BackgroundThrombin activatable fibrinolysis inhibitor (TAFI) is a plasma zymogen, which can be converted to activated TAFI (TAFIa) through proteolytic cleavage by thrombin, plasmin, and most effectively thrombin in complex with the endothelial cofactor thrombomodulin (TM). TAFIa is a carboxypeptidase that cleaves carboxyl terminal lysine and arginine residues from protein and peptide substrates, including plasminogen-binding sites on cell surface receptors. Carboxyl terminal lysine residues play a pivotal role in enhancing cell surface plasminogen activation to plasmin. Plasmin has many critical functions including cleaving components of the extracellular matrix (ECM), which enhances invasion and migration of cancer cells. We therefore hypothesized that TAFIa could act to attenuate metastasis.MethodsTo assess the role of TAFIa in breast cancer metastasis, in vitro migration and invasion assays, live cell proteolysis and cell proliferation using MDA-MB-231 and SUM149 cells were carried out in the presence of a TAFIa inhibitor, recombinant TAFI variants, or soluble TM.ResultsInhibition of TAFIa with potato tuber carboxypeptidase inhibitor increased cell invasion, migration and proteolysis of both cell lines, whereas addition of TM resulted in a decrease in all these parameters. A stable variant of TAFIa, TAFIa-CIIYQ, showed enhanced inhibitory effects on cell invasion, migration and proteolysis. Furthermore, pericellular plasminogen activation was significantly decreased on the surface of MDA-MB-231 and SUM149 cells following treatment with various concentrations of TAFIa.ConclusionsTaken together, these results indicate a vital role for TAFIa in regulating pericellular plasminogen activation and ultimately ECM proteolysis in the breast cancer microenvironment. Enhancement of TAFI activation in this microenvironment may be a therapeutic strategy to inhibit invasion and prevent metastasis of breast cancer cells.
The analysis of craquelure found on art paintings has been shown to provide supportive information regarding an art painting's geographical origins and authenticity. Craquelure represents the unique crack formations on paintings that can be traced back to the materials and methods employed by the artist, which is usually confined to the particular geographical area in which the painting was created or stored. It has been shown that different art paintings created in the same geographical location, during a similar time period, exhibit similar craquelure formation patterns. To alleviate expertise in the classification of craquelure patterns to their corresponding region of origin, a computer algorithm has been developed to complete such a task, as well as to monitor the growth and changes in craquelure formations. Mathematical morphology was used to extract the craquelure patterns from a greyscale image before converting it to a binary image. Specific features were then extracted from the binary image and fed to a discriminant analysis classifier for classification. The extracted craquelure network is then saved to a storage database for the purpose of monitoring the painting's crack formation over time. In this report, a set of previously captured craquelure images were used to test the developed algorithm. The results in this paper demonstrate that the computer algorithm is capable of classifying the various craquelure patterns with an acceptable degree of accuracy. It is also shown that the developed algorithm can be used to detect the formation of new cracks as a way of monitoring an art painting's condition. This algorithm has direct applications in the detection of forgeries of art paintings and in the development of a 'health' monitoring system, especially for art paintings that are routinely transported between exhibits.
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