• 제목/요약/키워드: molecular replacement

검색결과 145건 처리시간 0.027초

비변색타입의 무용제형 상온 액상수지 (Non-Solvent Liquid Resin of Non-Discoloration Type at Room Temperature)

  • 문진복;목동엽;김규현
    • Korean Chemical Engineering Research
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    • 제47권6호
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    • pp.669-675
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    • 2009
  • 연질 PVC 대체를 위한 비변색 타입의 무용제형 상온 액상수지를 폴리올을 경화제로 사용하는 폴리우레탄수지 구조제어 설계를 통한 프리폴리머 합성방법을 응용하여 제조할 수 있었다. Macro-glycol, 분자량 및 반응조건의 영향 등을 고찰하여 최적의 작업성과 물성을 가지는 무용제형 상온액상수지를 제조하였으며, 우수한 기계적인 특성과 함께 유색작업을 위한 안료의 분산성 등에서도 우수하였고, Tg가 $-40^{\circ}C$의 값을 나타내었다. 또한 자외선 노출이나 질소산화물에 의한 황변특성도 개선할 수 있었다.

Glyco-engineering strategies for the development of therapeutic enzymes with improved efficacy for the treatment of lysosomal storage diseases

  • Oh, Doo-Byoung
    • BMB Reports
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    • 제48권8호
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    • pp.438-444
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    • 2015
  • Lysosomal storage diseases (LSDs) are a group of inherent diseases characterized by massive accumulation of undigested compounds in lysosomes, which is caused by genetic defects resulting in the deficiency of a lysosomal hydrolase. Currently, enzyme replacement therapy has been successfully used for treatment of 7 LSDs with 10 approved therapeutic enzymes whereas new approaches such as pharmacological chaperones and gene therapy still await evaluation in clinical trials. While therapeutic enzymes for Gaucher disease have N-glycans with terminal mannose residues for targeting to macrophages, the others require N-glycans containing mannose-6-phosphates that are recognized by mannose-6-phosphate receptors on the plasma membrane for cellular uptake and targeting to lysosomes. Due to the fact that efficient lysosomal delivery of therapeutic enzymes is essential for the clearance of accumulated compounds, the suitable glycan structure and its high content are key factors for efficient therapeutic efficacy. Therefore, glycan remodeling strategies to improve lysosomal targeting and tissue distribution have been highlighted. This review describes the glycan structures that are important for lysosomal targeting and provides information on recent glyco-engineering technologies for the development of therapeutic enzymes with improved efficacy. [BMB Reports 2015; 48(8): 438-444]

Therapeutic Use of Stem Cell Transplantation for Cell Replacement or Cytoprotective Effect of Microvesicle Released from Mesenchymal Stem Cell

  • Choi, Moonhwan;Ban, Taehyun;Rhim, Taiyoun
    • Molecules and Cells
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    • 제37권2호
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    • pp.133-139
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    • 2014
  • Idiopathic pulmonary fibrosis (IPF) is the most common and severe type of idiopathic interstitial pneumonias (IIP), and which is currently no method was developed to restore normal structure and function. There are several reports on therapeutic effects of adult stem cell transplantations in animal models of pulmonary fibrosis. However, little is known about how mesenchymal stem cell (MSC) can repair the IPF. In this study, we try to provide the evidence to show that transplanted mesenchymal stem cells directly replace fibrosis with normal lung cells using IPF model mice. As results, transplanted MSC successfully integrated and differentiated into type II lung cell which express surfactant protein. In the other hand, we examine the therapeutic effects of microvesicle treatment, which were released from mesenchymal stem cells. Though the therapeutic effects of MV treatment is less than that of MSC treatment, MV treat-ment meaningfully reduced the symptom of IPF, such as collagen deposition and inflammation. These data suggest that stem cell transplantation may be an effective strategy for the treatment of pulmonary fibrosis via replacement and cytoprotective effect of microvesicle released from MSCs.

Enhanced sialylation and in vivo efficacy of recombinant human α-galactosidase through in vitro glycosylation

  • Sohn, Youngsoo;Lee, Jung Mi;Park, Heung-Rok;Jung, Sung-Chul;Park, Tai Hyun;Oh, Doo-Byoung
    • BMB Reports
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    • 제46권3호
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    • pp.157-162
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    • 2013
  • Human ${\alpha}$-galactosidase A (GLA) has been used in enzyme replacement therapy for patients with Fabry disease. We expressed recombinant GLA from Chinese hamster ovary cells with very high productivity. When compared to an approved GLA (agalsidase beta), its size and charge were found to be smaller and more neutral. These differences resulted from the lack of terminal sialic acids playing essential roles in the serum half-life and proper tissue targeting. Because a simple sialylation reaction was not enough to increase the sialic acid content, a combined reaction using galactosyltransferase, sialyltransferase, and their sugar substrates at the same time was developed and optimized to reduce the incubation time. The product generated by this reaction had nearly the same size, isoelectric points, and sialic acid content as agalsidase beta. Furthermore, it had better in vivo efficacy to degrade the accumulated globotriaosylceramide in target organs of Fabry mice compared to an unmodified version.

Enoxaparin as an Anticoagulant in a Multipara with a Mechanical Mitral Valve: A Case Report

  • Yo Seb Lee;Jun Seok Kim
    • Journal of Chest Surgery
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    • 제56권6호
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    • pp.452-455
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    • 2023
  • Patients who have undergone mechanical valve replacement require anticoagulation therapy with warfarin to prevent thromboembolism. However, administering warfarin to pregnant patients increases their risk of warfarin embryopathy or central nervous system disorders. Consequently, safer alternatives, such as heparin or low-molecular-weight heparin injection, are substituted for warfarin. However, limited research has been conducted on this subject, with no large-scale studies and particularly few investigations involving multiparous patients. A patient who had previously undergone mechanical mitral valve replacement for atrial septal defect and mitral stenosis received anticoagulant therapy with enoxaparin during 2 pregnancies. Upon confirmation of pregnancy, warfarin was replaced with subcutaneously injected enoxaparin with a dosage of 1 mg/kg at 12-hour intervals. The enoxaparin dosage was controlled using an anti-factor Xa assay, with a target range of 0.3-0.7 IU/mL. Intravenous heparin injections were administered starting 3 days prior to the expected delivery date and were continued until delivery, after which warfarin was resumed. No complications were observed during the deliveries.

Dietary inclusion effects of phytochemicals as growth promoters in animal production

  • Valenzuela-Grijalva, Nidia Vanessa;Pinelli-Saavedra, Araceli;Muhlia-Almazan, Adriana;Dominguez-Diaz, David;Gonzalez-Rios, Humberto
    • Journal of Animal Science and Technology
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    • 제59권4호
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    • pp.8.1-8.17
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    • 2017
  • Growth promoters have been widely used as a strategy to improve productivity, and great benefits have been observed throughout the meat production chain. However, the prohibition of growth promoters in several countries, as well as consumer rejection, has led industry and the academy to search for alternatives. For decades, the inclusion of phytochemicals in animal feed has been proposed as a replacement for traditional growth promoters. However, there are many concerns about the application of phytochemicals and their impact on the various links in the meat production chain (productive performance, carcass and meat quality). Therefore, the effects of these feed additives are reviewed in this article, along with their potential safety and consumer benefits, to understand the current state of their use. In summary, the replacement of traditional growth promoters in experiments with broilers yielded benefits in all aspects of the meat production chain, such as improvements in productive performance and carcass and meat quality. Although the effects in pigs have been similar to those observed in broilers, fewer studies have been carried out in pigs, and there is a need to define the types of phytochemicals to be used and the appropriate stages for adding such compounds. In regard to ruminant diets, few studies have been conducted, and their results have been inconclusive. Therefore, it is necessary to propose more in vivo studies to determine other strategies for phytochemical inclusion in the production phases and to select the appropriate types of compounds. It is also necessary to define the variables that will best elucidate the mechanism(s) of action that will enable the future replacement of synthetic growth promoters with phytochemical feed additives.

Clinical and molecular characterization of Korean children with infantile and late-onset Pompe disease: 10 years of experience with enzyme replacement therapy at a single center

  • Kim, Min-Sun;Song, Ari;Im, Minji;Huh, June;Kang, I-Seok;Song, Jinyoung;Yang, Aram;Kim, Jinsup;Kwon, Eun-Kyung;Choi, Eu-Jin;Han, Sun-Ju;Park, Hyung-Doo;Cho, Sung Yoon;Jin, Dong-Kyu
    • Clinical and Experimental Pediatrics
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    • 제62권6호
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    • pp.224-234
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    • 2019
  • Purpose: Pompe disease (PD) is an autosomal recessive disorder caused by a deficiency of acid alpha-glucosidase resulting from pathogenic GAA variants. This study describes the clinical features, genotypes, changes before and after enzyme replacement therapy (ERT), and long-term outcomes in patients with infantile-onset PD (IOPD) and late-onset PD (LOPD) at a tertiary medical center. Methods: The medical records of 5 Korean patients (2 male, 3 female patients) diagnosed with PD between 2002 and 2013 at Samsung Medical Center in Seoul, Republic of Korea were retrospectively reviewed for data, including clinical and genetic characteristics at diagnosis and clinical course after ERT. Results: Common initial symptoms included hypotonia, cyanosis, and tachycardia in patients with IOPD and limb girdle weakness in patients with LOPD. Electrocardiography at diagnosis revealed hypertrophic cardiomyopathy in all patients with IOPD who showed a stable disease course during a median follow-up period of 10 years. Patients with LOPD showed improved hepatomegaly and liver transaminase level after ERT. Conclusion: As ERT is effective for treatment of PD, early identification of this disease is very important. Thus, patients with IOPD should be considered candidates for clinical trials of new drugs in the future.

The cloning and characterization of the small GTP-binding Protein RacB in rice.

  • Jung, Young-Ho;Jaw, Nam-Soo
    • 한국식물병리학회:학술대회논문집
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    • 한국식물병리학회 2003년도 정기총회 및 추계학술발표회
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    • pp.81.2-82
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    • 2003
  • Plants have evolved along with pathogens, and they have developed sophisticated defense systems against specific microorganisms to survive. G-protons are considered one of the upstream signaling components working as a key for the defense signal transduction pathway. For activation and inactivation of G-protein, GTP-biding proteins are involved. GTP -binding proteins are found in all organisms. Small GTP-binding proteins, having masses of 21 to 30kD, belong to a superfamily, often named the Ras supefamily because the founding members are encoded by human Ras genes initially discovered as cellular homologs of the viral ras oncogene. Members of this supefamily share several common structural features, including several guanine nucleotide binding domains and an effector binding domain. However, exhibiting a remarkable diversity in both structure and function. They are important molecular switches that cycle between the GDP-bound inactive form into the GTP-bound active form through GDP/GTP replacement. In addition, most GTP-binding proteins cycle between membrane-bound and cytosolic forms. such as the RAC family are cytosolic signal transduction proteins that often are involved in processing of extracellular stimuli. Plant RAC proteins are implicated in regulation of plant cell architecture secondary wall formation, meristem signaling, and defense against pathogens. But their molecular mechanisms and functions are not well known. We isolated a RacB homolog from rice to study its role of defense against pathogens. We introduced the constitutively active and the dominant negative forms of the GTP-hinging protein OsRacB into the wild type rice. The dominant negative foms are using two forms (full-sequence and specific RNA interference with RacB). Employing southern, and protein analysis, we examine to different things between the wild type and the transformed plant. And analyzing biolistic bombardment of onion epidermal cell with GFP-RacB fusion protein revealed association with the nucle.

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Functional Modification of a Specific RNA with Targeted Trans-Splicing

  • Park, Young-Hee;Kim, Sung-Chun;Kwon, Byung-Su;Jung, Heung-Su;Kim, Kuchan;Lee, Seong-Wook
    • Genomics & Informatics
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    • 제2권1호
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    • pp.45-52
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    • 2004
  • The self-splicing group I intron from Tetrahymena thermophila has been demonstrated to perform splicing reaction with its substrate RNA in the trans configuration. In this study, we explored the potential use of the trans-splicing group I ribozymes to replace a specific RNA with a new RNA that exerts any new function we want to introduce. We have chosen thymidine phosphorylase (TP) RNA as a target RNA that is known as a valid cancer prognostic factor. Cancer-specific expression of TP RNA was first evaluated with RT-PCR analysis of RNA from patients with gastric cancer. We determined next which regions of the TP RNA are accessible to ribozymes by employing an RNA mapping strategy, and found that the leader sequences upstream of the AUG start codon appeared to be particularly accessible. A specific ribozyme recognizing the most accessible sequence in the TP RNA with firefly luciferase transcript as a 3' exon was then developed. The specific trans-splicing ribozyme transferred an intended 3' exon tag sequence onto the targeted TP transcripts, resulting in a more than two fold induction of the reporter activity in the presence of TP RNA in mammalian cells, compared to the absence of the target RNA. These results suggest that the Tetrahymena ribozyme can be a potent anti-cancer agent to modify TP RNAs in tumors with a new RNA harboring anti-cancer activity.

Cryparin 유전자의 promoter 분석을 위한 cryparin 유전자 치환체의 순수 제조 (Construction of a Pure Cryparin-null Mutant for the Promoter Analysis of Cryparin Gene)

  • 김명주;양문식;김대혁
    • 한국균학회지
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    • 제26권4호통권87호
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    • pp.450-457
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    • 1998
  • Cryparin은 Cryphonectria parasitica의 세포벽에 풍부한 소수성 단백질에 속한다. cryparin은 비록 하나의 유전자에 의해 발현되지만 액체배양 후 48시간이 지나면 발현된 전체 유전자중에서 22%를 차지할 정도의 높은 발현 양상을 나타낸다. 또한 cryparin은 RNA mycovirus인 Cryphonectria hypovirus 1의 감염에 의해 발현이 현저히 억제되는 유전자로 알려졌다. 이미 지난 실험(Kim et al., 1999)에서 상동염색체간의 재조합을 이용하여 cryparin 유전자를 항생제 hygromycin B 저항성 유전자로 치환한 치환체를 제조하였다. 발현율이 매우 높으면서도 virus에 의해 밀접하게 영향받는 cryparin 유전자의 promoter 분석을 위하여서는 대상이 되는 유전자 치환을 위한 vector만을 포함하며, 분석에 이용될 여러 유전자 운반체들이 어느 한곳에만 삽입되도록 하는 성질을 가진 균주의 개발이 필요하다. 그러나 지난번 실험의 결과 얻어진 cryparin 치환체는 치환용 vector외에도 무작위로 삽입된 vector가 존재하고 나아가 새로운 vector들이 어느 한곳에만 삽입되도록 하는 성질을 갖지 못하였다. 따라서 본 실험에서는 cryparin 유전자 치환체와 영양요구성 돌연변이체인 균주간의 교잡을 이용하여 분석 대상이 되는 유전자의 치환에 이용된 vector만을 포함하며, 분석에 이용될 여러 유전자 운반체들이 genome내의 어느 한곳에만 삽입되도록 하는 성질을 가진 균주를 제조하였다.

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