Coxsackie-adenovirus receptor expression is enhanced in pancreas from patients with type 1 diabetes

Objectives: One of the theories connecting enterovirus (EV) infection of human islets with type 1 diabetes (T1D) is the development of a fertile field in the islets. This implies induction of appropriate proteins for the viral replication such as the coxsackie–adenovirus receptor (CAR). The aim of this study was to investigate to what extent CAR is expressed in human islets of Langerhans, and what conditions that would change the expression. Design: Immunohistochemistry for CAR was performed on paraffin-embedded pancreatic tissue from patients with T1D (n=9 recent onset T1D, n=4 long-standing T1D), islet autoantibody-positive individuals (n=14) and non-diabetic controls (n=24) individuals. The expression of CAR was also examined by reverse transcription PCR on microdissected islets (n=5), exocrine tissue (n=5) and on explanted islets infected with EV or exposed to chemokines produced by EV-infected islet cells. Results: An increased frequency of patients with T1D and autoantibody-positive individuals expressed CAR in the pancreas (p<0.039). CAR staining was detected more frequently in pancreatic islets from patients with T1D and autoantibody-positive subjects (15/27) compared with (6/24) non-diabetic controls (p<0.033). Also in explanted islets cultured in UV-treated culture medium from coxsackievirus B (CBV)-1-infected islets, the expression of the CAR gene was increased compared with controls. Laser microdissection of pancreatic tissue revealed that CAR expression was 10-fold higher in endocrine compared with exocrine cells of the pancreas. CAR was also expressed in explanted islets and the expression level decreased with time in culture. CBV-1 infection of explanted islets clearly decreased the expression of CAR (p<0.05). In contrast, infection with echovirus 6 did not affect the expression of CAR. Conclusions: CAR is expressed in pancreatic islets of patients with T1D and the expression level of CAR is increased in explanted islets exposed to proinflammatory cytokines/chemokines produced by infected islets. T1D is associated with increased levels of certain chemokines/cytokines in the islets and this might be the mechanism behind the increased expression of CAR in TID islets

Agent Exchange: CDA Communication Ontology and Protocols.

Agent Exchange project addresses issues like e-business and agent communication security. The developed protocols and ontology for Continual Double Auction allow community to be started and trade. Traders can control the accounts ant get information from exchanges, put the bid to sell/buy to the exchange, exchanges are allowed to secure check traders'solvency and realize a commodity transaction. In the here presented variant of Continuous Double Auction orders to buy ant orders to sell remain in the auction until they are accomplished, canceled by their owner or by appointed deadline. The remaining of the order in the auction doesn'tdepend on accomplishing another orders not being matching this one. The protocols and ontology are being tested on the basic Agent Exchange community.Available from STL Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi

Agent Exchange: CDA Communication Ontology and Protocols.

Agent Exchange project addresses issues like e-business and agent communication security. The developed protocols and ontology for Continual Double Auction allow community to be started and trade. Traders can control the accounts ant get information from exchanges, put the bid to sell/buy to the exchange, exchanges are allowed to secure check traders'solvency and realize a commodity transaction. In the here presented variant of Continuous Double Auction orders to buy ant orders to sell remain in the auction until they are accomplished, canceled by their owner or by appointed deadline. The remaining of the order in the auction doesn't depend on accomplishing another orders not being matching this one. The protocols and ontology are being tested on the basic Agent Exchange community.Available from STL Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi

Immune System Methods for Information Security Systems.

Immune system of vertebrates, which is distributed, self-protected and able of adaptability, as model for development of information security system (ISS) is discussed in this paper. The research is oriented to defense of computer nets against Denial of Service (DoS) attacks provided by malicious data packets.Available from STL Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi

Minimal PhD Report: Multi-Agent Systems.

The problem of the electronic trading, auctions and their models, and electronic auctioneers are described this text. The agent has to serve the user's interests by indirect negotiating with other agents. The agent has to be able to sell and buy goods according the user's orders. This agent must be semiautonomous and in coordination with teammates look for the most advantageous offers on the known auctions.Available from STL Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi

Bezpecna komunikace v multi-agentnich systemech.

Area of multi-agent systems (MAS) currently evolves rapidly on both, research and application basis. It is necessary to ensure a communication security during data transfer in real applications (in industry or e-business). Currently there are several libraries or programming language extensions offering security services available. However they are tailored to specific operating systems and thus useless, when an agents' mobility is required. WE propose a novel approach to the communication security useable for the mobile agents and with transparency to a programming language (operating system). Role of the central security authority, necessary for a correct function of security in MAS, is discussed here as well. Present-day systems are not able to work when this authority fails, but it is possible to partially eliminate this problem. Proposed approach has been implemented and verified within the multi-agent platform JADE.Available from STL Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi

Bezpecna komunikace v multi-agentnich systemech.

Area of multi-agent systems (MAS) currently evolves rapidly on both, research and application basis. It is necessary to ensure a communication security during data transfer in real applications (in industry or e-business). Currently there are several libraries or programming language extensions offering security services available. However they are tailored to specific operating systems and thus useless, when an agents' mobility is required. WE propose a novel approach to the communication security useable for the mobile agents and with transparency to a programming language (operating system). Role of the central security authority, necessary for a correct function of security in MAS, is discussed here as well. Present-day systems are not able to work when this authority fails, but it is possible to partially eliminate this problem. Proposed approach has been implemented and verified within the multi-agent platform JADE.Available from STL Prague, CZ / NTK - National Technical LibrarySIGLECZCzech Republi

Enterovirus infection of human islets of Langerhans affects beta-cell function resulting in disintegrated islets, decreased glucose stimulated insulin secretion and loss of Golgi structure

Aims/hypothesis: In type 1 diabetes (T1D), most insulin-producing beta cells are destroyed, but the trigger is unknown. One of the possible triggers is a virus infection and the aim of this study was to test if enterovirus infection affects glucose stimulated insulin secretion and the effect of virus replication on cellular macromolecules and organelles involved in insulin secretion. Methods: Isolated human islets were infected with different strains of coxsackievirus B (CVB) virus and the glucose-stimulated insulin release (GSIS) was measured in a dynamic perifusion system. Classical morphological electron microscopy, large-scale electron microscopy, so-called nanotomy, and immunohistochemistry were used to study to what extent virus-infected beta cells contained insulin, and real-time PCR was used to analyze virus induced changes of islet specific genes. Results: In islets infected with CVB, GSIS was reduced in correlation with the degree of virus-induced islet disintegration. The expression of the gene encoding insulin was decreased in infected islets, whereas the expression of glucagon was not affected. Also, in islets that were somewhat disintegrated, there were uninfected beta cells. Ultrastructural analysis revealed that virus particles and virus replication complexes were only present in beta cells. There was a significant number of insulin granules remaining in the virus-infected beta cells, despite decreased expression of insulin mRNA. In addition, no typical Golgi apparatus was detected in these cells. Exposure of islets to synthetic dsRNA potentiated glucose-stimulated insulin secretion. Conclusions/interpretation: Glucose-stimulated insulin secretion; organelles involved in insulin secretion and gene expression were all affected by CVB replication in beta cells

Coxsackie-adenovirus receptor expression is enhanced in pancreas from patients with type 1 diabetes

Objectives: One of the theories connecting enterovirus (EV) infection of human islets with type 1 diabetes (T1D) is the development of a fertile field in the islets. This implies induction of appropriate proteins for the viral replication such as the coxsackie-adenovirus receptor (CAR). The aim of this study was to investigate to what extent CAR is expressed in human islets of Langerhans, and what conditions that would change the expression. Design: Immunohistochemistry for CAR was performed on paraffin-embedded pancreatic tissue from patients with T1D (n=9 recent onset T1D, n=4 long-standing T1D), islet autoantibody-positive individuals (n=14) and non-diabetic controls (n=24) individuals. The expression of CAR was also examined by reverse transcription PCR on microdissected islets (n=5), exocrine tissue (n=5) and on explanted islets infected with EV or exposed to chemokines produced by EV-infected islet cells. Results: An increased frequency of patients with T1D and autoantibody-positive individuals expressed CAR in the pancreas (p&lt;0.039). CAR staining was detected more frequently in pancreatic islets from patients with T1D and autoantibody-positive subjects (15/27) compared with (6/24) non-diabetic controls (p&lt;0.033). Also in explanted islets cultured in UV-treated culture medium from coxsackievirus B (CBV)-1-infected islets, the expression of the CAR gene was increased compared with controls. Laser microdissection of pancreatic tissue revealed that CAR expression was 10-fold higher in endocrine compared with exocrine cells of the pancreas. CAR was also expressed in explanted islets and the expression level decreased with time in culture. CBV-1 infection of explanted islets clearly decreased the expression of CAR (p&lt;0.05). In contrast, infection with echovirus 6 did not affect the expression of CAR. Conclusions: CAR is expressed in pancreatic islets of patients with T1D and the expression level of CAR is increased in explanted islets exposed to proinflammatory cytokines/chemokines produced by infected islets. T1D is associated with increased levels of certain chemokines/cytokines in the islets and this might be the mechanism behind the increased expression of CAR in TID islets