Effectiveness of management of innovative activities in regional socio-economic systems

Development of innovative activities in Russia’s economy is determined by its character in regional socio-economic systems, as a basis of national economy. Increased attention to regional management is caused by the fact that various problems and tasks of a certain area cannot be solved at another level. Basic problems of modern management include the development of innovative activities which ought to form favorable conditions for positive dynamics of innovational sphere that influences the competitiveness of the area and, consequently, of economic development. Orienting at the specifics of business activities, regional authorities, while taking into account the level of innovational activity of their area, should form effective tools for managing innovational processes. At present, management of innovational development of regional socio-economic systems requires paying attention to peculiarities and factors of external and internal environment, according to economic, social, and political aspects of development of a territory and country on the whole. The authors offer the indicator “effectiveness of management of innovative activities in regional socio-economic systems” and substantiate its content as a meaningful feature for managing innovative activities of an area, which is formed under the influence of endogenous and exogenous factors. Effectiveness of management of innovative activities in regional socioeconomic systems is determined by tandem usage of two values of “controllability of innovational process in region” and coefficient of effectiveness of management of innovative activities in regional socio-economic systems.peer-reviewe

Synaptotagmin oligomerization is essential for calcium control of regulated exocytosis

Regulated exocytosis, which underlies many intercellular signaling events, is a tightly controlled process often triggered by calcium ion(s) (Ca2+). Despite considerable insight into the central components involved, namely, the core fusion machinery [soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)] and the principal Ca2+ sensor [C2-domain proteins like synaptotagmin (Syt)], the molecular mechanism of Ca2+-dependent release has been unclear. Here, we report that the Ca2+-sensitive oligomers of Syt1, a conserved structural feature among several C2-domain proteins, play a critical role in orchestrating Ca2+-coupled vesicular release. This follows from pHluorin-based imaging of single-vesicle exocytosis in pheochromocytoma (PC12) cells showing that selective disruption of Syt1 oligomerization using a structure-directed mutation (F349A) dramatically increases the normally low levels of constitutive exocytosis to effectively occlude Ca2+-stimulated release. We propose a parsimonious model whereby Ca2+-sensitive oligomers of Syt (or a similar C2-domain protein) assembled at the site of docking physically block spontaneous fusion until disrupted by Ca2+ Our data further suggest Ca2+-coupled vesicular release is triggered by removal of the inhibition, rather than by direct activation of the fusion machinery

Selective G-Quadruplex DNA Recognition by a New Class of Designed Cyanines

A variety of cyanines provide versatile and sensitive agents acting as DNA stains and sensors and have been structurally modified to bind in the DNA minor groove in a sequence dependent manner. Similarly, we are developing a new set of cyanines that have been designed to achieve highly selective binding to DNA G-quadruplexes with much weaker binding to DNA duplexes. A systematic set of structurally analogous trimethine cyanines has been synthesized and evaluated for quadruplex targeting. The results reveal that elevated quadruplex binding and specificity are highly sensitive to the polymethine chain length, heterocyclic structure and intrinsic charge of the compound. Biophysical experiments show that the compounds display significant selectivity for quadruplex binding with a higher preference for parallel stranded quadruplexes, such as cMYC. NMR studies revealed the primary binding through an end-stacking mode and SPR studies showed the strongest compounds have primary KD values below 100 nM that are nearly 100-fold weaker for duplexes. The high selectivity of these newly designed trimethine cyanines for quadruplexes as well as their ability to discriminate between different quadruplexes are extremely promising features to develop them as novel probes for targeting quadruplexes in vivo

REGIONALIZATION OF MANAGEMENT PROCESS BY INNOVATIVE ACTIVITY

Summary. In current market conditions, the economy and Russia's accession to international trade scholars and experts from various fields of knowledge paying special attention to a huge set of regional problems. The growing role of regional research determines the level of establishing effective mechanisms for the implementation of the economic interests of actors as well as economic development and improving the quality of human life is the priority objectives of federal, regional and local authorities. Today, the Russian economic science faces a global goal - to develop ways and means of transformation of the Russian economy and bring it to a path of sustainable, innovative development, providing new quality of life. Achieving this goal must surely be a central task of the Russian economics and politics, as in the near future and the long term In article authors opened the maintenance of determinants of innovative development of the territory, mediated by strengthening of regionalization of management by innovative activity: condition of resource and innovative potential; the developed forms and nature of interaction between public authorities of regional level, local community and business; applied forms of integration of subjects of managing for realization of their innovative potential due to expansion of opportunities of participation in the perspective directions of scientific and technical, economic and social development; system of the incentives developing favorable conditions for introduction and development of innovative technologies, and also increases in the enterprise activity, formed by the external institutional environment; regional economic policy as instrument of increase of efficiency of innovative activity

EFFECT OF ANTIHYPERTENSIVE THERAPY ON METABOLIC PROFILE AND ERECTILE FUNCTION IN HYPERTENSIVE MEN WITH HIGH CARDIOVASCULAR RISK: FOCUS ON THE COMBINATION OF LISINOPRIL AND AMLODIPINE

Aim. To study the antihypertensive and metabolic effects of lisinopril plus amlodipine combination in hypertensive men with high cardiovascular risk.Materials and methods. Hypertensive men (n=21) with high cardiovascular risk (SCORE scale >5%) aged 30-59 y.o. were included in the study. Questionnaire survey, blood pressure (BP) and heart rate measuring, anthropometric studies, evaluation of the plasma lipid profile, uric acid level and glucose tolerance test were performed at baseline and at the end of the study. Erectile function was assessed by International index of erectile function (IIEF) score. After the cancellation of previous antihypertensive drugs patients were prescribed lisinopril 10 mg QD and amlodipine 5 mg QD. The duration of the study was 6 months.Results. In 4 weeks of the treatment systolic and diastolic BP decreased by 9.3 and 5.2%, and in 24 weeks – by 14.7 and 7.2% respectively (p<0.05). Target BP levels were achieved in 85% of patients. Antihypertensive therapy during 6 months had no significant effect on the plasma lipid profile, glucose and uric acid levels. The mild to moderate-mild erectile dysfunction were detected in 35% of men before therapy. Erectile function indices in hypertensive men with high cardiovascular risk had not changed during combined antihypertensive therapy.Conclusion. Antihypertensive therapy with lisinopril and amlodipine in hypertensive men with high cardiovascular risk during 6 months led to a statistically significant reduction of BP level without affect plasma lipid profile, glucose and uric acid levels as well as erectile function

Review of suppliers of medicines and pharmacy products

The aim of the study – to analyze the specifics of the work the wholesale link in the pharmaceutical market.Цель исследования – проанализировать специфику работы оптового звена фармацевтического рынка

Cardiovascular risk, metabolic disturbances, and the choice of antihypertensive therapy

Aim. To study antihypertensive and metabolic effects of combined antihypertensive therapy with fixed doses of ACE inhibitor and thiazide-like diuretic (Noliprel®), in comparison with ACE inhibitor monotherapy (ramipril). Material and methods. The study included 44 men, aged 30-65 years, with Stage I-II arterial hypertension (AH) and at least one manifestation of metabolic disturbances (dyslipidemia, pre-diabetes, or hyperuricemia). All participants were divided into two groups: Group I received ramipril, and Group II was administered a combination of ACE inhibitor and thiazide-like diuretic (Noliprel®/ forte). Results. Medication doses were increased in patients who failed to achieve target blood pressure (BP) levels. At baseline and after 6 months of the treatment, all patients underwent BP and heart rate (HR) measurement, electrocardiography (ECG) at rest, and the assessment of lipid profile, fasting and post-load (2 hours) glucose, insulin resistance (IR) index, uric acid (UA) and potassium (К+), as well as total coronary risk level. Conclusion. In men with AH and metabolic disturbances, combined antihypertensive therapy with fixed doses of ACE inhibitor and thiazide-like diuretic, as well as ACE inhibitor monotherapy, demonstrated good antihyperten-sive effectiveness and no deterioration in metabolic parameters. Combined antihypertensive therapy was associated with a reduction in coronary risk by 30 %

Synaptotagmin oligomerization is essential for calcium control of regulated exocytosis

Regulated exocytosis, which underlies many intercellular signaling events, is a tightly controlled process often triggered by calcium ion(s) (Ca2+). Despite considerable insight into the central components involved, namely, the core fusion machinery [soluble N-ethylmaleimide?sensitive factor attachment protein receptor (SNARE)] and the principal Ca2+ sensor [C2-domain proteins like synaptotagmin (Syt)], the molecular mechanism of Ca2+-dependent release has been unclear. Here, we report that the Ca2+-sensitive oligomers of Syt1, a conserved structural feature among several C2-domain proteins, play a critical role in orchestrating Ca2+-coupled vesicular release. This follows from pHluorin-based imaging of single-vesicle exocytosis in pheochromocytoma (PC12) cells showing that selective disruption of Syt1 oligomerization using a structure-directed mutation (F349A) dramatically increases the normally low levels of constitutive exocytosis to effectively occlude Ca2+-stimulated release. We propose a parsimonious model whereby Ca2+-sensitive oligomers of Syt (or a similar C2-domain protein) assembled at the site of docking physically block spontaneous fusion until disrupted by Ca2+. Our data further suggest Ca2+-coupled vesicular release is triggered by removal of the inhibition, rather than by direct activation of the fusion machinery.Fil: Bello, Oscar Daniel. University of Yale. School of Medicine; Estados Unidos. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Mendoza. Instituto de Histologia y Embriologia de Mendoza Dr. Mario H. Burgos. Grupo Vinculado de Investigacion y Desarrollo Biotecnologico Aplicado Al Diagnostico Al Ihem | Universidad Nacional de Cuyo. Facultad de Ciencias Medicas. Instituto de Histologia y Embriologia de Mendoza Dr. Mario H. Burgos. Grupo Vinculado de Investigacion y Desarrollo Biotecnologico Aplicado Al Diagnostico Al Ihem.; Argentina. University College London; Estados UnidosFil: Jouannot, Ouardane. University of Yale. School of Medicine; Estados UnidosFil: Chaudhuri, Arunima. University of Yale. School of Medicine; Estados UnidosFil: Stroeva, Ekaterina. University of Yale. School of Medicine; Estados UnidosFil: Coleman, Jeff. University of Yale. School of Medicine; Estados UnidosFil: Volynski, Kirill E.. University College London; Reino UnidoFil: Rothman, James E.. University of Yale. School of Medicine; Estados Unidos. University College London; Estados UnidosFil: Krishnakumar, Shyam S.. University of Yale. School of Medicine; Estados Unidos. University College London; Estados Unido