Novel Association of ABO Histo-Blood Group Antigen with Soluble ICAM-1: Results of a Genome-Wide Association Study of 6,578 Women

While circulating levels of soluble Intercellular Adhesion Molecule 1 (sICAM-1) have been associated with diverse conditions including myocardial infarction, stroke, malaria, and diabetes, comprehensive analysis of the common genetic determinants of sICAM-1 is not available. In a genome-wide association study conducted among 6,578 participants in the Women's Genome Health Study, we find that three SNPs at the ICAM1 (19p13.2) locus (rs1799969, rs5498 and rs281437) are non-redundantly associated with plasma sICAM-1 concentrations at a genome-wide significance level (P<5×10−8), thus extending prior results from linkage and candidate gene studies. We also find that a single SNP (rs507666, P = 5.1×10−29) at the ABO (9q34.2) locus is highly correlated with sICAM-1 concentrations. The novel association at the ABO locus provides evidence for a previously unknown regulatory role of histo-blood group antigens in inflammatory adhesion processes

Macrophage biology in development, homeostasis and disease

Macrophages the most plastic cells of the hematopoietic system are found in all tissues and exhibit great functional diversity. They have roles in development, homeostasis, tissue repair, and immunity. While anatomically distinct, resident tissue macrophages exhibit different transcriptional profiles, and functional capabilities, they are all required for the maintenance of homeostasis. However, these reparative and homeostatic functions can be subverted by chronic insults, resulting in a causal association of macrophages with disease states. In this review, we discuss how macrophages regulate normal physiology and development and provide several examples of their pathophysiologic roles in disease. We define the “hallmarks” of macrophages performing particular functions, taking into account novel insights into the diversity of their lineages, identity, and regulation. This diversity is essential to understand because macrophages have emerged as important therapeutic targets in many important human diseases

A New Promise for an Old Place: The Revitalization and re-Visioning of a Rural Small Town

As part of the Appalachian Teaching Project, this presentation by Emory & Henry students focuses on efforts for community and economic development in Glade Spring, Virginia and the first stages of a multi-year, multi-pronged effort to offer logistical, technical, and strategic support for efforts to rebuild and revitalize this small rural community located three miles from Emory & Henry College. Students will have worked collaboratively with members of the Glade Spring community to develop a marketing plan that will be used to recruit businesses and social entrepreneurial initiatives to the Glade Town Square. Also involved in this is research and data gathering to support the community’s application for economic development grants. Glade Spring was partially destroyed by a tornado in April 2011. At the time, it was on the cusp of major redevelopment projects, initiated from a new cadre of community leaders. Like most rural communities, Glade Spring has witnessed the demise of its vital local economy, the removal of its people to places offering more economic opportunities and the decline in its quality of life for those who remain. Many thought that the destruction wrought in the tornado was the death knell for the place. Since April 2011, however, the town has regained and redoubled its stride. This project highlights lessons learned in the rebuilding effort, extending those lessons for positive and proactive growth

Retail default prediction by using sequential minimal optimization technique

This paper employed sequential minimal optimization (SMO) to develop default prediction model in the US retail market. Principal components analysis is used for variable reduction purposes. Four standard credit scoring techniques-na�ve Bayes, logistic regression, recursive partitioning and artificial neural network-are compared to SMO, using a sample of 195 healthy firms and 51 distressed firms over five time periods between 1994 and 2002. The five techniques perform well in predicting default particularly one year before financial distress. Furthermore, the prediction still remains sound even 5 years before default. No single methodology has the absolute best classification ability, as the model performance varies in terms of different time periods and variable groups. External influences have greater impacts on the na�ve Bayes than other techniques. In terms of similarity with Moody's ranking, SMO excelled over other techniques in most of the time periods. Copyright © 2008 John Wiley & Sons, Ltd.

Flow cytometric analysis of the human articular chondrocyte phenotype in vitro.

AbstractObjective To develop flow cytometry for the study of human articular cartilage cell phenotype and to validate the method on chondrocytes cultured in different in-vitro systems.Methods Chondrocyte phenotype was modulated by culturing the cells under differentin-vitro conditions: i.e. in monolayer and in suspension culture in gelled agarose. Monolayer cultured chondrocyte phenotype was assayed by immunohistochemical staining with monoclonal antibodies against chondrocyte-specific aggrecan, type II and I collagen. Flow cytometry was used to quantify the proportions of chondrocytes expressing these extracellular matrix molecules in both culture conditions. To exclude the effects of cell-harvesting methods on the presence of cell-bound ECM molecules, non-proteolytic isolation procedures were used to obtain the chondrocytes for flow cytometry. Subconfluent cells from monolayer cultures were detached with EDTA. Chondrocytes cultured in gelled agarose were obtained after the agarose was enzymatically digested with agarase.Results Immunohistochemical staining showed that monolayer-cultured chondrocytes, in the presence of serum, gradually lost the expression of chondrocyte-specific aggrecan and type II collagen, while type I collagen was increasingly expressed. Flow cytometry allowed monolayer cultured chondrocyte phenotype to be assessed reproducibly. Chondrocyte phenotype was characterized through the cell membrane-associated extracellular matrix antigens. EDTA, used to obtain single cells from monolayer cultures, did not affect the cell-associated matrix. Where the chondrocytes had been cultured in gelled agarose, flow cytometry allowed quantification of the percentages of chondrocytes maintaining or reexpressing their original phenotype. The agarase digestion procedure used to isolate the cells from the agarose gel did not affect the plasma membrane-associated extracellular matrix antigens.Conclusion Flow cytometry allows quantification of cells expressing aggrecan, type II and I collagen in their cell-associated extracellular matrix. A continuously increasing number of specific monoclonal antibodies will broaden the range of applications offered by this method