• 제목/요약/키워드: New mutant

검색결과 228건 처리시간 0.02초

Investigation of genomic integration of GX-12, a new anti-HIV DNA vaccine, into host cellular DNA following intramuscular injection in rats

  • Kang, Kyung-Koo;Park, Min-Seul;Ahn, Jun-Kook;Baik, Dae-Hyun;Lee, Dong-Sup;Park, Jae-Hun;Ahn, Byoung-Ok;Kim, Won-Bae
    • 한국독성학회:학술대회논문집
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    • 한국독성학회 2002년도 Molecular and Cellular Response to Toxic Substances
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    • pp.199-200
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    • 2002
  • GX-12 is a naked DNA vaccine developed by research team of Dong-A Pharmaceutical Company, Green Cross Company and Genexine for the treatment of HIV infection. It consists of four separate plasmids (pGX10-GE HX, pGX10-dpol JR, pGX10-VN/TV JR, pGX10-hIL-12m), which were constructed by inserting the HIV-1 gag-env, pol, regulatory genes and a human IL-12 mutant gene into pGX10 plasmid vectors.(omitted)

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새로운 플루오로 퀴놀론계 항균제에 대한 내성 MRSA 균주의 In Vitro 선발과 그 내성 기전 분석 (In Vitro Selection of MRSA Strains Resistant to Some New Fluoroquinolone Antibiotics and Characterization of their Resistance Mechanisms)

  • 윤은정;김현지;이춘영;최응칠;심미자
    • 약학회지
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    • 제52권3호
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    • pp.219-224
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    • 2008
  • Clinically isolated methicillin-resistant Staphylococcus aureus strains were exposed to subinhibitory concentration of DW286, DW-224a, gemifloxacin, trovafloxacin, sparfloxacin and ciprofloxacin during 26- to 39-days period. Subculturing led to resistance development, and most of the selected mutants were above susceptible breakpoints. Selected mutants had broad cross resistance to other quinolone antibiotics and only one mutant was completely susceptible to all fluoroquinolones. Twenty five among 42 mutants revealed mutations on DNA gyrase and topoisomerase IV by sequencing. Also 16 mutants had fluoroquinolones MICs that were 4-32 times lower in the presence of reserpine. In conclusion, alterations in DNA gyrase or topoisomerase IV and action of efflux pumping out system are the resistance mechanisms of DW-224a.

Mutation Hotspots in the β-Catenin Gene: Lessons from the Human Cancer Genome Databases

  • Kim, Sewoon;Jeong, Sunjoo
    • Molecules and Cells
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    • 제42권1호
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    • pp.8-16
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    • 2019
  • Mutations in the ${\beta}-catenin$ gene (CTNNB1) have been implicated in the pathogenesis of some cancers. The recent development of cancer genome databases has facilitated comprehensive and focused analyses on the mutation status of cancer-related genes. We have used these databases to analyze the CTNNB1 mutations assembled from different tumor types. High incidences of CTNNB1 mutations were detected in endometrial, liver, and colorectal cancers. This finding agrees with the oncogenic role of aberrantly activated ${\beta}-catenin$ in epithelial cells. Elevated frequencies of missense mutations were found in the exon 3 of CTNNB1, which is responsible for encoding the regulatory amino acids at the N-terminal region of the protein. In the case of metastatic colorectal cancers, in-frame deletions were revealed in the region spanning exon 3. Thus, exon 3 of CTNNB1 can be considered to be a mutation hotspot in these cancers. Since the N-terminal region of the ${\beta}-catenin$ protein forms a flexible structure, many questions arise regarding the structural and functional impacts of hotspot mutations. Clinical identification of hotspot mutations could provide the mechanistic basis for an oncogenic role of mutant ${\beta}-catenin$ proteins in cancer cells. Furthermore, a systematic understanding of tumor-driving hotspot mutations could open new avenues for precision oncology.

새로운 미립질 돌연변이 창출 (New Mutants for Endosperm and Embryo Characters in Rice)

  • 김광호;허문회;박순직;고희종
    • 한국작물학회지
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    • 제36권3호
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    • pp.197-203
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    • 1991
  • 화청벼와 IR24의 수정란에 N-methyl-N-nitros-ourea(MNU)를 처리하여 여러 종류의 배란 및 배 돌연변이체를 유기하였다. 그 결과는 다음과 같이 요약된다. 1. 변이체들에 대한 외관특성, SEM 검경 특성 및 amylose 함량 분석을 통하여 각각 dull, 찰성, 심백, 분질, sugary, shrunken, 유색종피 변이체들로 명명하였다. 2. 변이체들 중에서는 심백 변이체들의 비율이 74.8%로 가장 높았다. 3. 47320(dull)을 제외한 모든 변이 형질은 단순열성 돌연변이인 것으로 나타났다.

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Unraveling the Role of Cytochrome P450 as a Key Regulator Lantipeptide Production in Streptomyces globisporus

  • Da-Ran Kim;Su In Lee;Youn-Sig Kwak
    • The Plant Pathology Journal
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    • 제39권6호
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    • pp.566-574
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    • 2023
  • The aim of this study was to investigate the regulation of lantipeptide production in Streptomyces globisporus SP6C4, which produces the novel antifungal lantipeptides conprimycin and grisin, and to identify the role of cytochrome P450 (P450) in tis regulation. To investigate the regulation of lantipeptide production, we created gene deletion mutants, including ΔP450, ΔtsrD, ΔlanM, ΔP450ΔtsrD, and ΔP450ΔlanM. These mutants were characterized in terms of their morphology, sporulation, attachment, and antifungal activity against Fusarium oxysporum. The gene deletion mutants showed distinct characteristics compared to the wild-type strain. Among them, the ΔP450ΔlanM double mutant exhibited a recovery of antifungal activity against F. oxysporum, indicating that P450 plays a significant role in regulating lantipeptide production in S. globisporus SP6C4. Our findings highlight the significant role of P450 in the regulation of lantipeptide production and morphological processes in S. globisporus. The results suggest a potential link between P450-mediated metabolic pathways and the regulation of growth and secondary metabolism in SP6C4, thereby highlighting P450 as a putative target for the development of new antifungal agents.

Analysis of Disease Progression-Associated Gene Expression Profile in Fibrillin-1 Mutant Mice: New Insight into Molecular Pathogenesis of Marfan Syndrome

  • Kim, Koung Li;Choi, Chanmi;Suh, Wonhee
    • Biomolecules & Therapeutics
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    • 제22권2호
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    • pp.143-148
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    • 2014
  • Marfan syndrome (MFS) is a dominantly inherited connective tissue disorder caused by mutations in the gene encoding fibrillin-1 (FBN1) and is characterized by aortic dilatation and dissection, which is the primary cause of death in untreated MFS patients. However, disease progression-associated changes in gene expression in the aortic lesions of MFS patients remained unknown. Using a mouse model of MFS, FBN1 hypomorphic mouse (mgR/mgR), we characterized the aortic gene expression profiles during the progression of the MFS. Homozygous mgR mice exhibited MFS-like phenotypic features, such as fragmentation of elastic fibers throughout the vessel wall and were graded into mgR1-4 based on the pathological severity in aortic walls. Comparative gene expression profiling of WT and four mgR mice using microarrays revealed that the changes in the transcriptome were a direct reflection of the severity of aortic pathological features. Gene ontology analysis showed that genes related to oxidation/reduction, myofibril assembly, cytoskeleton organization, and cell adhesion were differentially expressed in the mgR mice. Further analysis of differentially expressed genes identified several candidate genes whose known roles were suggestive of their involvement in the progressive destruction of aorta during MFS. This study is the first genome-wide analysis of the aortic gene expression profiles associated with the progression of MFS. Our findings provide valuable information regarding the molecular pathogenesis during MFS progression and contribute to the development of new biomarkers as well as improved therapeutic strategies.

원심 임펠러가 장착된 발효조에서 G. hansenii에 의한 미생물셀룰로오스 생산 (Production of Bacterial Cellulose by Gluconacetobacter hansenii Using a New Bioreactor Equipped with Centrifugal Impellers)

  • 칸살만;쉐자드오머;칸타우스;하정환;박중곤
    • Korean Chemical Engineering Research
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    • 제47권4호
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    • pp.506-511
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    • 2009
  • 미생물셀룰로오스의 생산성을 높이기 위하여 원심(centrifugal) 임펠러와 경사원심(inclined centrifugal) 임펠러가 사용되었다. 발효조 내의 유체흐름 형태와 부피산소전달 계수가 고찰되었으며 원심 임펠러 및 경사원심 임펠러가 장착된 발효조 내에서 G. hansenii PJK 균주에 의하여 미생물 셀룰로오스가 생산되었다. 유체는 발효조 하부에서 원심 임펠러의 실린더 내부를 통과하여 발효조 벽면을 향해 순환되었다. 임펠러의 회전속도 100 rpm에서 부피산소전달계수는 터바인 임펠러 계에 비하여 경사원심 임펠러의 경우는 23%, 원심 임펠러의 경우는 15%에 불과하였다. 하지만 미생물셀룰로오스 생산 불능 돌연변이주로의 전환이 방지되어 20 rpm의 경사원심 임펠러의 회전속도에서 미생물셀룰로오스의 생산량이 터바인임펠러의 최적회전속도 300 rpm에서의 미생물셀룰로오스 생산량과 같았다.

Characterization and Prognosis Significance of JAK2 (V617F), MPL, and CALR Mutations in Philadelphia-Negative Myeloproliferative Neoplasms

  • Singdong, Roongrudee;Siriboonpiputtana, Teerapong;Chareonsirisuthigul, Takol;Kongruang, Adcharee;Limsuwanachot, Nittaya;Sirirat, Tanasan;Chuncharunee, Suporn;Rerkamnuaychoke, Budsaba
    • Asian Pacific Journal of Cancer Prevention
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    • 제17권10호
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    • pp.4647-4653
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    • 2016
  • Background: The discovery of somatic acquired mutations of JAK2 (V617F) in Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPNs) including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) has not only improved rational disease classification and prognostication but also brings new understanding insight into the pathogenesis of diseases. Dosage effects of the JAK2 (V617F) allelic burden in Ph-negative MPNs may partially influence clinical presentation, disease progression, and treatment outcome. Material and Methods: Pyrosequencing was performed to detect JAK2 (V617F) and MPL (W515K/L) and capillary electrophoresis to identify CALR exon 9 mutations in 100 samples of Ph-negative MPNs (38.0 PV, 55 ET, 4 PMF, and 3 MPN-U). Results: The results showed somatic mutations of JAK2 (V617F) in 94.7% of PV, 74.5% of ET, 25.0% of PMF, and all MPN-U. A high proportion of JAK2 (V617F) mutant allele burden (mutational load > 50.0%) was predominantly observed in PV when compared with ET. Although a high level of JAK2 (V617F) allele burden was strongly associated with high WBC counts in both PV and ET, several hematological parameters (hemoglobin, hematocrit, and platelet count) were independent of JAK2 (V617F) mutational load. MPL (W515K/L) mutations could not be detected whereas CALR exon 9 mutations were identified in 35.7% of patients with JAK2 negative ET and 33.3% with JAK2 negative PMF. Conclusions: The JAK2 (V617F) allele burden may be involved in progression of MPNs. Furthermore, a high level of JAK2 (V617F) mutant allele appears strongly associated with leukocytosis in both PV and ET.

Brassinosteroid의 대사공학 (Metabolic Engineering of the Brassinosteroid Biosynthetic Pathways)

  • 이미옥;송기홍;이현경;정지윤;최빛나리;최성화
    • 한국식물생명공학회:학술대회논문집
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    • 한국식물생명공학회 2002년도 추계학술대회
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    • pp.69-75
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    • 2002
  • Sterols play two major roles in plants: a bulk component in biological membranes and precursors of plant steroid hormones. Physiological effects of plant steroids, brassinosteroids (BRs), include cell elongation, cell division, stress tolerance, and senescence acceleration. Arabidopsis mutants that carry genetic defects in BR biosynthesis or its signaling display characteristic phenotypes, such as short robust inflorescences, dark-green round leaves, and sterility. Currently there are more than 100 dwarf mutants representing 7 genetic loci in Arabidopsis. Mutants of 6 loci, dwf1/dim1/cbb1, cpd/dwf3, dwf4, dwf5, det2/dwf6, dwf7 are rescued by exogenous application of BRs, whereas bri1/dwf2 shares phenotypes with the above 6 loci but are resistant to BRs. These suggest that the 6 loci are defective in BR biosynthesis, and the one locus is in BR signaling. Biochemical analyses, such as intermediate feeding tests, examining the levels of endogenous BR, and molecular cloning of the genes revealed that dwf7, dwf5, and dwf1 are defective in the three consecutive steps of sterol biosynthesis, from episterol to campesterol via 5-dehydroepisterol. Similarly, det2/dwf6, dwf4, and cpd/dwf3 were shown to be blocked in $D^4$ reduction, 22a-hydroxylation, and 23 a-hydroxylation, respectively. A signaling mutant bri1/dwf2 carries mutations in a Leucine-rich repeat receptor kinase. Interestingly, the bri1 mutant was shown to accumulate significant amount of BRs, suggesting that signaling and biosynthesis are dynamically coupled in Arabidopsis. Thus It is likely that transgenic plants over-expressing the rate-limiting step enzyme DWF4 as well as blocking its use by BRI1 could dramatically increase the biosynthetic yield of BRs. When applied industrially, BRs will boost new sector of plant biotechnology because of its potential use as a precursor of human steroid hormones, a novel lead compound for cholesterol-lowering effects, and a various application in plant protection.

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대두를 이용한 Lovastatin 대량생산용 Seed Culture의 제조기술 (Development of Seed Culture Using Soybean for Mass Production of Lovastatin with Aspergillus terreus ATCC 20542 Mutant)

  • 김수정;고희선;김현수
    • 한국식품영양과학회지
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    • 제37권5호
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    • pp.666-670
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    • 2008
  • 본 연구는 Asp. terreus ATCC 20542 변이주로부터 lovastatin 생산용 seed culture의 대량제조를 위한 방법을 개발한 것이다. 배양체의 선발, 분석 및 최적 배양용기를 검토한 결과 대두를 이용하여 petri dish(${\phi}150{\times}20mm$)에 배양하였을 때 lovastatin의 생산성이 우수하였다. 포자의 발아 촉진을 위하여 대두에 Asp. terreus를 접종한 다음 열처리를 달리하여, 각 전배양체를 미강에 본배양하였다. 본배양액을 추출한 후 HPLC를 이용하여 lovastatin 생산량을 검토한 결과 $30^{\circ}C$에서 1시간 동안 열처리한 전배양체가 본배양 12일째에 가장 높은 lovastatin 생산성을 보이며, in vitro assay 결과, 대두를 $30^{\circ}C$에서 1시간 열처리하여 본배양하였을 경우에 HMG-CoA reductase가 82% 저해되는 것으로 나타났다. 따라서 기존의 포자현탁액 접종법보다 대두를 이용한 방법이 더욱 높은 HMG-CoA reductase 저해활성 및 배양시간의 단축성을 보여 산업화에 유리한 것으로 사료되었다.