Programmed cell death ligand 1 alleviates psoriatic inflammation by suppressing IL-17A production from programmed cell death 1-high T cells

Kim, J.H.,Choi, Y.J.,Lee, B.H.,Song, M.Y.,Ban, C.Y.,Kim, J.,Park, J.,Kim, S.E.,Kim, T.G.,Park, S.H.,Kim, H.P.,Sung, Y.C.,Kim, S.C.,Shin, E.C. Mosby 2016 The journal of allergy and clinical immunology Vol.137 No.5

<P>Background: Psoriasis is one of the most common chronic inflammatory diseases of the skin. Recently, IL-17-producing T cells have been shown to play a critical role in psoriatic inflammation. Programmed cell death 1 (PD-1) is a coinhibitory receptor expressed on T cells in various chronic inflammatory diseases; however, the expression and function of PD-1 during psoriatic inflammation have not previously been characterized. Objective: We examined PD-1 expression on IL-17A-producing T cells from imiquimod-treated mice and patients with psoriasis. Additionally, we investigated the therapeutic effect of recombinant programmed cell death ligand 1 (PD-L1) protein on imiquimod-induced psoriatic inflammation. Methods: PD-1 expression on IL-17A-producing gamma delta T cells from imiquimod-treated mice was examined by means of multicolor flow cytometric analysis. In the psoriatic skin of patients, PD-1 and IL-17A expression was analyzed by using immunofluorescence. The therapeutic effect of PD-L1-Fc fusion protein (PD-L1-Fc) was assessed in imiquimod-treated mice ex vivo and in vivo. Results: During imiquimod-induced psoriatic inflammation, PD-1 is overexpressed on CD27(-)V gamma 1(-) gamma delta T cells. Furthermore, PD-1 expression on IL-17A(+) T cells was confirmed in psoriatic skin tissues from patients and imiquimod-treated mice. In the CD27(-)V gamma 1(-) gamma delta T-cell population, V gamma 4(-) gamma delta T cells with V gamma 6 mRNA expression showed a high level of PD-1 expression. Furthermore, these PD-1(hi)V gamma 4(-)(V gamma 6(+)) gamma delta Tcells were specialized for anti-CD3-induced IL-17A production, which was inhibited by PD-L1-Fc treatment. In imiquimod-treated mice PD-L1-Fc reduced psoriatic inflammation when given alone and enhanced the therapeutic effect of anti-p40 when given in combination. Conclusion: PD-1 is overexpressed in IL-17A-producing T cells in both imiquimod-treated mice and patients with psoriasis. Moreover, recombinant PD-L1-Fc alleviates psoriatic inflammation in imiquimod-treated mice.</P>

소 모색관련 유전자 MC1R 의 RCR - RFLP Marker 를 이용한 한우육 판별

정의룡,김우태,김연수,한상기 한국동물자원과학회 2000 한국축산학회지 Vol.42 No.4

The melanocortin 1 receptor(MClR) plays a central role in regulation of eumelanin(black/brown) and phaeomelanin(red/yellow) pigment synthesis within the mammalian melanocytes. Mutations within the gene encoding MC1R have been shown to explain coat colour variations within several species including cattle. This study was performed to develop the identification technique of Hanwoo meat using MC1R gene associated with the coat colors of cattle. Alleles of the MC1R locus were detected by PCR-RFLP analysis and genotype frequency and DNA sequences of MC1R gene were compared among cattle breeds. Genomic DNA was extracted from meat or blood samples of five breeds including Hanwoo(n=200), Holstein(n=100), Angus(n=20), Hereford(n=20) and Charolais(n=20). The MC1R gene was used to amplify 739bp and 173bp of the bovine E-locus corresponding to positions 228-966 and 318-490, respectively, using the two specific primers. The amplified products were digested with Bse118 I or Msp I and Aci I enzymes, and DNA fragments were separated by gel electrophoresis for RFLP genotype analysis. Six genotypes, E^D/E^D E^D/E^+, E^D/e, E^+/E^+,E^+/e and e/e, controlled by three alleles E^D, E^+ and e were observed in MC1 locus. When the amplified DNA product(739bp) was digested with Bse118 I enzyme, Hanwoo meat showed a single band of 739bp, whereas two fragments of 531bp and 208bp were detected in Holstein meat and Angus breed, respectively. Also, in the RFLP patterns using Msp I enzyme, Hanwoo meat produced two fragments of 535bp and 174bp, while three fragments of 328bp, 207bp and 174bp were observed in Holstein meat and Angus breeds, respectively. Therefore, breed-specific RFLP markers showing distinct differences between these breeds were found by PCR-RFLP analysis. When the amplified DNA product(173bp) was digested with Aci I enzyme to classify subtype of E allele, the E^D allele produced three fragments of 97, 68 and 8bp, while the E^+ and d alleles produced two fragments of 173 and 8bp according to the Aci I recognition sequence. Among the six genotypes, two genotypes of E^+/e and e/e were observed in Hanwoo and their frequencies were 0.07 and 0.93, respectively. However, the E^D/ED and E^D/e genotypes were present in Holstein and E^D/E^D, E^D/E^+ and E^D/e genotypes in Angus breeds. Therefore, the E^+/e and e/e genotypes observed in Hanwoo and E^D/E^D, E^D/E^+ and E^D/e genotypes detected only in Holstein and Angus breeds may be useful as breed-specific DNA markers for distinguishing between Hanwoo meat and Holstein and Angus meats. When comparing MC1R sequences among Hanwoo, Holstein and Angus, a Gly → Val amino acid change due to a single base(G) deletion at colon 104 was found in Hanwoo. Consequently, breed specific RFLP genotypes of MC1R gene related to bovine coat colors could be used as DNA markers for identification of Hanwoo meat from Holstein and Angus meats.

Characterization of Interface States in MOS Systems by Using Photonic High-Frequency Capacitance-Voltage Responses

S.J.Song,H.T.Kim,S.S.Chi,M.S.Kim,W.S.Chang,S.D.Cho,H.T.Shin,T.E.Kim,H.J.Kang,D.J.Kim,D.M.Kim 한국물리학회 2002 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.41 No.6

Based on the photonic high-frequency capacitance-voltage response of Metal-Oxide-Semiconductor capacitors, we report an improved characterization method for the analyzing of interface states in MOS systems. An optical source with a photonic energy $E_{ph}$ = 0.943 eV ($\lambda$ = 1314.5 nm) is employed for photonic deep-depletion (fast sweep rate) high-frequency Capacitance-Voltage (photonic DD HF-CV) characterization of interface states distributed in the photo-responsive energy band. Using the photonic DD HF-CV characterization, we obtained a U-shaped distribution of $D_{it}$ over ($E_V + E_g/2 - q\phi_f) < E_t < (E_V + E_g/2 - q\phi_f + q\phi_S$) for N-type Metal-Oxide-Semiconductor capacitors and ($E_C - E_g/2 - q\phi_f + q\phi_S) < E_t < (E_C - E_g/2 - q\phi_f$) for P-type Metal-Oxide-Semiconductor capacitors.

Seroprevalence of Toxoplasma gondii and Trichinella spiralis infections in wild boars (Sus scrofa) in Korea

Kang, S.W.,Doan, H.T.T.,Noh, J.H.,Choe, S.E.,Yoo, M.S.,Kim, Y.H.,Reddy, K.E.,Nguyen, T.T.D.,Van Quyen, D.,Nguyen, L.T.K.,Kweon, C.H.,Jung, S.C. Elsevier 2013 Parasitology international Vol.62 No.6

Toxoplasma gondii and Trichinella spiralis are important zoonotic pathogens with worldwide distributions. In Korea, several outbreaks of human toxoplasmosis and trichinellosis due to the consumption of infected wild animals have been reported. The purpose of this study was to determine the seroprevalence of T. gondii and T. spiralis infections in wild boars killed in Korea from December 2009 to October 2011. A total of 521 wild boars hunted in eight provinces were examined for antibodies to T. gondii and T. spiralis by using commercial ELISA kits. Overall, 25.1% of serum samples from individual boars were seropositive for T. gondii and 1.7% were seropositive for T. spiralis. Seropositive for T. gondii was found in the boars in all the eight provinces investigated and for T. spiralis in four provinces. This is the first report on the seroprevalence of T. gondii and T. spiralis infections in wild boars in Korea. The consumption of undercooked wild boar meat may expose humans to a high risk of infection.

Optical subthreshold current method for extracting the interface states in MOS systems

Kim, M.S.,Nam, I.C.,Kim, H.T.,Shin, H.T.,Kim, T.E.,Park, H.S.,Kim, K.S.,Kim, K.H.,Choi, J.B.,Min, K.S.,Kim, D.J.,Kang, D.W.,Kim, D.M. IEEE 2004 IEEE electron device letters Vol.25 No.2

Optical subthreshold current method (OSCM) is proposed for characterizing the interface states in MOS systems using the current-voltage characteristics under a photonic excitation. An optical source with a subbandgap (E<SUB>ph</SUB>>E<SUB>g</SUB>) photonic energy (E<SUB>ph</SUB>=0.943 eV, P<SUB>opt</SUB>=+5 dBm), which is less than the silicon bandgap (E<SUB>g</SUB>=1.12;eV), is employed for the optical subthreshold current characterization of interface states in the photoresponsive energy band. We applied the OSCM method under a subbandgap photonic excitation to MOS systems with a poly-Si gate and verified a U-shaped distribution of interface trap density D<SUB>it</SUB>=10<SUP>10</SUP>∼10<SUP>12</SUP> eV<SUP>-1</SUP>cm<SUP>-2</SUP> for n- and p-type MOSFETs with W/L=30 μm/1.2 μm.

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>

PCR - SSCP 기법을 이용한 소 MC1R 유전자의 다형성 분석 및 한우육 감별

정의룡,김우태,김연수,한상기 한국동물자원과학회 2001 한국축산학회지 Vol.43 No.1

The single-strand conformation polymorphism(SSCP) is a point mutation screening method based on changes in the secondary structure in a defined single-stranded DNA fragment caused by a change in sequence. This study was performed to develop the identification technique of Hanwoo meat using PCR-SSCP marker of MC1R gene associated with the coat colors of cattle. Hanwoo, Holstein and imported cattle breeds(Angus, Hereford and Charolais) were used for the detection of PCR-SSCP genotypes of MC1R gene. The specific primers were used to amplify a 138bp and a 390bp of the bovine E-locus(including point mutation) corresponding to positions 318-455 and 318-707, respectively, in the MC1R gene. For SSCP genotype analysis, the PCR products were denatured at 95℃ for 5min, loaded on a 12-15% nondenaturing polyacrylamide gel and detected by silver staining. When the PCR product of 138bp was separated by gel electrophoresis, two genotypes of E^+/e and e/e were detected only in Hanwoo meat, but E^D/E^D and E^D/e and E^D/E^D genotypes were observed in Holstein meat and Angus breed, respectively. Also, in the SSCP analysis using PCR product of 390bp, Hanwoo meat produced banding pattern of two fragments, while single fragment was observed in Holstein meat and Angus breed. Therefore, breed-specific SSCP markers showing distinct differences between Hanwoo and Holstein and Angus were found by PCR-SSCP analysis. This study shows that the PCR-SSCP technique is relatively simple, fast and a practical tool for determination of MC1R genotypes of cattle breeds when compared with PCR-RFLP method. Therefore, the PCR-SSCP markers of MC1R gene could be used as DNA markers for identification of Hanwoo meat from Holstein and Angus meats.

AFLP Marker를 이용한 한국 재래돼지의 유전적 다양성 및 품종식별

정의룡,김우태,김연수,이정구,한상기 한국동물자원과학회 2001 한국축산학회지 Vol.43 No.6

본 연구는 한국재래돼지의 순수 혈통정립 및 유전자원 보존을 목적으로 AFLP 다형성을 분석하고 이를 유전적 표지인자로 이용하여 재래돼지의 유전적 특성을 분자 수준에서 규명하고 품종 집단내 유전적 변이성과 품종 특이적인 DNA marker를 탐색하며 동시에 타품종들과의 유전적 근연관계를 추정하기 위해 수행하였다. 13종류의 selective primer 조합형을 이용하여 분석한 결과 총 band의 수는 611개로 각 조합형 당 평균 47개의 band가 확인되었으며 이 가운데 다형적 band가 152개로 다형성 수준은 약24.5%였다. 한국 재래돼지의 다형율과 유전적 다양성 값은 각각 29.8%와 2.9로 개량종에 비해서 다소 높은 경향이었다. 한편, 13종류의 primer 조합형 가운데 E35/T38 및 E38/H13 primer 조합형에서 품종간의 차이를 나타내는 DNA marker가 확인되었다. 특히, 재래돼지에서 검출된 E35/T38 primer 조합형의 0.50kb, 0.25kb 및 0.38kb의 DNA band는 개량종과 명확히 구별되어 이들 품종 특이적 DNA band는 한국 재래돼지의 품종식별에 유용한 표지인자로 이용 가능할 것으로 기대된다. 품종간 유전적 근연관계에서 한국 재래돼지는 Hampshire종과 유전적 유사성이 가장 높은 것으로 추정되었다. 본 연구에서 검출한 한국 재래돼지의 AFLP 유전자 지문은 재래돼지 집단의 유전적 변이성 및 타 품종과의 근연관계 분석뿐만 아니라 경제형질과 연관된 marker 개발에 유용한 DNA 표지인자로 활용할 수 있을 것으로 기대된다. For the purpose of genetic conversation and utilization of Korean native pig(KNP) as a valuable animal genetic resource, DNA polymorphisms of AFLP (amplified fragment length polymorphisms) as genetic markers were analyzed in KNP and foreign pig breeds (Landrace, Duroc, Hamphsire and Yorkshire). Using these AFLP markers, the genetic structure and characteristics of KNP population were analyzed at the DNA level and the genetic variability and diversity within and between breed population were evaluated. Breed-specific DNA marker for KNP was screened, and phylogenetic relationship within and among breeds were estimated. A total of 611 AFLP markers were amplified by 13 selective primer combinations, and the average number of bands per primer combination was 47.0. Among them 152 bands were polymorphic (24.5%). The rate of polymorphisms and genetic diversity values of KNP (29.8% and 2.90) was higher than these of other foregin breeds. E35/T38 and E38/H13 primer combinations produced AFLP banding patterns which clearly discriminated between KNP and other foreign pig breeds. Three bands(0.50kb, 0.25kb and 0.20kb) identified in E35/T38 and two bands(0.45kb and 0.38kb) identified in E38/H13 primer combinations were present in all of the KNP examined, but not present in the foreign pig breeds. Therefore, these two primer combinations could be used as breed-specific DNA markers for breed identification of KNP. In comparison of genetic distances among pig breeds, KNP was the most closely related to the Hampshire breed. AFLP fingerprints may be useful for genetic variability and relationships and development of breed-specific DNA markers in pig breeds.

AFLP Marker 를 이용한 한우의 유전자 지문 분석

정의룡,김우태,김연수,한상기 한국동물자원과학회 2000 한국축산학회지 Vol.42 No.4

This study was conducted to investigate genetic variability and to develop the breed-specific DNA markers of Hanwoo (Korean cattle) and to estimate phylogenetic relationships among Hanwoo, Chinese Yanbian cattle and other foreign cattle breeds (Holstein, Angus, Charolais and Hereford) using AFLP markers as a new DNA fingerprinting technique. Genomic DNA was digested with a particular combination of two restriction enzymes with 4 base (Mse I and Taq I) and 6 base (EcoR I and Hind III) recognition sites, ligated to restriction specific adapters and amplified using the selective primer combinations. In the Hanwoo breed, the number of scorable AFLP bands detected per primer combination varied from 37 to 102, with an average of 66.1 using 13 primer combinations. A total of 859 markers were generated and 568 bands were polymorphic (66%). Among the primer combinations, E35/H12, M11/T32, E38/H13 and E32/H11 primer combinations showed a high level of polymorphism with 0.93, 0.89, 0.86 and 0.83, respectively. Therefore, these primer combinations were effective for AFLP analysis of Hanwoo. The level of polymorphism of Hanwoo was similar to that of Chinase Yanbian cattle (65%) and higher than those of other foreign cattle breeds (48% to 55%). E35/H32 and T32/M13 primer combinations generated AFLP fingerprinting showing individual-specific of Hanwoo. M13/H13 and T32/M13 primer combinations produced breed-specific DNA markers when compared AFLP DNA bands between breeds. Three bands (0.84kb, 0.70kb and 0.64kb) identified in M13M13 primer combination and two bands (0.25kb and 0.24kb) identified in T32/M13 primer combination were found to be unique in Hanwoo. Therefore, these AFLP DNA bands could be used as putative breed-specific DNA markers for Hanwoo breed identification. In comparison of genetic distances, Hanwoo was the most closely related to the Chinase Yanbian cattle, followed by the Hereford and Holstein breeds. AFLP fingerprints may be useful for parentage testing, pedigree analysis, genetic variability and relationships and for the development of DNA markers linked to economic traits in Hanwoo.

Effects of Resveratrol and Essential Oils on Growth Performance, Immunity, Digestibility and Fecal Microbial Shedding in Challenged Piglets

Ahmed, S.T.,Hossain, M.E.,Kim, G.M.,Hwang, J.A.,Ji, H.,Yang, C.J. Asian Australasian Association of Animal Productio 2013 Animal Bioscience Vol.26 No.5

A study was conducted to evaluate the effects of resveratrol and essential oils from medicinal plants on the growth performance, immunity, digestibility, and fecal microbial shedding of weaned piglets. A total of 48 weaned piglets (8 kg initial weight, 28-d-old) were randomly allotted to four dietary treatments with 3 replications of 4 piglets each. The dietary treatments were NC (negative control; basal diet), PC (positive control; basal diet+0.002% apramycin), T1 (basal diet+0.2% resveratrol), and T2 (basal diet+0.0125% essential oil blend). All piglets were orally challenged with 5 ml culture fluid containing $2.3{\times}10^8$ cfu/ml of Escherichia coli KCTC 2571 and $5.9{\times}10^8$ cfu/ml Salmonella enterica serover Typhimurium. The PC group (p<0.05) showed the highest average daily gain (ADG) and average daily feed intake (ADFI) throughout the experimental period, although feed conversion ratio (FCR) was improved in the T1 group (p>0.05). Serum IgG level was increased in the T1 group, whereas TNF-${\alpha}$ levels was reduced in the supplemented groups compared to control (p<0.05). The PC diet improved the dry matter (DM) digestibility, whereas PC and T2 diets improved nitrogen (N) digestibility compared to NC and T1 diets (p<0.05). Fecal Salmonella and E. coli counts were reduced in all treatment groups compared to control (p<0.05). Fecal Lactobacillus spp. count was increased in the T2 group compared to others (p<0.05). Dietary treatments had no significant effect on fecal Bacillus spp. count throughout the entire experimental period. Based on these results, resveratrol showed strong potential as antibiotic alternatives for reversing the adverse effects of weaning stress on growth performance, immunity and microbial environment in E. coli and Salmonella-challenged piglets.