Effect of Crystallization Modes in TIPS-Pentacene/Insulating Polymer Blends on the Gas Sensing Properties of Organic Field-Effect Transistors

Blending organic semiconductors with insulating polymers has been known to be an effective way to overcome the disadvantages of single-component organic semiconductors for high-performance organic field-effect transistors (OFETs). We show that when a solution processable organic semiconductor (6,13-bis(triisopropylsilylethynyl)pentacene, TIPS-pentacene) is blended with an insulating polymer (PS), morphological and structural characteristics of the blend films could be significantly influenced by the processing conditions like the spin coating time. Although vertical phase-separated structures (TIPS-pentacene-top/PS-bottom) were formed on the substrate regardless of the spin coating time, the spin time governed the growth mode of the TIPS-pentacene molecules that phase-separated and crystallized on the insulating polymer. Excess residual solvent in samples spun for a short duration induces a convective flow in the drying droplet, thereby leading to one-dimensional (1D) growth mode of TIPS-pentacene crystals. In contrast, after an appropriate spin-coating time, an optimum amount of the residual solvent in the film led to two-dimensional (2D) growth mode of TIPS-pentacene crystals. The 2D spherulites of TIPS-pentacene are extremely advantageous for improving the field-effect mobility of FETs compared to needle-like 1D structures, because of the high surface coverage of crystals with a unique continuous film structure. In addition, the porous structure observed in the 2D crystalline film allows gas molecules to easily penetrate into the channel region, thereby improving the gas sensing properties

Activation of PERK Signaling Attenuates Aβ-Mediated ER Stress

Alzheimer's disease (AD) is characterized by the deposition of aggregated beta-amyloid (Aβ), which triggers a cellular stress response called the unfolded protein response (UPR). The UPR signaling pathway is a cellular defense system for dealing with the accumulation of misfolded proteins but switches to apoptosis when endoplasmic reticulum (ER) stress is prolonged. ER stress is involved in neurodegenerative diseases including AD, but the molecular mechanisms of ER stress-mediated Aβ neurotoxicity still remain unknown. Here, we show that treatment of Aβ triggers the UPR in the SK-N-SH human neuroblastoma cells. Aβ mediated UPR pathway accompanies the activation of protective pathways such as Grp78/Bip and PERK-eIF2α pathway, as well as the apoptotic pathways of the UPR such as CHOP and caspase-4. Knockdown of PERK enhances Aβ neurotoxicity through reducing the activation of eIF2α and Grp8/Bip in neurons. Salubrinal, an activator of the eIF2α pathway, significantly increased the Grp78/Bip ER chaperone resulted in attenuating caspase-4 dependent apoptosis in Aβ treated neurons. These results indicate that PERK-eIF2α pathway is a potential target for therapeutic applications in neurodegenerative diseases including AD

Vaccinia-Related Kinase 2 Mediates Accumulation of Polyglutamine Aggregates via Negative Regulation of the Chaperonin TRiC

Misfolding of proteins containing abnormal expansions of polyglutamine (polyQ) repeats is associated with cytotoxicity in several neurodegenerative disorders, including Huntington's disease. Recently, the eukaryotic chaperonin TRiC hetero-oligomeric complex has been shown to play an important role in protecting cells against the accumulation of misfolded polyQ protein aggregates. It is essential to elucidate how TRiC function is regulated to better understand the pathological mechanism of polyQ aggregation. Here, we propose that vaccinia-related kinase 2 (VRK2) is a critical enzyme that negatively regulates TRiC. In mammalian cells, overexpression of wild-type VRK2 decreased endogenous TRiC protein levels by promoting TRiC ubiquitination, but a VRK2 kinase-dead mutant did not. Interestingly, VRK2-mediated downregulation of TRiC increased aggregate formation of a polyQ-expanded huntingtin fragment. This effect was ameliorated by rescue of TRiC protein levels. Notably, small interference RNA-mediated knockdown of VRK2 enhanced TRiC protein stability and decreased polyQ aggregation. The VRK2-mediated reduction of TRiC protein levels was subsequent to the recruitment of COP1 E3 ligase. Among the members of the COP1 E3 ligase complex, VRK2 interacted with RBX1 and increased E3 ligase activity on TRiC in vitro. Taken together, these results demonstrate that VRK2 is crucial to regulate the ubiquitination-proteosomal degradation of TRiC, which controls folding of polyglutamine proteins involved in Huntington's disease.open118Ysciescopu

The Effects of Immobilization Stress on the Synthesis and the Catabolism of Dopamine and Norepinephrine in the Rat Hypothalamus

Immobilization stress was adopted as a prototype stress model for studying the effects of stress on dopaminergic and noradrenergic neuronal activity in the rat hypothalamus. Norepinephrine content was significantly increased after 4 hours of immobilization stress. Also, the turnover rates of both dopamine and norepinephrine were found to be significantly increased after the stress, providing the evidence of increased synthesis rates of both neurotransmitters. These findings were consistent with the increase in plasma corticosterone and catecholamine levels. The activities of tyrosine hydroxylase and dopamine-j1-hydroxylase, the synthesizing enzymes for catecholamines, were significantly increased after the stress, while that of monoamine oxidase, the catabolizing enzyme, did not change to a significant degree at all. Kinetic analysis of tyrosine hydroxylase, the rate-limiting step in catecholamine biosynthesis, revealed that Vmax was significantly increased after the stress without significant change of Km. These findings suggest that dopamine and norepinephrine may playa significant role in mediating stress responses by increasing their neuronal activities

Bacterial Uracil Modulates Drosophila DUOX-Dependent Gut Immunity via Hedgehog-Induced Signaling Endosomes

SummaryGenetic studies in Drosophila have demonstrated that generation of microbicidal reactive oxygen species (ROS) through the NADPH dual oxidase (DUOX) is a first line of defense in the gut epithelia. Bacterial uracil acts as DUOX-activating ligand through poorly understood mechanisms. Here, we show that the Hedgehog (Hh) signaling pathway modulates uracil-induced DUOX activation. Uracil-induced Hh signaling is required for intestinal expression of the calcium-dependent cell adhesion molecule Cadherin 99C (Cad99C) and subsequent Cad99C-dependent formation of endosomes. These endosomes play essential roles in uracil-induced ROS production by acting as signaling platforms for PLCβ/PKC/Ca2+-dependent DUOX activation. Animals with impaired Hh signaling exhibit abolished Cad99C-dependent endosome formation and reduced DUOX activity, resulting in high mortality during enteric infection. Importantly, endosome formation, DUOX activation, and normal host survival are restored by genetic reintroduction of Cad99C into enterocytes, demonstrating the important role for Hh signaling in host resistance to enteric infection