Requirement for Specific Proteases in Cancer Cell Intravasation as Revealed by a Novel Semiquantitative PCR-Based Assay

AbstractProteases are crucial for cancer metastasis, but due to lack of assays, their role in intravasation has not yet been tested. We have developed a human Alu sequence PCR-based assay to quantitate intravasated cells in an in vivo model. We demonstrated that metalloproteinases (MMPs), and most likely MMP-9, are required for intravasation by showing that marimastat, an inhibitor of MMPs, reduced intravasation by more than 90%, and that only tumor cell lines expressing MMP-9 intravasated. Cells with low surface urokinase plasminogen activator (uPA) and uPA receptor (uPAR) were also incapable of intravasation, despite the presence of high levels of MMP-9. We concluded that breaching of the vascular wall is a rate-limiting step for intravasation, and consequently for metastasis, and that cooperation between uPA/uPAR and MMP-9 is required to complete this step

The Role of Agreement Technologies in the Definition of Adaptive Software Architectures

The growing complexity of software systems is causing a re-conception of their development and maintenance strategies. Humans should be relieved from an important part of these tasks, which should be performed by systems themselves, leading to consider self-adaptation as a basic architectural concern. Simultaneously, Multi-Agent Systems (MAS) have been developed as a generic approach to solve complex problems. They describe self-aware structures,conceived to be flexible and to be able to adapt to different situations. Advances approaches use organizations to provide further structuring, taking the form of complex agent architectures. Among them, Agreement Technologies (AT) provides an explicit insight into those architectural abstractions. However, they still do not provide mechanisms to change their composition patterns and element types, which are necessary to achieve real self-adaptivity. In this article, we propose an architectural solution for this: the required dynamism will be supported by an emergent agreement - an evolving architectural structure, based on combining predefined controls and protocols. These are handled in the context of the service-oriented, agent-based and organization-centric framework defined in AT and provided by their implementation within the THOMAS platform. This work provides the first architectural abstractions to support this emergent structure. A real-world example showing the interest of this approach is also provided, and some conclusions about its applicability are finally outlined.Sociedad Argentina de Informática e Investigación Operativ

AN ENZYMATIC FUNCTION ASSOCIATED WITH TRANSFORMATION OF FIBROBLASTS BY ONCOGENIC VIRUSES : I. CHICK EMBRYO FIBROBLAST CULTURES TRANSFORMED BY AVIAN RNA TUMOR VIRUSES

Chick embryo fibroblast cultures develop fibrinolytic activity after transformation by Rous sarcoma virus (RSV). This fibrinolytic activity is not present in normal cultures, and it does not appear after infection with either nontransforming strains of avian leukosis viruses or cytocidal RNA and DNA viruses. In cultures infected with a temperature sensitive mutant of RSV the onset of fibrinolysis appears after exposure to permissive temperatures and precedes by a short interval the appearance of morphological evidence of transformation. See PDF for Structure The rate of fibrinolysis in transformed cultures depends on the nature of the serum that is present in the growth medium: some sera (e.g., monkey or chicken serum) promote high enzymatic activity, while others (calf, fetal bovine) do not. Some sera contain inhibitors of the fibrinolysin. Based on the effect of a small number of known inhibitors, at least one step of the fibrinolytic process shows specificity resembling that of trypsin. The sera of sarcoma-bearing chickens contain an inhibitor of the fibrinolysin, whereas normal chicken sera do not. For general discussion, conclusions, and summary see the accompanying paper, part II, (J. Exp. Med. 137:112)

Bacteriophages fEV-1 and fD1 Infect Yersinia pestis

Bacteriophages vB_YpeM_fEV-1 (fEV-1) and vB_YpeM_fD1 (fD1) were isolated from incoming sewage water samples in Turku, Finland, using Yersinia pestis strains EV76 and KIM D27 as enrichment hosts, respectively. Genomic analysis and transmission electron microscopy established that fEV-1 is a novel type of dwarf myovirus, while fD1 is a T4-like myovirus. The genome sizes are 38 and 167 kb, respectively. To date, the morphology and genome sequences of some dwarf myoviruses have been described; however, a proteome characterization such as the one presented here, has currently been lacking for this group of viruses. Notably, fEV-1 is the first dwarf myovirus described for Y. pestis. The host range of fEV-1 was restricted strictly to Y. pestis strains, while that of fD1 also included other members of Enterobacterales such as Escherichia coli and Yersinia pseudotuberculosis. In this study, we present the life cycles, genomes, and proteomes of two Yersinia myoviruses, fEV-1 and fD1

Bacteriophages fEV-1 and fD1 Infect Yersinia pestis

Bacteriophages vB_YpeM_fEV-1 (fEV-1) and vB_YpeM_fD1 (fD1) were isolated from incoming sewage water samples in Turku, Finland, using Yersinia pestis strains EV76 and KIM D27 as enrichment hosts, respectively. Genomic analysis and transmission electron microscopy established that fEV-1 is a novel type of dwarf myovirus, while fD1 is a T4-like myovirus. The genome sizes are 38 and 167 kb, respectively. To date, the morphology and genome sequences of some dwarf myoviruses have been described; however, a proteome characterization such as the one presented here, has currently been lacking for this group of viruses. Notably, fEV-1 is the first dwarf myovirus described for Y. pestis. The host range of fEV-1 was restricted strictly to Y. pestis strains, while that of fD1 also included other members of Enterobacterales such as Escherichia coli and Yersinia pseudotuberculosis. In this study, we present the life cycles, genomes, and proteomes of two Yersinia myoviruses, fEV-1 and fD1

Molecular Dynamics Simulations of Phase Transition in AgNO3

Structural phase transition in AgNO3 at high temperature is simulated by molecular dynamics. The simulations are based on the potentials calculated from the Gordon–Kim modified electron-gas formalism extended to molecular ionic crystals. AgNO3 transforms into rhombohedral structure at high temperature and the phase transition is associated with the rotations of the NO3 ions and displacements of the NO3 and Ag ions

Bimodal distribution of RNA expression levels in human skeletal muscle tissue

<p>Abstract</p> <p>Background</p> <p>Many human diseases and phenotypes are related to RNA expression, levels of which are influenced by a wide spectrum of genetic and exposure-related factors. In a large genome-wide study of muscle tissue expression, we found that some genes exhibited a bimodal distribution of RNA expression, in contrast to what is usually assumed in studies of a single healthy tissue. As bimodality has classically been considered a hallmark of genetic control, we assessed the genome-wide prevalence, cause, and association of this phenomenon with diabetes-related phenotypes in skeletal muscle tissue from 225 healthy Pima Indians using exon array expression chips.</p> <p>Results</p> <p>Two independent batches of microarrays were used for bimodal assessment and comparison. Of the 17,881 genes analyzed, eight (<it>GSTM1, HLA-DRB1, ERAP2, HLA-DRB5, MAOA, ACTN3, NR4A2</it>, and <it>THNSL2</it>) were found to have bimodal expression replicated in the separate batch groups, while 24 other genes had evidence of bimodality in only one group. Some bimodally expressed genes had modest associations with pre-diabetic phenotypes, of note <it>ACTN3 </it>with insulin resistance. Most of the other bimodal genes have been reported to be involved with various other diseases and characteristics. Association of expression with <it>cis </it>genetic variation in a subset of 149 individuals found all but one of the confirmed bimodal genes and nearly half of all potential ones to be highly significant expression quantitative trait loci (eQTL). The rare prevalence of these bimodally expressed genes found after controlling for batch effects was much lower than the prevalence reported in other studies. Additional validation in data from separate muscle expression studies confirmed the low prevalence of bimodality we observed.</p> <p>Conclusions</p> <p>We conclude that the prevalence of bimodal gene expression is quite rare in healthy muscle tissue (<0.2%), and is much lower than limited reports from other studies. The major cause of these clearly bimodal expression patterns in homogeneous tissue appears to be <it>cis</it>-polymorphisms, indicating that such bimodal genes are, for the most part, eQTL. The high frequency of disease associations reported with these genes gives hope that this unique feature may identify or actually be an underlying factor responsible for disease development.</p

The Role of Agreement Technologies in the Definition of Adaptive Software Architectures

The growing complexity of software systems is causing a re-conception of their development and maintenance strategies. Humans should be relieved from an important part of these tasks, which should be performed by systems themselves, leading to consider self-adaptation as a basic architectural concern. Simultaneously, Multi-Agent Systems (MAS) have been developed as a generic approach to solve complex problems. They describe self-aware structures,conceived to be flexible and to be able to adapt to different situations. Advances approaches use organizations to provide further structuring, taking the form of complex agent architectures. Among them, Agreement Technologies (AT) provides an explicit insight into those architectural abstractions. However, they still do not provide mechanisms to change their composition patterns and element types, which are necessary to achieve real self-adaptivity. In this article, we propose an architectural solution for this: the required dynamism will be supported by an emergent agreement - an evolving architectural structure, based on combining predefined controls and protocols. These are handled in the context of the service-oriented, agent-based and organization-centric framework defined in AT and provided by their implementation within the THOMAS platform. This work provides the first architectural abstractions to support this emergent structure. A real-world example showing the interest of this approach is also provided, and some conclusions about its applicability are finally outlined.Sociedad Argentina de Informática e Investigación Operativ