Image quality enhancement of transparent waveguide display using a twisted nematic mode polymer-stabilized liquid crystal.

In this study, a twisted nematic mode polymer-stabilized liquid crystal (TN mode PSLC) integrated with a crossed polarizer was used to create a transparent waveguide display. When a voltage was applied, the PSLC scattered the waveguide light with a high polarization selectivity such that no substantial loss of the outgoing light intensity was observed after integrating the polarizer. However, with a crossed polarizer, in the ON state, the background light was not only scattered but also absorbed by the analyzer. Using this device configuration, with a 12 µm cell gap and 7% monomer concentration, we successfully realized a normally transparent waveguide display. The contrast ratio of the waveguide outgoing light was 26 and that of the undesired background reached 90. This device can display images due to waveguide edge-lit light scattering and simultaneously block the background information to improve the image quality.

Multiple effects of digoxin on subsets of cancer-associated genes through the alternative splicing pathway.

The signaling characteristics of Na(+)/K(+)-ATPase are distinct from its ion pumping activity. Cardiac glycosides modulate the Na(+)/K(+)-ATPase protein complex upon binding, activate downstream signaling pathways and increase [Ca(2+)]i. Recent studies demonstrate that the depletion of p53 and hypoxia-induced factor 1α proteins is caused by cardiac glycosides. However, the detailed mechanisms governing this process are not well known. In this study, we showed that the depletion of p53 proteins by digoxin involved not only inhibition of protein synthesis but also inhibition at the post-transcriptional level. Post-transcriptional regulation occurs via down-regulation of SRSF3, the primary splicing factor responsible for the switch from p53α to the p53ß isoform. Digoxin also modulated G2/M arrest, DNA damage and apoptosis through the p53-dependent pathway in HeLa cells. In addition, digoxin was involved in epithelial-mesenchymal-transition progression via E-cadherin reduction and snail induction. Digoxin had similar effects to caffeine, another SRSF3-reduced agent, on the cell cycle profile and DNA damage of cells. Interestingly, combined digoxin and caffeine treatment blocked cell cycle progression and conferred resistance to cell death via snail induction. These findings demonstrate that down-regulation of splicing factor, such as SRSF3, to alter cell cycle progression, cell death and invasion is a potential target for the drug repositioning of cardiac glycosides.

Caffeine induces tumor cytotoxicity via the regulation of alternative splicing in subsets of cancer-associated genes.

Caffeine causes a diverse range of pharmacological effects that are time- and concentration-dependent and reversible. The detailed mechanisms of caffeine in tumor suppression via tumor suppressor protein p53 remain unclear. The isoforms of p53 are physiological proteins that are expressed in normal cells and generated via alternative promoters, splicing sites and/or translational initiation sites. In this study, we investigated how caffeine modulated cell cycle arrest and apoptosis via the expression of various alternatively spliced p53 isoforms. Caffeine reduced p53α expression and induced the expression of p53ß, which contains an alternatively spliced p53 C-terminus. In HeLa cells, the expression levels of many serine/arginine-rich splicing factors, including serine/arginine-rich splicing factors 2 and 3, were altered by caffeine. Serine/arginine-rich splicing factor 3 was a promising candidate for the serine/arginine-rich splicing factors responsible for the alternative splicing of p53 in response to caffeine treatment. In addition to p53-dependent functions, multiple target genes of serine/arginine-rich splicing factor 3 suggest that caffeine can regulate epithelial-mesenchymal-transition and hypoxic conditions to inhibit the survival of tumor cells. In summary, our data provide a new pathway of caffeine-modulated tumor suppression via the alternative splicing of the target genes of serine/arginine-rich splicing factor 3.

Dual roles for lysine 490 of promyelocytic leukemia protein in the transactivation of glucocorticoid receptor-interacting protein 1.

Glucocorticoid receptor-interacting protein 1 (GRIP1), a p160 family nuclear receptor co-activator protein, has three activation domains that recruit at least three secondary co-activators: CBP/p300, co-activator-associated arginine methyltransferase 1, and coiled-coil co-activator, which exhibits histone acetyltransferase and/or arginine methyltransferase activities. The regulatory mechanisms underlying the co-activation functions of GRIP1, which associates with promyelocytic leukemia protein (PML) in PML-nuclear bodies, are not well-understood. This study showed that PML specifically and dramatically enhanced the C-terminal transactivation activity of GRIP1 by directly binding to GRIP1 but only when it was sumoylated. Most of the transactivation activity resided in the N-terminal PML regions that are conserved among isoforms. Three N-terminal sumoylation residues (Lys 65, 160, and 490) exhibited differential roles in the regulation of GRIP1 activity, and the sumoylation of Lys 490 acted as the primary nuclear localization signal of PML. While GRIP1 transactivation was stimulated to a similar degree by PML (K490R), located in the nucleus, and wild-type PML, PML (K490D) and the C-truncated mutant PML1-489 both displayed an epinuclear localization and were mostly inactive in stimulating GRIP. Based on these data, nuclear foci, nuclear localization, and the sumoylation status of Lys 490 were not essential for the enhancement of GRIP1 activity by PML, but the charge status of Lys 490 was important for subcellular localization of PML and cross-talk between its N- and C-terminal regions to modulate transcriptional activation. Taken together, these results provide insight into the regulatory mechanisms of PML that control the functional activities of GRIP1.

Effects of CAPE-like compounds on HIV replication in vitro and modulation of cytokines in vivo.

OBJECTIVES: Five CAPE-like compounds, namely caffeic acid phenethyl ester (CAPE), methyl caffeate (MC), ethyl 3-(3,4-dihydroxyphenyl)acrylate (EC), phenethyl dimethyl caffeate (PEDMC) and phenethyl 3-(4-bromophenyl)acrylic (BrCAPE) were tested for their anti-HIV replication in vitro and immune modulation effects in vivo. METHODS: Short-term cytotoxicity was assessed by Trypan Blue stain and MTT assay. For antiviral assays, M-tropic (strain JRCSF), T-tropic (strain NL-4-3) and dual tropic (strain 89.6) HIV isolates were used in peripheral blood mononuclear cell (PBMC) culture. RESULTS: None of these CAPE-like compounds showed significant cytotoxicity in the treatment of PBMCs. By P24 EIA tests, CAPE, MC and EC significantly inhibited HIV replication in PBMC cells, but PEDMC and BrCAPE showed only slightly inhibitory effects. The in vivo modulatory effects on six cytokines [interleukin (IL)-2, IL-4, IL-6, interferon (IFN)-gamma, granulocyte-macrophage colony-stimulating factor (GM-CSF) and soluble Fas] were analysed. BALB/c mice treated with different doses or not treated with these CAPE-like chemicals showed that cytokines were increased to different extents by the different treatments. However, the concentrations of IL-6 and GM-CSF were not significantly affected by administration of any of these compounds (P > 0.05). CONCLUSIONS: The different effects of treatments on anti-HIV replication and cytokine modulation suggested that these compounds affect virological and immunological response via different mechanisms. The virological and immunological mechanisms and response to these treatments need to be elaborated in further studies in order to derive the structural features of more effective compounds. Since neither death nor pathological change in the mice were observed in this study, these CAPE-like compounds are worth studying further as potential chemotherapy agents for anti-HIV infection and cytokine modulation.