• Title/Summary/Keyword: Induced resistance

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Phenotypic Suppression of Rad53 Mutation by CYC8 (CYC8에 의한 rad53 돌연변이의 표현형 억제에 대한 연구)

  • Park, Kyoung-Jun;Choi, Do-Hee;Kwon, Sung-Hun;Kim, Joon-Ho;Bae, Sung-Ho
    • Korean Journal of Microbiology
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    • v.46 no.2
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    • pp.122-126
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    • 2010
  • RAD53 functions as an effector kinase of checkpoint pathways in Saccharomyces cerevisiae, which plays a central role to regulate many downstream cellular processes in response to DNA damage. It also involves in transcriptional activation of various genes including RNR genes which encode the key enzyme required for dNTP synthesis. In this study, we identified CYC8 as a suppressor for the hydroxyurea sensitivity of $rad53{\Delta}$ mutation. $Rad53{\Delta}$ mutant transformed with a multi-copy plasmid containing CYC8 showed increased hydroxyurea resistance. In contrast, TUP1 which forms a complex with CYC8 did not function as a suppressor. In the case of mutations, both $cyc8{\Delta}$ and $tup1{\Delta}$ suppressed hydroxyurea sensitivity of $rad53{\Delta}$. Since CYC8 can propagate as a prion in yeast, overexpression of CYC8 induced misfolding of the normal CYC8 proteins, resulting in dominant cyc8-phenotype. Therefore, it is suggested that CYC8 can act as a multi-copy suppressor due to its prion property. It was observed that the levels of RNR transcription were increased in the yeast strains containing either multi-copies of CYC8 gene or $cyc8{\Delta}$ mutation, suggesting that the increased level of RNR will elevate the intracellular pools of dNTPs, which, in turn, suppress the phenotype of $rad53{\Delta}$ mutation.

Immunogenicity of staphylococcal enterotoxin C mutant antigen in mice and dairy cows (포도상구균 장내 C 형 변이독소 (SEC mutant)의 면역원성에 대한 연구)

  • Chang, Byoung-sun;Joo, Yi-seok;Moon, Jin-san;Seo, Keun-seok;Yang, Soo-jin;Kim, So-hyun;Park, Yong-ho
    • Korean Journal of Veterinary Research
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    • v.41 no.2
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    • pp.177-188
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    • 2001
  • Mastitis is one of the most significant cause of economic loss to the dairy industry. Especially, Staphylococcus aureus is a major contagious mastitis-causing pathogen in dairy cattle. Because of its high transmission rate and resistance to antibiotic therapy, staphylococcal mastitis presents a constant threat to the dairy industry. Staphylococcal enterotoxin C(SEC) produced by S aureus has been known as one of superantigens which are able to stimulate a large proportion of T lymphocytes independently of their antigenic specificity. In this experiment, we have conducted preliminary studies with mice and lactating cows to evaluate the immunogenicity and safety of the experimental vaccine consists of SEC mutant antigen on controlling the bovine mastitis associated with S aureus infections. The average value of somatic cell counts in quarter milk, isolation rate of S aureus were consistently decreased in SEC-SER vaccinated groups, whereas antibody titers were highly increased in SEC-SER vaccinated groups. Peripheral blood were also collected from the lactating cows to determine the proportion of leukocyte subpopulation associated with humoral immunity(HI) and cell mediated immunity(CMI). Proportion of leukocyte subpopulation expressing $BoCD2^+$(total T lymphocyte), $BoCD4^+$(T helper cell), $BoCD8^+$(T cytotoxic/suppressor cell) and NonT/NonB lymphocyte which are involved in CMI in SEC-SER vaccinated groups were decreased for the initial stage after first vaccination and then increased from ten weeks after first vaccination maintaining elevated level till 14 weeks after vaccination. In contrast, proportion of monocyte, MHC class II and B lymphocyte which are associated with the production of primary immune response in SEC-SER vaccinated groups were increased for the initial period and then decreased from ten weeks after first vaccination. We present evidence that vaccination of SEC-SER mutant antigen in lactating cows induced a significant proliferation of bovine T lymphocytes. These results suggest that SEC-SER mutant antigen used in this experiment might be one of potential immunogen in developing innovative vaccine against bovine IMI associated with S aureus. Additional challenge trials should be carried out to evaluate substantial protection against S aureus under the commercial farm conditions.

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Pseudomonas aeruginosa Exotoxin A Induces Apoptosis in Chemoresistant YD-9 Human Oral Squamous Carcinoma Cell Line Via Accumulation of p53 and Activation of Caspases (항암제에 저항성을 가지는 YD-9 human oral squamous carcinoma cell line에서 Pseudomonas aeruginosa exotoxin A의 p53 단백질 누적과 caspase를 활성화 경로를 통해 유도된 세포자멸사)

  • Kim, Gyoo-Cheon;Gil, Young-Gi
    • Journal of Life Science
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    • v.19 no.8
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    • pp.1047-1054
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    • 2009
  • Oral squamous carcinoma (OSC) cells present resistance to chemotherapeutic agents-mediated apoptosis in the late stages of malignancy. Advances in the understanding of bacterial toxins have produced new strategies for the treatment of cancers. It was demonstrated here that Pseudomonas aeruginosa exotoxin A (PEA) significantly decreased the viability of chemoresistant YD-9 cells in the apoptosis mechanism. Apoptotic manifestations were evident through changes in nuclear morphology and generation of DNA fragmentation. PEA treatment induced caspase-3, -6 and -9 cleavage, and activation. These events preceded proteolysis of the caspase substrates poly (ADP-ribose) polymerase (PARP), DNA fragmentation factor 45 (DFF45), and lamin A in YD-9 cells. The reduction of mitochondrial membrane potential, release of cytochrome c and SmacjDlABLO from mitochondria to cytosol, andtranslocation of AlF into nucleus were shown. While p53, p21 and $14-3-3{\gamma}$ were upregulated, cyclin Band cdc2 were downregulated by PEA treatment. Taken together, PEA induces apoptosis in chemoresistant YD-9 cells via activation of caspases, mitochondrial events and regulation of cell cycle genes.

Isolation and Characterization of Phosphate Solubilizing Bacteria Pantoea Species as a Plant Growth Promoting Rhizobacteria (식물 생장 촉진 활성을 가진 인산분해 미생물 Pantoea 종의 분리 및 특성 규명)

  • Yun, Chang Yeon;Cheong, Yong Hwa
    • Journal of Life Science
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    • v.26 no.10
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    • pp.1163-1168
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    • 2016
  • Plant growth-promoting rhizobacteria (PGPR) have gained worldwide importance and acceptance due to their agricultural benefits. These microorganisms are potential tools for sustainable agriculture, with effects on plant growth, biofertilization, induced systemic resistance, and biocontrol of plant pathogens. In this study, four different Pantoea species were isolated from field soil, and their plant growth-promoting characteristics were studied. Based on 16S rDNA gene sequencing analyses, the se were grouped into Pantoea ananatis, Pantoea citrea, Pantoea dispersa, Pantoea vagans and named as Pa1, Pc1, Pd1, Pv1, respectively. All of these strains have their ability for solubilization of insoluble phosphate depending on pH decrease at the range around pH 5 at 1days after inoculation and production of plant hormone indole acetic acid (IAA) with 85.3±16.3 μg/ml of Pa1, 183.9±16.8 μg/ml of Pc1, 28.8±17.3 μg/ml of Pd1 and 114.1±16.5 μg/ml of Pv1, respectively. Pa1, Pc1 and Pd1 also have high activity for production of gibberellin (GA3) hormone with 331.1±19.2 μg/ml of Pa1, 288.5±16.8 μg/ml of Pc1, 309.2±18.2 μg/ml of Pd1, but Pv1 does not. Furthermore, all these species have significantly promoted the growth of the lettuce seedling plants at the range around 32~37% for fresh weight and 10~15% for shoot length enhancement, so that these microbe could be used as a potential bio-fertilizer agents.

Molecular Aspects of Japanese Encephalitis Virus Persistent Infection in Mammalian Cells

  • Park Sun-Hee;Won Sung Yong;Park Soo-Young;Yoon Sung Wook;Han Jin Hyun;Jeong Yong Seok
    • Proceedings of the Microbiological Society of Korea Conference
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    • 2000.05a
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    • pp.23-36
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    • 2000
  • Japanese encephalitis virus (JEV) is the causative agent of a mosquito-borne encephalitis and is transmitted to human via persistently infected mosquito vectors. Although the virus is known to cause only acute infection, there were reports that showed neurological sequelae, latent infection in peripheral mononuclear cells, and recurrence of the disease after acute encephalitis. Innate resistance of certain cell lines, abnormal SN1 expression of the virus, and anti-apoptotic effect of cullular bcl-2 have been suggested as probable causes of JEV persistence even in the absence of defective interfering (DI) particles. Although possible involvement of DI particles in JEV persistence was suggested, neither has a direct evidence for DI presence nor its molecular characterization been made. Two questions asked in this study are whether the DI virus plays any role in JEV persistent infection if it is associated with and what type of change(s) can be made in persistently infected cells to avoid apoptosis even with the continuous virus replication, DI-free standard stock of JEV was infected in BHK-21, Vero, and SW13 cells and serial high multiplicity passages were performed in order to generate DI particles. There different-sized DI RNA species which were defective in both structural and nonstructural protein coding genes. Rescued ORFs of the DI genome maintained in-frame and the presence of replicative intermediate or replicative form RNA of the DI particles confirmed their replication competence. On the other hand, several clones with JEV persistent infection were established from the cells survived acute infections during the passages. Timing of the DI virus generation during the passages seemed coincide to the appearance of persistently infected cells. The DI RNAs were identified in most of persistently infected cells and were observed throughout the cell maintenance. One of the cloned cell line maintained the viral persistence without DI RNA coreplication. The cells with viral persistence released the reduced but continuous infectious JEV particle for up to 9 months and were refractory to homologous virus superinfection but not to heterologous challenges. Unlike the cells with acute infection these cells were devoid of characteristic DNA fragmentation and JEV-induced apoptosis with or without homologous superinfection. Therefore, the DI RNA generated during JEV undiluted serial passage on mammalian cells was shown to be biologically active and it seemed to be responsible, at least in part, for the establishment and maintenance of the JEV persistence in mammalian cells. Viral persistence without DI RNA coreplication, as in one of the cell clones, supports that JEV persistent infection could be maintained with or without the presence of DI particles. In addition, the fact that the cells with JEV persistence were resistant against homologous virus superinfection, but not against heterologous one, suggests that different viruses have their own and independent pathway for cytopathogenesis even if viral cytopathic effect could be converged to an apoptosis after all.

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Seismic Responses Control of Coupled Shear Wall Structures Using LRBs (LRB를 이용한 병렬전단벽 구조물의 지진응답제어)

  • Park, Yong-Koo;Kim, Hyun-Su;Ko, Hyun;Kim, Min-Gyun;Lee, Dong-Guen
    • Journal of the Earthquake Engineering Society of Korea
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    • v.14 no.6
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    • pp.1-9
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    • 2010
  • Most of shear wall structures require openings in shear walls and thus shear walls are linked by floor slabs or coupling beams resulting in the coupled shear wall structures. When these structures are subjected to seismic excitations, excessive shear forces are induced in coupling beams. Accordingly, brittle failure of coupling beams may occur or shear walls may yield first. To avoid this problem, damping devices can be installed in coupling beams. It can increase the vibration control effect and improve the seismic resistance performance of the coupled shear wall structure by avoiding stress concentration and the brittle failure of coupling beams. Based on this background research, an LRB (lead rubber bearing) was introduced in the middle of the coupling beam in this study and the authors investigated the seismic response control effect and stress distribution of the proposed system. To this end, a modeling technique that can effectively predict the structural behavior of coupled shear wall structures has been proposed. With this proposed technique, time history analyses of the example coupled shear wall structure subjected to seismic excitation were performed and the vibration control effects of the seismic responses were investigated.

Phase transition of (Bi, Pb)-2223 superconductor induced by Fe3O4 addition

  • Ko, Y.J.;Oh, J.Y.;Song, C.Y.;Yang, D.S.;Tran, D.H.;Kang, B.
    • Progress in Superconductivity and Cryogenics
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    • v.21 no.4
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    • pp.1-5
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    • 2019
  • We investigated the effect of Fe3O4 addition on the critical temperature of (Bi, Pb)-2223 polycrystalline samples. Bi1.6Pb0.4Sr2Ca2Cu3O10+δ + x wt. % Fe3O4 (x = 0.0, 0.2, 0.4, 0.6, and 0.8) samples were prepared by using a solid-state reaction method. The analysis of X-ray diffraction data indicates that as Fe3O4 is added, dominant phase of the sample changes from Bi-2223 to Bi-2212 with an increasing Bi-2201 phase. The transition temperature of the samples drastically decreased with the Fe3O4 addition. The resistance data of samples with x = 0.2 and 0.4 showed a double transition indicating a coexistence of Bi-2223 and Bi-2212 phase while the samples with x = 0.6 and 0.8 showed a single transition with a semiconducting behavior. This phase transition may originate from changes in local structure of the Bi-2223 system by Fe3O4 addition. Analysis of the pair distribution function of the Cu-O pair in the CuO2 plane calculated from extended X-ray absorption fine structure data revealed that the oxygen coordination of copper ion changes from CuO4 planar type (x = 0.0 - 0.4) to CuO5 pyramidal type (x = 0.6, 0.8). The correlated Debye-Waller factor, providing information on the atomic disorder within the CuO2 plane, shows an inverse relation to the coordination number. These results indicate that addition of Fe3O4 changes the oxygen distribution around Cu in the CuO2 plane, causing a phase transition from Bi-2223 to more stable Bi-2212/Bi-2201 phases.

Inhibition of SIRT1 Sensitizes TRAIL-Resistant MCF-7 Cells by Upregulation of DR5 and Inhibition of c-FLIP (SIRT1 억제에 의한 DR5 발현증강과 c-FLIP 발현저해 작용으로 사람유방암세포 MCF-7의 TRAIL 감수성 증강)

  • Lee, Su-Hoon;Kim, Hak-Bng;Kim, Mi-Ju;Lee, Jae-Won;Bae, Jae-Ho;Kim, Dong-Wan;Kang, Chi-Dug;Kim, Sun-Hee
    • Journal of Life Science
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    • v.22 no.10
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    • pp.1277-1285
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    • 2012
  • The tumor necrosis, factor-related, apoptosis-inducing ligand (TRAIL) is regarded as a potentially useful anticancer agent with excellent selectivity for cancer cells. However, a considerable number of cancer cells are resistant to apoptosis induction by TRAIL. Developing strategies to overcome this resistance are important for the successful use of TRAIL for cancer therapy. Here, we revealed that siRNA-mediated downregulation of SIRT1 or SIRT1 inhibitor Amurensin G upregulated DR5 and c-Myc and downregulated c-$FLIP_{L/S}$ and Mcl-1, which was associated with sensitization of TRAIL-resistant MCF-7 cells to TRAIL. This result was followed by the activation of caspases, PARP cleavage, and downregulation of Bcl-2 in both TRAIL-treated MCF-7 cells transfected with SIRT1 siRNA and cells co-treated with Amurensin G and TRAIL. Our results suggest that the induction of DR5 and downregulation of c-FLIP via suppression of SIRT1 expression may be a useful strategy to increase the susceptibility of TRAIL-resistant cancer cells to TRAIL-induced cell death.

Cariporide Enhances the DNA Damage and Apoptosis in Acid-tolerable Malignant Mesothelioma H-2452 Cells

  • Lee, Yoon-Jin;Bae, Jin-Ho;Kim, Soo-A;Kim, Sung-Ho;Woo, Kee-Min;Nam, Hae-Seon;Cho, Moon-Kyun;Lee, Sang-Han
    • Molecules and Cells
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    • v.40 no.8
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    • pp.567-576
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    • 2017
  • The $Na^+/H^+$ exchanger is responsible for maintaining the acidic tumor microenvironment through its promotion of the reabsorption of extracellular $Na^+$ and the extrusion of intracellular $H^+$. The resultant increase in the extracellular acidity contributes to the chemoresistance of malignant tumors. In this study, the chemosensitizing effects of cariporide, a potent $Na^+/H^+-exchange$ inhibitor, were evaluated in human malignant mesothelioma H-2452 cells preadapted with lactic acid. A higher basal level of phosphorylated (p)-AKT protein was found in the acid-tolerable H-2452AcT cells compared with their parental acid-sensitive H-2452 cells. When introduced in H-2452AcT cells with a concentration that shows only a slight toxicity in H-2452 cells, cariporide exhibited growth-suppressive and apoptosis-promoting activities, as demonstrated by an increase in the cells with pyknotic and fragmented nuclei, annexin V-PE(+) staining, a $sub-G_0/G_1$ peak, and a $G_2/M$ phase-transition delay in the cell cycle. Preceding these changes, a cariporide-induced p-AKT down-regulation, a p53 up-regulation, an ROS accumulation, and the depolarization of the mitochondrial-membrane potential were observed. A pretreatment with the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 markedly augmented the DNA damage caused by the cariporide, as indicated by a much greater extent of comet tails and a tail moment with increased levels of the p-histone H2A.X, $p-ATM^{Ser1981}$, $p-ATR^{Ser428}$, $p-CHK1^{Ser345}$, and $p-CHK2^{Thr68}$, as well as a series of pro-apoptotic events. The data suggest that an inhibition of the PI3K/AKT signaling is necessary to enhance the cytotoxicity toward the acidtolerable H-2452AcT cells, and it underlines the significance of proton-pump targeting as a potential therapeutic strategy to overcome the acidic-microenvironment-associated chemotherapeutic resistance.

Physiological effect induced by relaxation aroma (이완 유도 향으로 발생된 생리적 효과)

  • 백은주;이윤영;문창현;전병배;양해주
    • Proceedings of the Korean Society for Emotion and Sensibility Conference
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    • 1999.11a
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    • pp.233-237
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    • 1999
  • Aromatherapy는 향을 이용하여 생리적 및 심리적 효과를 나타내는 치료법이다. 향의 종류에 따라 여러 효과들이 나타나고 있는데 본 연구에서는 이완 유도향 제품을 개발하기 위해 자율신경계로부터의 신호인 Galvanic skin resistance(GSR), 피부온도, 심박수 등과 뇌파에서의 변화를 측정하여 이완의 정도를 측정하고자 하였다. 실험방법은 4 종류의 aromatherapy용으로 조제된 복합향(#2033, #2026, #11, #13)을 이용하고 피검자는 후각기능이 정상이며 물리적 및 심리적 stress가 없고, 음주, 담배를 3일전까지 경험이 없는 군을 택하였다. 향을 주는 시간은 1분으로 하였으며 순서에 의한 효과를 없애기 위해 4 종류를 random order에 의해 실시하였다. 대조군으로는 증류수를 이용하여 실험 전, 실험 중, 실험 후에서 각각 측정하였으며 또한 각성효과가 좋은 jasmine과 이완 효과를 보이는 lavender를 같은 protocol로 시행하여 이완의 효과를 비교하였다. 뇌파는 FFT분석에 따라 각 주파수 영역 즉 beta, alpha, theta, delta로 나누어 분석하였다. Jasmine과 lavender의 이완 효과에서는 GSR의 변화와 HRV의 변화를 보고한 바 있다(백,1998). 또한 심리불안 효과와 향 이미지 검사를 동시에 시행하여 주관적지표로 삼았다. 실험 결과에서는 이러한 4 종류의 향은 모두 GSR의 현저한 감소 효과를 보였으며, 심박수와 피부온도의 감소경향을 나타내었다. 자율신경계 반응에 따라 4 종류 향의 이완 효과의 순서를 결정할 수 있었다. 주관적 검사와의 상관관계도 잘 나타났으며 이미지는 이완 정도와 섬세하다 항목이 잘 반영되었다. 뇌파의 변화에서는 의미 있는 변화는 보이지 않았다. 결론적으로 relaxation 효과는 GSR를 비롯한 자율신경계지표에서 잘 반영되었다.^2$=.792가 되었다. 설명되는 누적분산값은 67.18%였다.주관적 평가의 결과와 객관적 평가 결과를 이용해 마직물의 태를 평가하는 산출식을 제시하였다. 태 평가치의 경우 16가지 특성치를 모두 넣는 방법과 stepwise 방법, 또 Kawabatark 사용한 순차적 군 회귀법의 세가지 방법의 회귀식 중 16가지 특성치를 모두 넣는 방법의 결정계수가 가장 높았다.tosterone농도는 107.7$\pm$12.0 pmol/l이었고, 남성의 타액내 농도는 274.2$\pm$22.1 pmol/l이었다. 이상의 결과로 보아 본 연구에서 정립된 EIA 방법은 RIA를 대신하여 소규모의 실험실에서도 활용할 수 있을 것으로 사려된다.또한 상실기 이후 배아에서 합성되며, 발생시기에 따라 그 영향이 다르고 팽창과 부화에 관여하는 것으로 사료된다. 더욱이, 조선의 ${\ulcorner}$구성교육${\lrcorner}$이 조선총독부의 관리하에서 실행되었다는 것을, 당시의 사범학교를 중심으로 한 교육조직을 기술한 문헌에 의해 규명시켰다.nd of letter design which represents -natural objects and was popular at the time of Yukjo Dynasty, and there are some documents of that period left both in Japan and Korea. "Hyojedo" in Korea is supposed to have been influenced by the letter design. Asite- is also considered to have been "Japanese Letter Jobcheso." Therefore, the purpose of this study is to look in

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