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Suppression of Interferon-mediated Anti-HBV Response by a Single CpG Methylation in 5``UTR of TRIM22
( Eun-sook Park ),( Doo Hyun Kim ),( Ah Ram Lee ),( Soree Park ),( Heewoo Sim ),( Juhee Won ),( Kyun-hwan Kim ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1
Background & Aims: Interferons (IFNs) mediate direct antiviral activity. It plays a crucial role in early host immune response against viral infections. However, IFN therapy for hepatitis B virus (HBV) infection is known to be less effective than in other viral infections. Methods: We explored the cellular targets of HBV in response to IFNs using proteome-wide screening. Results: We identified the down- or up-regulated proteins in model cells after the IFN treatment using LC-MS/MS. We found the several downregulated IFN-stimulated genes (ISGs) including TRIM22 known as an antiviral protein against retroviruses. We demonstrated that HBx suppresses the transcription of TRIM22 through a single CpG methylation at its 5``UTR, which further reduces the IRF1 binding affinity thereby suppressing the IFNs-stimulated induction of TRIM22. Conclusion: Our findings were verified using a mouse model and primary human hepatocytes (PHHs) and may provide a mechanism how HBV evade host innate immune system.
Lim, Keo-Heun,Park, Eun-Sook,Kim, Doo Hyun,Cho, Kyung Cho,Kim, Kwang Pyo,Park, Yong Kwang,Ahn, Sung Hyun,Park, Seung Hwa,Kim, Kee-Hwan,Kim, Chang Wook,Kang, Hong Seok,Lee, Ah Ram,Park, Soree,Sim, Heew British Medical Association 2018 Gut Vol.67 No.1
<P>Conclusions We verified our findings using a mouse model, primary human hepatocytes and human liver tissues. Our data elucidate a mechanism by which HBV evades the host innate immune system.</P>
Direct Detection of Drug-Resistant Hepatitis B Virus in Serum Using a Dendron-Modified Microarray
( Doo Hyun Kim ),( Hong Seok Kang ),( Seong-suk Hur ),( Seobo Sim ),( Sung Hyun Ahn ),( Yong Kwang Park ),( Eun-sook Park ),( Ah Ram Lee ),( Soree Park ),( So Young Kwon ),( Jeong-hoon Lee ),( Kyun-hw 대한간학회 2018 Gut and Liver Vol.12 No.3
Background/Aims: Direct sequencing is the gold standard for the detection of drug-resistance mutations in hepatitis B virus (HBV); however, this procedure is time-consuming, labor-intensive, and difficult to adapt to high-throughput screening. In this study, we aimed to develop a dendron-modified DNA microarray for the detection of genotypic resistance mutations and evaluate its efficiency. Methods: The specificity, sensitivity, and selectivity of dendron-modified slides for the detection of representative drug-resistance mutations were evaluated and compared to those of conventional slides. The diagnostic accuracy was validated using sera obtained from 13 patients who developed viral breakthrough during lamivudine, adefovir, or entecavir therapy and compared with the accuracy of restriction fragment mass polymorphism and direct sequencing data. Results: The dendron-modified slides significantly outperformed the conventional microarray slides and were able to detect HBV DNA at a very low level (1 copy/μL). Notably, HBV mutants could be detected in the chronic hepatitis B patient sera without virus purification. The validation of our data revealed that this technique is fully compatible with sequencing data of drug-resistant HBV. Conclusions: We developed a novel diagnostic technique for the simultaneous detection of several drug-resistance mutations using a dendron-modified DNA microarray. This technique can be directly applied to sera from chronic hepatitis B patients who show resistance to several nucleos(t)ide analogues. (Gut Liver 2018;12:331-341)
Park, Sang-Won,Kim, Soree,Jung, YounJoon The Royal Society of Chemistry 2015 Physical chemistry chemical physics Vol.17 No.43
<P>We study how dynamic heterogeneity in ionic liquids is affected by the length scale of structural relaxation and the ionic charge distribution by the molecular dynamics simulations performed on two differently charged models of ionic liquid and their uncharged counterpart. In one model of ionic liquid, the charge distribution in the cation is asymmetric, and in the other it is symmetric, while their neutral counterpart has no charge with the ions. It is found that all the models display heterogeneous dynamics, exhibiting subdiffusive dynamics and a nonexponential decay of structural relaxation. We investigate the lifetime of dynamic heterogeneity, <I>τ</I><SUB>dh</SUB>, in these systems by calculating the three-time correlation functions to find that <I>τ</I><SUB>dh</SUB> has in general a power-law behavior with respect to the structural relaxation time, <I>τ</I><SUB><I>α</I></SUB>, <I>i.e.</I>, <IMG SRC='http://www.rsc.org/ej/CP/2015/c5cp03390j/c5cp03390j-t2.gif'>. Although the dynamics of the asymmetric-charge model is seemingly more heterogeneous than that of the symmetric-charge model, the exponent is found to be similar, <I>ζ</I><SUB>dh</SUB>≈ 1.2, for all the models studied in this work. The same scaling relation is found regardless of interactions, <I>i.e.</I>, with or without Coulomb interaction, and it holds even when the length scale of structural relaxation is long enough to become the Fickian diffusion. This fact indicates that <I>τ</I><SUB>dh</SUB> is a distinctive time scale from <I>τ</I><SUB><I>α</I></SUB>, and the dynamic heterogeneity is mainly affected by the short-range interaction and the molecular structure.</P> <P>Graphic Abstract</P><P>We find a general power-law behavior: <IMG SRC='http://www.rsc.org/ej/CP/2015/c5cp03390j/c5cp03390j-t1.gif'>, where <I>ζ</I><SUB>dh</SUB>≈ 1.2 for all the ionic liquid models, regardless of charges and the length scale of structural relaxation. <IMG SRC='http://pubs.rsc.org/services/images/RSCpubs.ePlatform.Service.FreeContent.ImageService.svc/ImageService/image/GA?id=c5cp03390j'> </P>
Heterogeneous dynamics and its length scale in simple ionic liquid models: a computational study
Kim, Soree,Park, Sang-Won,Jung, YounJoon The Royal Society of Chemistry 2016 Physical chemistry chemical physics Vol.18 No.9
<P>We numerically investigate the dynamic heterogeneity and its length scale found in coarse-grained ionic liquid model systems. In our ionic liquid model systems, cations are modeled as dimers with a positive charge, while anions are modeled as monomers with a negative charge, respectively. To study the effect of the charge distributions on the cations, two ionic liquid models with different charge distributions are used and the model with a neutral charge is also considered as a counterpart. To reveal the heterogeneous dynamics in the model systems, we examine spatial distributions of displacement and time distributions of exchange and persistence times. All the models show a significant increase of the dynamic heterogeneity as the temperature is lowered. The dynamic heterogeneity is quantified via the well-known four-point susceptibility, chi(4)(t), which measures the fluctuations of a time correlation function. The dynamic correlation length is calculated by fitting the dynamic structure factor, S-4(k, t), with the Ornstein-Zernike form at the time scale at which the dynamic heterogeneity reaches the maximum value. The obtained time and length scales exhibit a power law relation at the low temperatures, similar to various supercooled liquid models. In particular, the charged model systems show unusual crossover behaviors which are not observed in the uncharged model system. We ascribe the crossover behavior to the enhanced cage effect caused by charges on the particles.</P>
Development of DLP 3D Printer with Multiple Composite Materials
황소리(SoRee Hwang),이종원(JongWon Lee),이소향(SoHyang Lee),홍대기(DaeGi Hong),박민수(MinSoo Park) Korean Society for Precision Engineering 2020 한국정밀공학회지 Vol.37 No.5
Since most commercialized DLP 3D printers fabricate 3D structures by sinking materials to Vat using a bottom-up method, it is difficult to use various materials simultaneously and there are many restrictions on printing composite materials. Especially, composite resin mixed with various functional powders in photo curable resin generally has high viscosity, causing difficult material flow in the bottom-up method when using Vat. Additionally, most of the previously presented methods for fabricating multi-material structure use individual curing for each material, so the adhesion force at the contact surface is less than 50% compared to single material. Thus, in this paper, we propose a new type of DLP 3D printer that combines Material Extrusion and the DLP system. The proposed equipment can supply high viscosity composite material resins to a specific area to cure various materials simultaneously. This method will enable fabrication of multiple composite material structures with sufficient adhesion force. The tensile test will be performed to verify suitability of the proposed method.
( Jeong-ju Yoo ),( Eun-sook Park ),( Ah Ram Lee ),( Doo Hyun Kim ),( Sung Hyun Ahn ),( Hee Woo Sim ),( Soree Park ),( Hong Seok Kang ),( Ju Hee Won ),( Yea Na Ha ),( Gu-choul Shin ),( So Young Kwon ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1
Aims: Tenofovir disoproxil fumarate (TDF) is the most potent nucleoside analog for the treatment of chronic hepatitis B virus (HBV) infection. Genotypic resistance to tenofovir has not yet been reported. This study aimed to characterise HBV mutations that confer tenofovir resistance. Methods: Two consecutive patients with viral breakthrough during treatment with TDF-containing regimens were prospectively enrolled. The gene encoding HBV reverse transcriptase (RT) was sequenced. Nine HBV clones harbouring a series of mutations in the RT gene were constructed by site-directed mutagenesis. Drug susceptibility of each clone was determined by Southern blot analysis and real-time PCR. Relative frequency of mutants were evaluated by ultra-deep sequencing. Results: (Please understand that actual mutation site numbers were replaced by bold, underlined alphabetical letters since they are now confidential due to embargo policy.) Seven mutations (rtSaaaC [C], rtHbbbY [Y], rtDcccE [E], rtVdddL, rtLeeeM, rtMfffV, and rtLgggI) were commonly found in viral isolates from both patients after viral breakthrough; C, Y, and E were novel mutations. An HBV mutant harbouring all three mutations (CYE) was resistant to tenofovir. The IC<sub>50</sub> values for wild-type HBV and the CYE mutant were 3·8 ± 0·6 μM and 14·1 ± 1·8 μM, respectively. Ultra-deep sequencing showed that CYE mutant was dominant than any other mutant in both patients. All tenofovir-resistant mutants had similar susceptibility to a core inhibitor, NVR 3-778 (IC<sub>50</sub> < 0·4 μM) compared with wild-type (IC<sub>50</sub> = 0·4). Conclusions: Our study reveals that a novel triple mutation (CYE) is associated with tenofovir-resistance. These results demonstrate that tenofovir-resistant HBV mutants can emerge, although the genetic barrier is high. A novel core inhibitor might be a potential rescue therapy for tenofovir-resistant HBV.