Molecular Characterization and Localization of the NAD(P)H Oxidase Components gp91-phox and p22-phox in Endothelial Cells

The production of reactive oxygen species (ROS) within endothelial cells may have several effects, including alterations in the activity of paracrine factors, gene expression, apoptosis, and cellular injury. Recent studies indicate that a phagocyte-type NAD(P)H oxidase is a major source of endothelial ROS. In contrast to the high-output phagocytic oxidase, the endothelial enzyme has much lower biochemical activity and a different substrate specificity (NADH.NADPH). In the present study, we (1) cloned and characterized the cDNA and predicted amino acid structures of the 2 major subunits of rat coronary microvascular endothelial cell NAD(P)H oxidase, gp91-phox and p22-phox; (2) undertook a detailed comparison with phagocytic NADPH oxidase sequences; and (3) studied the subcellular location of these subunits in endothelial cells. Although these studies revealed an overall high degree of homology (.90%) between the endothelial and phagocytic oxidase subunits, the endothelial gp91-phox sequence has potentially important differences in a putative NADPH-binding domain and in putative glycosylation sites. In addition, the subcellular location of the endothelial gp91-phox and p22-phox subunits is significantly different from that reported for the neutrophil oxidase, in that they are predominantly intracellular and collocated in the vicinity of the endoplasmic reticulum. This first detailed characterization of gp91-phox and p22-phox structure and location in endothelial cells provides new data that may account, in part, for the differences in function between the phagocytic and endothelial NAD(P)H oxidases.

Future Selves: Career choices of young disabled people

There is growing recognition that gaining the views of young people is crucial for understanding issues that affect their lives. However, to date, very little is known about the way in which disabled children, make sense of their identities, and create a sense of their past and their imagined futures over time. This three year study, funded by the European Social Fund, and conducted by Dr Sonali Shah and colleagues at the University of Nottingham, used various methods to explore how physically disabled students, in full-time special or mainstream education, make choices concerning their occupational futures. It identified the factors that shape their educational and career related choices and chances, and explored how social relations, social processes, and social policies influenced the extent to which their aspirations were achieved. This study presents disabled children and young people as critical social actors who are telling their own stories of how social structures and processes shape their choices and aspirations for their future selves. It illustrates the importance of consulting children and young people about issues concerning their lives, and not rely solely on adults’ conceptions of childhood. The young disabled people’s experiences and views can be used to develop a new flexible system which offers the benefits of mainstream and special education, and facilitates young disabled people’s self-determination to make choices to participate in and contribute to their independent futures.