• Title/Summary/Keyword: fibril

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End-to-end Structural Restriction of α-Synuclein and Its Influence on Amyloid Fibril Formation

  • Hong, Chul-Suk;Park, Jae Hyung;Choe, Young-Jun;Paik, Seung R.
    • Bulletin of the Korean Chemical Society
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    • v.35 no.12
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    • pp.3542-3546
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    • 2014
  • Relationship between molecular freedom of amyloidogenic protein and its self-assembly into amyloid fibrils has been evaluated with ${\alpha}$-synuclein, an intrinsically unfolded protein related to Parkinson's disease, by restricting its structural plasticity through an end-to-end disulfide bond formation between two newly introduced cysteine residues on the N- and C-termini. Although the resulting circular form of ${\alpha}$-synuclein exhibited an impaired fibrillation propensity, the restriction did not completely block the protein's interactive core since co-incubation with wild-type ${\alpha}$-synuclein dramatically facilitated the fibrillation by producing distinctive forms of amyloid fibrils. The suppressed fibrillation propensity was instantly restored as the structural restriction was unleashed with ${\beta}$-mercaptoethanol. Conformational flexibility of the accreting amyloidogenic protein to pre-existing seeds has been demonstrated to be critical for fibrillar extension process by exerting structural adjustment to a complementary structure for the assembly.

Development of Inhibitors of $\beta$-Amyloid Plaque Formation

  • Kim, Dong-Jin
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2006.04a
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    • pp.123-135
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    • 2006
  • Alzheimer's disease (AD) is the most common form of dementia in the aging population and is clinically characterized by a progressive loss of cognitive abilities. Pathologically, it is defined by the appearance of senile plaques - extracellular insoluble, congophilic protein aggregates composed of amyloid $\beta$ (A$\beta$) and neurofibrillary tangles (NFTs) - inyracellular lesions consisting of paired helical filaments from hyperphosphorylated cytoskeletal tau protein as described by Alois Alzheimer a century ago. These hallmarks still serve as the major criteria for a definite diagnosis of the disease. Consequently, one of the key strategy for drug development in this disease area focuses on reducing the concentration of cerebral A$\beta$ plaque by using substances that inhibit A$\beta$ fibril formation. We focused on developing inhibitors by synthesizing several kinds of aromatic molecules. The synthetic compounds were initially screened to evaluate the effective compound by tioflavin T fluorescence assay. The selected effective compounds were tested cytotoxicity and protective effect from A$\beta$-induced neuronal toxicity by cell based MTT assay with HT22 hippocampal neurons. The BBB permeability on effectors was also tested in in vitro co-culture model(HUVEC/C6 cell line). The behavior test wea carried out in mutant APP/PS1 transgenic mouse model of Alzheimer's disease. And inhibition of A$\beta$ fibril formation by the effective compound was monitored with transmitted electron microscopic images.

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Structural Properties of Fibril-forming Segments of α-Synuclein

  • Yoon, Je-Seong;Park, Joon-Ho;Jang, Soon-Min;Lee, Kyung-Hee;Shin, Seo-Min
    • Bulletin of the Korean Chemical Society
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    • v.30 no.3
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    • pp.623-629
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    • 2009
  • We have performed replica-exchange molecular dynamics simulations on 41 residue peptide mainly composed of NAC (non A$\beta$ component) sequence in $\alpha$-Synuclein. To investigate conformational characteristics of intrinsically unstructured peptides, we carried out structural analysis on the ‘representative structures’ for ensemble of structures occurring at different temperatures. The secondary structure profile obtained from our simulations suggests that the NAC region of $\alpha$-synuclein can be divided into roughly three helical-like segments. It is found that the overall helix-turn-helix like topology is conserved even though the conformational fluctuations grow as the temperature increases. The coordinate-based and the distance-based representative structures exhibit noticeable differences at higher temperatures while they are similar at lower temperatures. It is found that structural variations for the coordinate-based representative structures are much larger, suggesting that distance-based representative structures provide more reliable information concerning characteristic features of intrinsically unstructured proteins. The present analysis also indicates that the conformational features of representative structures at high temperatures might be related to those in membrane or low pH environment.

Study of Operation Condition of Biofilter Using Fibril-form Matrix for Odor Gas Removal (악취가스 제거를 위안 섬유상 담체를 적용한 바이오필터 운전조건에 관한 연구)

  • Jeong Gwi-Taek;Lee Gwang-Yeon;Byun Ki-Young;Lee Kyoung-Min;Sunwoo Chang-Shin;Lee Woo-Tae;Park Chan-Young;Kim Do-Hyeong;Cha Jin-Myoung;Jang Young-Seon;Park Don-Hee
    • KSBB Journal
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    • v.20 no.5 s.94
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    • pp.341-344
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    • 2005
  • This research was performed for developing of biological treatment process of odor gas such as MEK, $H_2S$, and toluene, which was generated from the food waste recycling process. To establish the operational conditions of odor gas removal by small-scale biofiltration equipment, it was continuously operated by using toluene as a treating odor object. When the odor treating microorganisms were adhered to fibril form biofilter, high removal efficiency over $93\%$ was obtained by biofilm formation. At 400 ppm of inlet odor gas concentration and 10 sec of retention time, the removal efficiency was $76\%$ and $93\%$ in 1 st stage reactor and End stage reactor, respectively. However, the removal efficiency remained over $97\%$ at the operational conditions above 15 sec of retention time.

ON THE DISCREPANCY OF CORONAL MAGNETIC FIELDS IN SOLAR OPTICS AND RADIO

  • MA YUE-HuA;LI XIAO-QING
    • Journal of The Korean Astronomical Society
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    • v.29 no.spc1
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    • pp.309-311
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    • 1996
  • It is analysed the discrepancy about the coronal magnetic field between solar optic and solar radio using magnetic fibril concept with filling factor and fractal structure model. The magnetic field of $\~$ 100 G considered in solar optics is mean value in a large scale, and that of $\~$1000 G in solar should be the value of fine structures inside 'macro' loop.

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Analyses for Identification of Methacrylamide Graft-Polymerized Silk (메타크릴아마이드 그라프트 중합견의 분석 방법)

  • ;M.R
    • Journal of Sericultural and Entomological Science
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    • v.29 no.1
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    • pp.64-68
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    • 1987
  • 견에 대한 비닐단량체의 증량가공에 있어서 메타크릴아마이드(metacrylamide) 크라프트 가공견의 판별 방법을 확립하기 위하여 가공견에 대한 정성분석과 미세구조를 관찰한 결과 가공견의 용해성 및 실소함유량은 미가공견에 비하여 저하되었으며 IR-Spectra도 파장 1385cm-1, 1210cm-1에서 미가공견과 다른 흡수 peak를 보였고 가공견의 pyrogram은 메타크릴아마이드의 세분해로 미가공견에서는 나타나지 않은 또 다른 peak를 보였다. 또한 가공견의 표면미세구조는 미가공견에 비하여 fibril이 팽대하여져 거친 면을 보였다.

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Synthesis of 6-[2-(Benzoxazol-2-ylmethylamino )ethoxy]-1-Alkyl­1 H-lndole-2-Carboxylic Acid and Inhibitory Activity on $\beta$-Amyloid Aggregation

  • Lee, Sun-Mi;Jeon, Raok
    • Archives of Pharmacal Research
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    • v.28 no.11
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    • pp.1219-1223
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    • 2005
  • 6-[2-(Benzoxazol-2-ylmethylamino)ethoxy]-1-alkyl-1H-indole-2-carboxylic acids were designed and synthesized as $\beta$-amyloid (A$\beta$) fibril assembly inhibitors. Their inhibitory activity on A$\beta$, aggregation was evaluated by thioflavin T assay although their activities were insignificant.

Preparation and Characterization of Microcrystalline Chitin from Crab Shell (게 껍질로부터 Microcrystalline Chitin 제조와 특성 규명)

  • 김성배
    • KSBB Journal
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    • v.11 no.4
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    • pp.481-488
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    • 1996
  • In spite of diverse applications of chitin derivatives, commercial use of chitin has been limited due to highly resistance to chemicals and the absense of proper solvents. One of methods to reduce such high resistance to chemicals is to make microcrystalline chitin(MCC) by hydrolysis of chitin. Presently, MCC is produced mainly by using high concentration of acid, but this treatment requires an extensive posttreatment to remove or recover acid. An alternative process for MCC production was developed by using dilute hydrochloric acid with ultrasound and hydrogen peroxide. The major parameters for this process were found to be acid concentration, swelling time and temperature, and irradiation time and frequency of ultrasound. The effects of these parameters on MCC molecular weight were investigated. The molecular weight of MCC produced at a typical condition was around 30,000 which was approximately 1/8 of that of chitin and approached to a constant value. This phenomenon was explained by introducing the model of molecular arrangement of cellulose. SEM analysis showed that both chitin and MCC had a fibrous shaped morphology and the fibril size of MCC was much smaller than that of chitin.

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End-Terminal Capping Effect on Mechanical Property of Transthyretin (TTR105-115) Amyloid Fibril (End-terminal Capping 효과가 아밀로이드 섬유의 기계적 특성에 미치는 영향 연구)

  • Choi, Hyunsung;Lee, Myeongsang;Na, Sungsoo
    • Transactions of the Korean Society of Mechanical Engineers A
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    • v.41 no.7
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    • pp.621-627
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    • 2017
  • The understanding of the mechanical properties of amyloid fibers, which induce various neurodegenerative diseases, is directly related to the amyloid growth mechanism. Diverse studies have been performed on amyloid fibers from the viewpoint of disease epidemiology. Recently, attempts have been made to use amyloid fibers as new materials because of their notable mechanical properties and self-aggregation abilities. In this study, the mechanical properties of transthyretin (TTR105-115), which induces cardiovascular disease, were evaluated using a molecular dynamics (MD) simulation. In particular, the effect of the end-terminal capping on the structural stability of TTR105-115 was evaluated. The mechanical behavior and properties of TTR105-115 were measured by steered molecular dynamics (SMD). We clarified the factors affecting the mechanical properties of these materials and suggested the possibility of utilizing them as nature inspired materials.

Effect of Tetracycline-HCL in Root Conditioning;A SEM Study (염산테트라싸이클린을 이용한 치근면처리의 효과)

  • Kim, Eun-Jung;Heer, Yeek;Lee, Man-Sup;Kwon, Young-Hyuk
    • Journal of Periodontal and Implant Science
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    • v.30 no.1
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    • pp.121-134
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    • 2000
  • Root conditioning has introduced to dissolve the smear layer and to produce surface demineralization, resulting to exposure of dentin collagen fibril and opening of dentinal tubules. The purpose of the present study was to examine the effect of different concentration and application time of tetracycline-HCL on root conditioning. Total 40 root specimen were prepared from 20 periodontitis-prone human single rooted tooth. The specimen were treated with tetracycline-HCL solution(20mg/ml, 50mg/ml, 100mg/ml)for 20 sec, 3 min, 5 min., and saline for 30 sec. The application method was rubbing method with cotton pellet. Under the scanning electron microscopy(20KV), the extent of smear removal and opening of the dentinal tubules were examined at x 3000. The following results were obtained. 1. Treatment of root specimen with saline did not remove the smear layer and open the dentinal tubules. 2. Treatment of root specimen with different concentration of tetracycline-HCL for 20 sec also did not remove the smear layer completely. 3. Treatment of root specimen with different concentration of tetracycline-HCL for 3 min opened the dentinal tubules and removed smear layer. 4. Treatment of root specimen with 50mg/ml of tetracycline-HCL for 3 min showed collagen fibril within the opened dentinal tubules. In conclusion, the effect of root conditioning with tetracycline-HCL is more dependent on the application time than the application concentration. Root conditioning with 50mg/ml tetracycline-HCL for 3 min is enough for obtaining the periodontal regeneration.

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