Multiple heterologous M2 extracellular domains presented on virus-like particles confer broader and stronger M2 immunity than live influenza A virus infection

Kim, M.C.,Lee, J.S.,Kwon, Y.M.,O, E.,Lee, Y.J.,Choi, J.G.,Wang, B.Z.,Compans, R.W.,Kang, S.M. Elsevier/North-Holland 2013 Antiviral research Vol.99 No.3

The influenza M2 ectodomain (M2e) is poorly immunogenic and has some amino acid changes among isolates from different host species. We expressed a tandem repeat construct of heterologous M2e sequences (M2e5x) derived from human, swine, and avian origin influenza A viruses on virus-like particles (M2e5x VLPs) in a membrane-anchored form. Immunization of mice with M2e5x VLPs induced protective antibodies cross-reactive to antigenically different influenza A viruses and conferred cross protection. Anti-M2e antibodies induced by heterologous M2e5x VLPs showed a wider range of cross reactivity to influenza A viruses at higher levels than those by live virus infection, homologous M2e VLPs, or M2e monoclonal antibody 14C2. Fc receptors were found to be important for mediating protection by immune sera from M2e5x VLP vaccination. The present study provides evidence that heterologous recombinant M2e5x VLPs can be more effective in inducing protective M2e immunity than natural virus infection and further supports an approach for developing an effective universal influenza vaccine.

Supplemented vaccination with tandem repeat M2e virus-like particles enhances protection against homologous and heterologous HPAI H5 viruses in chickens

Song, B.M.,Kang, H.M.,Lee, E.K.,Jung, S.C.,Kim, M.C.,Lee, Y.N.,Kang, S.M.,Lee, Y.J. Butterworths ; Elsevier Science Ltd 2016 Vaccine Vol.34 No.5

Highly pathogenic avian influenza (HPAI) H5 viruses derived from A/Goose/Guangdong/1/96 have been continuously circulating globally, severely affecting the public health and poultry industries. The matrix 2 protein ectodomain (M2e) is considered a promising candidate for a universal cross-protective influenza vaccine that provides more effective control over HPAI H5 viruses harboring variant hemagglutinin (HA)-antigens. Here, we evaluated the protective efficacy of a tandem repeat construct of heterologous M2e presented on virus-like particles (M2e5x VLPs) either alone or as a supplement against HPAI H5 viruses in a chicken model. Chickens immunized with M2e5x VLPs alone induced M2e-specific antibodies but were not protected against HPAI H5. The homo- and cross-protective efficacy of M2e5x VLP-supplemented vaccination of chickens was also examined. Importantly, supplementation with M2e5x VLPs induced significantly higher levels of antibodies specific for M2e and different viruses as well as provided improved protection against homologous and heterologous HPAI H5 viruses. Considering the limited efficacy of inactivated vaccines, supplement vaccination with M2e5x VLPs may be an effective measure for preventing outbreaks of HPAI viruses that have the ability to constantly change their antigenic properties in poultry.

정상인 및 당뇨병환자에서의 경구당부하시 혈중 Insulin과 C-Peptide의 변동

이명철,고창순,최성재,김응진,민헌기 대한핵의학회 1977 핵의학 분자영상 Vol.11 No.1

저자들은 정상인 및 당뇨병환자에서 insulin과 C-peptide의 변동양상의 의의를 관찰하고 또한 비만이 insulin 반응에 영향을 끼치는 것을 보고자 정상인 15명 (비비만형 10명, 비만형 5명), 중등도당뇨병환자 22례 (비비만형 13례, 비만형 9례) 및 중증당뇨병환자 9례, 총 46명을 대상으로 경구적 당부하시험을 시행하고 각 혈중 insulin과 C-peptide를 방사면역법으로 측정하여 다음과 같은 결과를 얻었기에 보고하는 바이다. 1) 10명의 비비만형정상인에서의 insulin치는 공복시 및 100 gm 경구당부하후 30, 60, 90, 120분에서 각각 15.7±3.4, 48.3±9.8, 4.4±6.7, 37.4±6.5 및 26.0±4.2uU/ml(Mean±S.E.)이고 C-peptide는 각각 1.9±0.3, 3.9±0.6, 6.3±0.6, 5.7±0.5 및 4.0±0.5 ng/ml로서 insulin가 C-peptide 평행한 반응을 보였고 insulin은 30분에서 최고치를 나타낸 반면 C-peptide는 60분에서 최고치를 보였다. 2) 비만형정상인 5례에서 insulin은 각각 38.9±12.3, 59.5±12.3, 59.2±17.1, 56.1±20.0 및 48.4±17.2uU/ml이고 C-peptide는 각각 5.5±0.4, 6.8±0.5, 7.9±0.8, 7.9±0.8 및 7.8±2.0ng/ml로서 비비만형에 비하여 반응이 현저히 증가함을 보였다. 3) 13례의 비비만형중등도당뇨병환자의 혈장내 insulin은 각각 27.1±4.9, 44.1±6.0, 37.3±6.6, 35.5±8.1 및 34.7±10.7uU/ml이고 C-peptide는 각각 2.7±0.4, 4.9±0.7, 6.5±0.5, 7.0±0.3 및 6.7±1.0ng/ml로서 비비만형정상군에 비하여 insulin 및 C-peptide의 차이는 없으나 지연되는 양상을 보였다. 4) 비비만형중등도당뇨병환자 9명에서의 insulin은 각각 22.1±7.9, 80.0±19.3, 108.0±27.0, 62.0±17.6 및 55.5±10.1 uU/ml이었으며 C-peptide는 5.2±0.4, 8.0±1.0, 10.4±1.6, 10.4±1.7 및 10.0±10ng/ml로서 insulin과 C-peptide 반응이 비비만형중둥도당뇨병환자군에 비해 각각 항진됨을 볼 수 있었다. 5) 중증당뇨병환자 9례에서의 혈중 insulin은 8.0±3.8, 12.1±3.5, 16.8±4.6, 19.6±5.2 및 15.0±5.0uU/ml이며 C-peptide는 1.6±0.3, 2.4±0.4, 4.1±0.6, 4.0±0.8 및 4.5±0.7ng/ml로서 insulin과 C-peptide가 각각 현저히 감소하였다. 이 각 당뇨병환자군에서의 총 insulin 및 C-peptide 면적, 그리고 insulinogenic index와 C-peptide index를 산출한 결과 당뇨병정도에 따른 유의한 차이를 관찰하였다. The present study was undertaken to evaluate the significance of the insulin and the C-peptide rseponse to oral glucose loads in normal and diabetic subjects and to establish the effects of the obesity. In this study, the authors have measured plasma insulin and C-peptide by means of radioimmunoassay in 10 nonobese normal, 5 obese normal, 13 nonobese moderate diabetic patients, 9 obese moderate diabetic patients and 9 severe diabetic patients. The results obtained were as follows; 1) In 10 nonobese normal subjects, the plasma insulin level at fasting state and at 30, 60, 90, and 120 min after oral glucose loads were 15.7±3.4, 48.3±9.8, 40.4±6.7, 37.4±6.5 and 26.0±4.2uU/ml(Mean±S.E.) and C-peptide were 1.9±0.3, 3.9±0.6, 6.3±0.6, 5.7±0.5 and 4.0±0.5ng/ml. The change of C-peptide was found to go almost parallel with that of insulin and the insulin value reaches to the highest level at 30 min whereas C-peptide reaches to its peak at 60min. 2) The plasma insulin level in 5 obese normal subjects were 38.5±12.3, 59.2±17.1, 56.1±20.0 and 48.4±17.2 uU/ml and the C-peptide were 5.5±0.4, 6.8±0.5, 7.9±0.8, 7.9±0.8 and 7.8±2.0ng/ml. The insulin response appeared to be greater than nonobese normal subjects. 3) In 13 nonobese moderate diabetic patients, the plasma insulin levels were 27.1±4.9, 44.1±6.0, 37.3±6.6, 35.5±8.1 and 34.7±10.7uU/ml and the C-peptide levels were 2.7±0.4, 4.9±0.7, 6.5±0.5, 7.0±0.3 and 6.7±1.0ng/ml. There was little significance compared to nonobese normal groups but delayed pattern is noted. 4) In 9 obese moderated diabetic patients, the plasma insulin levels were 22.1±7.9, 80.0±19.3, 108.0±27.0, 62.0±17.6 and 55.5±10.luU/ml and the C-peptide levels were 5.2±0.4, 8.0±1.0, 10.4±1.6, 10.4±1.7 and 10.1±1.0ng/ml and its response was also greater than that of nonobese moderate diabetic patients. 5) The plasma insulin concentrations in 9 severe diabetic subjects were 8.0±3.8, 12.1±3.5, 16.8±4.6, 19.6±5.2 and 15.0±5.0uU/ml and the C-peptide levels were 1.6±0.3, 2.4/ml and the insulin and C-peptide responses were markedly reduced in severe diabetic groups. 6) There were significant differences between each groups of patients on the magnitude of total insulin or C-peptide areas, the insulinogenic index and the C-peptide index. $quot;

Measurement of the top quark mass in the dileptonic tt¯ decay channel using the mass observables Mbℓ , MT2 , and Mbℓν in pp collisions at s=8 TeV

Sirunyan, A. M.,Tumasyan, A.,Adam, W.,Asilar, E.,Bergauer, T.,Brandstetter, J.,Brondolin, E.,Dragicevic, M.,Erö,, J.,Flechl, M.,Friedl, M.,Frü,hwirth, R.,Ghete, V. M.,Hartl, C.,Hö,rmann, N American Physical Society 2017 Physical Review D Vol.96 No.3

<P>A measurement of the top quark mass (M-t) in the dileptonic t (t) over bar decay channel is performed using data from proton-proton collisions at a center-of-mass energy of 8 TeV. The data was recorded by the CMS experiment at the LHC and corresponds to an integrated luminosity of 19.7 +/- 0.5 fb(-1). Events are selected with two oppositely charged leptons (l = e, mu) and two jets identified as originating from b quarks. The analysis is based on three kinematic observables whose distributions are sensitive to the value of Mt. An invariant mass observable, M-bl, and a 'stransverse mass' observable, M-T2, are employed in a simultaneous fit to determine the value of M-t and an overall jet energy scale factor (JSF). A complementary approach is used to construct an invariant mass observable, M-blv, that is combined with M-T2 to measure M-t. The shapes of the observables, along with their evolutions in M-t and JSF, are modeled by a nonparametric Gaussian process regression technique. The sensitivity of the observables to the value of M-t is investigated using a Fisher information density method. The top quark mass is measured to be 172.22 +/- 0.18(stat)(-0.93)(+0.89) (syst) GeV.</P>

Supplementation of oil-based inactivated H9N2 vaccine with M2e antigen enhances resistance against heterologous H9N2 avian influenza virus infection

Park, J.K.,Lee, D.H.,Cho, C.H.,Yuk, S.S.,To, E.O.,Kwon, J.H.,Noh, J.Y.,Kim, B.Y.,Choi, S.W.,Shim, B.S.,Song, M.K.,Lee, J.B.,Park, S.Y.,Choi, I.S.,Song, C.S. Elsevier Scientific Pub. Co 2014 Veterinary microbiology Vol.169 No.3

Avian influenza virus (AIV) subtype H9N2 has been evolving rapidly and vaccine escape variants have been reported to cause circulation of infections and economic losses. In the present study, we developed and evaluated ectodomain of the AIV matrix 2 (M2e) protein as a supplementing antigen for oil-based inactivated H9N2 vaccine to increase resistance against vaccine escape variants. AIV H9N2 M2e antigen was expressed in Escherichia coli and supplemented to inactivated H9N2 oil emulsion vaccine. Specific pathogen-free chickens received a single injection of inactivated H9N2 oil emulsion vaccines with or without M2e supplementation. At three weeks post vaccination, hemagglutination inhibition tests and enzyme-linked immunosorbent assays were performed to determine serological immune responses. Challenge study using a vaccine escape H9N2 variant was performed to evaluate the efficacy of M2e supplementation. M2e antigen supplemented in oil emulsion vaccine was highly immunogenic, and a single M2e-supplemented vaccination reduced challenge virus replication and shedding more effectively than non-supplemented vaccination.

Development of additive [¹¹C]CO₂ target system in the KOTRON-13 cyclotron and its application for [¹¹C]radiopharmaceutical production

Moon, B.S.,Lee, H.J.,Lee, W.K.,Hur, M.G.,Yang, S.D.,Lee, B.C.,Kim, S.E. North-Holland Physics Pub 2015 Nuclear instruments & methods in physics research. Vol.356 No.-

The KOTRON-13 cyclotron, which was developed in South Korea for the production of medical radioisotopes, has the structural limitation of only one beam-output port, restricting the production of the carbon-11 isotope. In the present study, we investigate the design of a switchable target system and develop an effective carbon-11 target in the KOTRON-13 cyclotron, for combination with the fluorine-18 target. The target system was designed by introducing a sliding-type element between the fluorine-18 and carbon-11 targets, a tailor-made C-11 target and its cooling system. For the efficient production of [<SUP>11</SUP>C]CO<SUB>2</SUB>, the desirable target shape and internal volume were determined by a Stopping and Range of Ions in Matter (SRIM) simulation program, and the target grid was modified to resist the cavity pressure during beam irradiation. We evaluated the [<SUP>11</SUP>C]CO<SUB>2</SUB> production while varying the material and thickness of the target foil, oxygen content of the nitrogen gas, and target loading pressure. Using sliding-type equipment including an additional gate valve and a high vacuum in a beam line, the bi-directional conversion between the fluorine-18 and carbon-11 targets was efficient regarding the accurate beam irradiation on both targets. The optimal [<SUP>11</SUP>C]CO<SUB>2</SUB> production for 30min irradiation at 60μA (86.6+/-1.7GBq in the target at EOB) was observed at a thickness of 19μm with HAVAR® material as a target foil and a target loading pressure of 24bar with nitrogen plus 300ppb of oxygen gas. Additionally, the coolant cavity system in the target grid and target chamber is useful to remove the heat transferred to the target body by the internal convection of water and thereby ensure the stability of the [<SUP>11</SUP>C]CO<SUB>2</SUB> production under a high beam current. In the application of C-11 labeled radiopharmaceuticals such as [<SUP>11</SUP>C]PIB, [<SUP>11</SUP>C]DASB, [<SUP>11</SUP>C]PBR28, [<SUP>11</SUP>C]Methionine and [<SUP>11</SUP>C]Clozapine, the radiochemical yields were shown to be 25-38% (decay corrected) with over 166GBq/μmol of specific activity. Consequently, the additive carbon-11 target system was successfully developed in only one output port of the KOTRON-13 cyclotron and exhibited the stable production of C-11 labeled radiopharmaceuticals.

Cosmic evolution of stellar quenching by AGN feedback: clues from the Horizon-AGN simulation

Beckmann, R. S.,Devriendt, J.,Slyz, A.,Peirani, S.,Richardson, M. L. A.,Dubois, Y.,Pichon, C.,Chisari, N. E.,Kaviraj, S.,Laigle, C.,Volonteri, M. Oxford University Press 2017 MONTHLY NOTICES- ROYAL ASTRONOMICAL SOCIETY Vol.472 No.1

<P>The observed massive end of the galaxy stellar mass function is steeper than its predicted dark matter halo counterpart in the standard Lambda cold dark matter paradigm. In this paper, we investigate the impact of active galactic nuclei (AGN) feedback on star formation in massive galaxies. We isolate the impact of AGN by comparing two simulations from the HORIZON suite, which are identical except that one also includes supermassive black holes (SMBHs) and related feedback models. This allows us to cross-identify individual galaxies between simulations and quantify the effect of AGN feedback on their properties, including stellar mass and gas outflows. We find that massive galaxies (M-* >= 10(11) M-circle dot) are quenched by AGN feedback to the extent that their stellar masses decrease by up to 80 per cent at z = 0. SMBHs affect their host halo through a combination of outflows that reduce their baryonic mass, particularly for galaxies in the mass range 10(9) M-circle dot <= M-* <= 10(11) M-circle dot, and a disruption of central gas inflows, which limits in situ star formation. As a result, net gas inflows on to massive galaxies, M-* >= 10(11) M-circle dot, drop by up to 70 per cent. We measure a redshift evolution in the stellar mass ratio of twin galaxies with and without AGN feedback, with galaxies of a given stellar mass showing stronger signs of quenching earlier on. This evolution is driven by a progressive flattening of the M-SMBH-M-* relation with redshift, particularly for galaxies with M-* <= 10(10) M-circle dot. M-SMBH/M-* ratios decrease over time, as falling average gas densities in galaxies curb SMBH growth.</P>

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.

TmSR-C, scavenger receptor class C, plays a pivotal role in antifungal and antibacterial immunity in the coleopteran insect Tenebrio molitor

Kim, S.G.,Jo, Y.H.,Seong, J.H.,Park, K.B.,Noh, M.Y.,Cho, J.H.,Ko, H.J.,Kim, C.E.,Tindwa, H.,Patnaik, B.B.,Bang, I.S.,Lee, Y.S.,Han, Y.S. Pergamon Press ; Elsevier Science Ltd 2017 Insect biochemistry and molecular biology Vol.89 No.-

Scavenger receptors (SRs) constitute a family of membrane-bound receptors that bind to multiple ligands. The SR family of proteins is involved in removing cellular debris, oxidized low-density lipoproteins, and pathogens. Specifically, class C scavenger receptors (SR-C) have also been reported to be involved in phagocytosis of gram-positive and -negative bacteria in Drosophila and viruses in shrimp. However, reports are unavailable regarding the role of SR-C in antifungal immune mechanisms in insects. In this study, a full-length Tenebrio molitor SR-C (TmSR-C) sequence was obtained by 5'- and 3'-Rapid amplification of cDNA ends-polymerase chain reaction (RACE-PCR). The TmSR-C full-length cDNA comprised 1671 bp with 5'- and 3'-untranslated regions of 23- and 107-bp, respectively. TmSR-C encodes a putative protein of 556 amino acid residues that is constitutively expressed in all tissues of late instar larvae and 2-day-old adults, with the highest transcript levels observed in hemocytes of larvae and adults. TmSR-C mRNA showed a 2.5-fold and 3-fold increase at 24 and 6 h after infection with Candida albicans and β-glucan, respectively. Immunoassay with TmSR-C polyclonal antibody showed induction of the putative protein in the cytosols of hemocytes at 3 h after inoculation of C. albicans. RNA interference (RNAi)-based gene silencing and phagocytosis assays were used to understand the role of TmSR-C in antifungal immunity. Silencing of TmSR-C transcripts reduced the survivability of late instar larvae at 2 days post-inoculation of C. albicans, Escherichia coli, or Staphylococcus aureus. Furthermore, in TmSR-C-silenced larvae, there was a decline in the rate of microorganism phagocytosis. Taken together, results of this study suggest that TmSR-C plays a pivotal role in phagocytosing not only fungi but also gram-negative and -positive bacteria in T. molitor.

Identification of a Novel SNP Associated with Meat Quality in C/EBP${\alpha}$ Gene of Korean Cattle

Shin, S.C.,Kang, M.J.,Chung, E.R. Asian Australasian Association of Animal Productio 2007 Animal Bioscience Vol.20 No.4

CCAAT/enhancer binding protein ${\alpha}$($C/EBP{\alpha}$) plays an important role in lipid deposition and adipocyte differentiation. In order to find genetic markers to improve the meat quality of Korean cattle, the bovine $C/EBP{\alpha}$ gene was chosen as a candidate gene to investigate its association with carcass and meat quality traits in Korean cattle. A single nucleotide polymorphism (SNP) was identified at position 271 (A/C substitution) of coding region in the $C/EBP{\alpha}$ gene. A PCR-RFLP procedure with restriction enzyme SmaI was developed for determining the marker genotypes. The frequencies of alleles C and A and were 0.374 and 0.626, respectively. The genotype frequencies for CC, AC and AA were 12.9, 49.0 and 38.1%, respectively, in Korean cattle population. The frequencies of genotype were in agreement with Hardy-Weinberg equilibrium. Association analysis indicated that the gene-specific SNP marker of $C/EBP{\alpha}$ showed a significant association with marbling score (p<0.05). The animals with AA genotype had higher marbling score than those with the AC or CC genotype. Although further studies are needed to validate our results, the $C/EBP{\alpha}$ gene could be useful as a genetic marker for carcass and meat quality traits in Korean cattle.