-player in both the brain and periphery.

Transition from amplitude to oscillation death via Turing bifurcation.

Coupled oscillators are shown to experience two structurally different oscillation quenching types: amplitude death (AD) and oscillation death (OD). We demonstrate that both AD and OD can occur in one system and find that the transition between them underlies a classical, Turing-type bifurcation, providing a clear classification of these significantly different dynamical regimes. The implications of obtaining a homogeneous (AD) or inhomogeneous (OD) steady state, as well as their significance for physical and biological applications and control studies, are also pointed out.

Electronic implementation of a repressilator with quorum sensing feedback.

We investigate the dynamics of a synthetic genetic repressilator with quorum sensing feedback. In a basic genetic ring oscillator network in which three genes inhibit each other in unidirectional manner, an additional quorum sensing feedback loop stimulates the activity of a chosen gene providing competition between inhibitory and stimulatory activities localized in that gene. Numerical simulations show several interesting dynamics, multi-stability of limit cycle with stable steady-state, multi-stability of different stable steady-states, limit cycle with period-doubling and reverse period-doubling, and infinite period bifurcation transitions for both increasing and decreasing strength of quorum sensing feedback.

[Interaction of surface-active base with fraction of membrane-bound Williams's protons].

In the process of mitochondrial respiratory H(+)-pumps functioning, the fraction membrane-bound protons (R-protons), which have an excess of free energy is formed. According to R.J.

[Immunocytochemical identification of synaptotagmin 1, syntaxin 1, N-type Ca(2+)-channel and nicotinic cholinoreceptor in motor neuromuscular junctions of earthworm somatic muscle Lumbricus terrestris].

The somatic muscle of earthworm contains myoneural synapses forming clusters of "synaptic buttons". In these "buttons", the proteins syntaxin 1, synaptotagmin 1 and alpha 1B subunit of the Ca(2+)-channel of N-type were identified. We suppose that "synaptic buttons" contain a limited number of active zones due to their small size (1-2 microm) and the pattern of distribution of proteins of exo-endocytotic cycle.

Inhomogeneous stationary and oscillatory regimes in coupled chaotic oscillators.

The dynamics of linearly coupled identical Lorenz and Pikovsky-Rabinovich oscillators are explored numerically and theoretically. We concentrate on the study of inhomogeneous stable steady states ("oscillation death (OD)" phenomenon) and accompanying periodic and chaotic regimes that emerge at an appropriate choice of the coupling matrix. The parameters, for which OD occurs, are determined by stability analysis of the chosen steady state.

"Quorum sensing" generated multistability and chaos in a synthetic genetic oscillator.

We model the dynamics of the synthetic genetic oscillator Repressilator equipped with quorum sensing. In addition to a circuit of 3 genes repressing each other in a unidirectional manner, the model includes a phase-repulsive type of the coupling module implemented as the production of a small diffusive molecule-autoinducer (AI). We show that the autoinducer (which stimulates the transcription of a target gene) is responsible for the disappearance of the limit cycle (LC) through the infinite period bifurcation and the formation of a stable steady state (SSS) for sufficiently large values of the transcription rate.

[Investigation vesicle cycle in nerve formations in somatic muscle of the earthworm Lumbricus terrestris].

Luminous spots with a diameter of 1-2 microm, which are clusters of "synaptic buds", were revealed in the muscular wall of the earthworm using endocytotic fluorescent dyes FM1-43, FM2-10 and FM4-64. Application of the membrane probe Dil that is capable of being subjected to anterograde axonal transport to abdominal ganglia of the nervous chain, and subsequent (in a day) staining of nerve formations by endocytotic dye FM4-64 showed complete imposition of the emission data of the dyes that fluoresce in different parts of the spectrum. Using fluorescent marker DiBAC4(3) showed an increased emission of neural elements with increasing concentration of K+ in the extracellular environment.

Aggregation of some water-soluble derivatives of chitin in aqueous solutions: Role of the degree of acetylation and effect of hydrogen bond breaker.

By dynamic light scattering in combination with fluorescence spectroscopy and TEM it was shown that aggregation in aqueous solutions is inherent not only to chitosan, but also to two other water-soluble derivatives of chitin: O-carboxymethylchitin and di-N,N-carboxymethylchitosan. Aggregation is observed even for the samples without N-acetyl-d-glucosamine units, which remain upon incomplete chemical modification of chitin, indicating that specific interactions between residual chitin repeat units cannot be the main reason for the aggregation. At the same time, 7M urea weakens the aggregation, thus testifying that hydrogen bonding and/or hydrophobic interactions are partially responsible for this phenomenon.

[Ionic and molecular mechanisms of beta-amyloid-induced depolarization of the mouse skeletal muscle fibres].

Excess production and accumulation of beta-amyloid peptide (betaAP) are central for pathogenesis of Alzheimer's disease. Numerous studies showed that betaAP possessed wide range of toxic effects on neurons, however the mechanism of betaAP influence on another types of excitable cells, for example, skeletal muscle fibres, is unknown. In electrophysiological experiments on the mouse diaphragm, we found for the first time that betaAP (25-35 fragment, 10-6 M) disturbs the processes of the resting membrane potential generation in muscle fibres, leading to depolarization by two mechanisms: 1) inhibition of Na+,K(+)-ATPase, which leads to loss of impact of this pump to the resting membrane potential; 2) increase of membrane cationic permeability due to formation of "amyloid" channels blocked with Zn2+ ions.

Interaction of Escherichia coli RNA polymerase with artificial promoters, containing nonnucleotide spacers.

To study the functional role of the spacer region between two consensus -10 and -35 elements of promoters, recognized by E. coli RNA polymerase, the model promoter-like DNA duplexes containing nonnucleotide inserts (mimicking 17-mer spacer) either in one or both strands, were constructed. The modified duplexes can form the heparin-resistant binary complexes with RNA polymerase.

An electronic analog of synthetic genetic networks.

An electronic analog of a synthetic genetic network known as the repressilator is proposed. The repressilator is a synthetic biological clock consisting of a cyclic inhibitory network of three negative regulatory genes which produces oscillations in the expressed protein concentrations. Compared to previous circuit analogs of the repressilator, the circuit here takes into account more accurately the kinetics of gene expression, inhibition, and protein degradation.