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Different Mediators (different + mediator)
Selected AbstractsCholesterol and Kir channelsIUBMB LIFE, Issue 8 2009Irena Levitan Abstract To date, most of the major types of Kir channels, Kir2s, Kir3s, Kir4s, and Kir6s, have been found to partition into cholesterol-rich membrane domains and/or to be regulated by changes in the level of membrane cholesterol. Surprisingly, however, in spite of the structural similarities between different Kirs, effects of cholesterol on different types of Kir channels vary from cholesterol-induced decrease in the current density (Kir2 channels) to the loss of channel activity by cholesterol depletion (Kir4 channels) and loss of channel coupling by different mediators (Kir3 and Kir6 channels). Recently, we have gained initial insights into the mechanisms responsible for cholesterol-induced suppression Kir2 channels, but mechanisms underlying cholesterol sensitivity of other Kir channels are mostly unknown. The goal of this review is to present a summary of the current knowledge of the distinct effects of cholesterol on different types of Kir channels in vitro and in vivo. © 2009 IUBMB IUBMB Life 61(8): 781,790, 2009 [source] Treatment of experimental arthritis by inducing immune tolerance with human adipose-derived mesenchymal stem cellsARTHRITIS & RHEUMATISM, Issue 4 2009Manuel A. González Objective Rheumatoid arthritis (RA) is a chronic autoimmune disease caused by loss of immunologic self tolerance and characterized by chronic joint inflammation. Adult mesenchymal stem cells (MSCs) were recently found to suppress effector T cell responses and to have beneficial effects in various immune disorders. The purpose of this study was to examine a new therapeutic strategy for RA based on the administration of human adipose-derived MSCs (AD-MSCs). Methods DBA/1 mice with collagen-induced arthritis were treated with human AD-MSCs after disease onset, and clinical scores were determined. Inflammatory response was determined by measuring the levels of different mediators of inflammation in the joints and serum. The Th1-mediated autoreactive response was evaluated by determining the proliferative response and cytokine profile of draining lymph node cells stimulated with the autoantigen. The number of Treg cells and the suppressive capacity on self-reactive Th1 cells were also determined. Results Systemic infusion of human AD-MSCs significantly reduced the incidence and severity of experimental arthritis. This therapeutic effect was mediated by down-regulating the 2 deleterious disease components: the Th1-driven autoimmune and inflammatory responses. Human AD-MSCs decreased the production of various inflammatory cytokines and chemokines, decreased antigen-specific Th1/Th17 cell expansion, and induced the production of antiinflammatory interleukin-10 in lymph nodes and joints. Human AD-MSCs also induced de novo generation of antigen-specific CD4+CD25+FoxP3+ Treg cells with the capacity to suppress self-reactive T effector responses. Conclusion Human AD-MSCs emerge as key regulators of immune tolerance by inducing the generation/activation of Treg cells and are thus attractive candidates for a cell-based therapy for RA. [source] Pyrroloquinoline quinone-dependent carbohydrate dehydrogenase: Activity enhancement and the role of artificial electron acceptorsBIOTECHNOLOGY JOURNAL, Issue 8 2010Juozas Kulys Professor Abstract Pyrroloquinoline quinone (PQQ)-dependent glucose dehydrogenase (PQQ-GDH) offers a variety of opportunities for applications, e.g. in highly sensitive biosensors and electrosynthetic reactions. Here we report on the acceleration (up to 4.9 x 104 -fold) of enzymatic ferricyanide reduction by artificial redox mediators (enhancers). The reaction mechanism includes reduction of the PQQ-GDH by glucose followed by oxidation of the reduced PQQ cofactor with either ferricyanide or a redox mediator. A synergistic effect occurs through the oxidation of a reduced mediator by ferricyanide. Using kinetic description of the coupled reaction, the second order rate constant for the reaction of an oxidized mediator with the reduced enzyme cofactor (kox) can be calculated. For different mediators this value is 2.2 x 106,1.6 x 108 M -1s -1 at pH 7.2 and 25°C. However, no correlation of the rate constant with the midpoint redox potential of the mediator could be established. For low-potential mediators the synergistic effect is proportional to the ratio of kox(med)/kox(ferricyanide), whereas for the high-potential mediators the effect depends on both this ratio and the concentration of the oxidized mediator, which can be calculated from the Nernst equation. The described effect can be applied in various ways, e.g. for substrate reactivity determination, electrosynthetic PQQ cofactor regeneration or building of new highly sensitive biosensors. [source] Proactivity Directed Toward the Team and Organization: The Role of Leadership, Commitment and Role-breadth Self-efficacyBRITISH JOURNAL OF MANAGEMENT, Issue 3 2009Karoline Strauss Employees' proactive behaviour is increasingly important for organizations seeking to adapt in uncertain economic environments. This study examined the link between leadership and proactive behaviour. We differentiated between organizational leadership and team leadership and proposed that transformational leadership by team leaders would enhance commitment to the team, which would predict team member proactivity. In contrast, transformational leadership by leaders of the organization would enhance commitment to the organization, which we expected to predict organization member proactivity. Transformational leadership on both levels was expected to increase employees' role-breadth self-efficacy, the confidence necessary to engage in proactive behaviour. Our results demonstrate the importance of leadership as an antecedent of proactive work behaviour and suggest that leadership at different levels influences proactivity via different mediators. Transformational team leaders seem to facilitate proactivity by increasing employees' confidence to initiate change. Transformational organizational leaders on the other hand increase proactivity by enhancing employees' commitment to the organization. [source] |