Redox control of indoleamine 2,3-dioxygenase expression and activity in human monocyte-derived dendritic cells is independent of changes in oxygen tension.

Dendritic cells (DCs) initiate adaptive immune responses to pathogens and tumours and maintain tolerance to self and innocuous antigens. These functions occur in organs and tissues exhibiting wide variations in nutrients, growth factors, redox and oxygen tension. Understanding how these microenvironmental factors influence DCs to affect immunological outcomes is of increasing relevance with the emerging success of DC-based cellular vaccines. In a previous study, we examined whether redox, an important environmental cue, could influence DC expression of the immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO). IDO-competent DCs promote long-term immune homoeostasis by limiting exaggerated inflammatory responses and directing regulatory T-cell effector function. To alter redox, we manipulated the activity of the cystine/glutamate antiporter, which functions to maintain intracellular and extracellular redox. The results of that study showed that redox perturbation strongly induced IDO expression and activity in DCs. While this study was performed using standard cell culture techniques with DCs cultured under 5% CO2 and 20% O2, it is clear that DCs capture and present antigens in inflamed tissues and secondary lymphoid organs which exhibit low oxygen tension (1-5% O2). Therefore, here we investigated whether oxygen tension influences DC expression of IDO in the context of homoeostatic and altered redox.

Occupational performance and the transition to powered mobility: a pilot study.

OBJECTIVE: This quantitative study describes the transition from manual to powered mobility and its influence on occupational performance (organization of daily tasks, assumption of responsibility, roles, interests) and feelings of competence, adaptability, and self-esteem. METHOD: The Occupational Performance History Interview (OPHI) was used with a convenience sample of 8 participants with both static and progressive conditions to measure retrospectively changes in occupational performance after the change from a manual wheelchair to a powered mobility device (PMD). The Psychosocial Impact of Assistive Device Scale (PIADS) was used to measure participants' perceptions of the impact of the PMD on their competence, adaptability, and self-esteem. RESULTS: A comparison of the pretest and posttest means on the OPHI scores showed a significant improvement in occupational performance (p = .001) after the introduction of PMDs. The PIADS scores showed a positive impact of 2 or greater for 75% of the participants on 19 of 26 items. Scores were similar to scores in a PIADS database of persons with comparable conditions. No significant relationship between occupational performance and psychosocial impact was demonstrated. CONCLUSION: Results suggest that the transition to a PMD enhances occupational performance, competence, adaptability, and self-esteem for persons with severe mobility impairments.

Distinct mechanisms regulate slow-muscle development.

Vertebrate muscle development begins with the patterning of the paraxial mesoderm by inductive signals from midline tissues [1, 2]. Subsequent myotome growth occurs by the addition of new muscle fibers. We show that in zebrafish new slow-muscle fibers are first added at the end of the segmentation period in growth zones near the dorsal and ventral extremes of the myotome, and this muscle growth continues into larval life. In marine teleosts, this mechanism of growth has been termed stratified hyperplasia [3]. We have tested whether these added fibers require an embryonic architecture of muscle fibers to support their development and whether their fate is regulated by the same mechanisms that regulate embryonic muscle fates. Although Hedgehog signaling is required for the specification of adaxial-derived slow-muscle fibers in the embryo [4, 5], we show that in the absence of Hh signaling, stratified hyperplastic growth of slow muscle occurs at the correct time and place, despite the complete absence of embryonic slow-muscle fibers to serve as a scaffold for addition of these new slow-muscle fibers. We conclude that slow-muscle-stratified hyperplasia begins after the segmentation period during embryonic development and continues during the larval period. Furthermore, the mechanisms specifying the identity of these new slow-muscle fibers are different from those specifying the identity of adaxial-derived embryonic slow-muscle fibers. We propose that the independence of early, embryonic patterning mechanisms from later patterning mechanisms may be necessary for growth.