• Title/Summary/Keyword: beta type

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Cloning and Analysis of a Type II Polyketide Synthase Gene Cluster from Streptomyces toxytricini NRRL 15,443

  • Yoo An-Na;Demirev Atanas V.;Lee, Ji-Seon;Kim, Sang-Dal;Nam Doo-Hyun
    • Journal of Microbiology
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    • v.44 no.6
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    • pp.649-654
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    • 2006
  • A standard type II polyketide synthase (PKS) gene cluster was isolated while attempting to clone the biosynthetic gene for lipstatin from Streptomyces toxytricini NRRL 15,443. This result was observed using a Southern blot of a PstI-digested S. toxytricini chromosomal DNA library with a 444 bp amplified probe of a ketosynthase (KS) gene fragment. Four open reading frames [thioesterase (TE), $\beta$-ketoacyl systhase (KAS), chain length factor (CLF), and acyl carrier protein (ACP)], were identified through the nucleotide sequence determination and analysis of a 4.5 kb cloned DNA fragment. In order to confirm the involvement of a cloned gene in lipstatin biosynthesis, a gene disruption experiment for the KS gene was performed. However, the resulting gene disruptant did not show any significant difference in lipstatin production when compared to wild-type S. toxytricini. This result suggests that lipstatin may not be synthesized by a type II PKS.

A Kinetic Study on Michael-type Reactions of 1-(X-Substituted Phenyl)-2-propyn-1-ones with Amines: Effect of Amine Nature on Reactivity and Mechanism

  • Um, Ik-Hwan;Hwang, So-Jeong;Lee, Eun-Ju
    • Bulletin of the Korean Chemical Society
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    • v.29 no.4
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    • pp.767-771
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    • 2008
  • Second-order rate constants have been measured spectrophotometrically for the Michael-type reaction of 1-(Xsubstituted phenyl)-2-propyn-1-ones (2a-f) with amines in $H_2O$ at 25.0 ${\pm}$ 0.1 ${^{\circ}C}$. A linear Brønsted-type plot is obtained with ${\beta}_{nuc}$ = 0.25 ${\pm}$ 0.02, a typical $\beta_{nuc}$ value for reactions which proceed through a stepwise mechanism with attack of amine on the electrophilic center being the rate-determining step. Secondary alicyclic amines are found to be more reactive than isobasic primary amines. The Hammett plot for the reactions of 2a-f with morpholine is not linear, i.e., the substrate with a strong electron-donating group (e.g., 4-MeO) exhibits a negative deviation from the Hammett plot. However, the Yukawa-Tsuno plot for the same reactions exhibits an excellent linear correlation with ρ = 0.62 and r = 0.82. Thus, it has been proposed that the nonlinear Hammett plot is not due to a change in the ra te-determining step but due to ground-state stabilization through resonance interactions.

Expression of β-arrestin 1 in Gastric Cardiac Adenocarcinoma and its Relation with Progression

  • Wang, Li-Guang;Su, Ben-Hua;Du, Jia-Jun
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5671-5675
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    • 2012
  • Objective: Arrestins act as mediators of G protein-coupled receptor (GPCR) desensitization and trafficking, also actin as a scaffold for many intracellular signaling network. The role that ${\beta}$-arrestin 1 plays in gastric cardiac adenocarcinoma (GCA) and its clinicopathologic significance are untouched. Methods: Fifty patients with gastric cardiac adenocarcinoma were retrospectively enrolled and ${\beta}$-arrestin 1 was detected using immunohistochemistry in tissue samples. Results: Nuclear expression of ${\beta}$-arrestin 1 was observed in 78% of GCA samples (39/50) and cytoplasmic expression in 70% (35/50). ${\beta}$-arrestin 1 could be found in both nucleus and cytoplasm of 54% GCA (27/50) or in either of them in 94% (47/50). ${\beta}$-arrestin 1 protein positivity in well/moderately differentiated carcinomas was significantly higher than that in poorly differentiated carcinomas (P=0.005). We found increased expression of ${\beta}$-arrestin 1 in cytoplasm was correlated with lymph nodal metastasis (P=0.002) and pathological lymph nodal staging (P=0.030). We also found ${\beta}$-arrestin 1 to be over-expressed in glandular epithelia cells of mucinous adenocarcinoma, a tumour type associated with an adverse outcome of gastric cardiac adenocarcinoma (P=0.022). Conclusion: ${\beta}$-arrestin 1 is over-expressed in the nucleus and/or cytoplasm of gastric cardiac adenocarcinoma. However, ${\beta}$-arrestin 1 has no relationship with the prognosis of gastric cardiac adenocarcinoma (P>0.05). Our data imply that ${\beta}$-arrestin 1 in cytoplasm may be involved in differentiation and metastasis of gastric cardiac adenocarcinoma.

Interaction Models of Substrate Peptides and β-Secretase Studied by NMR Spectroscopy and Molecular Dynamics Simulation

  • Lee, Jee-Young;Lee, Sung-Ah;Kim, Jin-Kyoung;Chae, Chi-Bom;Kim, Yangmee
    • Molecules and Cells
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    • v.27 no.6
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    • pp.651-656
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    • 2009
  • The formation of ${\beta}$-amyloid peptide ($A{\beta}$) is initiated from cleavage of amyloid precursor protein (APP) by a family of protease, ${\alpha}$-, ${\beta}$-, and ${\gamma}$-secretase. Sub W, a substrate peptide, consists of 10 amino acids, which are adjacent to the ${\beta}$-cleavage site of wild-type APP, and Sub M is Swedish mutant with double mutations on the left side of the ${\beta}$-cleavage site of APP. Sub W is a normal product of the metabolism of APP in the secretary pathway. Sub M is known to increase the efficiency of ${\beta}$-secretase activity, resulting in a more specific binding model compared to Sub W. Three-dimensional structures of Sub W and Sub M were studied by CD and NMR spectroscopy in water solution. On the basis of these structures, interaction models of ${\beta}$-secretase and substrate peptides were determined by molecular dynamics simulation. Four hydrogen bonds and one water-mediated interaction were formed in the docking models. In particular, the hydrogen bonding network of Sub M-BACE formed spread over the broad region of the active site of ${\beta}$-secretase (P5-P3'), and the side chain of P2- Asn formed a hydrogen bond specifically with the side chain of Arg235. These are more favorable to the cleavage of Sub M by ${\beta}$-secretase than Sub W. The two substrate peptides showed different tendency to bind to ${\beta}$-secretase and this information may useful for drug development to treat and prevent Alzheimer's disease.

Enhancement of radiation effect using beta-lapachone and underlying mechanism

  • Ahn, Ki Jung;Lee, Hyung Sik;Bai, Se Kyung;Song, Chang Won
    • Radiation Oncology Journal
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    • v.31 no.2
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    • pp.57-65
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    • 2013
  • Beta-lapachone (${\beta}$-Lap; 3,4-dihydro-2, 2-dimethyl-2H-naphthol[1, 2-b]pyran-5,6-dione) is a novel anti-cancer drug under phase I/II clinical trials. ${\beta}$-Lap has been demonstrated to cause apoptotic and necrotic death in a variety of human cancer cells in vitro and in vivo. The mechanisms underlying the ${\beta}$-Lap toxicity against cancer cells has been controversial. The most recent view is that ${\beta}$-Lap, which is a quinone compound, undergoes two-electron reduction to hydroquinone form utilizing NAD(P)H or NADH as electron source. This two-electron reduction of ${\beta}$-Lap is mediated by NAD(P)H:quinone oxidoreductase (NQO1), which is known to mediate the reduction of many quinone compounds. The hydroquinone forms of ${\beta}$-Lap then spontaneously oxidizes back to the original oxidized ${\beta}$-Lap, creating futile cycling between the oxidized and reduced forms of ${\beta}$-Lap. It is proposed that the futile recycling between oxidized and reduced forms of ${\beta}$-Lap leads to two distinct cell death pathways. First one is that the two-electron reduced ${\beta}$-Lap is converted first to one-electron reduced ${\beta}$-Lap, i.e., semiquinone ${\beta}$-Lap $(SQ)^{{\cdot}-}$ causing production of reactive oxygen species (ROS), which then causes apoptotic cell death. The second mechanism is that severe depletion of NAD(P)H and NADH as a result of futile cycling between the quinone and hydroquinone forms of ${\beta}$-Lap causes severe disturbance in cellular metabolism leading to apoptosis and necrosis. The relative importance of the aforementioned two mechanisms, i.e., generation of ROS or depletion of NAD(P)H/NADH, may vary depending on cell type and environment. Importantly, the NQO1 level in cancer cells has been found to be higher than that in normal cells indicating that ${\beta}$-Lap may be preferentially toxic to cancer cells relative to non-cancer cells. The cellular level of NQO1 has been found to be significantly increased by divergent physical and chemical stresses including ionizing radiation. Recent reports clearly demonstrated that ${\beta}$-Lap and ionizing radiation kill cancer cells in a synergistic manner. Indications are that irradiation of cancer cells causes long-lasting elevation of NQO1, thereby sensitizing the cells to ${\beta}$-Lap. In addition, ${\beta}$-Lap has been shown to inhibit the repair of sublethal radiation damage. Treating experimental tumors growing in the legs of mice with irradiation and intraperitoneal injection of ${\beta}$-Lap suppressed the growth of the tumors in a manner more than additive. Collectively, ${\beta}$-Lap is a potentially useful anti-cancer drug, particularly in combination with radiotherapy.

Fine Structure of the Integumentary Cuticle and Epidermis of Perinereis aibuhitensis (Polychaeta: Nereidae) (두토막눈썹참갯지렁이 (Perinereis aibuhitensis) 피부계의 미세구조)

  • LEE Jung Sick;LIM Hyun-Sig
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.33 no.3
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    • pp.257-261
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    • 2000
  • Integumentary system of the polychaete, Perinezeis aibuhitensis was consisted cuticular, epidermal and dermal layers. Excretory pores opened in cuticular layer, which is covered with epicuticular projections. The hemidesmosomes were observed between supporting cell and basal area of cuticular layer. The epidermal layer was consisted supporting cells and unicellular glands. Supporting cell was relatively larger than the other neighbouring cells, and the nucleus had one to two nucleolus. Cytoplasm of the supporting cell had well-developed intracellular organs such as tonofilaments, mitochondria, rough endoplasmic reticula, free ribosomes and pigment granules of electron dense. The gland cells were reacted with blue in AB-PAS, and classified into the three types such as ${\alpha},\;{\beta}\;and\;{\gamma}$ from the transmission electron microscopic observation. Type ${\alpha}$ gland cell was ovoid and the cytoplasm had well-developed tonofilaments and membrane bounded secretory granules of $0.8{\~}1.5 {\mu}m$ in diameter. Type ${\beta}$ gland cell had a large vacuole and secretory granules of $0.5{\~}0.8 {\mu}m$, which scattered evenly in the cytoplasm. Type ${\gamma}$ gland cell had well-developed endoplasmic reticulum, Golgi auparatus and secretory granules of $0.2{\~}0.3 {\mu}m$ in diameter. The electron density of this granules was the highest among the granules.

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Weight control behavior in women college students and factors influencing behavior (일부 여대생의 체중조절행위와 영향 요인)

  • Yang, Hyun-Young;Byeon, Young-Soon
    • Journal of Korean Academy of Fundamentals of Nursing
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    • v.19 no.2
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    • pp.190-200
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    • 2012
  • Purpose: The purpose of this study was to provide basic data for the development of weight control programs to maintain and promote healthy behavior in women college students by identifying their weight control behaviors and factors that influence these behaviors. Method: Data were collected from 300 women student participants and were analyzed using descriptive statistics, t-test, ANOVA, Pearson correlation coefficients, and multiple regression with the SPSS 18.0 program. Result: Weight control behavior showed a significant difference according to participants' gender role identity type. Weight control behaviors were correlated with self-efficacy, body image, objective BMI, and ideal BMI. Factors influencing weight control behavior were self-efficacy (${\beta}$= .449, $p$<.001), secret method for weight loss (${\beta}$= .181, $p$<.001), monthly allowance below 200,000 won (${\beta}$= .156, $p$= .006), weight control support from others (${\beta}$= .124, $p$= .013), eating breakfast (${\beta}$= .119, $p$= .015), and age (${\beta}$= .113, $p$= .023) with R-sq. value of 45.3%. Conclusion: The results of the study indicate that development of interventions for weight control behavior and health education for college women should reflect identified factors influencing weight control behavior and gender role identity.