Here we demonstrate that interleukin-2-inducible T-cell kinase (Itk) signaling in cluster of differentiation 4-positive (CD4 Ϫ/Ϫ CD4 ϩ T cells show significant reduction in production of T-helper 1 (Th1) and Th17 cytokines and exhibit skewed T effector/T regulatory cell ratios. These results indicate that signaling by Itk promotes autoimmunity and CNS inflammation, suggesting that it may be a viable target for treatment of MS.

Fertility in mammals requires appropriate communication within the hypothalamic-pituitary-gonadal axis and the GnRH receptor (GnRHR) is a central conduit for this communication. The GnRHR resides in discrete membrane rafts and raft occupancy is required for signaling by GnRH. The present studies use immunoprecipitation and mass spectrometry to define peptides present within the raft associated with the GnRHR and flotillin-1, a key raft marker. These studies revealed peptides from the F0F1 ATP synthase complex. The catalytic subunits of the F1 domain were validated by immunoprecipitation, flow cytometry, and cell surface biotinylation studies demonstrating that this complex was present at the plasma membrane associated with the GnRHR. The F1 catalytic domain faces the extracellular space and catalyzes ATP synthesis when presented with ADP in normal mouse pituitary explants and a gonadotrope cell line. Steady-state extracellular ATP accumulation was blunted by coadministration of inhibitory factor 1, limiting inorganic phosphate in the media, and by chronic stimulation of the GnRHR. Steady-state extracellular ATP accumulation was enhanced by pharmacological inhibition of ecto-nucleoside triphosphate diphosphohydrolases. Kisspeptin administration induced coincident GnRH and ATP release from the median eminence into the hypophyseal-portal vasculature in ovariectomized sheep. Elevated levels of extracellular ATP augmented GnRH-induced secretion of LH from pituitary cells in primary culture, which was blocked in media containing low inorganic phosphate supporting the importance of extracellular ATP levels to gonadotrope cell function. These studies indicate that gonadotropes have intrinsic ability to metabolize ATP in the extracellular space and extracellular ATP may serve as a modulator of GnRH-induced LH secretion.

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In-Zn-Sn-O films were deposited on a polycarbonate (PC) substrate by a magnetron co-sputtering system using two cathodes (DC, RF) without substrate heating. Two types of ITO targets (target A: doped with 5 wt.% SnO2, target B: doped with 10 wt.% SnO2) were used as an In-Sn-O source. The ITO and ZnO targets were sputtered by DC and RF discharges, respectively, and the composition of the In-Zn-Sn-O films was controlled via the power ratio of each cathode. In the case of ITO target A, the lowest resistivity (4.3 × 10Ωcm) was obtained for the film deposited at the RF power (ZnO) of 55W. In the case of ITO target B, the lowest resistivity (2.9 × 10Ωcm) of the film was obtained at the RF power (ZnO) of 30W, which was attributed to the increase in carrier density. Hall mobility decreased with increasing carrier density, which could be explained by the increase in ionized impurity scattering.