Efficacy of HVT-IBD vector vaccine compared to attenuated live vaccine using in-ovo vaccination against a Korean very virulent IBDV in commercial broiler chickens

Roh, J.-H.,Kang, M.,Wei, B.,Yoon, R.-H.,Seo, H.-S.,Bahng, J.-Y.,Kwon, J.-T.,Cha, S.-Y.,Jang, H.-K. Elsevier 2016 Poultry science Vol.95 No.5

<P>The production performance, efficacy, and safety of two types of vaccines for infectious bursal disease virus (IBDV) were compared with in-ovo vaccination of Cobb 500 broiler chickens for gross and microscopic examination of the bursa of Fabricius, bursa/body weight (b/B) ratio, flow cytometry, and serologic response to Newcastle disease virus (NDV) vaccination. One vaccine was a recombinant HVT-IBD vector vaccine (HVT as for herpesvirus of turkeys) and the other was an intermediate plus live IBDV vaccine. A significant difference was detected at 21 d. Eight of 10 chickens that received the IBDV live vaccine had severe bursal lesions and a relatively low b/B ratio of 0.95, and an inhibited NDV vaccine response. On the other hand, the HVT-IBD vector vaccine resulted in mild bursal lesions and a b/B ratio of 1.89. Therefore, the live vaccine had lower safety than that of the HVT-IBD vector vaccine. To determine the protective efficacy, chickens were intraocularly challenged at 24 d. Eight of 10 chickens in the IBDV live vaccination group showed gross and histological lesions characterized by hemorrhage, cyst formation, lymphocytic depletion, and a decreased b/B ratio. In contrast, the HVT-IBD vector vaccinated chickens showed mild gross and histological lesions in three of 10 chickens with a b/B ratio of 1.36, which was similar to that of the unchallenged controls. Vaccinated chickens showed a significant increase in IBDV antibody titers, regardless of the type of vaccine used. In addition, significantly better broiler flock performance was observed with the HVT-IBD vector vaccine compared to that of the live vaccine. Our results revealed that the HVT-IBD vector vaccine could be used as an alternative vaccine to increase efficacy, and to have an improved safety profile compared with the IBDV live vaccine using in-ovo vaccination against the Korean very virulent IBDV in commercial broiler chickens.</P>

Aberrant ventral striatal responses during incentive processing in unmedicated patients with obsessive–compulsive disorder

Jung, W. H.,Kang, D.‐,H.,Han, J. Y.,Jang, J. H.,Gu, B.‐,M.,Choi, J.‐,S.,Jung, M. H.,Choi, C.‐,H.,Kwon, J. S. Blackwell Publishing Ltd 2011 Acta psychiatrica Scandinavica Vol.123 No.5

<P>Jung WH, Kang D‐H, Han JY, Jang JH, Gu B‐M, Choi J‐S, Jung MH, Choi C‐H, Kwon JS. Aberrant ventral striatal responses during incentive processing in unmedicated patients with obsessive–compulsive disorder.</P><P><B>Objective: </B> Obsessive–compulsive disorder (OCD) is characterized by the dysfunction of control and reward mechanisms. However, only few neuroimaging studies of OCD have examined the reward processing. We examined the neural responses during incentive processing in OCD.</P><P><B>Method: </B> Twenty unmedicated patients with OCD and 20 age‐, sex‐, and IQ‐matched healthy controls underwent functional magnetic resonance imaging while performing a modified monetary incentive delay task.</P><P><B>Results: </B> Compared with controls, patients with OCD showed increased ventral striatal activation in the no‐loss minus loss outcome contrast and a significant positive correlation between the ventral striatal activation and compulsion symptom severity. In addition, patients with OCD showed increased activations in the frontostriatal regions in the gain minus no‐gain outcomes contrast. During loss anticipation, patients with OCD showed less activations in the lateral prefrontal and inferior parietal cortices. However, during gain anticipation, patients with OCD and healthy controls did not differ in the ventral striatal activation.</P><P><B>Conclusion: </B> These findings provide neural evidence for altered incentive processing in unmedicated patients with OCD, suggesting an elevated sensitivity to negatively affect stimuli as well as dysfunction of the ventral striatum.</P>

Lactoferrin causes IgA and IgG2b isotype switching through betaglycan binding and activation of canonical TGF-β signaling

Jang, Y-S,Seo, G-Y,Lee, J-M,Seo, H-Y,Han, H-J,Kim, S-J,Jin, B-R,Kim, H-J,Park, S-R,Rhee, K-J,Kim, W-S,Kim, P-H Society for Mucosal Immunology 2015 Mucosal immunology Vol.8 No.4

<P>Lactoferrin (LF), a pleiotropic iron-binding glycoprotein, is known to modulate the humoral immune response. However, its exact role in Ig synthesis has yet to be elucidated. In this study, we investigated the effect of LF on Ig production by mouse B cells and its underlying mechanisms. LF, like transforming growth factor (TGF)-beta 1, stimulated B cells to produce IgA and IgG2b, while downregulating other isotypes. Using limiting dilution analysis, LF was shown to increase the frequency of IgA-secreting B-cell clones. This was paralleled by an increase in Ig germ-line alpha (GL alpha) transcripts, indicating that LF plays a role as an IgA switch factor. Interestingly, LF directly interacted with betaglycan (TGF-beta receptor III, T beta RIII) and in turn induced phosphorylation of T beta RI and Smad3 through formation of the T beta RIII/T beta RII/T beta RI complex, leading to IgA isotype switching. Peroral administration of LF increased intestinal/serum IgA production as well as number of IgA plasma cells in lamina propria. Finally, we found that LF has an adjuvant activity when nontoxigenic Salmonella typhimurium was inoculated perorally, conferring protection against intragastrical infection of toxigenic S. typhimurium. These results suggest that LF has an important effect on the mucosal/systemic IgA response and can contribute to protection against intestinal pathogens.</P>

Polymorphisms of <i>KCNJ11</i> (Kir6.2 gene) are associated with Type 2 diabetes and hypertension in the Korean population

Koo, B. K.,Cho, Y. M.,Park, B. L.,Cheong, H. S.,Shin, H. D.,Jang, H. C.,Kim, S. Y.,Lee, H. K.,Park, K. S. Blackwell Publishing Ltd 2007 Diabetic medicine Vol.24 No.2

<P>Abstract</P><P>Aims </P><P>Kir6.2 is found in the pancreatic B-cell, cardiac and skeletal muscle and non-vascular smooth muscle. <I>KCNJ11</I>, encoding Kir6.2, has been shown to be associated with both Type 2 diabetes mellitus and cardiovascular disease in several populations. In this study, we investigated whether polymorphisms in <I>KCNJ11</I> are associated with Type 2 diabetes and other metabolic phenotypes in the Korean population.</P><P><B>Methods </B></P><P>We sequenced <I>KCNJ11</I> to identify common polymorphisms using 24 Korean DNA samples. Of the 14 polymorphisms found in <I>KCNJ11</I>, six common ones [genomic sequence (g.)−1709A>T, g.−1525T>C, g.67G>A (E23K), g.570C>T (A190A), g.1009A>G (I337V), and g.1388C>T] were genotyped in 761 Type 2 diabetic patients and in 630 non-diabetic subjects.</P><P><B>Results</B> </P><P>All the polymorphic loci in <I>KCNJ11</I> are in strong linkage disequilibrium in the Korean population and act as one haplotype block. g.67G>A and g.1009A>G were associated with an increased risk of Type 2 diabetes [age, sex, and body mass index (BMI)-adjusted odds ratios (OR) = 1.376 (1.085–1.745), <I>P</I> = 0.008 and 1.411 (1.111–1.791), <I>P</I> = 0.005, respectively], as was one haplotype (A-T-A-C-G-C in the order of polymorphisms as shown above) containing g.67A and g.1009G [OR = 1.359 (1.080–1.709), <I>P</I> = 0.009]. The haplotype (A-T-A-C-G-C) was also strongly associated with hypertension [OR = 1.655 (1.288–2.126), <I>P</I> < 0.001].</P><P><B>Conclusions </B></P><P>Polymorphisms in <I>KCNJ11</I> are associated with Type 2 diabetes and also with hypertension in the Korean population.</P>

Characterization of a wheat mutant missing low-molecular-weight glutenin subunits encoded by the B-genome

Lee, J.Y.,Kang, C.S.,Beom, H.R.,Jang, Y.R.,Altenbach, S.B.,Lim, S.H.,Kim, Y.M.,Park, C.S. Academic Press 2017 Journal of cereal science Vol.73 No.-

<P>DH2O, a new wheat mutant missing low-molecular weight glutenin subunits encoded by the Glu-B3 locus, was discovered among double haploid lines obtained from a cross between the Korean wheat cultivars Keumkang and Olgeuru. Absence of the Glu-B3 LMW-GS proteins was determined by one-dimensional gel electrophoresis (SDS-PAGE) and confirmed by two-dimensional gel electrophoresis (2-DGE) and tandem mass spectrometry (MS/MS). The deletion of Glu-B3 genes was also demonstrated using allele specific DNA markers. Basic agronomic traits, protein content, dough mixing properties and bread loaf volume of DH2O and parental wheat cultivars were evaluated in field-grown wheat over a two year period. This mutant is a valuable resource for understanding the function of individual LMW-GS alleles or genes at the Glu-B3 locus using either breeding or biotechnology approaches. (C) 2017 Elsevier Ltd. All rights reserved.</P>

Pulsed high intensity focused ultrasound increases penetration and therapeutic efficacy of monoclonal antibodies in murine xenograft tumors

Wang, S.,Shin, I.S.,Hancock, H.,Jang, B.s.,Kim, H.s.,Lee, S.M.,Zderic, V.,Frenkel, V.,Pastan, I.,Paik, C.H.,Dreher, M.R. Elsevier Science Publishers 2012 Journal of controlled release Vol.162 No.1

The success of radioimmunotherapy for solid tumors remains elusive due to poor biodistribution and insufficient tumor accumulation, in part, due to the unique tumor microenvironment resulting in heterogeneous tumor antibody distribution. Pulsed high intensity focused ultrasound (pulsed-HIFU) has previously been shown to increase the accumulation of <SUP>111</SUP>In labeled B3 antibody (recognizes Lewis<SUP>y</SUP> antigen). The objective of this study was to investigate the tumor penetration and therapeutic efficacy of pulsed-HIFU exposures combined with <SUP>90</SUP>Y labeled B3 mAb in an A431 solid tumor model. The ability of pulsed-HIFU (1MHz, spatial averaged temporal peak intensity=2685Wcm<SUP>-2</SUP>; pulse repetition frequency=1Hz; duty cycle=5%) to improve the tumor penetration and therapeutic efficacy of <SUP>90</SUP>Y labeled B3 mAb (<SUP>90</SUP>Y-B3) was evaluated in Le<SUP>y</SUP>-positive A431 tumors. Antibody penetration from the tumor surface and blood vessel surface was evaluated with fluorescently labeled B3, epi-fluorescent microscopy, and custom image analysis. Tumor size was monitored to determine treatment efficacy, indicated by survival, following various treatments with pulsed-HIFU and/or <SUP>90</SUP>Y-B3. The pulsed-HIFU exposures did not affect the vascular parameters including microvascular density, vascular size, and vascular architecture; although 1.6-fold more antibody was delivered to the solid tumors when combined with pulsed-HIFU. The distribution and penetration of the antibodies were significantly improved (p-value<0.05) when combined with pulsed-HIFU, only in the tumor periphery. Pretreatment with pulsed-HIFU significantly improved (p-value<0.05) survival over control treatments.

200 GeV/핵자 유황이온과 핵건판핵의 충돌에 의해 생성된 헬륨 파쇄핵의 극한파쇄 연구

김동철,송진섭,윤천실,정성헌,박인곤,김종오,김철수,김태연,이승희,조재희,천병구,김재률,김준원,김태익,박명렬,장한일,임인택 慶尙大學校 기초과학연구소 1992 基礎科學硏究所報 Vol.8 No.-

고에너지 중이온 원자핵과 핵건판의 충돌에서, 200GeV/핵자 유황이온에 의해 생성된 파쇄 헬륨핵(Z=2)의 실험실계의 방출각 분포는 표적핵에 무관한 회귀공식. dN=exp[a+k exp(η-y_b)]d[exp(η-y_b)]로 잘 표현된다. 여기에서 의사신속도 η=-ln[tan(θ/2)]이고, y_b는 실험실계의 입사입자(^32S)의 신속도이다. 이 공식에 의한 적합에서 k=-0.057±0.008로 얻어진다. 즉, 핵건판과 고에너지 중이온의 충돌에서 파쇄 헬륨핵의 exp(η-y_b)의 분포는 "극한파쇄" 현상을 잘 설명하고 있다. The angular distribution of emission angle θ of helium (Z=2) produced in the collisions of incident particles of 200 GeV/nucleon ^32S in nuclear emulsion is well expressed by dN=exp[a+k exp(η-y_b)]d[exp(η-y_b)] where the pseudorapidity is η=-ln[tan(θ/2)], the laboratory system primary rapidity is y_b, and k=-0.057+0.008. The shape of this frequency of occurrence distributions in terms of exp(η-y_b) attests to the validity of the concept of "limiting fragmentation" for helium projectile fragments produced in the projectile fragmentation regions of heavy ion collisions in nuclear emulsion.

Conduritol F, the discriminant marker between C. wilfordii and C. auriculatum by ¹H NMR spectroscopy

Jang, H.S.,Jeong, B.,Choi, S.Y.,Jang, G.H.,Park, K.C.,Kwon, Y.S.,Yang, H. Academic Press 2017 Microchemical Journal Vol. No.

<P>Quantitative H-1 nuclear magnetic resonance (qNMR) spectroscopy is a powerful and versatile technique to enable the absolute quantification of specific components in a mixture with excellent reproducibility and robustness. In the present study, qNMR analysis was applied to conduritol F, a chemical marker with the potential to distinguish between C wilfordii and C auriculatum. We found that the signals of H-5 and H-6 of conduritol F were well-separated from others with purities sufficient to be used to distinguish between C wilfordii and C. auriculatum. This simple methodology can be applied to identify one or two species in products or powdered herbs widely distributed in the markets. (C) 2017 Elsevier B.V. All rights reserved.</P>

Antiviral activity of KR-23502 targeting nuclear export of influenza B virus ribonucleoproteins

Jang, Y.,Lee, H.W.,Shin, J.S.,Go, Y.Y.,Kim, C.,Shin, D.,Malpani, Y.,Han, S.B.,Jung, Y.S.,Kim, M. Elsevier/North-Holland 2016 ANTIVIRAL RESEARCH Vol.134 No.-

<P>The spiro compound 5,6-dimethyl-3H,3'H-spiro(benzofuran-2,1'-isobenzofuran)-3,3'-dione (KR-23502) has antiviral activity against influenza A and more potently B viruses. The aim of this study is to elucidate its mechanism of action. Subcellular localization and time-course expression of influenza B viral proteins, nucleoprotein (NP) and matrix protein 1 (M1), showed that KR-23502 reduced their amounts within 5 h post-infection. Early steps of virus life cycle, including virus entry, nuclear localization of NP and viral RNA-dependent RNA replication, were not affected by KR-23502. Instead it interrupted a later event corresponding to nuclear export of NP and M1 proteins. Delivery of viral ribonucleoprotein (vRNP)-M1 complex has been known to be mediated by the viral nuclear export protein (NEP) through interaction with cellular chromosomal maintenance 1 (CRM1) protein. In this study, we experimentally demonstrated that the compound targets the nuclear export of vRNP. Moreover, a single mutation (aspartate to glycine) at amino acid position 54 in M1 [M1(D54G)] was detected after 18 passages in the presence of KR-23502 with a 2-fold increase in 50% effective concentration indicating that this compound has a relatively high genetic barrier to resistance. Interestingly, it was observed that proteasome-mediated degradation of M1 (D54G) was attenuated by KR-23502. In conclusion, we suggest that KR-23502 shows its anti-influenza activity by downregulating NEP/CRM1-mediated nuclear export of influenza vRNP and M1. KR-23502 provides a core chemical skeleton for further structure-based design of novel antivirals against influenza viruses. (C) 2016 Elsevier B.V. All rights reserved.</P>

A novel multigene cloning method for the production of a motile ATPase

Jang, M.S.,Song, W.C.,Shin, S.W.,Park, K.S.,Kim, J.,Kim, D.I.,Kim, B.W.,Um, S.H. Elsevier Science Publishers 2015 Journal of biotechnology Vol.207 No.-

<P>With the advent of nanotechnology, new functional modules (e.g., nanomotors, nanoprobes) have become essential in several medical fields. Generally, mechanical modulators systems are the principal components of most cutting-edge technologies in modern biomedical applications. However, the in vivo use of motile probes has raised many concerns due to their low sensitivity and non-biocompatibility. As an alternative, biological enzymatic engines have received increased attention. In particular, ATPases, which belong to a class of motile enzymes that catalyze chemical metabolic reactions, have emerged as a promising motor due to their improved biocompatibility and performance. However, ATPases usually suffer from lower functional activity and are difficult to express recombinantly in bacteria relative to their conventional and synthetic competitors. Here, we report a novel functional modified ATPase with both a simple purification protocol and enhanced motile activity. For this mutant ATPase, a new bacterial subcloning method was established. The ATPase-encoding sequence was redesigned so that the mutant ATPase could be easily produced in an Escherichia coli system. The modified thermophilic F-1-ATPase (mTF(1)-ATPase) demonstrated 17.8 unit/mg ATPase activity. We propose that derivatives of our ATPase may enable the development of novel in vitro and in vivo synthetic medical diagnostics, as well as therapeutics. (C) 2015 Elsevier B.V. All rights reserved.</P>