Pim-1 kinase enhances NFATc activity and neuroendocrine functions in PC12 cells

The activity of NFAR family transcription factors is tightly regulated in T cells via signaling pathways initiated by stimulation of the T cell receptor or its downstream effectors such as the Pim-1 serine/threonine kinase. Here, we demonstrate that NFATc-dependent transcription is inducible also in NGF-differentiated rat PC12 pheochromocytoma cells treated with phorbol esthers, calcium ionophores and/or forskolin and that the Pim-1 kinase can further potentiate the effects of these agents. PC 12 cells, share many characteristics with sympathetic neurons and can be induced to produce and release catecholamines, such as dopamine and noradrenaline, and inflammatory cytokines, such as interleukin 6. Interestingly, Pim-1 can synergize with forskolin-induced signaling pathways to stimulate also neuroendocrine functions of PC12 cells. (c) 2005 Elsevier B.V. All rights reserved

Functional state of the nigrostriatal system of Krushinsky – Molodkina rats during audiogenic seizure expression

Neurochemical mechanisms of initiation and expression of epileptic seizures are poorly explored, and there are no published data that could demonstrate the functional state of the neuromediator systems at the initial state of seizure in the animals genetically prone to seizure. In the current work, we studied the role of extracellular signal-regulated kinase (ERK1/2) in the regulation of the nigrostriatal glutamate, GABA and dopamine neurons of Krushinsky – Molodkina rats at clonus-tonus and ataxia stages of audiogenic seizure. We demonstrated upregulation of ERK1/2 activity upon audio stimulation which was accompanied by increased activation of Synapsin I in the striatum and substantia nigra in comparison to intact Krushinsky – Molodkina rats. The observed exocytosis activation led to secretion of glutamate in the striatum and, as a result, to stimulation of seizures. However, at clonus-tonus stage in the striatum we revealed the changes that could participate in further inhibition of seizure activity, such as increased phosphorylation of tyrosine hydroxylase upon increased ERK1/2 activity followed by activation of dopamine release in the pars compacta of the substantia nigra. At the same time, enhanced D2 and increased D1 dopamine receptor contents were observed. These data revealed attenuation of direct (pro-seizure) and indirect (anti-seizure) pathways of the regulation of the substantia nigra GABA neurons. We demonstrated activation of GABA in the substantia nigra pars reticulate, which probably results in the inhibition of glutamate neurons of the thalamus and could be one of the mechanisms inhibiting seizure activity during ataxia

Russia and the Arab Spring: supporting the counter-revolution

Russia’s response to the Arab Spring ranged from apprehension to deep anxiety and diverged significantly from the US and the EU responses. While initially welcoming the popular demands for political reform in North Africa, the Russian reaction rapidly became more critical as a result of Western military intervention into Libya and the threat of the spread of Islamist extremism. It was these twin fears which prompted the Russian leadership to adopt an uncompromizing stance towards Syria. While geopolitical factors certainly played a role in driving Russian strategy, domestic political factors were also more significant. As the Russian leadership felt internally threatened by the growing opposition within the country, conflict in the Middle East highlighted the perceived flaws of the imposition of Western liberal democracy and the virtues of Russia’s own model of state-managed political order. There was, as such, a significant ideational and ideological dimension to the Russian response to the Arab Spring

EXPRESSIVE FORMS OF ADDRESS BASED ON THE FEATURE OF ACQUAINTANCE AND KINSHIP OF COMMUNICANTS IN RUSSIAN AND SPANISH (COLUMBIAN AND COSTA RICAN VARIETIES)

The article discusses expressive forms of address in Russian and Spanish (as exemplified by its Colombian and Costa Rican varieties) in view of the factors influencing their formation: national-cultural specificity and both inter- and extralinguistic factors associated with it, psychological factors (ways of creating and modelling reality in a number of communicative situations by persons belonging to various Hispanic cultural communities) as well as language nomination itself. Depending on the expression and the prevalence of evaluativity and affectability in expressive forms of address, they are divided into groups; methods for analysing them are also listed. Expressive forms of address based on the degree of acquaintance or kinship of communicants undergo a detailed comparative analysis. Based on the obtained results, conclusions are drawn about the differences in the specifics of their situational and stylistic implementation as well as in the way of rendering various tonalities that are influenced by the ethnopsychological factor. The materials of the article may be of interest both for specialists in Russian and Spanish linguistics and for students of linguistic specialties

LIFE-THREATENING MANIFEST OF LONG-QT-SYNDROME

Aim. To complete DNA-diagnostics for the patients with syncopes and not showing clinically significant rhythm disorders, but with family anamnesis of sudden death. Material and methods. Clinical case. The patient 22 y.o. consulted at RSCS n.a.Petrovsky with the primary diagnosis of "inherited epilepsy" and complaints on presyncopes and dizziness. During examination there was no data found to prove the inherited epilepsy and clinically significant rhythm disorders. Taking into account the family anamnesis of sudden death a dignosis of "idiopathic ventricular tachycardia" was suggested and the patient underwent two-chamber rate-adaptive cardioverter-defibrillator Maximo II DR D284DRG implantation. DNA-testing revealed a mutation of p.R583H in the gene KCNQ1, that had been previously described as probable to cause type 1 long-QT-syndrome. During the next 12 month after implantation there were 2 proven strobes recorded. The patient was consulted by cardiologist to prescribe beta-blocker therapy.Results. Although there were no clinically significant heart rhythm disorders found, the patient with suspected family type of idiopathic ventricular tachicardia underwent cardioverter-defibrillator setting up procedure. Molecular-genetic methods helped to prove the diagnosis of "long-QT-syndrome type 1" and the cascade family screening was started to choose a treatment strategy for asymptopathic mutation bearers. Conclusion. By the example of the clinical case described we showed a significance of DNA-diagnostics in the diagnosis clarification, treatment strategy choice and sufficient medical-genetic consulting for the disease mentioned