Dysregulation of dopamine homeostasis and elevation of the cytosolic level of the transmitter have been suggested to underlie the vulnerability of catecholaminergic neurons in Parkinson's disease. Because several known mutations in ␣-synuclein or overexpression of the wild-type (WT) protein causes familial forms of Parkinson's disease, we investigated possible links between ␣-synuclein pathogenesis and dopamine homeostasis. Chromaffin cells isolated from transgenic mice that overexpress A30P ␣-synuclein displayed significantly increased cytosolic catecholamine levels as measured by intracellular patch electrochemistry, whereas cells overexpressing the WT protein and those from knock-out animals were not different from controls. Likewise, catechol concentrations were higher in L-DOPAtreated PC12 cells overexpressing A30P or A53T compared with those expressing WT ␣-synuclein, although the ability of cells to maintain a low cytosolic dopamine level after L-DOPA challenge was markedly inhibited by either protein. We also found that incubation with low-micromolar concentrations of WT, A30P, or A53T ␣-synuclein inhibited ATP-dependent maintenance of pH gradients in isolated chromaffin vesicles and that the WT protein was significantly less potent in inducing the proton leakage. In summary, we demonstrate that overexpression of different types of ␣-synuclein disrupts vesicular pH and leads to a marked increase in the levels of cytosolic catechol species, an effect that may in turn trigger cellular oxyradical damage. Although multiple molecular mechanisms may be responsible for the perturbation of cytosolic catecholamine homeostasis, this study provides critical evidence about how ␣-synuclein might exert its cytotoxicity and selectively damage catecholaminergic cells.
One of the most effective strategies of the lesbian-themed serial drama The L Word has been a double one: to produce sex scenes that ensure appeal for a premium-paying straight audience, while offering specific pleasures for queer viewers "in the know." Analyzing scenes from the show's first and second seasons, I will demonstrate how the hit Showtime series makes us all tourists, through the enticement of lesbian sex (a spectacle of attraction for straight and queer viewers alike) and through the wonderment of either "understanding" the other or "recognizing" oneself (fantasy of authenticity), through both "watching from a remove" and "being there."
The purpose of this chapter is to foreground the experiences of women of Color who serve in full-time, contingent faculty roles and interrogate the policies and practices that present both barriers and opportunities for these faculty members within the academy. Using a conceptual framework of previous literature in combination with critical race feminism and structuration theory, the authors discuss the ways in which identity (race, gender, and age) and position (contingent vs. tenure-track) influence faculty life and teaching. Throughout this discussion, the authors also introduce results from a study they conducted on Black women contingent faculty. The chapter concludes with the authors offering suggestions for institutional policy and practice.
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