[In silico Search for Tubulin Polymerization Inhibitors].

Cytostatic colchicine is widely used in the treatment of Familial Mediterranean fever, but it has several side effects. For finding new, more effective drugs with higher affinity and diminishside effects we carried out virtual screening of potential inhibitors of the main target of colchicine, the polymerization of tubulin by evaluating affinity 25745 compounds, structurally related to the colchicine. We have identified 11 commercially available compounds with higher affinity to tubulin. Compounds with highest binding scores include trimethoxybenzene and its derivatives; these compounds bind to the same site in similar orientation. Information provided can form the basis for design of new cytostatics.

[Influence of M680I and M694V mutations on pyrin's domain B30.2 tertiary structure and it's complex formation ability with caspase-1].

The M680I and M694V mutations located in the B30.2 pyrin domain are responsible for the manifestation of the most common forms of Familial Mediterranean fever. It is well known that a malfunction of the pyrin-caspase-1 complex is the main cause of inflammation in FMF. The purpose of this study was to identify possible changes in the tertiary structure of mutated B30.2 domain and to determine their potential consequences in the formation of the pyrin-caspase-1 complex. Using computer modeling, it was found that the above mutations change the tertiary structure of B30.2 domain, causing shifts of binding sites and altering the energy of interaction between B30.2 and caspase-1.

Mono- and polysynaptic connections between identified neurons in the system of the passive avoidance reflex of the snail.

The structure of the synaptic connections between identified sensory and giant command neurons of the parietal ganglia of the snail is examined. It is shown that the excitatory postsynaptic potential arising in the giant neuron in response to the generation of a single action potential in the presynaptic neuron consists of several monosynaptic components and may include polysynaptic components. It is hypothesized that monosynaptic components of the elementary excitatory postsynaptic potential that differ in the duration of the latent period and the dynamics of habituation may be associated with the activation of synaptic buttons on axon terminals of varying length.

The vision of the snail: the spectral sensitivity of the dark-adapted eye.

The spectral sensitivity of the dark-adapted eye of the snail Helix lucorum L. was investigated in semi-intact "optic cupoptic nerve-cerebral ganglion" preparations. The data of the recording of the electroretinogram in response to monochromatic radiation of varied intensities were used to plot the spectral sensitivity functions. The averaged spectral sensitivity function is well described by a Dartnall nomogram for the photopigment rhodopsin with a sensitivity peak at 496 nm.

[Vision in the snail: the morphology and electrical activity of the optic nerve]. / Zrenie vinogradnoi ulitki: morfologiia i élektricheskaia aktivnost' opticheskogo nerva.

Light stimulation of a snail's eye elicits spikes in the optic nerve with the latency less by 150-170 ms than that of a corresponding retinal ERG-reaction. This period is constant independently of the intensity of stimulus. Sensory part of the optic nerve consists of at least three types of fibres defining action potentials with different amplitudes and thresholds. Sensory branch of the optic nerve is terminated in the metacerebrum by two separate sets of axon terminals.

[The mono- and polysynaptic connections between identified neurons in the system of the passive defensive reflex in the edible snail]. / Mono- i polisinapticheskie sviazi mezhdu identifitsirovannymi neironami v sisteme passivno-oboronitel'nogo refleksa vinogradnoi ulitki.

A structure of synaptic connections between the identified sensory and giant command neurons of Helix lucorum was studied. It was found that EPSPs arising in the giant neuron as responses to single action potentials generation in sensory neuron consist of several monosynaptic and several polysynaptic components having different magnitude, latencies, and plasticity. The latencies of monosynaptic components are determined by different presynaptic terminals' lengths.

[Vision in the edible snail: the spectral sensitivity of the dark-adapted eye]. / Zrenie vinogradboi ulitki: spektral'naia chuvstvitel'nost' temno-adaptirovannogo glaza.

The spectral sensitivity of the dark-adapted eye of Helix lucorum L. was investigated using a semi-intact preparation "ball of the eye--optic nerve--cerebral ganglion". The amplitudes of responses of the electroretinogram to monochromatic stimuli of different intensities were used for a reconstruction of the spectral sensitivity. The averaged curve of the spectral sensitivity coincided well with the Dartnall's nomogram for a pigment having the maximum of spectral sensitivity near 496 nm.

The monosynaptic connection: modulating influence of opioid peptides on the plasticity of presynaptic neurons and identified synapses.

An investigation of the effect of opioid peptides (leucine-enkephalin and methionine-enkephalin) on the plastic properties of the system of monosynaptically connected LPa7-LPa3 and RPa3, and LPa8-LPa3 and RPa3, neurons in the brain of the edible snail was carried out. It was demonstrated that all three elements in the system under investigation (the presynaptic neuron, the postsynaptic neuron, and the synapse) display the same type of plasticity, i.e., habituation to rhythmic stimulation. The enkephalins exert a modulating effect on the plastic properties of the presynaptic neuron and synapse: they slow down the habituation of the presynaptic neuron in response to intracellular stimulation and the development of habituation at a level of the synapse as well. However, the changes in the character of the postsynaptic response in the presence of enkephalins are not the direct consequence of their influence on the plastic properties of the presynaptic neuron. In addition, the enkephalins decrease the efficiency of synaptic transmission in this system: they decrease the duration of the EPSP in the postsynaptic neuron.

[Vision in the edible snail. The morphology and total electrical activity of the retina]. / Zrenie vinogradnoi ulitki. Morfologiia i summarnaia élektricheskaia aktivnost' setchatki.

Recording of the integrative electrical activity of the retina of the snail and electron microscopic study of its eye have shown the following. The electrical activity of the photoreceptors is a source of the retinogram (ERG) of the snail. ERG reaction form is characterized by two phases of a response: the initial spike and the following slow fading. For each given value of the photometric brightness of a light signal there exists a low limit of its length, beginning from which the ERG reaction of the snail assumes the form described. The value of the ERG response is a logarithmic function of brightness of the light stimulus.

[The monosynaptic connection: the modulating effect of opioid peptides on the plasticity of presynaptic neurons and identified synapses]. / Monosinapticheskaia sviaz': moduliruiushchee vliianie opioidnykh peptidov na plastichnost' presinapticheskikh neironov i identifitsirovannykh sinapsov.

Study of opioid peptides (leucine-enkephalin and methionine-enkephalin) action on plastic properties of the system of monosynaptically connected neurones LPa7--LPa3, PPa3 and LPa8--LPa3, PPa3 was conducted in the snail brain. It has been shown that all three links in the system studied (presynaptic neurone, postsynaptic neurone and synapse) manifest one and the same type of plasticity--habituation to rhythmic stimulation. Enkephalins have a modulating action on plastic properties of the presynaptic neurone and synapse: they retard the habituation of the presynaptic neurone to intracellular stimulation and retard the development of habituation at synaptic level. However, changes in the character of postsynaptic response in the presence of enkephalins are not a direct consequence of their influence on plastic properties of the presynaptic neurone. Besides, enkephalines reduce the effectiveness of synaptic transmission in the given system: they reduce EPSP duration in the postsynaptic neurone.

Monosynaptic connection: identifiable synapses in the CNS of the edible snail.

The microanatomy of the pre- and postsynaptic neurons and the structure of the monosynaptic connection LPa7-LPa3 are described on the basis of planar reconstruction of sections of preparations of the CNS of the edible snail with neurons marked by heavy metal salts. Some physiological features of the presynaptic neuron and the monosynaptic connection were studied. The criteria for the identification of the LPa7 neuron according to its position in the ganglion, to the physiological reaction of LPa3, and to its microanatomy were determined. The position in the ganglion of three other neurons which form monosynaptic connections with LPa3 is described. The plasticity of the LPa7-LPa3 connection is demonstrated. The possibility of the realization of plasticity through the cutting off of individual synapses composing the connection is hypothesized. The results of 65 experiments on the identification of LPa7, the physiological characteristics of this cell, and its monosynaptic connection with LPa3, are summarized in this study. One preparation with a monosynaptic connection is reconstructed.

[The monosynaptic connection: identified synapses in the CNS of the edible snail]. / Monosinapticheskaia sviaz': identifitsiruemye sinapsy v TsNS vinogradnoi ulitki.

By electrophysiological and microanatomical methods of analysis of snail CNS small neurones it was shown that a number of neurones form a monosynaptic connection (MSC) with the gigantic polyfunctional neurone LPa3. By using cobalt and nickel staining, the structure of MSC cells LPa7--LPa3 was studied. Six identified synapses in two LPa3 processes zones were found. Physiological analysis showed that the revealed MSC was plastic. The described MSC with identified synapses is convenient for studying synaptic transmission mechanisms.

[Receptive field plasticity of a polyfunctional neuron in mollusks]. / Plastichnost' retseptivnogo polia polifunktsional'nogo neirona molliuska.

Plastic properties of the receptive field of the identified LPa3 neurone were studied on a semi-intact snail preparation. Mantle area representing part of the vast receptive field of the LPa3 neurone of the left parietal ganglion consists of three zones. The right part of the mantle is innervated by the right pallial and anal nerves; the former transmits to the CNS the short latency rapidly extinguishing component of the synaptic response, while the anal nerve--the slowly extinguishing long latency component. The left part of the mantle is innervated by the LPa3 neurone through the left pallial nerve which transmits the multi-component slowly extinguishing excitatory synaptic potential. The pneumostome area is innervated by the right pallial and anal nerves which transmit a non-extinguishing response. Thus, different areas of the mantle are linked to the LPa3 neurone by a system of parallel channels differing by their plastic properties.