Identification of a novel <i>FAM83H</i> mutation and microhardness of an affected molar in autosomal dominant hypocalcified amelogenesis imperfecta

Hyun, H.-K.,Lee, S.-K.,Lee, K.-E.,Kang, H.-Y.,Kim, E.-J.,Choung, P.-H.,Kim, J.-W. Blackwell Publishing Ltd 2009 International endodontic journal Vol.42 No.11

<P>Abstract</P><P>Aim </P><P>To determine the underlying molecular genetic aetiology of a family with the hypocalcified form of amelogenesis imperfecta and to investigate the hardness of the enamel and dentine of a known <I>FAM83H</I> mutation.</P><P>Methodology </P><P>Mutational screening of the <I>FAM83H</I> on the basis of candidate gene approach was performed. All exons and exon–intron boundaries was amplified and sequenced. A microhardness test was performed to measure the Vickers microhardness value.</P><P>Results </P><P>A novel nonsense mutation (c.1354C>T, p.Q452X) was identified in the last exon of <I>FAM83H</I>, which resulted in soft, uncalcified enamel. The affected enamel was extremely soft (about 17% of the normal control), but the underlying dentine was as hard as the normal control.</P><P>Conclusions </P><P>Mutational analysis revealed a novel mutation in <I>FAM83H</I> gene. Hardness of dentine was not affected by the mutation, whilst the enamel was extremely soft.</P>

Unraveling the Atomistic Sodiation Mechanism of Black Phosphorus for Sodium Ion Batteries by First-Principles Calculations

Hembram, K. P. S. S.,Jung, Hyun,Yeo, Byung Chul,Pai, Sung Jin,Kim, Seungchul,Lee, Kwang-Ryeol,Han, Sang Soo American Chemical Society 2015 The Journal of Physical Chemistry Part C Vol.119 No.27

<P>As opposed to the standard graphite anode used for lithium (Li) ion batteries (LIBs), a standard anode material for sodium (Na) ion batteries (NIBs) has not yet been reported. Black phosphorus is potentially very attractive as an anode material for NIBs, as it has a layered structure similar to graphite but a greater interlayer distance. In this work, we propose an atomistic mechanism for the sodiation of black phosphorus, based on first-principles calculations. The layered structure of black phosphorus is maintained up to the composition of Na<SUB>0.25</SUB>P, with <I>one-dimensional</I> sodiation (an intercalation process) occurring in the interlayer spaces of the black phosphorus, resulting in sliding of the phosphorene layers because one Na atom tends to bind to four P atoms. At Na levels beyond Na<SUB>0.25</SUB>P, the intercalation process changes to an alloying process. Sodiation exceeding the critical composition leads to breaking of P–P bonds and eventual formation of an amorphous phase from the layered Na<SUB><I>x</I></SUB>P structure. After the P–P bonds in the layered Na<SUB><I>x</I></SUB>P structure are broken, in a progress in which staggered P–P bonds are preferentially broken rather than planar P–P bonds, P<SUB>2</SUB> dumbbells are generated. As sodiation proceeds further, most of the P<SUB>2</SUB> dumbbells become isolated P atoms. Thus, in the amorphous Na<SUB>3</SUB>P phase, only low-coordinate P components such as isolated atoms (primarily) and dumbbells are found. We expect that our comprehensive understanding of the sodiation mechanism in black phosphorus will provide helpful guidelines in designing new types of black phosphorus anodes to obtain better performing NIBs.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jpccck/2015/jpccck.2015.119.issue-27/acs.jpcc.5b05482/production/images/medium/jp-2015-054822_0006.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/jp5b05482'>ACS Electronic Supporting Info</A></P>

Toward high efficiency organic photovoltaic devices with enhanced thermal stability utilizing P3HT-b-P3PHT block copolymer additives

Zhu, M.,Kim, H.,Jang, Y.,Park, S.,Ryu, D.,Kim, K.,Tang, P.,Qiu, F.,Kim, D.,Peng, J. Royal Society of Chemistry 2016 Journal of Materials Chemistry A Vol.4 No.47

<P>Organic photovoltaics (OPVs) have drawn an extensive amount of attention due to their low cost, processibility and flexibility. However, a cell based on a blend of poly(3-hexylthiophene) (P3HT) and [6,6]-phenyl-C-61-butyric acid methyl ester (PC61BM) has a limited power conversion efficiency (PCE) due to the short exciton diffusion length of similar to 10 nm. We address this issue by designing a series of all-conjugated diblock copolymers, poly(3-hexylthiophene)-b-poly(3-(6-diethylphosphonatohexyl) thiophene) (P3HT-b-P3PHT), intended for use as additives to improve the performance of P3HT:PC61BM-based photovoltaic devices. The PCE of the devices improved from 3.30% to 4.03% with the addition of P3HT-b-P3PHT (3 : 1). The thermal stability of devices with P3HT-b-P3PHT additives improved significantly relative to that of the P3HT:PC61BM reference device, where the devices including a copolymer with a higher P3PHT content exhibited a better thermal stability. It was found that the fill factor (FF) could be regulated by simply varying the block ratio of P3HT-b-P3PHT and played a crucial role in improving both the PCE and the thermal stability. The P3HT-b-P3PHT diffused at the P3HT:PC61BM interface, improved the miscibility between P3HT and PC61BM, optimized the nanoscale morphology of the photoactive layer, and reduced the active layer roughness, all of which improved the FF and thus contributed to an improvement in device performance.</P>

Efficient long-term amplification of hepatitis B virus isolates after infection of slow proliferating HepG2-NTCP cells

Kö,nig, Alexander,Yang, Jaewon,Jo, Eunji,Park, Kyu Ho Paul,Kim, Hyun,Than, Thoa Thi,Song, Xiyong,Qi, Xiaoxuan,Dai, Xinghong,Park, Soonju,Shum, David,Ryu, Wang-Shick,Kim, Jung-Hee,Yoon, Seung Kew,P Elsevier 2019 Journal of hepatology Vol.71 No.2

<P><B>Background & Aims</B></P> <P>As hepatitis B virus (HBV) spreads through the infected liver it is simultaneously secreted into the blood. HBV-susceptible <I>in vitro</I> infection models do not efficiently amplify viral progeny or support cell-to-cell spread. We sought to establish a cell culture system for the amplification of infectious HBV from clinical specimens.</P> <P><B>Methods</B></P> <P>An HBV-susceptible sodium-taurocholate cotransporting polypeptide-overexpressing HepG2 cell clone (HepG2-NTCPsec+) producing high titers of infectious progeny was selected. Secreted HBV progeny were characterized by native gel electrophoresis and electron microscopy. Comparative RNA-seq transcriptomics was performed to quantify the expression of host proviral and restriction factors. Viral spread routes were evaluated using HBV entry- or replication inhibitors, visualization of viral cell-to-cell spread in reporter cells, and nearest neighbor infection determination. Amplification kinetics of HBV genotypes B-D were analyzed.</P> <P><B>Results</B></P> <P>Infected HepG2-NTCPsec+ secreted high levels of large HBV surface protein-enveloped infectious HBV progeny with typical appearance under electron microscopy. RNA-seq transcriptomics revealed that HBV does not induce significant gene expression changes in HepG2-NTCPsec+, however, transcription factors favoring HBV amplification were more strongly expressed than in less permissive HepG2-NTCPsec−. Upon inoculation with HBV-containing patient sera, rates of infected cells increased from 10% initially to 70% by viral spread to adjacent cells, and viral progeny and antigens were efficiently secreted. HepG2-NTCPsec+ supported up to 1,300-fold net amplification of HBV genomes depending on the source of virus. Viral spread and amplification were abolished by entry and replication inhibitors; viral rebound was observed after inhibitor discontinuation.</P> <P><B>Conclusions</B></P> <P>The novel HepG2-NTCPsec+ cells efficiently support the complete HBV life cycle, long-term viral spread and amplification of HBV derived from patients or cell culture, resembling relevant features of HBV-infected patients.</P> <P><B>Lay summary</B></P> <P>Currently available laboratory systems are unable to reproduce the dynamics of hepatitis B virus (HBV) spread through the infected liver and release into the blood. We developed a slowly dividing liver-derived cell line which multiplies infectious viral particles upon inoculation with patient- or cell culture-derived HBV. This new infection model can improve therapy by measuring, in advance, the sensitivity of a patient’s HBV strain to specific antiviral drugs.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Cell culture system that mimicks complete HBV life cycle from entry to egress. </LI> <LI> Efficient <I>in vitro</I> infection with crude HBV patient sera. </LI> <LI> Up to 50- and 1,300-fold net amplification of patient- and cell culture-derived input HBV in the supernatant. </LI> <LI> Polyethylene glycol-independent HBV spread to adjacent cells, forming infected cell clusters. </LI> <LI> Evaluation of patient- and cell culture-derived HBV amplification w/wo antivirals over 8 weeks. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Foxp3 is a key downstream regulator of p53-mediated cellular senescence

Kim, J-E,Shin, J-S,Moon, J-H,Hong, S-W,Jung, D-J,Kim, J H,Hwang, I-Y,Shin, Y J,Gong, E-Y,Lee, D H,Kim, S-M,Lee, E Y,Kim, Y S,Kim, D,Hur, D,Kim, T W,Kim, K-p,Jin, D-H,Lee, W-J Macmillan Publishers Limited 2017 Oncogene Vol.36 No.2

<P>The downstream events and target genes of p53 in the process of senescence are not fully understood. Here, we report a novel function of the forkhead transcription factor Foxp3, which is a key player in mediating T-cell inhibitory functions, in p53-mediated cellular senescence. The overexpression of Foxp3 in mouse embryonic fibroblasts (MEFs) accelerates senescence, whereas Foxp3 knockdown leads to escape from p53-mediated senescence in p53-expressing MEFs. Consistent with these results, Foxp3 expression resulted in the induction of senescence in epithelial cancer cells, including MCF7 and HCT116 cells. Foxp3 overexpression also increased the intracellular levels of reactive oxygen species (ROS). The ROS inhibitor N-acetyl-L-cysteine rescued cells from Foxp3-expression-induced senescence. Furthermore, the elevated ROS levels that accompanied Foxp3 overexpression were paralleled by an increase in p21 expression. Knockdown of p21 in Foxp3-expressing MEFs abrogated the Foxp3-dependent increase in ROS levels, indicating that Foxp3 acts through the induction of p21 and the subsequent ROS elevation to trigger senescence. Collectively, these results suggest that Foxp3 is a downstream target of p53 that is sufficient to induce p21 expression, ROS production and p53-mediated senescence.</P>

p34 is a novel regulator of the oncogenic behavior of NEDD4-1 and PTEN

Hong, S-W,Moon, J-H,Kim, J-S,Shin, J-S,Jung, K-A,Lee, W-K,Jeong, S-Y,Hwang, J J,Lee, S-J,Suh, Y-A,Kim, I,Nam, K-Y,Han, S,Kim, J E,Kim, K-p,Hong, Y S,Lee, J-L,Lee, W-J,Choi, E K,Lee, J S,Jin, D-H,Kim, Macmillan Publishers Limited 2014 CELL DEATH AND DIFFERENTIATION Vol.21 No.1

PTEN is one of the most frequently mutated or deleted tumor suppressors in human cancers. NEDD4-1 was recently identified as the E3 ubiquitin ligase for PTEN; however, a number of important questions remain regarding the role of ubiquitination in regulating PTEN function and the mechanisms by which PTEN ubiquitination is regulated. In the present study, we demonstrated that p34, which was identified as a binding partner of NEDD4-1, controls PTEN ubiquitination by regulating NEDD4-1 protein stability. p34 interacts with the WW1 domain of NEDD4-1, an interaction that enhances NEDD4-1 stability. Expression of p34 promotes PTEN poly-ubiquitination, leading to PTEN protein degradation, whereas p34 knockdown results in PTEN mono-ubiquitination. Notably, an inverse correlation between PTEN and p34/NEDD4-1 levels was confirmed in tumor samples from colon cancer patients. Thus, p34 acts as a key regulator of the oncogenic behavior of NEDD4-1 and PTEN.

Feasibility of proposed single-nucleotide polymorphisms as predictive markers for targeted regimens in metastatic colorectal cancer

Kim, J C,Ha, Y J,Roh, S A,Choi, E Y,Yoon, Y S,Kim, K P,Hong, Y S,Kim, T W,Cho, D H,Kim, S Y,Kim, Y S Nature Publishing Group 2013 The British journal of cancer Vol.108 No.9

<P><B>Background:</B></P><P>Surrogate biomarkers for metastatic colorectal cancer (mCRC) are urgently needed to achieve the best outcomes for targeted therapy.</P><P><B>Methods:</B></P><P>A clinical association analysis was performed to examine the three single-nucleotide polymorphisms (SNPs) that were previously proposed as markers of chemosensitivity to the cetuximab (124 patients) and bevacizumab regimens (100 patients) in mCRC patients. In addition, biological correlations were examined for the candidate SNPs in terms of their regulatory pathway.</P><P><B>Results:</B></P><P>For cetuximab regimens, patients homozygous for the wild-type alleles (<I>GG</I>) of <I>LIFR rs3729740</I> exhibited a 1.9 times greater overall response rate (ORR) and 1.4 months longer progression-free survival (PFS) than those homozygous or heterozygous for the mutant allele (<I>GA</I> and <I>AA</I>; <I>P</I>=0.022 and 0.027, respectively). For bevacizumab regimens, patients homozygous for the minor alleles (<I>TT</I>) of <I>ANXA11 rs1049550</I> exhibited an ORR twice as high as those homozygous or heterozygous for the ancestral allele (<I>CC</I> and <I>CT</I>; <I>P</I>=0.031). Overall response rate gain was achieved up to 10% in patients with wild-type <I>LIFR rs3729740</I> patients either with wild-type <I>KRAS</I> or skin toxicity (<I>P</I>=0.001) respectively. Specifically in clones treated with cetuximab and bevacizumab regimens, active p-ERK and MMP-9 expressions were significantly reduced in clones expressing wild-type <I>LIFR rs3729740</I> (<I>P</I>=0.044) and in those expressing minor-type <I>ANXA11 rs1049550</I> (<I>P</I>=0.007), respectively.</P><P><B>Conclusion:</B></P><P><I>LIFR rs3729740</I> and possibly <I>ANXA11 rs1049550</I> may be useful as biomarkers for predicting whether mCRC patients are sensitive to relevant target regimens, although further validation in large cohorts is needed.</P>

Disruption of a regulatory loop between DUSP1 and p53 contributes to hepatocellular carcinoma development and progression

Hao, P.P.,Li, H.,Lee, M.J.,Wang, Y.P.,Kim, J.H.,Yu, G.R.,Lee, S.Y.,Leem, S.H.,Jang, K.Y.,Kim, D.G. Elsevier Science Publishers 2015 Journal of hepatology Vol.62 No.6

Background & Aims: Altered expression of dual specificity phosphatase 1 (DUSP1) is common in tumors including hepatocellular carcinoma (HCC), and is predictive of tumor progression and poor prognosis. However, the tumor suppressive role of DUSP1 has yet to be clearly elucidated. Methods: The molecular mechanisms of tumor suppression that were investigated were induction of apoptosis, cell cycle inhibition, and regulation of p53. Additionally, the antitumor effect of DUSP1 was assessed using a mouse model. Associated signaling pathways in HCC cells and tissues were examined. Results: Downregulation of DUSP1 expression was significantly correlated with poor differentiation (p<0.001) and advanced HCC stage (p=0.023). DUSP1 expression resulted in HCC suppression and longer survival (p=0.0002) in a xenoplant mice model. DUSP1 inhibited p38 MAPK phosphorylation and subsequently suppressed HSP27 activation, resulting in enhanced p53 phosphorylation at sites S15, S20, and S46 in HCC cells. Enhanced p53 activation induced the expression of target genes p21 and p27, which are linked to cell cycle arrest and apoptosis. Thus, DUSP1 was potentially linked to p53 activation via the p38 MAPK/HSP27 pathway. Wild-type but not mutant p53 transcriptionally upregulated DUSP1 via its DNA-binding domain. DUSP1 and p53 might collaborate to suppress tumors in hepatocarcinogenesis via a positive regulatory loop. Conclusions: Our results revealed that disruption of a positive regulatory loop between DUSP1 and p53 promoted HCC development and progression, providing a rationale for a therapeutic agent that restores DUSP1 in HCC.

Prevalences of Clonorchiasis and Metagonimiasis along Rivers in Jeonra-Nam-Do, Korea

Soh, C.T.,Lee, K.T.,Cho, K.M.,Ahn, Y.K.,Kim, S.J.,Chung, P.R.,Im, K.I.,Min, D.Y.,Lee, J.H.,Chang, J.K. INSTITUTE OF TROPICAL MEDICINE YONSEI UNIVERSITY 1976 YONSEI REPORTS ON TROPICAL MEDICINE Vol.7 No.1

전라남도 영산강 및 섬진강유역 주민의 간디스토마와 요꼬가와흡충 감염율의 조사 및 이들 패류매개성 기생충의 제1, 제2 중간숙주를 조사한 바 그 성적을 요약하면 다음과 같다(조사기간: 1975년 8,9월, 1976년 7,8월). 영산강 유역 영산강을 상류(YU), 중류(YM), 하류(YD)로 삼분하여 10개 표본지역을 선정, 조사하였다(표 1 참조). 상류는 광산군 송정읍의 상부지역으로 장성군과 담양군이 이에 해당되며 중류는 송정읍과 나주군 영산포읍 사이의 지역으로 광산군 일부와 나주군이 이에 해당되며 하류는 영산포읍이하의 나주군 일부와 함평군이 이에 해당된다. 1. 주민의 감열율 : 상류 3개지역, 중류 1개지역 그리고 하류 2개지역 등 6개지역 주민 359명을 대상으로 조사하였다. 상류지역의 간디스토마 감염율은 29.9%(69/231), 중류 38.5%(20/52), 하류 21.1%(16/76)이었다. 전체적으로는 29.2%(105/359)의 감염율을 나타내었으며 남자는 39.3%(79/201), 여자 15.4%(21/136)로 전자가 2.5배 이상의 감염상을 보였다. 2. 제 1 중간숙주 : 간디스토마의 제 1 중간숙주인 왜우렁(Parafossarulus manchouricus)의 조사는 상류 2개지역, 중류 4개지역, 하류 1개지역등 7개지역에서 채집한 980개를 검사하였으며 그 중 11개(1.1%)에서 간디스토마셀카리아를 검출하였다. 지역별로는 상류 1.8%(6/333), 중류 0.9%(5/553)가 양성이었으나 하류지역의 94개에서는 모두 음성이었다. 요꼬가와흡충의 제 1 중간숙주인 다슬기(Semisulcospira libertina)를 상, 중, 하류의 각 1개지역씩 3개지역에서 모두 179개를 채집하여 검사하였으나. 요꼬가와흡충 또는 페디스토마의 셀카리아는 검출할 수 없었다. 3. 제 2 중간숙주 : 전지역에서 9종의 담수어 263마리를 포획하여 검사한바 간디스토마메타셀카리아의 양성율은 참붕어에서 62.9%(22/35), 피리 5.7%(3/53), 납지리류 21.9%(7/32), 돌고기 17.6%(3/17), 그리고 끄리에서 14.3%(1/7)이었으나 붕어, 모래무지, 버들붕어 및 꺽지 등에서는 검출할 수 없었다. 요꼬가와흡충의 제2중간숙주인 은어는 채집 또는 포획할 수 없었다. 섬진강유역 전라남도 관내의 섬진강을 상, 중, 하류로 구분하여 각 유역별로 2개지역씩 선정, 6개지역에서 조사하였다(표 1 참조). Soh, C.T. et al. 표 1. 영산강 및 섬진강 유역 조사대상 지역 =================================================================================== 영산강 유역 ∥ 섬진강 유역 ------------------------------------------∥--------------------------------------- 지 역 *조사내용 ∥ 지 역 *조사내용 ------------------------------------------∥--------------------------------------- 상류 1. 장성군 황룡면 황룡리 P. 1.2. ∥상류 1. 곡성군 곡성면 동산리 P. 1. 2. 담양군 봉산면 삼지리 P. 1.2. ∥ 2. 곡성군 곡성면 석곡리 P. 1.2. 3. 담양군 금성면 금월리 P. ∥ 중류 1. 나주군 영산포읍 1. ∥중류 1. 구례군 구례읍 신월리 P. 1.2. 2. 나주군 산포면 산제리 1.2. ∥ 2. 곡성군 곡성면 압록리 2. 3. 나주군 남평면 남평리 1.2. ∥ 4. 광산군 동곡면 복용리 P. 1.2. ∥ 하류 1. 함평군 엄다면 학교리 P. 1.2. ∥하류 1. 광양군 다압면 신원리 2. 2. 나주군 다시면 신풍리 P. ∥ 2. 광양군 다압면 고사리 P. 1.2. 3. 나주군 문평면 용문리 2. ∥ ------------------------------------------------------------------------------------ *(주) P: 주민 감염율조사. 1: 제1 중간숙주조사. 2: 제2 중간 숙주조사. 상류는 전라북도와 전라남도의 경계선 이하에서 곡성군 곡성읍 상부와 섬진강의 지류인 보성강유역이 해당되며 중류지역은 섬진강과 보성강이 합류되는 곳에서부터 광양군 다압면의 상류지역으로 곡성군 일부와 구례군이 이에 해당되며 하류는 다압면이하로 광양군이 해당된다. 1. 주민의 감염율 : 상류 2개지역, 중하류 각 1개지역 등 4개지역에서 296명을 대상으로 조사하였던바 전체적으로 간디스토마 충란양성자는 21명(7.1%)인데 비해 요꼬가와흡충충란 양성자는 123명(41.6%)이었으며 지역별 간디스토마의 감염율은 상류 5.6%(7/124), 중류 7.4%(6/81), 하류 8.8%(8/91)이었으며 요꼬가와흡충은 상류29.0%(36/124), 중류 58.0%(47/81), 하류 44.0%(40/91)이었다. 요꼬가와흡충충란양성자의 경우 남자는 55.5%(81/146)로 여자의 28.0%(42/150)보다 약 2배 가량 높은 감염율을 보였다. 요꼬가와흡충충란은 전 연령층에서 검출되었으나 간디스토마는 19세이하에서는 검출되지 않았다. 한편 두 흡충의 혼합감염율은 5.7%(17/296)이었다. 2. 제 1 중간숙주 : 왜우렁은 중류지방에서만 채집되었으나 간디스토마셀카리아를 검출치 못하였고 다슬기는 모두 663개를 채집하여 검사한바 62개(9.4%)에서 요꼬가와흡충셀카리아를 검출하였다. 이를 지역별로 보면 상류 9.2%(39/427), 중류 4.8%(3/62), 하류 11.5%(20/174)의 양성율을 보였다. 3. 제 2 중간숙주 : 전지역에서 10종의 담수어 175마리를 포획하여 검사하였으나 간디스토마메타셀카리아는 검출치 못 하였다. 그러나 그중 은어에서는 35마리 전부에서 요꼬가와흡충메타셀카리아를 검출하였다. 이상의 성적으로 보아 영산강유역은 간디스토마의 만연지역이나 요꼬가와흡충의 만연은 볼 수 없었다. 그러나 섬진강유역은 요꼬가와흡충 및 간디스토마의 만연지역이라고 볼 수 있으나 이 지역의 간디스토마감염이 토착성인지는 더 추구되어야 할 과제라고 본다.

국내이용 말사료의 영양적 가치와 YEAST CULTURE 첨가시 소화율 , 광물질 이용율 및 혈액성상에 미치는 영향

김성민(S . M . Kim),김종민(C . M . Kim),이현기(H . K . Lee),박원표(W . P . Park),임영재(Y . J . Lim),김병진(B . J . Kim),정태영(T . Y . Chung) 한국영양사료학회 1991 韓國營養飼料學會誌 Vol.15 No.5