• 제목/요약/키워드: NEW DEVELOPMENT OF REGIONS

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Mechanisms of Myotonic Dystrophies 1 and 2

  • Lubov, Timchenko
    • The Korean Journal of Physiology and Pharmacology
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    • 제9권1호
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    • pp.1-8
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    • 2005
  • Myotonic Dystrophies type 1 and 2 (DM1/2) are neuromuscular disorders which belong to a group of genetic diseases caused by unstable CTG triplet repeat (DM1) and CCTG tetranucleotide repeat (DM2) expansions. In DM1, CTG repeats are located within the 3' untranslated region of myotonin protein kinase (DMPK) gene on chromosome 19q. DM2 is caused by expansion of CCTG repeats located in the first intron of a gene coding for zinc finger factor 9 on chromosome 3q. The CTG and CCTG expansions are located in untranslated regions and are expressed as pre-mRNAs in nuclei (DM1 and DM2) and as mRNA in cytoplasm (DM1). Investigations of molecular alterations in DM1 discovered a new molecular mechanism responsible for this disease. Expansion of un-translated CUG repeats in the mutant DMPK mRNA disrupts biological functions of two CUG-binding proteins, CUGBP and MNBL. These proteins regulate translation and splicing of mRNAs coding for proteins which play a key role in skeletal muscle function. Expansion of CUG repeats alters these two stages of RNA metabolism in DM1 by titrating CUGBP1 and MNBL into mutant DMPK mRNA-protein complexes. Mouse models, in which levels of CUGBP1 and MNBL were modulated to mimic DM1, showed several symptoms of DM1 disease including muscular dystrophy, cataracts and myotonia. Mis-regulated levels of CUGBP1 in newborn mice cause a delay of muscle development mimicking muscle symptoms of congenital form of DM1 disease. Since expansion of CCTG repeats in DM2 is also located in untranslated region, it is predicted that DM2 mechanisms might be similar to those observed in DM1. However, differences in clinical phenotypes of DM1 and DM2 suggest some specific features in molecular pathways in both diseases. Recent publications suggest that number of pathways affected by RNA CUG and CCUG repeats could be larger than initially thought. Detailed studies of these pathways will help in developing therapy for patients affected with DM1 and DM2.

Development of a New Type of Recombinant Hyaluronidase Using a Hexahistidine; Possibilities and Challenges in Commercialization

  • Park, Chaeri;Song, Yun-Kyoung;Kim, Young-Hyun;Jung, Yena;Park, Young-Ho;Song, Bong-Seok;Eom, Taekil;Kim, Ju-Sung;Kim, Sang-Hyun;Kim, Ji-Su;Kim, Sun-Uk;Lee, Sang-Rae;Kim, Ekyune
    • Journal of Microbiology and Biotechnology
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    • 제29권8호
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    • pp.1310-1315
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    • 2019
  • Hyaluronidases enhance therapeutic drug transport by breaking down the hyaluronan barrier to lymphatic and capillary vessels, facilitating their tissue absorption. Commercially available hyaluronidases are bovine in origin; however, they pose risks such as bovine spongiform encephalopathy. The present study aimed to develop a novel, highly active hyaluronidase and assess its function. Therefore, in order to find the most efficient active hyaluronidase, we produced several shortened hyaluronidases with partial removal of the N- or C-terminal regions. Moreover, we created an enzyme that connected six histidines onto the end of the hyaluronidase C-terminus. This simplified subsequent purification using $Ni^{2+}$ affinity chromatography, making it feasible to industrialize this highly active recombinant hyaluronidase which exhibited catalytic activity equal to that of the commercial enzyme. Therefore, this simple and effective isolation method could increase the availability of recombinant hyaluronidase for research and clinical purposes.

Begomoviruses and Their Emerging Threats in South Korea: A Review

  • Khan, Mohammad Sajid;Ji, Sang-He;Chun, Se-Chul
    • The Plant Pathology Journal
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    • 제28권2호
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    • pp.123-136
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    • 2012
  • Diseases caused by begomoviruses (family Geminiviridae, genus Begomovirus) constitute a serious constraint to tropical and sub-tropical agro-ecosystems worldwide. In recent years, they have also introduced in temperate regions of the world where they have great impact and are posing a serious threat to a variety of greenhouse crops. Begomoviral diseases can in extreme cases reduce yields to zero leading to catastrophic losses in agriculture. They are still evolving and pose a serious threat to sustainable agriculture across the world, particularly in tropics and sub-tropics. Till recently, there have been no records on the occurrence of begomoviral disease in South Korea, however, the etiology of other plant viral diseases are known since last century. The first begomovirus infected sample was collected from sweet potato plant in 2003 and since then there has been gradual increase in the begomoviral epidemics specially in tomato and sweet potato crops. So far, 48 begomovirus sequences originating from various plant species have been submitted in public sequence data base from different parts of the country. The rapid emergence of begomoviral epidemics might be with some of the factors like evolution of new variants of the viruses, appearance of efficient vectors, changing cropping systems, introduction of susceptible plant varieties, increase in global trade in agricultural products, intercontinental transportation networks, and changes in global climatic conditions. Another concern might be the emergence of a begomovirus complex and satellite DNA molecules. Thorough understanding of the pathosystems is needed for the designing of effective managements. Efforts should also be made towards the integration of the resistant genes for the development of transgenic plants specially tomato and sweet potato as they have been found to be widely infected in South Korea. There should be efficient surveillance for emergence or incursions of other begomoviruses and biotypes of whitefly. This review discusses the general characteristics of begomoviruses, transmission by their vector B. tabaci with an especial emphasis on the occurrence and distribution of begomoviruses in South Korea, and control measures that must be addressed in order to develop more sustainable management strategies.

Nigrospora Species Associated with Various Hosts from Shandong Peninsula, China

  • Hao, Yuanyuan;Aluthmuhandiram, Janith V.S.;Chethana, K.W. Thilini;Manawasinghe, Ishara S.;Li, Xinghong;Liu, Mei;Hyde, Kevin D.;Phillips, Alan J.L.;Zhang, Wei
    • Mycobiology
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    • 제48권3호
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    • pp.169-183
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    • 2020
  • Nigrospora is a monophyletic genus belonging to Apiosporaceae. Species in this genus are phytopathogenic, endophytic, and saprobic on different hosts. In this study, leaf specimens with disease symptoms were collected from host plants from the Shandong Peninsula, China. The fungal taxa associated with these leaf spots were studied using morphology and phylogeny based on ITS, TEF1, and TUB2 gene regions. In this article, we report on the genus Nigrospora with N. gorlenkoana, N. oryzae, N. osmanthi, N. rubi, and N. sphaerica identified with 13 novel host associations including crops with economic importance such as bamboo and Chinese rose.

A형 보튤리늄 톡신의 안면부 미용학적 적용 (Cosmetic Use of Botulinum Toxin Type A in the Face)

  • 강제구
    • 대한후두음성언어의학회지
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    • 제23권2호
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    • pp.111-118
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    • 2012
  • Botulinum toxin is a potent neurotoxin that is produced by the bacterium Clostridium botulinum. The agent causes muscle paralysis by preventing the release of acetylcholine at the neuromuscular junction of striated muscle. Botulinum toxin A (Botox, AllerganInc., Irvine, California) is the most potent of seven distinct toxin subtypes that are produced by the bacterium. The toxin was initially used clinically in the treatment of strabismus caused by hypertonicity of the extraocular muscles and was sub-sequently described in the treatment of multiple disorders of muscular spasticity and dystonia. In treating patients with Botox for blepharospasm, Carruthers and Carruthers [5] noticed an improvement in glabellar rhytids. This ultimately led to the introduction and development of Botox as a mainstay in the treatment of hyperfunctional facial lines in the upper face. Since its approval by the U.S. Food and Drug Administration for the treatment of facial rhytids (2002), botulinum toxin A has expanded into wide-spread clinical use. Forehead, glabellar, and periocular rhytids are the most frequently treated facial regions. Indications for alternative uses for Botox in facial plastic and reconstructive surgery are expanding. These include a variety of well-established procedures that use Botox as an adjunctive agent to enhance results. In addition, Botox injection is finding increased usefulness as an independent modality for facial rejuvenation and rehabilitation. The agent is used beyond its role in facial rhytids as an effective agent in the management of dynamic disorders of the face and neck. Botox injection allows the physician to precisely manipulate the balance between complex and conflicting muscular interactions, thus resetting their equilibrium state and exerting a clinical effect. This article will address some of the new and unique indications on Botox injection in the face (the lower face and neck, combination with fillers). Important points in terms of its clinical relevance will be stressed, such as an understanding of functional facial anatomy, the importance of precise injections, and correct dosing all are critical to obtaining natural outcomes.

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Comprehensive Study on Associations Between Nine SNPs and Glioma Risk

  • Liu, Hai-Bo;Peng, Yu-Ping;Dou, Chang-Wu;Su, Xiu-Lan;Gao, Nai-Kang;Tian, Fu-Ming;Bai, Jie
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권10호
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    • pp.4905-4908
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    • 2012
  • Aim: Glioma cancer is the most common type of adult brain tumor. Recent genome-wide association studies (GWAS) have identified various new susceptibility regions and here we conducted an extensive analysis of associations between 12 single nucleotide polymorphisms (SNPs) and glioma risk. Methods: A total of 197 glioma cases and 197 health controls were selected, and 9 SNPs in 8 genes were analyzed using the Sequenom MassARRAY platform and Sequenom Assay Design 3.1 software. Results: We found the MAF among selected controls were consistent with the MAF from the NCBI SNP database. Among 9 SNPs in 8 genes, we identified four significant SNP genotypes associated with the risk of glioma, C/C genotype at rs730437 and T/T genotype at rs1468727 in ERGF were protective against glioma, whereas the T/T genotype at rs1799782 in XRCC1 and C/C genotype at rs861539 in XRCC3 conferred elevated risk. Conclusion: Our comprehensive analysis of nine SNPs in eight genes suggests that the rs730437 and rs1468727 in ERGF, rs1799782 in XRCC1 gene, and rs861539 in XRCC3 gene are associated with glioma risk. These findings indicate that genetic variants of various genes play a complex role in the development of glioma.

Invertebrate Models Used for Characterization of Drug Dependence and Development of Anti-Drug Dependent Agents

  • Chang Hyun-Sook;Kim Ha-Won;Lee Dong-Hee
    • Biomolecules & Therapeutics
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    • 제14권1호
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    • pp.1-10
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    • 2006
  • Drug dependence deals a heavy socioeconomic burden to the society. For adolescents, the damage from drug dependence is greater than adults considering their higher susceptibility to drug effect and increasing chance for violence leading to criminal punishment process. Habitual drug use depends on genetic and environmental factors and the complex interactions between the two. Mammalian model systems have been useful in understanding the neurochemical and cellular impacts of abused drugs on specific regions of the brain, and in identifying the molecular targets of drugs. More elucidation is required whether biological effects of drugs actually cause the habitual dependence at the cellular level. Although there is much insight available on the nature of drug abuse problems, none of the systems designed to help drug dependent individuals is efficient in screening functional ingredients of the drug, and thus resulting in the failure of helping drug dependent individuals recover from drug dependence. Alternative model systems draw the attention of researchers, such as the invertebrate model systems of nematodes (Caenorhabditis elegans) and fruit flies (Drosophila melanogaster). These models should provide new insight into the mechanisms leading to the behavior of drug users (even functional studies analyzing molecular mechanism), and screening useful components to help remove drug dependence among drug users. The relatively simple anatomy and gene expression of the invertebrate model systems should enable researchers to coordinate current knowledge on drug abuse. Furthermore, the invertebrate model systems should facilitate advance in experiments on the susceptibility of specific genetic backgrounds and the interaction between genetic factors to drug dependence.

Cynomolgus Macaque Model for COVID-19 Delta Variant

  • Seung Ho Baek;Hanseul Oh;Bon-Sang Koo;Green Kim;Eun-Ha Hwang;Hoyin Jung;You Jung An;Jae-Hak Park;Jung Joo Hong
    • IMMUNE NETWORK
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    • 제22권6호
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    • pp.48.1-48.13
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    • 2022
  • With the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, which are randomly mutated, the dominant strains in regions are changing globally. The development of preclinical animal models is imperative to validate vaccines and therapeutics against SARS-CoV-2 variants. The objective of this study was to develop a non-human primate (NHP) model for SARS-CoV-2 Delta variant infection. Cynomolgus macaques infected with Delta variants showed infectious viruses and viral RNA in the upper (nasal and throat) and lower respiratory (lung) tracts during the acute phase of infection. After 3 days of infection, lesions consistent with diffuse alveolar damage were observed in the lungs. For cellular immune responses, all macaques displayed transient lymphopenia and neutrophilia in the early stages of infection. SARS-CoV-2 Delta variant spike protein-specific IgM, IgG, and IgA levels were significantly increased in the plasma of these animals 14 days after infection. This new NHP Delta variant infection model can be used for comparative analysis of the difference in severity between SARS-CoV-2 variants of concern and may be useful in the efficacy evaluation of vaccines and universal therapeutic drugs for mutations.

Development of a displacement-based design approach for modern mixed RC-URM wall structures

  • Paparoa, Alessandro;Beyer, Katrin
    • Earthquakes and Structures
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    • 제9권4호
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    • pp.789-830
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    • 2015
  • The recent re-assessment of the seismic hazard in Europe led for many regions of low to moderate seismicity to an increase in the seismic demand. As a consequence, several modern unreinforced masonry (URM) buildings, constructed with reinforced concrete (RC) slabs that provide an efficient rigid diaphragm action, no longer satisfy the seismic design check and have been retrofitted by adding or replacing URM walls with RC walls. Of late, also several new construction projects have been conceived directly as buildings with both RC and URM walls. Despite the widespread use of such construction technique, very little is known about the seismic behaviour of mixed RC-URM wall structures and codes do not provide adequate support to designers. The aim of the paper is therefore to propose a displacement-based design methodology for the design of mixed RC-URM edifices and the retrofit of URM buildings by replacing or adding selected URM walls with RC ones. The article describes also two tools developed for estimating important quantities relevant for the displacement-based design of structures with both RC and URM walls. The tools are (i) a mechanical model based on the shear-flexure interaction between URM and RC walls and (ii) an elastic model for estimating the contribution of the RC slabs to the overturning moment capacity of the system. In the last part of the article the proposed design method is verified through nonlinear dynamic analyses of several case studies. These results show that the proposed design approach has the ability of controlling the displacement profile of the designed structures, avoiding concentration of deformations in one single storey, a typical feature of URM wall structures.

학제에 따른 방사선(학)과 학생의 교육만족도 (Education Satisfaction by Students in Department of Radiologic Science according to Educational System)

  • 길종원;최성욱
    • 한국방사선학회논문지
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    • 제10권5호
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    • pp.343-349
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    • 2016
  • 본 연구는 2015년 04월 08일-06월 18일까지 대전 경상북도지역의 3년제 방사선(학)과 300명, 4년제 방사선학과 300명 총 600명을 대상으로 교육만족도를 평가하였다. 연구결과 3년제보다 4년제 방사선학과 학생들의 교육만족도가 유의하게 높았다(p<0.001). 그리고 남학생과 저학년에서 교육만족도가 높지만 일부 항목에서만 유의하였다(p<0.05, p<0.01,p<0.001). 3년제 방사선(학)과의 교육만족도를 높이기 위해서는 개설과목의 다양성 보다는 새롭고 전문적인 산학협력프로그램을 개발하여 적용하는 것이 더욱 효율적인 방법일 것이다.