PML fuses with retinoic acid receptor ␣ (RAR␣) in the t(15;17) translocation that causes acute promyelocytic leukemia (APL). In addition to localizing diffusely throughout the nucleoplasm, PML mainly resides in discrete nuclear structures known as PML oncogenic domains (PODs), which are disrupted in APL and spinocellular ataxia cells. We isolated the Fas-binding protein Daxx as a PML-interacting protein in a yeast two-hybrid screen. Biochemical and immunofluorescence analyses reveal that Daxx is a nuclear protein that interacts and colocalizes with PML in the PODs. Reporter gene assay shows that Daxx drastically represses basal transcription, likely by recruiting histone deacetylases. PML, but not its oncogenic fusion PML-RAR␣, inhibits the repressor function of Daxx. In addition, SUMO-1 modification of PML is required for sequestration of Daxx to the PODs and for efficient inhibition of Daxx-mediated transcriptional repression. Consistently, Daxx is found at condensed chromatin in cells that lack PML. These data suggest that Daxx is a novel nuclear protein bearing transcriptional repressor activity that may be regulated by interaction with PML.

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Limited information from human studies indicates that dietary quercetin supplementation influences blood lipid profiles, glycemic response, and inflammatory status, collectively termed cardiometabolic risks. We tested the hypothesis that quercetin-rich supplementation, derived from onion peel extract, improves cardiometabolic risk components in healthy male smokers in a randomized, double blinded, placebo-controlled parallel design. Randomly assigned subjects were instructed to take either the placebo (n = 43) or 100 mg quercetin capsules each day (n = 49) for 10 weeks. Anthropometric parameters and blood pressure were measured, and blood lipids, glucose, interleukin-6, and soluble vascular cell adhesion molecule-1 (sVCAM-1) were determined at baseline and after 10 weeks of quercetin supplementation. Quercetin-rich supplementation significantly reduced serum concentrations of total cholesterol (P < 0.05) and LDL-cholesterol (P < 0.01), whereas these effects were not shown in the placebo group. Furthermore, significant increases were observed in serum concentrations of HDL-cholesterol both in the placebo (P < 0.005) and quercetin-rich supplementation group (P < 0.001); however, changes in HDL-cholesterol were significantly greater in subjects receiving quercetin-rich supplementation than the placebo. Both systolic (P < 0.05) and diastolic blood pressure (P < 0.01) decreased significantly in the quercetin-rich supplementation group. Glucose concentrations decreased significantly after 10 weeks of quercetin-rich supplementation (P < 0.05). In contrast, no effects of quercetin-rich supplementation were observed for the inflammatory markers-IL-6 and sVCAM-1. Daily quercetin-rich supplementation from onion peel extract improved blood lipid profiles, glucose, and blood pressure, suggesting a beneficial role for quercetin as a preventive measure against cardiovascular risk.

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W ater-soluble conjugated polymers have been receiving increasingly greater attention owing to their potential applications in the areas of biosensing, bioimaging, and optoelectronics. For example, they have been successfully utilized in the biosensor applications to detect proteins, nucleic acids, and sugars. 1À6 These polymers can be prepared by attaching ionic side groups to the polymer backbone. However, their synthesis is tedious and their solubility is still limited in the water. Good water solubility or dispersibility of the conjugated polymers can alternatively be achieved by converting them into nanoparticles. 7À13 Such water-dispersible conjugated polymer nanoparticles (CPNs) have been exploited in different applications. For example, Landfester, Sherf, List, and coworkers have demonstrated the use of CPNs in optoelectronic applications including light-emitting diodes and photovoltaics and also as inks in inkjet printing. 14À19 Foulger and co-workers demonstrated the use of hybrid conjugated polymer nanoparticles composed of blue-and green-emitting polymers in the construction of organic light-emitting diodes (OLEDs). 20 The color tuning of the electroluminescence for the devices was achieved through energy transfer. These nanoparticles have also been used in biological applications such as fluorescent images, biosensors, and oxygen sensors. 21À27 Apart from these applications, color tuning is important for the optoelectronic applications, especially for energyefficient indoor and outdoor lighting. 28,29 Water-dispersible conjugated polymer nanoparticles can be prepared mainly by two methods, which are miniemulsion and reprecipitation. In the miniemulsion method, a two-phase system (oil-in-water) is used. 7,8 The polymer is dissolved in an organic solvent, which is not miscible with water, and added into a surfactant containing aqueous solution while sonicating. After the nanoparticle formation, the organic solvent is evaporated off to leave behind the conjugated nanoparticles stabilized by the surfactant. In the reprecipitation method, the polymer is dissolved in an organic * Address correspondence to dtuncel@fen.bilkent.edu.tr, volkan@bilkent.edu.tr.Received for review July 9, 2010 and accepted March 28, 2011. Published online 10.1021/nn103598qABSTRACT We report on the synthesis and characterization of water-dispersible, mechanically stable conjugated polymer nanoparticles (CPNs) in shelled architecture with tunable emission and controllable photometric properties via cross-linking. Using a reprecipitation method, whiteemitting polymer nanoparticles are prepared in different sizes by varying the concentration of polymer; the emission kinetics are tuned by controlling the shell formation. For this purpose, polyfluorene derivatives containing azide groups are selected that can be decomposed under UV light to generate very reactive species, which opportunely facilitate the inter-and intra-cross-linking of polymer chains to form shells. Nanoparticles before and after UV treatment are characterized by v...

Poly(ethylene glycol) methacrylate-based hydrogels containing thiol reactive maleimide functional groups have been synthesized using a novel Diels-Alder cycloaddition/cycloreversion-based strategy. Masked maleimide groups are directly incorporated into the hydrogel matrix during the gelation process by utilization of a furan protected maleimide containing methacrylate monomer. During the polymerization, the thermal deprotection of the maleimide groups in some of the monomer results in the formation of an in situ cross-linker that results in gelation. After gelation, the protected maleimide groups can be activated to their reactive forms via a thermal cycloreversion step. The efficiency of the gel formation, maleimide incorporation, and functionalization of the hydrogel were investigated. These reactive maleimide group embedded hydrogels can be efficiently derivatized with thiol containing molecules such as a fluorescent dye, BodipyC10SH. Thiolated biotin derivatives were covalently attached to these hydrogels under mild, reagent-free conditions. It was found that the extent of immobilization of FITC-streptavidin onto these biotinylated gels can be tailored by varying the density of maleimide groups in the parent hydrogels.

The free radical scavenging activity of water soluble natural antioxidants from Sargassum thunbergii, which is a brown marine alga, was evaluated by examining the radical scavenging activities of the extracts of hydrolyzates from S. thunbergii on hydroxyl, 1,1-diphenyl-2-picrylhydrazyl (DPPH), and alkyl radicals. A spin-trapping electron spin resonance (ESR) spectrometer was employed, and the results were compared for their ESR signal intensity. S. thunbergii was enzymatically hydrolyzed to prepare water soluble extracts by five carbohydrases (AMG, Celluclast, Termamyl, Ultraflo, and Viscozyme) and proteases (Alcalase, Flavorzyme, Kojizyme, Neutrase, and Protamex). The scavenging activity of the radicals increased with increased concentrations of the extracts. The scavenging results were higher for hydroxyl and alkyl radicals and lower for DPPH radical as compared with vitamin C as a reference. The hydrogen peroxide scavenging activity of the extracts was also investigated; the Alcalase extract showed the highest scavenging activity among the extracts prepared with the five proteases and five carbohydrates. In addition, the DNA damage was determined by using the comet assay with alkaline electrophoresis and was quantified by measuring the tail length. The preventive effect of Alcalase extract from S. thunbergii against DNA damage increased with increments of concentration of the enzymatic extracts.

The cytotoxic and antitumor activity of methanolic extract of rice hulls (MERH) were evaluated by the MTT-dye reduction assay against human colon cancer cells and the colonic aberrant crypt foci (ACF) assay in 1,2-dimethylhydrazine (DMH)-injected F344 male rats, respectively. MERH was found to be highly cytotoxic, with IC50 values of 0.5 microg/mL in vitro. Forty weeks of MERH supplementation (50 mg/kg of body weight/day) reduced colonic pre-neoplastic ACF formation by 35% (p < 0.01). An active compound, momilactone B, was isolated from MERH by silica gel chromatography, Sephadex LH-20 chromatography, and HPLC. The cytotoxic activity of momilactone B was evaluated by the MTT-dye reduction, lactate dehydrogenase (LDH), and colony-forming ability assays in human colon cancer HT-29 and SW620 cells. The results indicated that momilactone B from rice hulls might be a new candidate for chemotherapeutic agent against human colon cancer.