• Title/Summary/Keyword: PAK4

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cAMP Response Element-Binding Protein- and Phosphorylation-Dependent Regulation of Tyrosine Hydroxylase by PAK4: Implications for Dopamine Replacement Therapy

  • Won, So-Yoon;You, Soon-Tae;Choi, Seung-Won;McLean, Catriona;Shin, Eun-Young;Kim, Eung-Gook
    • Molecules and Cells
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    • v.44 no.7
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    • pp.493-499
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    • 2021
  • Parkinson's disease (PD) is characterized by a progressive loss of dopamine-producing neurons in the midbrain, which results in decreased dopamine levels accompanied by movement symptoms. Oral administration of l-3,4-dihydroxyphenylalanine (L-dopa), the precursor of dopamine, provides initial symptomatic relief, but abnormal involuntary movements develop later. A deeper understanding of the regulatory mechanisms underlying dopamine homeostasis is thus critically needed for the development of a successful treatment. Here, we show that p21-activated kinase 4 (PAK4) controls dopamine levels. Constitutively active PAK4 (caPAK4) stimulated transcription of tyrosine hydroxylase (TH) via the cAMP response element-binding protein (CREB) transcription factor. Moreover, caPAK4 increased the catalytic activity of TH through its phosphorylation of S40, which is essential for TH activation. Consistent with this result, in human midbrain tissues, we observed a strong correlation between phosphorylated PAK4S474, which represents PAK4 activity, and phosphorylated THS40, which reflects their enzymatic activity. Our findings suggest that targeting the PAK4 signaling pathways to restore dopamine levels may provide a new therapeutic approach in PD.

Molecular Docking Studies of p21-Activated Kinase-1 (PAK1) Inhibitors

  • Balupuri, Anand;Balasubramanian, Pavithra K.;Cho, Seung Joo
    • Journal of Integrative Natural Science
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    • v.9 no.3
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    • pp.161-165
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    • 2016
  • The p21-activated kinase-1 (PAK1) has emerged as a potential target for anticancer therapy. It is overexpressed in ovarian, breast and bladder cancers. This suggests that PAK1 may contribute to tumorigenesis. 4-azaindole derivatives are reported as potent PAK1 inhibitors. The present work deals with the molecular docking studies of 4-azaindoles with PAK1. Probable binding mode of these inhibitors has been identified by molecular modeling. Docking results indicated that hydrogen bonding interactions with Glu345 and Leu347 are responsible for governing inhibitor potency of the compounds. Additionally, Val284, Val328, Met344 and Leu396 were found to be accountable for hydrophobic interactions inside the active site of PAK1.

Efficiency in the Password-based Authenticated Key Exchange (패스워드 기반 인증 키 공유 프로토콜에서의 효율성)

  • 황정연;홍석희;박혜영;장상운;박영호;류희수
    • Journal of the Korea Institute of Information Security & Cryptology
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    • v.12 no.6
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    • pp.113-124
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    • 2002
  • Proposals for a password-based authenticated key exchange protocol that have been published so far almost concentrated on the provable security. But in a real environment such as mobile one, efficiency is a critical issue as security. In this paper we discuss the efficiency of PAK which is secure in the random oracle model [l]. Among 4 hash functions in PAK the instantiation for $H_1$, which outputs a verifier of the password, has most important effect on the computational efficiency. We analyze two different methods for $H_1$ suggested in [1] and we show that $H_{lq}$ has merits in transforming to EC or XTR variants as well as in the efficiency. As an efficient variant. we propose PAK2-EC and PAK2-XTR which do not require any additional step converting a hash output into a point of elliptic curve or XTR subgroup when compared to the previous work on the PAK[2]. Finally we compare PAK2 with the password-based authenticated key exchange protocols such as SPEKE, SRP, and AMP.

Large Scale Purification of KRF-001 on the Preparative HPLC (Preparative HPLC를 이용한 KRF-001의 대량분리정제)

  • 이항우;김무경정태숙복성해
    • KSBB Journal
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    • v.9 no.4
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    • pp.385-394
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    • 1994
  • Large scale purification to get antifungal antibiotic KRF-001 of 90% purity, was investigated using preparative HPLC. Crude KRF-001 was purified by XAD-7 adsorption chromatography, acid precipitation and microfiltration. Microfiltration was the most effective isolation method of crude KRF-001. The purification methods using C18 chromatography was convenient compared with the conventional methods. Delta PAK C18 column and Bonda PAK C18 column were adapted large scale purification of KRF-001. Gradient system of prep HPLC using Delta PAK C18 column was more effective. With these conditions, final recovery of KRF-001 yielded 77%.

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Rapid Preparation and Quality Control of $^{99m}Tc$-ECD, $MAG_3$ and MIBI using Microwave Heating and Sep-Pak Cartridges (마이크로웨이브와 Sep-Pak 카트리지를 이용한 $^{99m}Tc$-ECD, $MAG_3$, MIBI의 신속한 제조 및 정도관리)

  • Oh, Seung-Jun;Moon, Dae-Hyuk;Ryu, Jin-Sook;Lee, Hee-Kyung
    • The Korean Journal of Nuclear Medicine
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    • v.33 no.4
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    • pp.430-438
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    • 1999
  • Purpose: We evaluated a rapid preparation procedures for the labeling and quality control of $^{99m}Tc$-ECD, $MAG_3$, and MIBI using microwave heating and Sep-Pak cartridges. Materials and Methods: $^{99m}Tc$ labeling of ECD, $MAG_3$, and MIBI kit preparation was performed according to the package inserts with microwave heating modification. Heating time was 10-15 sec, and heating was performed with 3 mm plastic bottle with screw cap to prevent radiation contamination. Labeling efficiency was obtained with $C_{18}$ or Alumina N Sep-Pak cartridges. Results: The radiochemical purity of $93{\sim}96%$ for $^{99m}Tc$-ECD and $95{\sim}99%$ for $^{99m}Tc$-MIBI was obtained using Alumina N Sep-Pak cartridge. The optimum irradiation time of microwave method for 3 ml $^{99m}Tc$-labeled radiopharmaceutical solution was 10 sec for $^{99m}Tc$-ECD and $^{99m}Tc$-MIBI, and 15 sec for $^{99m}Tc-MAG_3$. The results of quality control data with Sep-Pak cartridges were well correlated with TLC method. The total preparation time of these radiopharmcaeuticals was $5{\sim}6min$ including quality control procedure. Conclusion: This study demonstrates that radiopharmaceuticals preparation by microwave heating and quality control by Sep-Pak cartridges can be efficiently utilized as an alternative to the recommended method by manufacturer's manual.

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Effect of Combined Treatment of Aqueous Chlorine Dioxide with Ultraviolet-C on the Quality of Red Chicory and Pak Choi during Storage (이산화염소수와 Ultraviolet-C 병합 처리에 따른 레드 치커리와 청경채의 저장 중 품질에 미치는 영향)

  • Kim, Hyun-Jin;Song, Hyeon-Jeong;Song, Kyung-Bin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.40 no.2
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    • pp.245-252
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    • 2011
  • The combined effects of 10 kJ/$m^2$ ultraviolet-C (UV-C) with 50 ppm aqueous chlorine dioxide ($ClO_2$) on the qualities of red chicory and pak choi were examined. After the treatment, the samples were stored at $4{\pm}1^{\circ}C$ for 7 days. The combined treatment of $ClO_2$/UV-C reduced the initial populations of total aerobic bacteria in the red chicory and pak choi by 2.64 and 2.55 log CFU/g, respectively, compared to those of the control. Also, the populations of yeast and molds in the red chicory and pak choi by combined treatment were reduced by 2.41 and 2.00 log CFU/g, respectively. In addition, after 7 days of storage the total aerobic bacteria populations in the red chicory and pak choi were reduced to 3.71 and 3.93 log CFU/g, compared to 6.31 and 6.62 log CFU/g for the control, resulting in a significant decrease. Hunter L, a, and b values of red chicory and pak choi were not significantly different among the treatments. Non-thermal treatment caused a negligible change in sensory evaluation. These results suggest that the combined treatment of 50 ppm $ClO_2$ with 10 kJ/$m^2$ UV-C can be useful for maintaining the qualities of red chicory and pak choi.

Effect of Nutrient Solution Composition Modification on the Internal Quality of Some Leaf Vegetables in Hydroponics (수경재배시 양액 조성 처리가 몇가지 엽채류의 내적 품질에 미치는 영향)

  • Kang, Ho-Min;Kim, Il-Seop
    • Journal of Bio-Environment Control
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    • v.16 no.4
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    • pp.348-351
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    • 2007
  • This study was conducted to find out the change of infernal quality, such as vitamin C and nitrate contents in some leaf vegetables grown hydropoincally in different nutrient conditions. Pak-choi (Brassica camperistis L. spp. chinesis Jusl.), chungchima (Lactuca sativa L. var. crispa cv. Chungchima) and romaine (Lactuca sativa L. var. longifolia Lam.) lettuces were cultivated for 2 weeks in 4 different nutrient solutions, such as tap water; no-nutrient, added $NH_4$, discarded $NO_3$, and supplied Yamazaki' solution for lettuce as a control. The growth of leaf vegetables was not different among nutrient solution treatments except tap water. The nitrate content showed the highest in control, and followed by $+NH_4$ treatment, $-NO_3$ and tap water treatment, regardless of kind of vegetables. The vitamin C content in 3 different vegetables showed the opposite result against nitrate content so that the treatment that showing the highest vitamin C content was tap water in romaine and chungchima lettuces, and $-NO_3$ treatment in pak-choi. The vitamin C and the nitrate content showed high correlations; $r=-0.614^*$ in pak-choi, $-0.651^*$ in romaine lettuce, and $-0.804^{**}$ in chungchima lettuce.

The Clinical Significance of STAT-PAK ULTRA FAST$^{(R)}$ and ICT Tuberculosis$^{(R)}$ for Serologic Diagnosis of Tuberculosis (폐결핵 진단을 위한 STAT-PAK ULTRA FAST$^{(R)}$와 ICT Tuberculosis$^{(R)}$의 유용성에 관한 연구)

  • Kim, Geun-Hwa;Park, Hee-Sun;Kim, Myung-Hoon;Kang, Dong-Won;Lee, Kyu-Seung;Ko, Dong-Seok;Suh, Jae-Chul;Jeong, Seong-Su;Kim, Ju-Ock;Kim, Sun-Young
    • Tuberculosis and Respiratory Diseases
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    • v.47 no.3
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    • pp.311-320
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    • 1999
  • Background: In recent years, tuberculosis has re-emerged as a major health problem in both industrialized & developing countries. Recent advances in identifying & purifying antigens secreted in active tuberculosis infection have lead to the development of serological assays based on a number of immunodominant antigens. To date, the most sensitive and specific of these antigens has been the 38-kDa antigen. Method: Two rapid membrane-based serologic assays using antigen(38-kDa) from mycobacterium tuberculosis for the diagnosis of tuberculosis were evaluated in 22 patients with smear-positive pulmonary tuberculosis, 14 patients with inactive pulmonary tuberculosis, and 9 patients with non-tuberculous lung disease. Result: The evaluation of validity(sensitivity, specificity, positive predictive value, negative predictive value, false positivity and false negativity) of STAT-PAK ULTRA FAST$^{(R)}$ were 77.3%, 28.6%, 63.0%, 44.4%, 71.4 %, and 22.7% for differential diagnosis of active pulmonary tuberculosis and inactive pulmonary tuberculosis, respectively. The evaluation of validity of STAT-PAK ULTRA FAST$^{(R)}$ were 77.3%, 33.3%, 73.9%, 37.5%, 66.7%, and 22.7% for differential diagnosis of active pulmonary tuberculosis and non-tuberculosis. The evaluation of validity of ICT Tuberculosis$^{(R)}$ were 54.5%, 57%, 66.7%, 44.4%, 42.9%, and 45.5% for differential diagnosis of active pulmonary tuberculosis and inactive pulmonary tuberculosis. The evaluation of validity of ICT Tuberculosis$^{(R)}$ were 54.5%, 100%, 100%, 47.4%, 0%, and 45.4% for differential diagnosis of active pulmonary tuberculosis and non-tuberculosis. Conclusion: We concluded no effectiveness of STAT-PAK ULTRA FAST$^{(R)}$ & ICT tuberculosis$^{(R)}$on serologic diagnosis of pulmonary tuberculosis. In the future, further large-scale study should be needed for serologic diagnosis of pulmonary tuberculosis.

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Influence of Varied Pre-planting N Levels in a Medium on the Growth of Chinese Cabbage and Pak-choi Seedlings in Paper Pot Raising (종이포트 육묘시 기비로 혼합된 질소 시비수준이 배추와 청경채 생장에 미치는 영향)

  • Kim, Hyun Cheul;Park, Myong Sun;Jang, Yoonah;An, Sewoong;Choi, Jong Myung
    • Journal of Bio-Environment Control
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    • v.28 no.4
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    • pp.342-351
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    • 2019
  • The optimum N concentrations incorporated as pre-planting nutrient charge fertilizer were determined for seedling raising using cylindrical paper pots. A root medium was formulated by blending of peat moss (particles smaller than 2.84 mm were 80-90%) and perlite (1 to 3 mm) with the ratio of 7:3 (v/v). The treatment N concentrations incorporated during the root medium formulation were adjusted to 0, 150, 250, 500, and $750mg{\cdot}L^{-1}$ and the concentrations of essential nutrients except N were equal in all treatments. After making of paper pots and putting into the 40-cell tray, the seeds of Chinese cabbage ('Chunmyeong Bom Baechu') and pak-choi ('Hanog cheonggyeongchae') were sown. During the raising of seedlings, weekly analysis of medium pH, EC and concentrations of inorganic elements were conducted. After 21 and 20 days after seed sowing of Chinese cabbage and pak-choi, the growth of the above-ground parts were measured and contents of inorganic elements in the plant tissues were analyzed. During the growing period, pH of the root media rose gradually and the EC decreased rapidly at week 3. The pH of root media at harvest was in the range of 5.3 to 5.9 in Chinese cabbage and 4.93 to 5.39 in pak-choi. Growth of the aboveground parts in terms of fresh and dry weight in both the plants were the highest in the $250mg{\cdot}L^{-1}$ N treatment and the lowest in the control treatment. The elevation of pre-planting N concentrations in root medium resulted in the increase of tissue N content and decrease of P, Ca, and Mg contents. The regression equation derived from the influence of varied pre-planting N concentrations on dry weight of above-ground tissue were $y=-0.0036x^2+0.0021x+0.0635$ ($R^2=0.9826$) in Chinese cabbage and $y=-0.16x^2+0.0009x+0.032$ ($R^2=0.991$) in pak-choi. When the low critical concentration of pre-plant N is taken at the point where dry weight of above-ground tissue is 10% less than maximum (0.40 g in Chinese cabbage and 0.16 g in pak-choi), those point are 0.36 g and 0.144 g per plant in Chinese cabbage and pak-choi, respectively. The lower critical N concentrations of root media calculated from the regression equations are $196mg{\cdot}L^{-1}$ for Chinese cabbage and $187mg{\cdot}L^{-1}$ for pak-choi. These results indicate that optimum pre-plant N concentrations for seedling raising using paper pots are in the range of 196 to $250mg{\cdot}L^{-1}$ for Chinese cabbage and 187 to $250mg{\cdot}L^{-1}$ for pak-choi.