Development and Function of CD94-Deficient Natural Killer Cells

The CD94 transmembrane-anchored glycoprotein forms disulfide-bonded heterodimers with the NKG2A subunit to form an inhibitory receptor or with the NKG2C or NKG2E subunits to assemble a receptor complex with activating DAP12 signaling proteins. CD94 receptors expressed on human and mouse NK cells and T cells have been proposed to be important in NK cell tolerance to self, play an important role in NK cell development, and contribute to NK cell-mediated immunity to certain infections including human cytomegalovirus. We generated a gene-targeted CD94-deficient mouse to understand the role of CD94 receptors in NK cell biology. CD94-deficient NK cells develop normally and efficiently kill NK cell-susceptible targets. Lack of these CD94 receptors does not alter control of mouse cytomegalovirus, lymphocytic choriomeningitis virus, vaccinia virus, or Listeria monocytogenes. Thus, the expression of CD94 and its associated NKG2A, NKG2C, and NKG2E subunits is dispensable for NK cell development, education, and many NK cell functions

Mechanism of RPE Cell Death in α-Crystallin Deficient Mice: A Novel and Critical Role for MRP1-Mediated GSH Efflux

Absence of α-crystallins (αA and αB) in retinal pigment epithelial (RPE) cells renders them susceptible to oxidant-induced cell death. We tested the hypothesis that the protective effect of α-crystallin is mediated by changes in cellular glutathione (GSH) and elucidated the mechanism of GSH efflux. In α-crystallin overexpressing cells resistant to cell death, cellular GSH was >2 fold higher than vector control cells and this increase was seen particularly in mitochondria. The high GSH levels associated with α-crystallin overexpression were due to increased GSH biosynthesis. On the other hand, cellular GSH was decreased by 50% in murine retina lacking αA or αB crystallin. Multiple multidrug resistance protein (MRP) family isoforms were expressed in RPE, among which MRP1 was the most abundant. MRP1 was localized to the plasma membrane and inhibition of MRP1 markedly decreased GSH efflux. MRP1-suppressed cells were resistant to cell death and contained elevated intracellular GSH and GSSG. Increased GSH in MRP1-supressed cells resulted from a higher conversion of GSSG to GSH by glutathione reductase. In contrast, GSH efflux was significantly higher in MRP1 overexpressing RPE cells which also contained lower levels of cellular GSH and GSSG. Oxidative stress further increased GSH efflux with a decrease in cellular GSH and rendered cells apoptosis-prone. In conclusion, our data reveal for the first time that 1) MRP1 mediates GSH and GSSG efflux in RPE cells; 2) MRP1 inhibition renders RPE cells resistant to oxidative stress-induced cell death while MRP1 overexpression makes them susceptible and 3) the antiapoptotic function of α-crystallin in oxidatively stressed cells is mediated in part by GSH and MRP1. Our findings suggest that MRP1 and α crystallin are potential therapeutic targets in pathological retinal degenerative disorders linked to oxidative stress

Selling, resistance and reconciliation: A critical discursive approach to subsidiary role evolution in MNCs

Studies of political dynamics between multinational corporation (MNC) parents and subsidiaries during subsidiary role evolution have largely focused on control and resistance. This paper adopts a critical discursive approach to enable an exploration of subtle dynamics in the way that both headquarter (HQ) and subsidiaries subjectively reconstruct their independent-interdependent relationships with each other during change. We draw from a real-time qualitative study of a revealing case of charter change in an important European subsidiary of an MNC attempting to build closer integration across European country operations. Our results illustrate the role of three discourses – selling, resistance and reconciliation –in the reconstruction of the subsidiary-parent relationship. From this analysis we develop a process framework that elucidates the important role of these three discourses in the reconstruction of subsidiary roles, showing how resistance is not simply subversive but an important part of integration. Our findings contribute to a better understanding of the micro-level political dynamics in subsidiary role evolution and how voice is exercised in MNCs. This study also provides a rare example of discourse-based analysis in an MNC context advancing our knowledge of how discursive methods can help to advance international business (IB) research more generally

Urban Living Labs: opportunities in and for planning

This chapter explores some of the most significant potentials of Living Lab environments in urban systems while viewing urban planning as the entire set of transformative practices possible and available in urban contexts. It explores three main potentials of Urban Living Labs, i.e., their being practice-based innovation environments, their capacity to create cross-boundary arenas where many diverse actors and organizations can interact, and, lastly, their being contexts for new modes of urban activism. This chapter also analyzes some challenges launched by Living Labs in urban environments and discusses some possible roles for planners who recognize Living Lab potentials as transformative drivers. Finally, considering the collective (public) experimental perspective introduced by Urban Living Labs, the idea of the city as a laboratory is discussed