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The UPR alleviates the protein load by both temporarily reducing the production of proteins via PERK-mediated translation inhibition , increasing levels of chaperone proteins via transcription mediated by XBP-1 and ATF6 and increasing the exit and degradation of misfolded proteins via the ERAD pathway XBPmediated 3. We hypothesize that torsinA normally acts as a pre-emptive regulator of the intracellular stress response in the ER and that deficits in torsinA activity in patients lead to a state of selective vulnerability, that along with other factors, manifest as dystonia. Prior genetic analyses of DYT1 dystonia patients have discerned that disease penetrance is correlated with a specific polymorphism, DH, in the coding sequence of torsinA Using a suite of transgenic nematode strains in conjunction with a quantitative in vivo fluorescent readout for the ER stress response, as well as correlative studies using mammalian fibroblasts that are either torsinA WT or null, we report that WT torsinA supports intracellular homeostasis and attenuates the consequences of protein misfolding stress. Ropes Submission Latex Free samples Knots Sexy women Worthless Catsuit Plugs The floor Ties 50 shades Black pantyhose Bound 2 Corsets Dark side Engine Erotic photography Masters Mistress. The presence of WT torsinA dramatically reduced the response to ER stress observed in these animals Fig. To confirm that the RNAi was specifically targeting xbp-1 , semi-quantitative RT—PCR was performed in these strains with and without RNAi treatment Fig.
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