165 research outputs found

    Comparative Assessment of the Factors and Conditions of the Formation of the Neoindustrial Social State in Russia and Germany

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    Russia and Germany are traditionally reputed as countries with socially oriented economies. Namely, these countries are also close by the index of the share of real sector of economy at GDP. And however, Germany is a founder of social market household largely defined its leadership in world economy, in current conditions of crisis of “the state of general welfare” the search of a new model of development for Germany is also important as for Russia stood on the way of modernization and neo-industrialization. In the article, the hypothesis about forming of the new model of development uniting the social orientation of economy, processes of neoindustrialization, and globalization is made. At the same time, the social orientation is the main aim of socio-economic development, neo-industrialization is a way to achieve it, and globalization is a criterion presupposing more effective use of resources. Theoretical backgrounds of development of “social state” are generalized in the works of German and Russian classics put the backgrounds of economic humanism, it has allowed to prove the fatality of modernization process without considering of deep mental backgrounds and civilization codes of the nation development. The methodological approaches to development of a new model of neo-industrial social state with emphasizing different levels: global, national, local, individual are worked out; and the technique for estimation of factors and conditions of its development is proposed. The technique is tested on the example of Russia and Germany. The comparative analysis conducted has allowed to make the conclusion about similarity of target guidelines, initial conditions, problems and ways of their solving in these countries, that is to be considered both in a strategy and a policy of socio-economic development of these countries and by their international partnership

    Comparative Assessment Of The Factors And Conditions Of The Formation Of The Neoindustrial Social State In Russia And Germany

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    Russia and Germany are traditionally considered to be countries with the social orientation of the economy. These countries are also close in terms of the share of real sector of economy in their GDP. And, although it is in Germany that the social market economy originated, which largely determined its leadership in the global economy, in the context of today’s crisis of the welfare state, the search of a new development model is as relevant for it as it is for Russia which has set off on the way to modernization and the neoindustrialization. The article suggests a hypothesis about the formation of a new development model which combines the social orientation of economy, the processes of the neo-industrialization and globalization. At the same time, social orientation is the main goal of socio-economic development, neo-industrialization is the way to achieve it, and globalization is the criterion that provides for more efficient use of resources. It is provided a summary of the theoretical basis for the development of a “social state” in the works of the German and Russian scholars who laid the foundations of economic humanism, which allowed to prove the futility of modernization which is implemented without due consideration of the deep mental bases and the civilization codes of the nation’s development. The methodological approaches to the formation of a new model of neo-industrial social state have been developed, which identifies several levels: global, national, local, individual, and suggested a methodology to assess the factors and conditions of its development. The method is tested on the example of Russia and Germany. The conducted comparative analysis allowed to come to the conclusion about the common nature of the targets, initial conditions, problems and the ways to their solution in these countries, which has to be taken into consideration in the development of the socioeconomic strategy and policy of the countries, as well as in the cooperation between them

    Annexin A2 mediates apical trafficking of renal Na(+)-K(+)-2Cl(-)-cotransporter

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    The furosemide-sensitive Na(+)-K(+)-2Cl(-)-cotransporter (NKCC2) is responsible for urine concentration, and helps maintain systemic salt homeostasis. Its activity depends on trafficking to, and insertion into, the apical membrane, as well as on phosphorylation of conserved N-terminal serine and threonine residues. Vasopressin (AVP), signaling via PKA and other kinases, activates NKCC2. Association of NKCC2 with lipid rafts facilitates its AVP-induced apical translocation and activation at the surface. Lipid raft microdomains typically serve as platforms for membrane proteins to facilitate their interactions with other proteins, but little is known about partners that interact with NKCC2. Yeast two-hybrid screening identified an interaction between NKCC2 and the cytosolic protein, annexin A2 (AnxA2). Annexins mediate lipid raft-dependent trafficking of transmembrane proteins, including the AVP-regulated water channel, aquaporin 2. Here, we demonstrate that AnxA2, which binds to phospholipids in a Ca(2+)-dependent manner and may organize microdomains, is co-distributed with NKCC2 to promote its apical translocation in response to AVP stimulation and low chloride hypotonic stress. NKCC2 and AnxA2 interact in a phosphorylation-dependent manner. Phosphomimetic AnxA2 carrying a mutant, Src-dependent phosphoacceptor (AnxA2-Y24D-GFP), enhanced surface expression and raft association of NKCC2 by 5-fold upon AVP stimulation, whereas PKC-dependent AnxA2-S26D-GFP did not. As the AnxA2 effect involved only non-phosphorylated NKCC2, it appears to affect NKCC2 trafficking. Overexpression or knockdown experiments further supported the role of AnxA2 in the apical translocation and surface expression of NKCC2. In summary, this study identifies AnxA2 as a lipid raft-associated trafficking factor for NKCC2 and provides mechanistic insight into the regulation of this essential cotransporter

    In Vivo Behavior of the Antibacterial Peptide Cyclo[RRRWFW], Explored Using a 3-Hydroxychromone-Derived Fluorescent Amino Acid

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    Labeling biomolecules with fluorescent labels is an established tool for structural, biochemical, and biophysical studies; however, it remains underused for small peptides. In this work, an amino acid bearing a 3-hydroxychromone fluorophore, 2-amino-3-(2-(furan-2-yl)-3-hydroxy-4-oxo-4H-chromen-6-yl)propanoic acid (FHC), was incorporated in a known hexameric antimicrobial peptide, cyclo[RRRWFW] (cWFW), in place of aromatic residues. Circular dichroism spectropolarimetry and antibacterial activity measurements demonstrated that the FHC residue perturbs the peptide structure depending on labeling position but does not modify the activity of cWFW significantly. FHC thus can be considered an adequate label for studies of the parent peptide. Several analytical and imaging techniques were used to establish the activity of the obtained labeled cWFW analogues toward animal cells and to study the behavior of the peptides in a multicellular organism. The 3-hydroxychromone fluorophore can undergo excited-state intramolecular proton transfer (ESIPT), resulting in double-band emission from its two tautomeric forms. This feature allowed us to get insights into conformational equilibria of the labeled peptides, localize the cWFW analogues in human cells (HeLa and HEK293) and zebrafish embryos, and assess the polarity of the local environment around the label by confocal fluorescence microscopy. We found that the labeled peptides efficiently penetrated cancerous cells and localized mainly in lipid-containing and/or other nonpolar subcellular compartments. In the zebrafish embryo, the peptides remained in the bloodstream upon injection into the cardinal vein, presumably adhering to lipoproteins and/or microvesicles. They did not diffuse into any tissue to a significant extent during the first 3 h after administration. This study demonstrated the utility of fluorescent labeling by double-emission labels to evaluate biologically active peptides as potential drug candidates in vivo

    The Antimicrobial Peptide Histatin-5 Causes a Spatially Restricted Disruption on the Candida albicans Surface, Allowing Rapid Entry of the Peptide into the Cytoplasm

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    Antimicrobial peptides play an important role in host defense against microbial pathogens. Their high cationic charge and strong amphipathic structure allow them to bind to the anionic microbial cell membrane and disrupt the membrane bilayer by forming pores or channels. In contrast to the classical pore-forming peptides, studies on histatin-5 (Hst-5) have suggested that the peptide is transported into the cytoplasm of Candida albicans in a non-lytic manner, and cytoplasmic Hst-5 exerts its candicidal activities on various intracellular targets, consistent with its weak amphipathic structure. To understand how Hst-5 is internalized, we investigated the localization of FITC-conjugated Hst-5. We find that Hst-5 is internalized into the vacuole through receptor-mediated endocytosis at low extracellular Hst-5 concentrations, whereas under higher physiological concentrations, Hst-5 is translocated into the cytoplasm through a mechanism that requires a high cationic charge on Hst-5. At intermediate concentrations, two cell populations with distinct Hst-5 localizations were observed. By cell sorting, we show that cells with vacuolar localization of Hst-5 survived, while none of the cells with cytoplasmic Hst-5 formed colonies. Surprisingly, extracellular Hst-5, upon cell surface binding, induces a perturbation on the cell surface, as visualized by an immediate and rapid internalization of Hst-5 and propidium iodide or rhodamine B into the cytoplasm from the site using time-lapse microscopy, and a concurrent rapid expansion of the vacuole. Thus, the formation of a spatially restricted site in the plasma membrane causes the initial injury to C. albicans and offers a mechanism for its internalization into the cytoplasm. Our study suggests that, unlike classical channel-forming antimicrobial peptides, action of Hst-5 requires an energized membrane and causes localized disruptions on the plasma membrane of the yeast. This mechanism of cell membrane disruption may provide species-specific killing with minimal damage to microflora and the host and may be used by many other antimicrobial peptides

    Transforming growth factor beta signaling: The master sculptor of fingers

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    Transforming growth factor beta (TGF?) constitutes a large and evolutionarily conserved superfamily of secreted factors that play essential roles in embryonic development, cancer, tissue regeneration, and human degenerative pathology. Studies of this signaling cascade in the regulation of cellular and tissue changes in the three-dimensional context of a developing embryo have notably advanced in the understanding of the action mechanism of these growth factors. In this review, we address the role of TGF? signaling in the developing limb, focusing on its essential function in the morphogenesis of the autopod. As we discuss in this work, modern mouse genetic experiments together with more classical embryological approaches in chick embryos, provided very valuable information concerning the role of TGF? and Activin family members in the morphogenesis of the digits of tetrapods, including the formation of phalanxes, digital tendons, and interphalangeal joints. We emphasize the importance of the Activin and TGF? proteins as digit inducing factors and their critical interaction with the BMP signaling to sculpt the hand and foot morphology

    Twenty-three unsolved problems in hydrology (UPH) – a community perspective

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    This paper is the outcome of a community initiative to identify major unsolved scientific problems in hydrology motivated by a need for stronger harmonisation of research efforts. The procedure involved a public consultation through on-line media, followed by two workshops through which a large number of potential science questions were collated, prioritised, and synthesised. In spite of the diversity of the participants (230 scientists in total), the process revealed much about community priorities and the state of our science: a preference for continuity in research questions rather than radical departures or redirections from past and current work. Questions remain focussed on process-based understanding of hydrological variability and causality at all space and time scales. Increased attention to environmental change drives a new emphasis on understanding how change propagates across interfaces within the hydrological system and across disciplinary boundaries. In particular, the expansion of the human footprint raises a new set of questions related to human interactions with nature and water cycle feedbacks in the context of complex water management problems. We hope that this reflection and synthesis of the 23 unsolved problems in hydrology will help guide research efforts for some years to come
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