• Title/Summary/Keyword: K-Ras

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A study of ribonuclease activity in venom of vietnam cobra

  • Nguyen, Thiet Van;Osipov, A.V.
    • Journal of Animal Science and Technology
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    • v.59 no.9
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    • pp.20.1-20.9
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    • 2017
  • Background: Ribonuclease (RNase) is one of the few toxic proteins that are present constantly in snake venoms of all types. However, to date this RNase is still poorly studied in comparison not only with other toxic proteins of snake venom, but also with the enzymes of RNase group. The objective of this paper was to investigate some properties of RNase from venom of Vietnam cobra Naja atra. Methods: Kinetic methods and gel filtration chromatography were used to investigate RNase from venom of Vietnam cobra. Results: RNase from venom of Vietnam cobra Naja atra has some characteristic properties. This RNase is a thermostable enzyme and has high conformational stability. This is the only acidic enzyme of the RNase A superfamily exhibiting a high catalytic activity in the pH range of 1-4, with $pH_{opt}=2.58{\pm}0.35$. Its activity is considerably reduced with increasing ionic strength of reaction mixture. Venom proteins are separated by gel filtration into four peaks with ribonucleolytic activity, which is abnormally distributed among the isoforms: only a small part of the RNase activity is present in fractions of proteins with molecular weights of 12-15 kDa and more than 30 kDa, but most of the enzyme activity is detected in fractions of polypeptides, having molecular weights of less than 9 kDa, that is unexpected. Conclusions: RNase from the venom of Vietnam cobra is a unique member of RNase A superfamily according to its acidic optimum pH ($pH_{opt}=2.58{\pm}0.35$) and extremely low molecular weights of its major isoforms (approximately 8.95 kDa for RNase III and 5.93 kDa for RNase IV).

Control and Mechanism of Tumor Promotion in UV-Carcinogenesis

  • Ueda, Masato;Budiyanto, Arief;Ashida, Masashi;Bito, Toshinori;Ichihashi, Masamitsu
    • Journal of Photoscience
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    • v.9 no.2
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    • pp.221-224
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    • 2002
  • Carcinogenesis can be theoretically divided to intiation step and promotion step. Intiation associates with genetic alterations including p53 tumor suppressor gene and ras oncogene. Promotion involves in clonal expansion of of an initiated cell by epigenetic mechanism, mainly through signal transduction and gene expression. Ultraviolet light (UV) acts as both initiator and promoter. Initiation is closely related with DNA damage induced by UV, including cyclobutane pyrimidine dimers, (6-4) photoproducts and 8-hydroxy-2'-deoxyguanosine. Cyclobutane pyrimidine dimers and (6-4) photoproducts are directly induced by UV, while 8-hydroxy-2'-deoxyguanosine is induced indirectly by the reactive oxygen species. Because initiation is an irreversal genetic event, while promotion is a reversal and epigenetic event, to know the molecular mechanisms of tumor promotion in UV-carcinogenesis is crucial to develop preventive medicine and suppress UV-carcinogenesis. Because ROS is also involved in signal transduction of the cell, anti-oxidant could be the good candidate of anti-promoting agent. Here, we describe the suppressive effect of UV-carcinogenesis by various anti-oxidant including olive oil. In addition, we discuss about the mechanism of UVB-induced expression of cyclooxygenase-2, which might be a representative molecule involved in promotion of UV-carcinogenesis.

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Study on the Water Quality simulation in the Tamjin River Basin by the application of Qual2K (QUAL2K의 적용에 의한 탐진강 유역의 수질모의 연구)

  • Park, Sung-Chun;Bang, Jae-Pil;Roh, Kyong-Bum;Jin, Young-Hoon
    • Proceedings of the Korea Water Resources Association Conference
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    • 2009.05a
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    • pp.2004-2008
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    • 2009
  • 최근 하천오염에 대한 중요성이 크게 대두되고 있으며, 하천 오염을 방지하기 위한 다양한 방법이 강구되고 있다. 이러한 하천 오염방지를 위한 노력의 일환으로 4대강 수계에 대한 수질오염총량제를 실시하고 있다. 수질오염초량제에 있어 중요한 것은 현재 하천의 상태 및 장래 하천의 상황 즉, 수질 상태를 파악하는 것이 중요하다. 이러한 현재 및 미래의 하천 수질 상태를 파악하기 위해 수질 모델링이 필요하다. 본 연구에서는 수질오염총량제를 시행하고 있는 탐진강유역을 연구 대상으로 선정하였다. 대상 하천수질을 모의하기 위한 모형 중에 가장 보편적이고 광범위하게 사용하고 있는 US EPA에서 개발한 Water Quality model 중에 Qual2E 모형의 단점을 보완하여 개발된 Excel기반의 후속모델 Qual2K를 이용하였다. 모형의 적용은 탐진강 유역을 두 개의 단위유역으로 나누어 한 개의 단위유역을 1개의 Reach로 설정하여 총 2개의 Reach를 형성하였다. 탐진호를 Head water로 설정하고 본류23km를 중심으로 유입되는 지천을 소구역의 점 오염원으로 간주하여 적용하였다. 모형의 반응계수는 실측자료를 사용하여 시행착오법에 의해 검토..보정하였으며, 수리입력계수의 산정은 HEC-RAS모형을 사용하여 수심-유량계수와 유속-유량계수를 산정하였다. 수질모의 항목은 실측자료 2007년 배출부하량을 바탕으로 하여, 수질오염총량제의 수질관리 기준인 BOD와 부영양화 물질 T-P로 정하였다. 검정자료와 보정자료는 2007년 수질관측소의 실측자료를 사용하였다. 유량조건은 하천수질환경기준의 설정근거인 저수량(Q275)을 기준으로 탐진강 유역의 수질을 모의 하였다. 그 결과 Qual2K를 이용해 탐진강 수질 모의 결과 검 보정에서 양호한 결과를 나타냈다.

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Species-specific Marker of Phytophthora pinifolia for Plant Quarantine in Korea (국내 식물검역대상 Phytophthora pinifolia의 PCR 검출을 위한 종 특이적 마커 개발)

  • Kim, Narae;Choi, You Ri;Seo, Mun Won;Song, Jeong Young;Kim, Hong Gi
    • The Korean Journal of Mycology
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    • v.44 no.2
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    • pp.103-107
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    • 2016
  • To establish a rapid and accurate detection of Phytophthora pinifolia, which is a quarantine pathogenic fungus in Korea, a species-specific primer was developed based on the ras-related protein (Ypt1) gene. Species-specific primer based on the DNA sequences of Ypt1 gene amplified 193 bp polymerase chain reaction (PCR) product for P. pinifolia. The primer pair yielded the predicted PCR product size exactly in testing with target pathogen DNAs, but not from the other 10 species of Phytophthora and 14 species of other phytopathogenic fungi. The primer pair also showed only the species-specific amplification curve on realtime PCR on target pathogen DNA. The detection sensitivity of real time PCR using species-specific primer pair was 10 to 100 times higher than conventional PCR, with 1 to $10pg/{\mu}L$.

Aberrant Methylation of RASSF2A in Tumors and Plasma of Patients with Epithelial Ovarian Cancer

  • Wu, Yu;Zhang, Xian;Lin, Li;Ma, Xiao-Ping;Ma, Ying-Chun;Liu, Pei-Shu
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.3
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    • pp.1171-1176
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    • 2014
  • Objective: The tumor suppressor gene, Ras-association domain family (RASSF)2A, is inactivated by promoter hypermethylation in many cancers. The current study was performed to evaluate the methylation status of RASSF2A in epithelial ovarian cancer (EOC) tissues and plasma, and correlations with gene expression and clinicopathologic characteristics. Method: We detected methylation of the RASSF2A gene in tissues and corresponding plasma samples from 47 EOC patients and 14 patients with benign ovarian tumors and 10 with normal ovarian tissues. The methylation status was determined by methylation-specific PCR while gene expression of mRNA was examined by RT-PCR. The EOC cell line, SKOV3, was treated with 5-aza-2'-deoxycytidine (5-azadC). Results: RASSF2A mRNA expression was significantly low in EOC tissues. The frequency of aberrant methylation of RASSF2A was 51.1% in EOC tissues and 36.2% in corresponding plasma samples, whereas such hypermethylation was not detected in the benign ovarial tumors and normal ovarian samples. The expression of RASSF2A mRNA was significantly down-regulated or lost in the methylated group compared to the unmethylated group (p<0.05). After treatment with 5-aza-dC, RASSF2A mRNA expression was significantly restored in the Skov3 cell line. Conclusion: Epigenetic inactivation of RASSF2A through aberrant promoter methylation may play an important role in the pathogenesis of EOC. Methylation of the RASSF2A gene in plasma may be a valuable molecular marker for the early detection of EOC.

A Case of Cardiofaciocutaneous Syndrome caused by BRAF gene mutation (BRAF 유전자의 돌연변이로 진단된 Cardiofaciocutaneous 증후군 1례)

  • Lee, Beom-Hee;Kim, Jae-Min;Lee, Jin-Joo;Kim, Gu-Hwan;Yoo, Han-Wook
    • Journal of Genetic Medicine
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    • v.6 no.1
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    • pp.87-90
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    • 2009
  • Cardiofaciocutaneous (CFC) syndrome is characterized by dysmorphic features, cardiac anomalies, and cutaneous abnormalities. CFC syndrome belongs to the class of Noonan-related diseases. CFC syndrome can be clinically differentiated from other Noonan-related diseases by the distinct craniofacial features of sparse hair, a hypoplastic supraorbital ridge, exophthalmos and nystagmus, and skin manifestations such as ichthyosis and hyperkeratosis. However, phenotypes can overlap among Noonan-related syndromes, including CFC syndrome. Recently, several genes in the RAS-MAPK pathway have been identified as disease-causing genes for Noonan-related diseases. Here, we report on a Korean girl diagnosed with CFC syndrome caused by a V-raf murine sarcoma viral oncogene homolog B1 (BRAF) gene mutation, and we discuss the phenotype-genotype heterogeneities in Noonan syndrome and Noonan-related diseases.

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Epithelial-mesenchymal Transition and Its Role in the Pathogenesis of Colorectal Cancer

  • Zhu, Qing-Chao;Gao, Ren-Yuan;Wu, Wen;Qin, Huan-Long
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.5
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    • pp.2689-2698
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    • 2013
  • Epithelial-to-mesenchymal transition (EMT) is a collection of events that allows the conversion of adherent epithelial cells, tightly bound to each other within an organized tissue, into independent fibroblastic cells possessing migratory properties and the ability to invade the extracellular matrix. EMT contributes to the complex architecture of the embryo by permitting the progression of embryogenesis from a simple single-cell layer epithelium to a complex three-dimensional organism composed of both epithelial and mesenchymal cells. However, in most tissues EMT is a developmentally restricted process and fully differentiated epithelia typically maintain their epithelial phenotype. Recently, elements of EMT, specially the loss of epithelial markers and the gain of mesenchymal markers, have been observed in pathological states, including epithelial cancers. Increasing evidence has confirmed its presence in human colon during colorectal carcinogenesis. In general, chronic inflammation is considered to be one of the causes of many human cancers including colorectal cancer(CRC). Accordingly, epidemiologic and clinical studies indicate that patients affected by ulcerative colitis and Crohn's disease, the two major forms of inflammatory bowel disease, have an increased risk of developing CRC. A large body of evidence supports roles for the SMAD/STAT3 signaling pathway, the NF-kB pathway, the Ras-mitogenactivated protein kinase/Snail/Slug and microRNAs in the development of colorectal cancers via epithelial-tomesenchymal transition. Thus, EMT appears to be closely involved in the pathogenesis of colorectal cancer, and analysis refered to it can yield novel targets for therapy.

Effect of Farnesyltransferase Inhibitor R115777 on Mitochondria of Plasmodium falciparum

  • Ha, Young Ran;Hwang, Bae-Geun;Hong, Yeonchul;Yang, Hye-Won;Lee, Sang Joon
    • Parasites, Hosts and Diseases
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    • v.53 no.4
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    • pp.421-430
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    • 2015
  • The parasite Plasmodium falciparum causes severe malaria and is the most dangerous to humans. However, it exhibits resistance to their drugs. Farnesyltransferase has been identified in pathogenic protozoa of the genera Plasmodium and the target of farnesyltransferase includes Ras family. Therefore, the inhibition of farnesyltransferase has been suggested as a new strategy for the treatment of malaria. However, the exact functional mechanism of this agent is still unknown. In addition, the effect of farnesyltransferase inhibitor (FTIs) on mitochondrial level of malaria parasites is not fully understood. In this study, therefore, the effect of a FTI R115777 on the function of mitochondria of P. falciparum was investigated experimentally. As a result, FTI R115777 was found to suppress the infection rate of malaria parasites under in vitro condition. It also reduces the copy number of mtDNA-encoded cytochrome c oxidase III. In addition, the mitochondrial membrane potential (${\Delta}{\Psi}m$) and the green fluorescence intensity of MitoTracker were decreased by FTI R115777. Chloroquine and atovaquone were measured by the mtDNA copy number as mitochondrial non-specific or specific inhibitor, respectively. Chloroquine did not affect the copy number of mtDNA-encoded cytochrome c oxidase III, while atovaquone induced to change the mtDNA copy number. These results suggest that FTI R115777 has strong influence on the mitochondrial function of P. falciparum. It may have therapeutic potential for malaria by targeting the mitochondria of parasites.

Oncomodulin/Truncated Protamine-Mediated Nogo-66 Receptor Small Interference RNA Delivery Promotes Axon Regeneration in Retinal Ganglion Cells

  • Cui, Zhili;Kang, Jun;Hu, Dan;Zhou, Jian;Wang, Yusheng
    • Molecules and Cells
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    • v.37 no.8
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    • pp.613-619
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    • 2014
  • The optic nerve often suffers regenerative failure after injury, leading to serious visual impairment such as glaucoma. The main inhibitory factors, including Nogo-A, oligodendrocyte myelin glycoprotein, and myelin-associated glycoprotein, exert their inhibitory effects on axonal growth through the same receptor, the Nogo-66 receptor (NgR). Oncomodulin (OM), a calcium-binding protein with a molecular weight of an ~12 kDa, which is secreted from activated macrophages, has been demonstrated to have high and specific affinity for retinal ganglion cells (RGC) and promote greater axonal regeneration than other known polypeptide growth factors. Protamine has been reported to effectively deliver small interference RNA (siRNA) into cells. Accordingly, a fusion protein of OM and truncated protamine (tp) may be used as a vehicle for the delivery of NgR siRNA into RGC for gene therapy. To test this hypothesis, we constructed OM and tp fusion protein (OM/tp) expression vectors. Using the indirect immunofluorescence labeling method, OM/tp fusion proteins were found to have a high affinity for RGC. The gel shift assay showed that the OM/tp fusion proteins retained the capacity to bind to DNA. Using OM/tp fusion proteins as a delivery tool, the siRNA of NgR was effectively transfected into cells and significantly down-regulated NgR expression levels. More importantly, OM/tp-NgR siRNA dramatically promoted axonal growth of RGC compared with the application of OM/tp recombinant protein or NgR siRNA alone in vitro. In addition, OM/tp-NgR siRNA highly elevated intracellular cyclic adenosine monophosphate (cAMP) levels and inhibited activation of the Ras homolog gene family, member A (RhoA). Taken together, our data demonstrated that the recombinant OM/tp fusion proteins retained the functions of both OM and tp, and that OM/tp-NgR siRNA might potentially be used for the treatment of optic nerve injury.

Restoration Modeling Analysis for Abandoned Channels of the Mangyeong River

  • Kim, Jae-Hoon;Julien, Pierre Y.;Ji, Un;Kang, Joon-Gu
    • Journal of Environmental Science International
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    • v.20 no.5
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    • pp.555-564
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    • 2011
  • This study examines the potential restoration of abandoned channels of the Mangyeong River in South Korea. To analyze the morphological changes and equilibrium conditions, a flow duration analysis was performed to obtain the discharge of 255 m3/s with a recurrence interval of 1.5 year. It is a gravel-bed stream with a median bed diameter of 36 mm. The reach-averaged results using HEC-RAS showed that the top width is 244 m, the mean flow depth is 1.11 m, the width/depth ratio is very high at 277, the channel velocity is 1.18 m/s, and the Froude number is also high at 0.42. The hydraulic parameters vary in the vicinity of the three sills which control the bed elevation. The total sediment load is 6,500 tons per day and the equivalent sediment concentration is 240 mg/l. The Engelund-Hansen method was closer to the field measurements than any other method. The bed material coarser than 33 mm will not move. The methods of Julien-Wargadalam and Lacey gave an equilibrium channel width of 83 m and 77 m respectively, which demonstrates that the Mangyeong River is currently very wide and shallow. The planform geometry for the Mangyeong River is definitely straight with a sinuosity as low as 1.03. The thalweg and mean bed elevation profiles were analyzed using field measurements in 1976, 1993 and 2009. The measured profiles indicated that the channel has degraded about 2 m since 1976. The coarse gravel material and large width-depth ratio increase the stability of the bed material in this reach.