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.

Experimental Pathogenesis of Pullorum Disease with the Local Isolate of Salmonella enterica serovar. enterica subspecies Pullorum in Pullets in Bangladesh

Haider, M.G.,Chowdhury, E.H.,Khan, M.A.H.N.A.,Hossain, M.T.,Rahman, M.S.,Song, H.J.,Hossain, M.M. The Korean Society of Poultry Science 2009 韓國家禽學會誌 Vol.35 No.4

이 실험은 추백리의 병원성을 연구하고자 2006년 2월부터 12월까지 Salmonella enterica serovar. enterica subspecies (S.) Pullorum 야외주를 분리한 후, 이를 건강한 닭에 실험적으로 감염시킨 다음 임상증상, 여러 기관의 육안 및 조직병리학적 검색과 아울러 공격주의 재분리와 동정을 시도하였다. S. Pullorum에 혈청학적으로 음성인 12주령의 100수의 암탉을 $A{\sim}E$까지 20수씩 5그룹으로 구분하였다. $A{\sim}DS$. Pullorum을 $10^6\;CFU$, $10^7\;CFU$, $2{\times}10^7\;CFU$, $10^8\;CFU$로 각각 경구 감염시켰고, E는 비감염 대조군으로 삼았다. 실험 방법으로는 부검, 조직병리학적 검사, Salmonella에 대한 세균 배양, 염색, 생화학적 특성을 조사하고 그 결과를 기술하였다. The research work was carried out to study the pathogenesis covering the clinical signs, gross and histopathological lesions in different organs, and reisolation and identification of the organisms after experimental infection with the local isolate of Salmonella enterica serovar. enterica subspecies (S.) Pullorum at different time interval of the experiment during the period February 2006 to December 2006. One hundred pullets (seronegative to S. Pullorum of 12 weeks age were purchased and divided into 5 (A, B, C, D and E) groups and each group consisted of 20 birds. Four groups (A, B, C and D) were infected orally with a dose of $10^6\;CFU$, $10^7\;CFU$, $2{\times}10^7\;CFU$, $10^8\;CFU$ of S. Pullorum, respectively, and one group (E) was treated as uninfected control. The used methods were necropsy and histopathology, culture of bacteria, staining and biochemical test of Salmonella. Five birds from each group were randomly selected and sacrificed $1^{st}$ week, $2^{nd}$, $3^{rd}$ and $4^{th}$ weeks of post infection (PI). From all the groups, the bacteriological samples (crop, liver, lung, heart, spleen, bile duodenum, ceca and blood) were collected with pre enriched in buffered peptone water in sterile poly bags. Liver, lungs, heart, spleen, intestine, etc. were collected in 10% buffered-formalin for histopathological examination. No clinical signs, gross and histopathological lesions were found in control group and no S. Pullorum was reisolated. Clinical sign of experimentally infected with S. Pullorum in pullets were loss of appetite (100%), slight depression (75%), ruffled feathers (85%), diarrhea (60%) and loss of weight (100%) in chickens. The feed intake and body weight at different weeks after PI differed significantly (p<0.01) among the groups. Grossly, the highest recorded lesion was button-like ulcer in the ceca (80%) and the lowest was white nodules in lungs (1.25%). S. Pullorum were reisolated from crop (91.25%), liver (91.25%), lung (83.75%), heart (71.25%), spleen (87.75%), bile (33.25%), duodenum (92.50%), ceca (97.50%) and from different group of infection (61.25%). The highest microscopic findings were intestinal and cecal mucosa and submucosa exhibited infiltration of mononuclear cells and congestion (96.25%), and the lowest finding was nodule formation in the lungs (3.75%). The pattern of the disease production by local isolate of S. Pullorum in Bangladesh is almost similar with other isolates in different countries.

닭의 동품종내 계통간 잡종강세 이용시험

박상문,김동곤,송기덕,오봉국 한국축산학회 1965 한국축산학회지 Vol.7 No.1

To induce hybrid vigor by the reciprocal crossing with SWL (Sung Whan Line), MWL (Minnesota Line), AWL (Dembro Line) and BWL (Derby Line) of single comb white leghorn, 1,330 hens were divided into 16 blacks (Diallal cross with four Line) and fed under condition of N.R.C. feeding standard. In this experiment, hatchability, fertility, mortality, body weight, days required on up to first egg laying date, egg weight, egg quality, winter pauses, intensity, feed utilization, number of eggs layed during the testing period of days and brooding were investigated. Cross breeds showed a little higher fertility and hatchability but there were no significance when their parents had high hatchability. Cross breeds M♀×A♂, M♀×E♂ and A♀×S♂ showed more than ½ decrease in mortality, however cross bred hen showed 2.27% more decrease in mortality than purebreeds. Cross breeds of 6 blocks among 16 blocks at 6 weeks showed significant (P$lt;0.01) difference in body weight. Heaviest cross breed among all blocks were S♀×A♂ and A♀×S♂. Generally adult cross breeds showed heaviest body weight; especially in S♀×A♂ and A♀×S♂ cross breeds showed heaviest body weight among them. Dates requiring on up to first egg laying (50% laying date in the blocks) were showen at cross breeds. Cross breeds shorten 16.42 days than purebreeds and A♀×M♂ was showed shortest clay (171.0 days) in all cross breeds. ♀M×A♂ (175.0 days) and M♀×B♂ (175.0 days) were excellent. Cross breed showed increased egg weight as follows : A♀×S♂ 56.0 g, B♀×M♂ 56.62 g B♀×A♂ 57.40 g and there was significant (P$lt;0.05) difference in egg weight between pure breed and cross breed (M♀×S♂ and B♀×A♂), However, their egg weight was same one as standard (56.0 g) Generally productive block showed light egg weight, because egg weight are related to egg production, Those eggs didn't show any progress in thickness, meat and blood spot. Winter pauses became more short and intensity was more higher than purebreeds. They produced more eggs during winter than purebreeds. Feed utilization was very high in cross breeds. than in purebreeds. The number of egg at 500 days testing period (Hen house) was M♀×B♂ : 201,08, S♀×B♂ : 200.73, B♀×S♂ : 200.21, M♀×S♂ : 197.28 and M♀×A♂ : 191.69 and number of egg per hen in the block was from 230 to 256 in a year. SWL and BWL cross was very excellent in any condition. Generally, we could say that the number of egg was increased by crossing and it showed at 1% level of significance, but cross breeds increased broodiness about 0.56% than did in pure breeds.

Oral Fluoropyrimidines (Capecitabine or S-1) and Cisplatin as First Line Treatment in Elderly Patients with Advanced Gastric Cancer: A Retrospective Study

Seol, Y. M.,Song, M. K.,Choi, Y. J.,Kim, G. H.,Shin, H. J.,Song, G. A.,Chung, J. S.,Cho, G. J. Oxford University Press 2009 Japanese journal of clinical oncology Vol.39 No.1

<P>BACKGROUND: This study aimed to evaluate the safety and efficacy of oral fluoropyrimidines and cisplatin therapy in elderly patients with untreated advanced gastric cancer (AGC) retrospectively. In addition, we evaluated the relative activity and toxicity of these agents in this patient population. METHODS: Clinical data from 72 patients with previously untreated AGC, who were treated with capecitabine/cisplatin and S-1/cisplatin, were reviewed. Oral fluoropyrimidines were administered orally twice a day on Days 1-14. The dose of capecitabine was 1250 mg/m(2) and that of S-1 was 50 mg [body surface area (BSA) < 1.5 m(3)] or 60 mg (BSA > 1.5 m(3)) twice a day. Cisplatin was administered intravenously on Day 1 (before the first dose of capecitabine or S-1) at a dose of 70 mg/m(2) over a 2 h period. The chemotherapy cycle was of 3 weeks (with oral capecitabine or S-1). RESULTS: Thirty-two and 40 patients received the S-1 and capecitabine regimens, respectively, and were included in the analysis. The S-1 protocol had a response rate of 40.6%, a median time-to-progression (TTP) of 5.4 months and a median survival of 9.6 months. The capecitabine had a response rate of 55%, a median TTP of 5.9 months and a median survival of 10.2 months. Each protocol had a similar incidence of Grade 3 or 4 adverse events. However, there was a higher rate of the hand-foot syndrome (6 versus 37%) and diarrhea (25 versus 32%) in the capecitabine group. CONCLUSION: Oral fluoropyrimidines and cisplatin in elderly patients with untreated AGC showed encouraging results. The treatment was well tolerated with a manageable toxicity profile. The comparison of S-1 with capecitabine showed that capecitabine had a slightly higher response rate (statistically not significant) in addition to a higher rate of adverse events such as the hand-foot syndrome and diarrhea. These data should be warranted with further prospective studies.</P>

Minimum permanents on two faces of the polytope of doubly stochastic matrices

Pula, K.,Song, S.Z.,Wanless, I.M. North Holland [etc.] 2011 Linear algebra and its applications Vol.434 No.1

We consider the minimum permanents and minimising matrices on the faces of the polytope of doubly stochastic matrices whose nonzero entries coincide with those of, respectively,U<SUB>m,n</SUB>=I<SUB>n</SUB>J<SUB>n,m</SUB>J<SUB>m,n</SUB>0<SUB>m</SUB>andV<SUB>m,n</SUB>=I<SUB>n</SUB>J<SUB>n,m</SUB>J<SUB>m,n</SUB>J<SUB>m,m</SUB>. Here J<SUB>r,s</SUB> denotes the rxs matrix all of whose entries are 1, I<SUB>n</SUB> is the identity matrix of order n and 0<SUB>m</SUB> is the mxm zero matrix. We conjecture that V<SUB>m,n</SUB> is cohesive but not barycentric for 1<n<m+m and that it is not cohesive for n≥m+m. We prove that it is cohesive for 1<n<m+m and not cohesive for n≥2m and confirm the conjecture computationally for n<2m≤200. We also show that U<SUB>m,n</SUB> is barycentric.

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.

Effect of Antimuscarinic Autoantibodies in Primary Sjögren’s Syndrome

Kim, N.,Shin, Y.,Choi, S.,Namkoong, E.,Kim, M.,Lee, J.,Song, Y.,Park, K. SAGE Publications 2015 Journal of dental research Vol.94 No.5

<P>The presence of functional autoantibodies against the muscarinic type 3 receptor (M3R) has been reported in primary Sjogren's syndrome (pSS). However, the pathogenic role of these autoantibodies in pSS development remains to be elucidated. In this experiment, we investigated a pathologic role of pSS autoantibodies (pSS IgG) associated with downregulation of the major histocompatibility complex I (MHC I) molecule with M3R through internalization. Anti-M3R autoantibodies in purified control and pSS IgG were detected using 4 synthesized cyclic M3R peptides by enzyme-linked immunosorbent assay. The binding reactivity of pSS IgG to M3R in situ was analyzed by a dual immunostaining method. Surface expression, interaction, and internalization of M3R with MHC I were analyzed by immunofluorescence confocal microscopy and biochemical assays. Synthetic cyclic peptides M3RP(205-221) and M3RP(520-527) showed significantly high reactivity with pSS IgG compared to the control IgG or the other 3 peptides (P < 0.05). Significantly high reactivity of pSS IgG to M3R in situ was observed. PSS IgG increased the interaction of membrane M3R with MHC I and induced their internalization in primary human submandibular gland cells. The pSS IgG-induced internalization of M3R with MHC I was significantly inhibited by the cholesterol-sequestering drug filipin. Our novel findingnamely, strong downregulation of the membrane MHC I with M3R through internalization of the cholesterol-rich microdomain associating with anti-M3R autoantibodiescould be an important mechanism contributing to the impaired salivation seen in pSS and linking secretory hypofunction to autoimmune pathogenesis.</P>

THE EVOLUTION OF THE GALAXY STELLAR MASS FUNCTION AT<i>z</i>= 4-8: A STEEPENING LOW-MASS-END SLOPE WITH INCREASING REDSHIFT

Song, Mimi,Finkelstein, Steven L.,Ashby, Matthew L. N.,Grazian, A.,Lu, Yu,Papovich, Casey,Salmon, Brett,Somerville, Rachel S.,Dickinson, Mark,Duncan, K.,Faber, Sandy M.,Fazio, Giovanni G.,Ferguson, He American Astronomical Society 2016 The Astrophysical Journal Vol.825 No.1

<P>We present galaxy stellar mass functions (GSMFs) at z = 4-8 from a rest-frame ultraviolet (UV) selected sample of similar to 4500 galaxies, found via photometric redshifts over an area of similar to 280 arcmin(2) in the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey (CANDELS)/Great Observatories Origins Deep Survey (GOODS) fields and the Hubble Ultra Deep Field. The deepest Spitzer/IRAC data to date and the relatively large volume allow us to place a better constraint at both the low- and high-mass ends of the GSMFs compared to previous space-based studies from pre-CANDELS observations. Supplemented by a stacking analysis, we find a linear correlation between the rest-frame UV absolute magnitude at 1500 angstrom (M-UV) and logarithmic stellar mass (log M-*) that holds for galaxies with log(M-*/M-circle dot) less than or similar to 10. We use simulations to validate our method of measuring the slope of the log M-*-M-UV relation, finding that the bias is minimized with a hybrid technique combining photometry of individual bright galaxies with stacked photometry for faint galaxies. The resultant measured slopes do not significantly evolve over z = 4-8, while the normalization of the trend exhibits a weak evolution toward lower masses at higher redshift. We combine the log M-*-M-UV distribution with observed rest-frame UV luminosity functions at each redshift to derive the GSMFs, finding that the low-mass-end slope becomes steeper with increasing redshift from alpha = -1.55(-0.07)(+0.08) at z = 4 to alpha = -2.25(-0.35)(+0.72) at z = 8. The inferred stellar mass density, when integrated over M-* = 10(8)-10(13) M-circle dot, increases by a factor of 10(-2)(+30) between z = 7 and z = 4 and is in good agreement with the time integral of the cosmic star formation rate density.</P>

ZNF509S1 downregulates PUMA by inhibiting p53K382 acetylation and p53-DNA binding

Jeon, B.N.,Yoon, J.H.,Han, D.,Kim, M.K.,Kim, Y.,Choi, S.H.,Song, J.,Kim, K.S.,Kim, K.,Hur, M.W. Elsevier Science 2017 Biochimica et biophysica acta. Gene regulatory mec Vol.1860 No.9

Expression of the POK family protein ZNF509L, and -its S1 isoform, is induced by p53 upon exposure to genotoxic stress. Due to alternative splicing of the ZNF509 primary transcript, ZNF509S1 lacks the 6 zinc-fingers and C-terminus of ZNF509L, resulting in only one zinc-finger. ZNF509L and -S1 inhibit cell proliferation by activating p21/CDKN1A and RB transcription, respectively. When cells are exposed to severe DNA damage, p53 activates PUMA (p53-upregulated modulator of apoptosis) transcription. Interestingly, apoptosis due to transcriptional activation of PUMA by p53 is attenuated by ZNF509S1. Thus we investigated the molecular mechanism(s) underlying the transcriptional attenuation and anti-apoptotic effects of ZNF509S1. We show that ZNF509S1 modulation of p53 activity is important in PUMA gene transcription by modulating post-translational modification of p53 by p300. ZNF509S1 directly interacts with p53 and inhibits p300-mediated acetylation of p53 lysine K382, with deacetylation of p53 K382 leading to decreased DNA binding at the p53 response element 1 of the PUMA promoter. ZNF509S1 may play a role not only in cell cycle arrest, by activating RB expression, but also in rescuing cells from apoptotic death by repressing PUMA expression in cells exposed to severe DNA damage.

Relaxor-like improper ferroelectricity induced by S_i.S_j-type collinear spin ordering in a M-type hexaferrite PbFe₆Ga₆O₁₉

Na, E.H.,Song, S.,Koo, Y.M.,Jang, H.M. Elsevier Science 2013 Acta materialia Vol.61 No.20

M-type hexaferrites with the magnetoplumbite structure are industrially mass produced uniaxial magnets that possess the simplest crystal structure among various hexaferrites. Herein we present an intriguing phenomenon of relaxor-like ferroelectricity observed in a M-type hexaferrite PbFe<SUB>6</SUB>Ga<SUB>6</SUB>O<SUB>19</SUB> (PFGO) single crystal. The unique feature of the present discovery is that the improper polarization (~30nCcm<SUP>-2</SUP> at 5K) with a direction parallel to hexagonal [11@?0] arises from the collinear S<SUB>i</SUB>.S<SUB>j</SUB>-type spin exchange coupling. This collinear coupling, in turn, is triggered by selective local spin reversal of the Fe<SUP>3+</SUP> magnetic moment at the octahedral 2a sublattice. The frequency-dependent dielectric data indicated relaxor-like responses of PFGO with the Vogel-Fulcher freezing temperature of ~17K. This freezing temperature for the polar-cluster reorientation coincided with the onset of a rapid decrease in polarization with temperature.