Construction of dextrin and isomaltose-assimilating brewer's yeasts for production of low-carbohydrate beer.

Most Saccharomyces spp. cannot degrade or ferment dextrin, which is the second most abundant carbohydrate in wort for commercial beer production. Dextrin-degrading brewer's bottom and top yeasts expressing the glucoamylase gene (GAM1) from Debaryomyces occidentalis were developed to produce low-carbohydrate (calorie) beers. GAM1 was constitutively expressed in brewer's yeasts using a rDNA-integration system that contained yeast CUP1 gene coding for copper resistance as a selective marker. The recombinants secreted active glucoamylase, displaying both α-1,4- and α-1,6-debranching activities, that degraded dextrin and isomaltose and consequently grew using them as sole carbon source. One of the recombinant strains expressing GAM1 hydrolyzed 96 % of 2 % (w/v) dextrin and 98 % of 2 % (w/v) isomaltose within 5 days of growth. Growth, substrate assimilation, and enzyme activity of these strains were characterized.

T-type Ca2+ channel blocker, KYS05047 induces G1 phase cell cycle arrest by decreasing intracellular Ca2+ levels in human lung adenocarcinoma A549 cells.

In a previous study, we found that the 3,4-dihydroquinazoline derivative, 4-(Benzylcarbamoylmethyl)-2-(biphenyl-4-ylamino)-3-(5-tert-butyloxycarbamoyl-1-pentyl)-3,4-dihydroquinazoline (KYS05047), was a selective T-type Ca(2+) channel blocker with anti-proliferative effects against various cancer cells. However, the mechanism responsible for its effects has not been studied. In this study, we investigated the effect of KYS05047 on cell cycle arrest and the mechanisms involved in human lung adenocarcinoma A549 cells. Among the G(1) phase cell cycle-related proteins examined, the levels of cyclin-dependent protein kinase (Cdk2) and Cdk4 were reduced by KYS05047 (7 µM), whereas the steady-state levels of cyclin D1 and E were unaffected. In addition, KYS05047 increased the protein level of p27(KIP1) and suppressed the kinase activities of Cdk2 and Cdk4. In addition, pretreatment with KCl, which increases intracellular Ca(2+) levels, prevented KYS05047-induced intracellular Ca(2+) decreases and cell cycle arrest. Furthermore, the administration of KYS05047 (2 or 10 mg/kg, po) for 21 days was also found to significantly inhibit tumor growth in an A549 xenograft nude mice model. In conclusion, our results suggested that KYS05047 induced G(1) phase cell cycle arrest in A549 cells associated with a decrease in intracellular Ca(2+) concentrations and inhibited the in vivo tumor growth of A549 xenograft mice.

In vivo evaluation of oral anti-tumoral effect of 3,4-dihydroquinazoline derivative on solid tumor.

An extension of our previously reported 3,4-dihydroquinazoline derivative is investigated. Oral anti-tumoral activity of 3,4-dihydroquinazoline derivative (KYS05090) as potent and selective T-type calcium channel blocker was in vivo evaluated against A549 xenograft in BALB/c(nu/nu) nude mice. The rate of tumor volume increment in mouse model with KYS05090-treated group was remarkably slower than that of control group. With respect to tumor weight, it exhibited 60% and 67% tumor growth inhibition through oral administration of 1 and 5mg/kg of bodyweight, respectively, compared to control and was more potent than paclitaxel (53%). In addition, KYS05090 (10 and 50mg/kg, po) was found to have a marked analgesic effect in acetic acid-induced writhing test, whereas it did not show any effect on hot plate test.

3D QSAR studies on 3,4-dihydroquinazolines as T-type calcium channel blocker by comparative molecular similarity indices analysis (CoMSIA).

A comparative molecular similarity indices analysis (CoMSIA) of a set of 42 3,4-dihydroquinazolines have been performed to find out the pharmacophore elements for T-type calcium channel blocking activity. The most potent compound, 33 (KYS05090) was used to align the molecules. As a result, we obtained 3D QSAR model which provided good predictivity for the training set (q(2)=0.642, r(2)=0.874) and the test set (r(pred)(2)=0.884). This model would guide the design of new chemical entities potentially having high potency.

Highly stretchable polymer-dispersed liquid crystal-based smart windows with transparent and stretchable hybrid electrodes.

We report on highly stretchable polymer dispersed liquid crystal (PDLC)-based smart windows using Ag nanowires (NWs) and conductive PEDOT:PSS hybrid electrodes. By bar coating a Ag NW and PEDOT:PSS mixed ink on a transparent and stretchable polyurethane (PU) substrate, we fabricated highly transparent and stretchable hybrid electrodes with a sheet resistance of 40 ohm per square, an optical transmittance of 82%, and a stretchability of 30% to replace conventional brittle ITO electrode. Bending and stretching tests demonstrated that the mechanical properties of the Ag NW and PEDOT:PSS hybrid electrode were better than those of the ITO/PU sample. The Ag NW/PEDOT:PSS hybrid film was employed as a transparent and stretchable electrode (TSE) in PDLC-based stretchable smart windows, an application that is impossible for brittle ITO-based smart windows. The stretchable PDLC-based smart windows exhibited an on-state transmittance of 56% at an applied voltage of 80 V and an off-state transmittance of 2% at 0 voltage. Unlike an ITO-based PDLC smart window, which is easily broken by stretching, the Ag NW/PEDOT:PSS hybrid electrode-based PDLC smart window was stretched up to 30%. Successful operation of the stretchable PDLC-based smart window indicates that Ag NW/PEDOT:PSS hybrid films are promising TSEs for cost-effective, large area, and stretchable smart windows.