A C1 inhibitor ortholog from rock bream (Oplegnathus fasciatus): Molecular perspectives of a central regulator in terms of its genomic arrangement, transcriptional profiles and anti-protease activities of recombinant peptide

Umasuthan, N.,Bathige, S.D.N.K.,Revathy, K.S.,Wickramaarachchi, W.D.N.,Wan, Q.,Whang, I.,Kim, E.,Park, M.A.,Park, H.C.,Lee, J. Pergamon Press ; Elsevier Science 2014 DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY Vol.42 No.2

C1 inhibitor (C1Inh), a member of serpin superfamily, is a crucial regulator of the activation of various plasmatic cascades associated with immunity and inflammation. This study describes the identification and characterization of a C1Inh gene from rock bream Oplegnathus fasciatus (OfC1Inh) at structural, expressional and functional levels. The cDNA-(2245bp) and corresponding gDNA-sequences (5.2kbp) of OfC1Inh were isolated from rock bream transcriptome- and BAC-libraries, respectively. Predicted amino acid sequence of OfC1Inh revealed a two-domain architecture composed of an N-terminal region with two Ig-like domains and a C-terminal region with a serpin domain. Tertiary model of OfC1Inh disclosed its active site topology. In the multi-exonic genomic arrangement of OfC1Inh, it consisted of eleven exons disjoined by ten introns as observed in few other fish homologs. Our comparative analysis indicated that the teleostean C1Inhs were distinct from their non-teleostean vertebrate counterparts in terms of their (1) extended N-terminal domains, (2) evolutionary divergence and (3) exon-intron distribution. The OfC1Inh had a TATA-deficient promoter with a putative initiator element, and two tandemly arranged downstream promoter elements. Several components associated with the immune and inflammatory transcriptional activation were also predicted to exist in 5' flanking region of OfC1Inh. The exclusive mRNA levels in liver and moderate levels in extra-hepatic tissues intimated the diversified importance of OfC1Inh in rock bream physiology. We also provide an evidence for the involvement of OfC1Inh in immune balance, based on its modulated transcription upon different PAMP (lipopolysaccharide and poly I:C)- or pathogen (Streptococcus iniae and rock bream irido virus)-challenges. A recombinantly expressed fusion protein [(r)OfC1Inh] was employed in demonstrating the anti-protease function of OfC1Inh. The (r)OfC1Inh exhibited detectable inhibitory activity against C1 esterase and thrombin, where the anti-C1 esterase role was shown to be potentiated by heparin. Taken together, the results of this study provide the first line of evidence for the possible involvement of a teleostean C1Inh in fish immunity, based on its expressional response(s) and inhibitory properties against two enzymes involved in biological cascades.

Evaluation of the zoonotic potential of a novel reassortant H1N2 swine influenza virus with gene constellation derived from multiple viral sources

Lee, J.H.,Pascua, P.N.Q.,Decano, A.G.,Kim, S.M.,Park, S.J.,Kwon, H.I.,Kim, E.H.,Kim, Y.I.,Kim, H.,Kim, S.Y.,Song, M.S.,Jang, H.K.,Park, B.K.,Choi, Y.K. Elsevier Science 2015 INFECTION GENETICS AND EVOLUTION Vol.34 No.-

In 2011-2012, contemporary North American-like H3N2 swine influenza viruses (SIVs) possessing the 2009 pandemic H1N1 matrix gene (H3N2pM-like virus) were detected in domestic pigs of South Korea where H1N2 SIV strains are endemic. More recently, we isolated novel reassortant H1N2 SIVs bearing the Eurasian avian-like swine H1-like hemagglutinin and Korean swine H1N2-like neuraminidase in the internal gene backbone of the H3N2pM-like virus. In the present study, we clearly provide evidence on the genetic origins of the novel H1N2 SIVs virus through genetic and phylogenetic analyses. In vitro studies demonstrated that, in comparison with a pre-existing 2012 Korean H1N2 SIV [A/swine/Korea/CY03-1½012 (CY03-1½012)], the 2013 novel reassortant H1N2 isolate [A/swine/Korea/CY0423/2013 (CY0423-12/2013)] replicated more efficiently in differentiated primary human bronchial epithelial cells. The CY0423-12/2013 virus induced higher viral titers than the CY03-1½012 virus in the lungs and nasal turbinates of infected mice and nasal wash samples of ferrets. Moreover, the 2013 H1N2 reassortant, but not the intact 2012 H1N2 virus, was transmissible to naive contact ferrets via respiratory-droplets. Noting that the viral precursors have the ability to infect humans, our findings highlight the potential threat of a novel reassortant H1N2 SIV to public health and underscore the need to further strengthen influenza surveillance strategies worldwide, including swine populations.

Comparison of First-Line Dual Combination Treatments in Hypertension: Real-World Evidence from Multinational Heterogeneous Cohorts

Seng Chan You,Sungjae Jung,Joel N. Swerdel,Patrick B. Ryan,Martijn J. Schuemie,Marc A. Suchard,Seongwon Lee,Jaehyeong Cho,George Hripcsak,Rae Woong Park,Sungha Park 대한심장학회 2020 Korean Circulation Journal Vol.50 No.1

Background and Objectives: 2018 ESC/ESH Hypertension guideline recommends 2-drug combination as initial anti-hypertensive therapy. However, real-world evidence for effectiveness of recommended regimens remains limited. We aimed to compare the effectiveness of first-line anti-hypertensive treatment combining 2 out of the following classes: angiotensin-converting enzyme (ACE) inhibitors/angiotensin-receptor blocker (A), calcium channel blocker (C), and thiazide-type diuretics (D). Methods: Treatment-naïve hypertensive adults without cardiovascular disease (CVD) who initiated dual anti-hypertensive medications were identified in 5 databases from US and Korea. The patients were matched for each comparison set by large-scale propensity score matching. Primary endpoint was all-cause mortality. Myocardial infarction, heart failure, stroke, and major adverse cardiac and cerebrovascular events as a composite outcome comprised the secondary measure. Results: A total of 987,983 patients met the eligibility criteria. After matching, 222,686, 32,344, and 38,513 patients were allocated to A+C vs. A+D, C+D vs. A+C, and C+D vs. A+D comparison, respectively. There was no significant difference in the mortality during total of 1,806,077 person-years: A+C vs. A+D (hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.97−1.20; p=0.127), C+D vs. A+C (HR, 0.93; 95% CI, 0.87−1.01; p=0.067), and C+D vs. A+D (HR, 1.18; 95% CI, 0.95−1.47; p=0.104). A+C was associated with a slightly higher risk of heart failure (HR, 1.09; 95% CI, 1.01−1.18; p=0.040) and stroke (HR, 1.08; 95% CI, 1.01−1.17; p=0.040) than A+D. Conclusions: There was no significant difference in mortality among A+C, A+D, and C+D combination treatment in patients without previous CVD. This finding was consistent across multi-national heterogeneous cohorts in real-world practice.

Controllable modification of the conduction properties of carbon nanotube devices through deposition of a metal overlayer onto the sidewalls

Park, N.,Lee, A.R.,Kim, H.S.,Kim, J.J.,Lee, J.O. North-Holland 2012 Physica E, Low-dimensional systems & nanostructure Vol.44 No.7

The effects of metal contacts and metal overlayers on the electrical properties of carbon nanotubes (CNTs) were studied. We show that the conduction properties of a CNT device can be controllably designed through metal depositions on the sidewall even though the conduction type is not clearly defined by the work function of the contact metal. The conversion from an n-type to a p-type conductor was observed with deposition of an overlayer using a large work function metal (Pd), whereas a p-type to n-type conversion was observed with deposition of an overlayer using a low work function metal (Ti). This behavior was attributed to charge transfer doping or the local bending of nanotube bands beneath the metal overlayer. First-principle calculations revealed that charge transfer doping may be uniquely defined by the work function difference if a metal layer forms a weak contact with the sidewall of a CNT.

Irreversible field-induced magnetic phase transitions and properties of Ho₃Co

Baranov, N V,Goto, T,Hilscher, G,Markin, P E,Michor, H,Mushnikov, N V,Park, J-G,Yermakov, A A IOP Pub 2005 Journal of physics, an Institute of Physics journa Vol.17 No.21

<P>The results of magnetic susceptibility, magnetization, electrical resistivity and specific heat measurements performed on Ho<SUB>3</SUB>Co single crystals show that this compound exhibits two different antiferromagnetic structures: AF<SUB>II</SUB> at 8 K<<I>T</I>< 22 K and AF<SUB>I</SUB> below <I>T</I><SUB>t</SUB>≈8 K. Below the Néel temperature <I>T</I><SUB>N</SUB> = 22 K the application of a magnetic field along the main crystallographic directions induces magnetic phase transitions which are accompanied by giant magnetoresistance. At <I>T</I><<I>T</I><SUB>t</SUB> the field-induced phase transitions along the <B><I>c</I></B>- and <B><I>b</I></B>-axes are found to be irreversible, and a small ferromagnetic component is observed along the <B><I>a</I></B>-axis. These peculiarities are associated with the non-Kramers character of the Ho ion and with the presence of a complex incommensurate magnetic structure of Ho<SUB>3</SUB>Co below <I>T</I><SUB>N</SUB>. The temperature coefficient of the electrical resistivity for Ho<SUB>3</SUB>Co above <I>T</I><SUB>N</SUB> over a wide temperature range is found to differ from that observed for other R<SUB>3</SUB>Co compounds. Such a behaviour is attributed to the presence of an additional contribution to the conduction electron scattering by spin fluctuations induced by f–d exchange in the itinerant d-electron subsystem. The value of this extra contribution and its temperature range is suggested to depend on the spin value of the R ion. The excess of the effective magnetic moment per R ion, which is observed in Ho<SUB>3</SUB>Co and in other R<SUB>3</SUB>M type compounds, is also attributed to spin fluctuations induced by f–d exchange.</P>

Differential effects of triterpene glycosides, frondoside A and cucumarioside A₂-2 isolated from sea cucumbers on caspase activation and apoptosis of human leukemia cells

Jin, J.O.,Shastina, V.V.,Shin, S.W.,Xu, Q.,Park, J.I.,Rasskazov, V.A.,Avilov, S.A.,Fedorov, S.N.,Stonik, V.A.,Kwak, J.Y. North-Holland Pub ; Elsevier Science Ltd 2009 FEBS letters Vol.583 No.4

Frondoside A is a pentaoside having an acetyl moiety at the aglycon ring and xylose as a third monosaccharide residue. Cucumarioside A<SUB>2</SUB>-2 is a pentaoside having glucose as a third monosaccahride unit. We compared the effects of frondoside A and A<SUB>2</SUB>-2 for cell death-inducing capability with close attention paid to structure-activity relationships. Both frondoside A and A<SUB>2</SUB>-2 strongly induced apoptosis of leukemic cells. Frondoside A-induced apoptosis was more potent and rapid than A<SUB>2</SUB>-2-induced apoptosis. A<SUB>2</SUB>-2-induced but not frondoside A-induced apoptosis was caspase-dependent. This suggests that holothurians may induce apoptosis of leukemic cells caspase-dependently or -independently, depending on the holothurian structure.

Spin Dynamics of the S = 1/2 Pyrochlore System Cu_2(OH)_3Cl Studied by Using High-frequency ESR

J. S. Park,최광용,A. N. Ponomaryov,Z. Wang,J. van Tol,옥강민,장지훈,S. W. Yoon,서병진 한국물리학회 2011 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.58 No.2

We report a magnetization and electron spin resonance (ESR) study of the clinoatacamite Cu_2(OH)_3Cl, which is known to have a S = 1/2 distorted pyrochlore lattice. The static magnetic susceptibility shows a strong increase at temperatures below T_(N2) = 6.4 K without any appreciable anomalies at T_(N1) = 18.1 K. The magnetization vs. field curve exhibits the presence of a weak ferromagnetic moment of 0.1 µB/Cu at T = 2 K, possibly due to an antisymmetric Dzyaloshinsky-Moriya (DM) interaction and/or weak ferromagnetic interplane interactions. From the ESR linewidth, we estimate the magnitude of the DM interaction as 10% of the leading isotropic exchange interaction, J ∼ 170 K. The temperature dependence of the linewidth is characterized by three distinct temperature regions: (i) a high-temperature exchange narrowing region at temperatures above 170 K, (ii) a two-dimensional short-range ordered region at temperatures between 170 K and 36 K, and (iii) a low-temperature region at temperatures below 36 K where an antiferromagnetic-like resonance mode develops. The evolution of the ESR linewidth is comparable to that of the S = 1/2 kagomé lattice in Cu_3Zn(OH)_6Cl_2 [Zorko et al., Phys. Rev. Lett. 101, 02640 (2008)]. This suggests that the magnetic properties of Cu_2(OH)_3Cl may be described in terms of a stack of kagomé lattices.

BubR1 as a prognostic marker for recurrence-free survival rates in epithelial ovarian cancers

Lee, Y-K,Choi, E,Kim, M A,Park, P-G,Park, N-H,Lee, H Nature Publishing Group 2009 The British journal of cancer Vol.101 No.3

<P><B>Background:</B></P><P>Epithelial ovarian cancer is one of the most lethal malignancies, and has a high recurrence rate. Thus, prognostic markers for recurrence are crucial for the care of ovarian cancer. As ovarian cancers frequently exhibit chromosome instability, we aimed at assessing the prognostic significance of two key mitotic kinases, BubR1 and Aurora A.</P><P><B>Methods:</B></P><P>We analysed paraffin-embedded tissue sections from 160 ovarian cancer patients whose clinical outcomes had been tracked after first-line treatment.</P><P><B>Results:</B></P><P>The median recurrence-free survival in patients with a positive and negative expression of BubR1 was 27 and 83 months, respectively (<I>P</I><0.001). A positive BubR1 expression was also associated with advanced stage, serous histology and high grade. In contrast, Aurora A immunostaining did not correlate with any of the clinical parameters analysed.</P><P><B>Conclusion:</B></P><P>BubR1, but not Aurora A, is a prognostic marker for recurrence-free survival rates in epithelial ovarian cancers.</P>

Sequential transcriptome analysis of human liver cancer indicates late stage acquisition of malignant traits

Marquardt, J.U.,Seo, D.,Andersen, J.B.,Gillen, M.C.,Kim, M.S.,Conner, E.A.,Galle, P.R.,Factor, V.M.,Park, Y.N.,Thorgeirsson, S.S. Elsevier Science Publishers 2014 Journal of hepatology Vol.60 No.2

Background & Aims: Human hepatocarcinogenesis is as a multi-step process starting from dysplastic lesions to early carcinomas (eHCC) that ultimately progress to HCC (pHCC). However, the sequential molecular alterations driving malignant transformation of the pre-neoplastic lesions are not clearly defined. This lack of information represents a major challenge in the clinical management of patients at risk. Methods: We applied next-generation transcriptome sequencing to tumor-free surrounding liver (n=7), low- (n=4) and high-grade (n=9) dysplastic lesions, eHCC (n=5) and pHCC (n=3) from 8 HCC patients with hepatitis B infection. Integrative analyses of genetic and transcriptomic changes were performed to characterize the genomic alterations during hepatocarcinogenesis. Results: We report that changes in transcriptomes of early lesions including eHCC were modest and surprisingly homogenous. Extensive genetic alterations and subsequent activation of prognostic adverse signaling pathways occurred only late during hepatocarcinogenesis and were centered on TGFβ, WNT, NOTCH, and EMT-related genes highlighting the molecular diversity of pHCC. We further identify IGFALS as a key genetic determinant preferentially down-regulated in pHCC. Conclusions: Our results define new hallmarks in molecular stratification and therapy options for patients at risk for HCC, and merit larger prospective investigations to develop a modified clinical-decision making algorithm based on the individualized next-generation sequencing analyses.

Monolithic and shrinkage-free hydrophobic silica aerogels via new rapid supercritical extraction process

Mahadik, D.B.,Lee, Y.K.,Chavan, N.K.,Mahadik, S.A.,Park, H.H. PRA Press ; Elsevier Science Ltd 2016 The Journal of supercritical fluids Vol.107 No.-

Aerogels have unusual mechanical and thermal properties and are useful in thermal insulation applications. However, aerogel production can be a tedious process if aerogels are made using supercritical extraction of a solvent from a sol-gel matrix. We employ a new rapid and simple supercritical extraction process that is better than conventional methods. This technique relies on rapid heating of the sol in a confined mold under a 50bar initial pressure supplied by dry N<SUB>2</SUB> gas in an autoclave. The initial pre-pressure of N<SUB>2</SUB> gas and base catalyst concentration dictate whether aerogels or xerogels are formed. A model is presented based on the various experimental results that predicts that gelation occurred after the solvent reached a supercritical state. Aerogels produced using this new rapid supercritical extraction process are monolithic, shrinkage-free, have a prescribed shape and size, and possess high surface area (~800m<SUP>2</SUP>/g) and low thermal conductivity (~0.035-0.041W/(mK)). The hydrophobicity as measured by water contact angle was enhanced from 119<SUP>o</SUP> to 158<SUP>o</SUP> using a hydrophobic co-precursor in the sol.