• Title/Summary/Keyword: Host resistance

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Development of Anticancer Prodrugs and Tumor Specific Adjuvant Prodrugs for Chemotherapy

  • Moon, Ki-Young
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2000.04a
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    • pp.8-9
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    • 2000
  • Despite the advances made in the past few decades in cancer chemotherapy, many conventional anticancer drugs display relatively poor selectivity for cancer cells. The nonselectivity of anticancer drugs and the development of anticancer drug resistance have been recognized as serious limitations in their clinical usefulness. Therefore, a major challenge in cancer chemotherapy is the development of new anticancer agents with improved selectivity for tumor cells as well as the prevention of the host cell resistance, both of which result in the improvement of therapeutic effect against cancer cells. Cyclophosphamide (CP), a widely used anticancer agent, is a prodrug that is activated by hepatic microsomal mixed-function oxidase (MFO) catalyzed C$_4$- hydroxylation. The resulting 4-hydroxycyclophosphamide (4-OH-CP) is converted to the ring-opened tautomer to aldophosphamide (Aldo) which subsequently undergoes a base- catalyzed ${\beta}$-elimination to generate cytotoxic phosphoramide mustard (PDA) and acrolein. The cytotoxic activity of CP is attributed to the aziridinium ion species derived from PDA that cross-links interstrand DNA.

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Development of Free Running System for 2m-class Ship Models (2m급 모형선용 자유항주시스템 개발)

  • Shin, Hyun-Kyoung;Kim, Min-Sung
    • Journal of the Society of Naval Architects of Korea
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    • v.45 no.3
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    • pp.247-257
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    • 2008
  • In this paper, a free running system, which is developed recently for a 2m-class ship models, will be introduced. For the remote control of hardware, GUI of software packages was developed using Visual Basic 6.0, and Host PC with Positioning Board manages Servo drive. Then the drive operates propeller and rudder. Its control performance will be shown. Also its adaptability to the resistance, manoeuverability and seakeeping model tests will be considered through the installation on a KTTC standard ship model from MOERI.

Selection of Entomopathogenic Fungi Against Bemisia tabaci and Culture Characterization on Spent Coffee Grounds Medium (담배가루이에 대한 곤충병원성 곰팡이 선발 및 커피박 배지에서의 배양 특성 )

  • Jang, Ji-Won;Heo, In-Ji;Hwang, Dong-Young;Kim, Seul-Ki;Shin, Tae-Young
    • Korean Journal of Organic Agriculture
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    • v.31 no.4
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    • pp.427-439
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    • 2023
  • The silverleaf whitefly, Bemisia tabaci, is a major pest distributing worldwide damaging over 900 host plant species, and is highly resistant to chemical pesti- cides. Due to the high pesticide resistance of whitefly, there is a need for alternatives to chemical control. Entomopathogenic fungi are candidates for biological pesticide that can overcome the resistance problem of chemical pesticide. Therefore, in this study, we tested pathogenicity of the entomopathogenic fungi to select high insec- ticidal activity against whitefly. As a result, IPBL-C (Cordyceps fumosorosea) and IPBL-F (Metarhizium pinghaense) isolates showed high insecticidal activity against whitefly. Additionally, as a result of culturing the selected isolates on spent coffee grounds medium, the conidia of IPBL-F produced on coffee grounds medium showed five times higher heat stability after heat treatment at 45℃ for one hour than conidia produced on PDA medium.

Acibenzolar-S-Methyl(ASM)-Induced Resistance against Tobamoviruses Involves Induction of RNA-Dependent RNA Polymerase(RdRp) and Alternative Oxidase(AOX) Genes

  • Madhusudhan, Kallahally Nagendra;Deepak, Saligrama Adavigowda;Prakash, Harishchandra Sripathi;Agrawal, Ganesh Kumar;Jwa, Nam-Soo;Rakwal, Randeep
    • Journal of Crop Science and Biotechnology
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    • v.11 no.2
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    • pp.127-134
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    • 2008
  • Tobamoviruses are the major viral pathogens of tomato and bell pepper. The preliminary results showed that Acibenzolar-Smethyl(ASM; S-methylbenzo(1,2,3) thiadiazole-7-carbothiate) pre-treatment to tomato and tobacco plants reduces the concentration of Tomato mosaic tobamovirus(ToMV) and Tobacco mosaic tobamovirus(TMV) in tomato and bell pepper seedlings, respectively. Pre-treatment of the indicator plant(Nicotiana glutinosa) with the ASM followed by challenge inoculation with tobamoviruses produced a reduced number and size of local lesions(67 and 79% protection over control to TMV and ToMV inoculation, respectively). In order to understand the mechanism of resistance the gene expression profiles of antiviral genes was examined. RT-PCR products showed higher expression of two viral resistance genes viz., alternative oxidase(AOX) and RNA dependent RNA polymerase(RdRp) in the upper leaves of the ASM-treated tomato plants challenge inoculation with ToMV. Further, the viral concentration was also quantified in the upper leaves by reverse transcription PCR using specific primer for movement protein of ToMV, as well as ELISA by using antisera against tobamoviruses. The results provided additional evidence that ASM pre-treatment reduced the viral movement to upper leaves. The results suggest that expressions of viral resistance genes in the host are the key component in the resistance against ToMV in the inducer-treated tomato plants.

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Transgenic cucumber expressing the 54-kDa gene of Cucumber fruit mottle mosaic virus is highly resistance and protect non-transgenic scions from soil infection

  • Gal-On, A.;Wolf, D.;Antignus, Y.;Patlis, L.;Ryu, K.H.;Min, B.E.;Pearlsman, M.;Lachman, O.;Gaba, V.;Wang, Y.;Yang. J.;Zelcer, A.
    • Proceedings of the Korean Society of Plant Pathology Conference
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    • 2003.10a
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    • pp.148.2-149
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    • 2003
  • Cucumber fruit mottle mosaic tobamovirus (CFMMV) causes severe mosaic symptoms with yellow mottling on leaves and fruits, and occasionally severe wilting of cucumber plants. No genetic source of resistance against this virus has been identified. The genes coding for the coat protein or the putative 54-kDa replicase were cloned into binary vectors under control of the SVBV promoter. Agrobacterium-mediated transformation was peformed on cotyledon explants of a parthenocarpic cucumber cultivar with superior competence for transformation. R1 seedlings were evaluated for resistance to CFMMV infection by lack of symptom expression, back inoculation on an alternative host and ELISA. From a total of 14 replicase-containing R1 lines, 8 exhibited immunity, while only 3 resistant lines were found among a total of 9 CP-containing lines. Line 144 homozygous for the 54-kDa replicase was selected for further resistance analysis. Line 144 was immune to CFMMV infection by mechanical and graft inoculation, or by root infection following planting in CFMMV-contaminated soil. Additionally, line 144 showed delay of symptom appearance following infection by other cucurbit-infecting tobamoviruses. Infection of line 144 plants with various potyviruses and cucumber mosaic cucumovirus did not break the resistance to CFMMV. The mechanism of resistance of line 144 appears to be RNA-mediated, however the means is apparently different from the gene silencing phenomenon. Homozygote line 144 cucumber as rootstock demonstrated for the first time protection of a non-transformed scion from soil inoculation with a soil borne pathogen, CFMMV.

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Proteomics in Insecticide Toxicology

  • Park, Byeoung-Soo;Lee, Sung-Eun
    • Molecular & Cellular Toxicology
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    • v.3 no.1
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    • pp.11-18
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    • 2007
  • Mechanisms of insecticide resistance found in insects may include three general categories. Modified behavioral mechanisms can let the insects avoid the exposure to toxic compounds. The second category is physiological mechanisms such as altered penetration, rapid excretion, lower rate transportation, or increased storage of insecticides by insects. The third category relies on biochemical mechanisms including the insensitivity of target sites to insecticides and enhanced detoxification rate by several detoxifying mechanisms. Insecticides metabolism usually results in the formation of more water-soluble and therefore more readily eliminated, and generally less toxic products to the host insects rather than the parent compounds. The representative detoxifying enzymes are general esterases and monooxygenases that catalyze the toxic compounds to be more water-soluble forms and then secondary metabolism is followed by conjugation reactions including those catalyzed by glutathione S-transferases (GSTs). However, a change in the resistant species is not easily determined and the levels of mRNAs do not necessarily predict the levels of the corresponding proteins in a cell. As genomics understands the expression of most of the genes in an organism after being stressed by toxic compounds, proteomics can determine the global protein changes in a cell. In this present review, it is suggested that the environmental proteomic application may be a good approach to understand the biochemical mechanisms of insecticide resistance in insects and to predict metabolomic changes leading to physiological changes of the resistant species.

Analytical Electron Microscopy and Atomic Force Microscopy Reveal a Physical Mechanism of Silicon-Induced Rice Resistance to Blast

  • Kim Ki Woo;Han Seong Sook;Kim Byung Ryun;Park Eun Woo
    • Proceedings of the Korean Society of Plant Pathology Conference
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    • 2005.10a
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    • pp.15-20
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    • 2005
  • Locations of silicon accumulation in rice leaves and its possible association with resistance to rice blast were investigated by analytical electron microscopy and atomic force microscopy. A blast-susceptible cultivar, Jinmi, and partially resistant cultivars, Hwaseong and Suwon345, were grown under a hydroponic culture system with modified Yoshida's nutrient solution. Electron-dense silicon layers were frequently found beneath the cuticle in epidermal cell walls of silicon-treated plants. Increasing levels of silicon were detected in the outer regions of epidermal cell walls. Silicon was present mainly in epidermal cell walls, middle lamella, and Intercellular spaces within subepidermal tissues. Furthermore, silicon was prevalent throughout the leaf surface with relatively small deposition on stomatal guard cells in silicon-treated plants. Force-distance curve measurements revealed relative hardness and smaller adhesion force in silicon-treated plants (18.65 uN) than control plants (28.39 uN). Moreover, force modulation microscopy showed higher mean height values of elastic Images In silicon-treated plants(1.26 V) than in control plants (0.44 V), implying the increased leaf hardness by silicon treatment. These results strongly suggest that silicon-induced cell wall fortification of rice leaves may be closely associated with enhanced host resistance to blast.

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Histological and Ultrastructural Study of Susceptible and Age-related Resistance Responses of Pepper Leaves to Colletotrichum cocodes Infection

  • Hong, Jeum-Kyu;Lee, Yeon-Kyeong;Jeun, Yong-Chull;Hwang, Byung-Kook
    • The Plant Pathology Journal
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    • v.17 no.3
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    • pp.128-140
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    • 2001
  • Infection of pepper leaves by Colletotrichum cocodes at the two- and eight-leaf stages caused susceptible and resistant lesions 96 h after inoculation, respectively. At the two-leaf stage, progressive symptom development occurred on the infected leaves. In contrast, localized necrotic spots were characteristic symptoms at the eight-leaf stage. Infected leaves at the two-leaf stage exhibited cell death accompanied by the accumulation of autofluorescent compounds. At the eight-leaf stage, pepper leaves infected by the anthracnose fungus displayed localized autofluorescence from the symptoms. Infection of pepper leaves by C. cocodes at the two-leaf stage resulted in its rapidand massive colonization of all the leaf tissues including the vascular tissue, together with cytoplasmic collapse, distortion of chloroplasts, and disruption of host cell walls. However, penetration of C. cocodes was very limited in the older leaf tissues of pepper plants at the eight-leaf stage. Fungal hyphae grew only in the intramural spaces of the epidermal cell walls at this stage. Occlusion of amorphous material in xylem vessels, aggregation of fibrillar material in inter-cellular spaces, and deposition of protein bodies were found as resistance responses to C. cocodes.

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Initial estimates of the economical attractiveness of a nuclear closed Brayton combined cycle operating with firebrick resistance-heated energy storage

  • Chavagnat, Florian;Curtis, Daniel
    • Nuclear Engineering and Technology
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    • v.50 no.3
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    • pp.488-493
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    • 2018
  • The Firebrick Resistance-Heated Energy Storage (FIRES) concept developed by the Massachusetts Institute of Technology aims to enhance profitability of the nuclear power industry in the next decades. Studies carried out at Massachusetts Institute of Technology already provide estimates of the potential revenue from FIRES system when it is applied to industrial heat supply, the likely first application. Here, we investigate the possibility of operating a power plant (PP) with a fluoride-salt-cooled high-temperature reactor and a closed Brayton cycle. This variant offers features such as enhanced nuclear safety as well as flexibility in design of the PP but also radically changes the way of operating the PP. This exploratory study provides estimates of the revenue generated by FIRES in addition to the nominal revenue of the stand-alone fluoride-salt-cooled high-temperature reactor, which are useful for defining an initial design. The electricity price data is based on the day-ahead markets of Germany/Austria and the United States (Iowa). The proposed method derives from the equation of revenue introduced in this study and involves simple computations using MatLab to compute the estimates. Results show variable economic potential depending on the host grid but stress a high profitability in both regions.

Antibiotic resistance in Neisseria gonorrhoeae: broad-spectrum drug target identification using subtractive genomics

  • Umairah Natasya Mohd Omeershffudin;Suresh Kumar
    • Genomics & Informatics
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    • v.21 no.1
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    • pp.5.1-5.13
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    • 2023
  • Neisseria gonorrhoeae is a Gram-negative aerobic diplococcus bacterium that primarily causes sexually transmitted infections through direct human sexual contact. It is a major public health threat due to its impact on reproductive health, the widespread presence of antimicrobial resistance, and the lack of a vaccine. In this study, we used a bioinformatics approach and performed subtractive genomic methods to identify potential drug targets against the core proteome of N. gonorrhoeae (12 strains). In total, 12,300 protein sequences were retrieved, and paralogous proteins were removed using CD-HIT. The remaining sequences were analyzed for non-homology against the human proteome and gut microbiota, and screened for broad-spectrum analysis, druggability, and anti-target analysis. The proteins were also characterized for unique interactions between the host and pathogen through metabolic pathway analysis. Based on the subtractive genomic approach and subcellular localization, we identified one cytoplasmic protein, 2Fe-2S iron-sulfur cluster binding domain-containing protein (NGFG RS03485), as a potential drug target. This protein could be further exploited for drug development to create new medications and therapeutic agents for the treatment of N. gonorrhoeae infections.