Development of Human Pancreatic Innervation

Human pancreatic innervation is of particular interest due to its possible role in the pathogenesis of such diseases as diabetes mellitus, pancreatitis and pancreatic cancer. Despite the clinical importance, data concerning pancreatic innervation during human ontogeny and in various disorders are very limited. In this chapter, we present a review on human pancreatic autonomic innervation on the basis of the literature data and our previous results. Special attention is paid to the innervation of the endocrine pancreas. Gradual branching of neural network was seen during human pancreatic development. Innervation of the foetal pancreas is more abundant than in adults. In agreement with previous observations, we have revealed a close integration and similarity between endocrine cells and nervous elements in the developing human pancreas. Moreover, simultaneous interactions between the nervous system components, epithelial cells and endocrine cells were detected in the pancreas during prenatal human development. It has been suggested that pancreatic innervation plays an important role not only in regulation of endocrine and exocrine activity but also in normal islet morphogenesis

Barnase as a New Therapeutic Agent Triggering Apoptosis in Human Cancer Cells

RNases are currently studied as non-mutagenic alternatives to the harmful DNA-damaging anticancer drugs commonly used in clinical practice. Many mammalian RNases are not potent toxins due to the strong inhibition by ribonuclease inhibitor (RI) presented in the cytoplasm of mammalian cells.In search of new effective anticancer RNases we studied the effects of barnase, a ribonuclease from Bacillus amyloliquefaciens, on human cancer cells. We found that barnase is resistant to RI. In MTT cell viability assay, barnase was cytotoxic to human carcinoma cell lines with half-inhibitory concentrations (IC(50)) ranging from 0.2 to 13 microM and to leukemia cell lines with IC(50) values ranging from 2.4 to 82 microM. Also, we characterized the cytotoxic effects of barnase-based immunoRNase scFv 4D5-dibarnase, which consists of two barnase molecules serially fused to the single-chain variable fragment (scFv) of humanized antibody 4D5 that recognizes the extracellular domain of cancer marker HER2. The scFv 4D5-dibarnase specifically bound to HER2-positive cells and was internalized via receptor-mediated endocytosis. The intracellular localization of internalized scFv 4D5-dibarnase was determined by electronic microscopy. The cytotoxic effect of scFv 4D5-dibarnase on HER2-positive human ovarian carcinoma SKOV-3 cells (IC(50) = 1.8 nM) was three orders of magnitude greater than that of barnase alone. Both barnase and scFv 4D5-dibarnase induced apoptosis in SKOV-3 cells accompanied by internucleosomal chromatin fragmentation, membrane blebbing, the appearance of phosphatidylserine on the outer leaflet of the plasma membrane, and the activation of caspase-3.These results demonstrate that barnase is a potent toxic agent for targeting to cancer cells

Component Processes of Decision Making in a Community Sample of Precariously Housed Persons: Associations With Learning and Memory, and Health-Risk Behaviors

The Iowa Gambling Task (IGT) is a widely used measure of decision making, but its value in signifying behaviors associated with adverse, “real-world” consequences has not been consistently demonstrated in persons who are precariously housed or homeless. Studies evaluating the ecological validity of the IGT have primarily relied on traditional IGT scores. However, computational modeling derives underlying component processes of the IGT, which capture specific facets of decision making that may be more closely related to engagement in behaviors associated with negative consequences. This study employed the Prospect Valence Learning (PVL) model to decompose IGT performance into component processes in 294 precariously housed community residents with substance use disorders. Results revealed a predominant focus on gains and a lack of sensitivity to losses in these vulnerable community residents. Hypothesized associations were not detected between component processes and self-reported health-risk behaviors. These findings provide insight into the processes underlying decision making in a vulnerable substance-using population and highlight the challenge of linking specific decision making processes to “real-world” behaviors

International Approaches to the Analysis of the Phenomena of BRICS Transregionalism

The article analyzes the essence, location, status, and role of the informal BRICS grouping. The authors examine and compare the different points of view on this phenomenon and believe that the comparative and economical approaches that dominate in the contemporary studies of the BRICS are unproductive. While member countries of the Association are experiencing economic slowdown or recession, BRICS is gradually becoming a political phenomenon of the global world.BRICS is considered the center of an impact of the regional leaders on three continents. A specifi c model of communication of the member countries of the BRICS and their partners is polylogue as one of the methods to solve the problem of equitable participation of all countries of the global world in the process of global governance. In the geopolitical framework of the BRICS and their partners, it is the formation of an extra-American zone of interaction, which will gradually evolve into a Global nonWestern project.

The Russian Public Consciousness Metamorphoses in Conditions of Technogenic Sociocultural Reality

A problem of complex philosophic analysis of the Russian public consciousness transformation in conditions of technogenic sociocultural reality (processes of technological development, informatization, and virtualization, axiologisation of the technogenic and deaxiologisation of the humanistic) is the objective of the research. Special attention is paid to determining technogenic metamorphoses and structural and functional trends of public consciousness dynamics in Russia. Content and structural and functional technogenic public consciousness metamorphoses are reflected by conjugating philosophical methodology of research with the categorical apparatus and methods of social psychology, cultural-historical psychology and social cognitive science. The scientific novelty of research consists in revealing main technogenic Russian public consciousness metamorphoses as well as in determining the following structural and functional trends; a) an additional intermediate mechanism between a human and public consciousness has emerged; b) opportunity to obtain a ready-made cognitive product promote reducing cognitive and social human activity as well as rupture of the individual and public consciousness; c) information field grows, as well as its fragmentation, depending on the possibilities of access and individual preferences; d) information values of "novelty" and "speed" have changed not only the type of human existence, but the mechanisms of public consciousness functioning as well; e) for modern man escapism into zones of the virtual and of the irrational becomes more and more important, and this changes the ontological attributes of public consciousness

Quantitative analysis of nucleolar chromatin distribution in the complex convoluted nucleoli of Didinium nasutum (Ciliophora)

We have earlier shown that the typical Didinium nasutum nucleolus is a complex convoluted branched domain, comprising a dense fibrillar component located at the periphery of the nucleolus and a granular component located in the central part. Here our main interest was to study quantitatively the spatial distribution of nucleolar chromatin structures in these convoluted nucleoli. There are no "classical" fibrillar centers in D.nasutum nucleoli. The spatial distribution of nucleolar chromatin bodies, which play the role of nucleolar organizers in the macronucleus of D.nasutum, was studied using 3D reconstructions based on serial ultrathin sections. The relative number of nucleolar chromatin bodies was determined in macronuclei of recently fed, starved D.nasutum cells and in resting cysts. This parameter is shown to correlate with the activity of the nucleolus. However, the relative number of nucleolar chromatin bodies in different regions of the same convoluted nucleolus is approximately the same. This finding suggests equal activity in different parts of the nucleolar domain and indicates the existence of some molecular mechanism enabling it to synchronize this activity in D. nasutum nucleoli. Our data show that D. nasutum nucleoli display bipartite structure. All nucleolar chromatin bodies are shown to be located outside of nucleoli, at the periphery of the fibrillar component