An increase in neuronal burst activities in the subthalamic nucleus (STN) is a well-documented electrophysiological feature of Parkinson disease (PD). However, the causal relationship between subthalamic bursts and PD symptoms and the ionic mechanisms underlying the bursts remain to be established. Here, we have shown that T-type Ca 2+ channels are necessary for subthalamic burst firing and that pharmacological blockade of T-type Ca 2+ channels reduces motor deficits in a rat model of PD. Ni 2+ , mibefradil, NNC 55-0396, and efonidipine, which inhibited T-type Ca 2+ currents in acutely dissociated STN neurons, but not Cd 2+ and nifedipine, which preferentially inhibited L-type or the other non-T-type Ca 2+ currents, effectively diminished burst activity in STN slices. Topical administration of inhibitors of T-type Ca 2+ channels decreased in vivo STN burst activity and dramatically reduced the locomotor deficits in a rat model of PD. Cd 2+ and nifedipine showed no such electrophysiological and behavioral effects. While low-frequency deep brain stimulation (DBS) has been considered ineffective in PD, we found that lengthening the duration of the low-frequency depolarizing pulse effectively improved behavioral measures of locomotion in the rat model of PD, presumably by decreasing the availability of T-type Ca 2+ channels. We therefore conclude that modulation of subthalamic T-type Ca 2+ currents and consequent burst discharges may provide new strategies for the treatment of PD.

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Glutathione S-transferases (GSTs) have been well documented to be involved in diverse aspects of biotic and abiotic stresses, especially detoxification processes. Whether they regulate plant development remains unclear. Here, we report on our isolation by reverse transcription-polymerase chain reaction of a plant GST, AtGSTU17, from Arabidopsis (Arabidopsis thaliana) and demonstrate that its expression is regulated by multiple photoreceptors, especially phytochrome A (phyA) under all light conditions. Further physiological studies indicated that AtGSTU17 participates in various aspects of seedling development, including hypocotyl elongation, anthocyanin accumulation, and far-red light-mediated inhibition of greening with a requirement of functional phyA. The loss-of-function mutant of AtGSTU17 (atgstu17) resulted in reduced biomass of seedlings and number of lateral roots in the presence of auxin, as well as insensitivity to abscisic acid (ABA)-mediated inhibition of root elongation, with similarity to different phyA mutant alleles. Moreover, the root phenotype conferred by atgstu17 was reflected by histochemical b-glucuronidase staining of AtGSTU17 promoter activity with the addition of auxin or ABA. Further microarray analysis of wild-type Columbia and atgstu17 seedlings treated with far-red irradiation or ABA revealed that AtGSTU17 might modulate hypocotyl elongation by positively regulating some light-signaling components and negatively regulating a group of auxin-responsive genes and modulate root development by negatively controlling an auxin transport protein in the presence of ABA. Therefore, our data reveal that AtGSTU17 participates in light signaling and might modulate various aspects of Arabidopsis development by affecting glutathione pools via a coordinated regulation with phyA and phytohormones.

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Background: The TGF-b signaling pathway is crucial in the progression and metastasis of malignancies. We investigated whether the serum TGF-b1 level was related to the outcomes of patients treated with sorafenib for advanced hepatocellular carcinoma (HCC).Experimental Design: We selected patients who had received sorafenib-containing regimens as first-line therapy for advanced HCC between 2007 and 2012. Serum TGF-b1 levels were measured and correlated with the treatment outcomes. The expression TGF-b1 and the sensitivity to sorafenib were examined in HCC cell lines.Results:Ninety-one patients were included; 62 (68%) were hepatitis B virus surface antigen (þ), and 11 (12%) were antihepatitis C virus (þ). High (! median) pretreatment serum TGFb1 levels (median 13.7 ng/mL; range, 3.0-41.8) were associated