10 research outputs found
The role of the Kaliningrad region in the development of Russian-German relations
Germany is one of the principal partners
of the Russian Federation. The Kaliningrad
region plays a significant role in the development
of partnership between the two countries,
but the existing opportunities for development
are not fully exploited. This article
analyses the development, current state and
prospects of an increasing role of the region
in Russian-German cooperation. The authors
emphasize the role of the Immanuel Kant Baltic
Federal University as one of the leaders in
the development of research and cultural
links with German universities and research
foundations. This publication is based on the
authors' presentation at the round table discussion
on the cooperation between Russian
and German partner regions held on September
23, 2011 in the framework of the 8th International
Conference on Transborder Cooperation:
the Russian Federation, the European
Union, and Norway (September 22—23,
2011, Kaliningrad). The article considers
topical issues of Russian-German economic
and cultural relations in the Kaliningrad region,
which facilitate the development of Russian
strategy for the integration of northwestern
constituent entities into the economic
and cultural space of the Baltic region
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Thermal Stability of the Human Immunodeficiency Virus Type 1 (HIV-1) Receptors, CD4 and CXCR4, Reconstituted in Proteoliposomes
Background: The entry of human immunodeficiency virus (HIV-1) into host cells involves the interaction of the viral exterior envelope glycoprotein, gp120, and receptors on the target cell. The HIV-1 receptors are CD4 and one of two chemokine receptors, CCR5 or CXCR4. Methodology/Principal Findings: We created proteoliposomes that contain CD4, the primary HIV-1 receptor, and one of the coreceptors, CXCR4. Antibodies against CD4 and CXCR4 specifically bound the proteoliposomes. CXCL12, the natural ligand for CXCR4, and the small-molecule CXCR4 antagonist, AMD3100, bound the proteoliposomes with affinities close to those associated with the binding of these molecules to cells expressing CXCR4 and CD4. The HIV-1 gp120 exterior envelope glycoprotein bound tightly to proteoliposomes expressing only CD4 and, in the presence of soluble CD4, bound weakly to proteoliposomes expressing only CXCR4. The thermal stability of CD4 and CXCR4 inserted into liposomes was examined. Thermal denaturation of CXCR4 followed second-order kinetics, with an activation energy (E) of 269 kJ/mol (64.3 kcal/mol) and an inactivation temperature (T) of 56°C. Thermal inactivation of CD4 exhibited a reaction order of 1.3, an E of 278 kJ/mol (66.5 kcal/mol), and a T of 52.2°C. The second-order denaturation kinetics of CXCR4 is unusual among G protein-coupled receptors, and may result from dimeric interactions between CXCR4 molecules. Conclusions/Significance: Our studies with proteoliposomes containing the native HIV-1 receptors allowed an examination of the binding of biologically important ligands and revealed the higher-order denaturation kinetics of these receptors. CD4/CXCR4-proteoliposomes may be useful for the study of virus-target cell interactions and for the identification of inhibitors
Thermal Stability of the Human Immunodeficiency Virus Type 1 (HIV-1) Receptors, CD4 and CXCR4, Reconstituted in Proteoliposomes
BACKGROUND: The entry of human immunodeficiency virus (HIV-1) into host cells involves the interaction of the viral exterior envelope glycoprotein, gp120, and receptors on the target cell. The HIV-1 receptors are CD4 and one of two chemokine receptors, CCR5 or CXCR4. METHODOLOGY/PRINCIPAL FINDINGS: We created proteoliposomes that contain CD4, the primary HIV-1 receptor, and one of the coreceptors, CXCR4. Antibodies against CD4 and CXCR4 specifically bound the proteoliposomes. CXCL12, the natural ligand for CXCR4, and the small-molecule CXCR4 antagonist, AMD3100, bound the proteoliposomes with affinities close to those associated with the binding of these molecules to cells expressing CXCR4 and CD4. The HIV-1 gp120 exterior envelope glycoprotein bound tightly to proteoliposomes expressing only CD4 and, in the presence of soluble CD4, bound weakly to proteoliposomes expressing only CXCR4. The thermal stability of CD4 and CXCR4 inserted into liposomes was examined. Thermal denaturation of CXCR4 followed second-order kinetics, with an activation energy (E(a)) of 269 kJ/mol (64.3 kcal/mol) and an inactivation temperature (T(i)) of 56°C. Thermal inactivation of CD4 exhibited a reaction order of 1.3, an E(a) of 278 kJ/mol (66.5 kcal/mol), and a T(i) of 52.2°C. The second-order denaturation kinetics of CXCR4 is unusual among G protein-coupled receptors, and may result from dimeric interactions between CXCR4 molecules. CONCLUSIONS/SIGNIFICANCE: Our studies with proteoliposomes containing the native HIV-1 receptors allowed an examination of the binding of biologically important ligands and revealed the higher-order denaturation kinetics of these receptors. CD4/CXCR4-proteoliposomes may be useful for the study of virus-target cell interactions and for the identification of inhibitors
A multifactorial assessment of carcinogenic risks of radon for the population residing in a Russian radon hazard zone
Background: Results of numerous epidemiologic studies of carcinogenic effects of indoor radon conducted in different countries in the past 40 years remain controversial. To assess the contribution of the residential radon exposure in the development of lung cancer in the population of the Russian region with a high radon hazard we conducted a cancer epidemiology study based on a multifactorial analysis. Methods: The study was conducted in the town of Lermontov situated in the area with high background radon concentrations and lung cancer rates of the Caucasian Mineral Water Region of Russia. High indoor radon levels were found in the houses of urban residents, mostly employed by the mining and chemical enterprise. The cohort consisted of 122 lung cancer cases and 208 controls. Each of 330 study participants was characterized by a set of 23 indices reflecting known lung cancer risk factors. We also collected data on occupational and residential radon exposure of all subjects. Results: The analysis of a combined effect of 23 different lung cancer risk factors based on pattern recognition methods showed that the contribution of the non-occupational radon exposure was only about 2% whereas that of the occupational radon exposure equaled 15%. Conclusion: Our findings showed that the effect of the residential radon exposure on the lung cancer rate was 15-20 times weaker than the effects of the main risk factors such as smoking, occupational hazards, chronic lung diseases, social and household factors, etc., although for the population of Lermontov this factor was 2-3 times stronger than that found in the Ural towns of Russia
RhII-catalyzed de-symmetrization of ethane-1,2-dithiol and propane-1,3-dithiol yields metallo-β-lactamase inhibitors
Diversity-oriented synthesis (DOS) is a rich source for novel lead structures in Medicinal Chemistry. In this study, we present a DOS-compatible method for synthesis of compounds bearing a free thiol moiety. The procedure relies on Rh(II)-catalyzed coupling of dithiols to diazo building blocks. The synthetized library was probed against metallo-β-lactamases (MBLs) NDM-1 and VIM-1. Biochemical and biological evaluation led to identification of novel potent MBL inhibitors with antibiotic adjuvant activity
Golgi maturation-dependent glycoenzyme recycling controls glycosphingolipid biosynthesis and cell growth via GOLPH3
Glycosphingolipids are important components of the plasma membrane where they modulate the activities of membrane proteins including signalling receptors. Glycosphingolipid synthesis relies on competing reactions catalysed by Golgi-resident enzymes during the passage of substrates through the Golgi cisternae. The glycosphingolipid metabolic output is determined by the position and levels of the enzymes within the Golgi stack, but the mechanisms that coordinate the intra-Golgi localisation of the enzymes are poorly understood. Here, we show that a group of sequentially-acting enzymes operating at the branchpoint among glycosphingolipid synthetic pathways binds the Golgi-localised oncoprotein GOLPH3. GOLPH3 sorts these enzymes into vesicles for intra-Golgi retro-transport, acting as a component of the cisternal maturation mechanism. Through these effects, GOLPH3 controls the sub-Golgi localisation and the lysosomal degradation rate of specific enzymes. Increased GOLPH3 levels, as those observed in tumours, alter glycosphingolipid synthesis and plasma membrane composition thereby promoting mitogenic signalling and cell proliferation. These data have medical implications as they outline a novel oncogenic mechanism of action for GOLPH3 based on glycosphingolipid metabolism