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      • 비육돈에 미생물제제 급여시 분뇨 특성에 미치는 효과

        곽정훈,최동윤,박치호,김재환,정광화,양창범,유용희,천현식,라창식,Kwag, J.H.,Choi, D.Y.,Park, Ch.H.,Kim, J.H.,Jeong, K.H.,Yang, Ch.B.,Yoo, Y.H.,Chen, H.S.,La, C.S. 한국축산환경학회 2007 축산시설환경학회지 Vol.13 No.3

        본시험은 비육돈사료에 미생물제제를 사료에 미생물제제 A 및 B 0.1 미생물제제 C를 0.2% 혼합 급여할 경우 사료섭취량 및 돈분의 오염물질 배설농도에 미치는 영향을 분석하기 위하여 4처리$\times$반복당 5두로서 총 20두를 공시하여 실시하였는데 그 결과를 요약하면 다음과 같다. 1. 비육돈의 일일 평균사료섭취량은 대조구 3.15 kg/일.두였고 미생물A, B, C구는 각각 3.14kg/일/두, 3.31, 3.42로 미생물제제 C구에서 일일 사료섭취량이 가장 높게 조사되었으며(p<0.05), 2. 일일평균 음수량은 사료섭취량이 높았던 미생물 C구에서 3.95kg/일/두로 가장 높게 조사되었다(p<0.05). 3. 미생물제제 처리구별로 분뇨배설량은 사료섭취량이 높았던 미생물제제 C구에서 가장 많이 배설되는 것으로 조사되었으며(p<0.05), 돈뇨의 배설량도 미생물제제 C구에서 2.23kg/일/두에서 높았다(p<0.05). 4. 돈분뇨의 수분 함량은 및 비료성분인 T-N, $P_{2}O_{5}$, $K_{2}O$ 성분도 처리 간에 큰 차이를 보이지 않았다(p<0.05). 5. 돈분뇨의 평균 BOD 농도는 돈분의 경우 미생물제제 B, C제제 급여구가 유의적으로 높게 조사되었다(p<0.05). 그리고 돈뇨의 BOD의 경우에는 대조구에서 $8,657.5mg/{\ell}$로 가장 높은 것으로 조사되었다(p<0.05). 6. COD 농도는 대조구에서 가장 높게 조사되었으며(p<0.05). 돈뇨의 경우에는 미생물제제 A급여구에서 평균 $9,545mg/{\ell}$로 가장 높았다(p<0.05). 7. SS 농도는 미생물제제 B급여구에서 가장 높게 조사되었으며(p<0.05), 돈분뇨중의 T-N 농도는 처리구간에 유의적인 차이가 나타나지 않았다(p<0.05). 그리고 T-P 농도의 경우에는 미생물제제 C급여구에서 유의적인 차이가 나는 것으로 조사되었다(p<0.05). 이상의 결과를 요약해보면 비육돈에 미생물제제 혼합급여시 사료섭취량과 음수량을 증가시키는데 효과가 있는 것으로 조사되었으나, 비료성분 배설량에는 큰 차이를 보이지 않는 것으로 조사되었으나, BOD 등 오염물질농도의 경우에는 미생물제제 A급여구에서 가장 낮게 조사되어 비육돈사료에 미생물제제 급여시 오염물질 저감효과가 있는 것으로 조사되었다. Study for the effect of three different microbial feed additives(henceforth MA-A, MA-B, and MA-C) on feed coversion rate, and physical and chemical characteristics of swine finisher was conducted. MA-B had higher number of Lactobacillus spp. and yeast, compared to any other. The amylase activity of MA-B was also higher than any other. The daily feed intake rates of pigs fed control, MA-A, MA-B and MA-C were 3.15, 3.14, 3.31 and 3.42 kg, respectively. MA-C had the highest weight gain. However, there was no significant difference between treatments. The weights of feces daily excreted by pigs fed control, MA-A, MA-B, and MA-C were 2.14, 2.02, 2.18, and 2.23 kg/day, respectively. The volume of urine daily excreted by pigs fed control, MA-A, MA-B, and MA-C were 3.14, 3.26, 3.27, and $3.41\;{\ell}/day$, respectively. Water content, T-N, $P_{2}O_{5}$, and $K_{2}O$ in swine manure were not significantly different between treatments. The BOD were between 42,576 and $67,450\;mg/{\ell}$ for feces and were between 5,882.5 and $8,657.5\;mg/{\ell}$ for urine, respectively. The SS were between 138,000 and $180,000\;mg/{\ell}$ for feces and were between 875.0 and $1450.0mg/{\ell}$ for urine, respectively.

      • 육성돈에 미생물제제 급여시 분뇨 특성에 미치는 효과 연구

        곽정훈,최동윤,박치호,김재환,정광화,양창범,유용희,라창식,Kwag, J.H.,Choi, D.Y.,Park, Ch.H.,Kim, J.H.,Jeong, K.H.,Yang, Ch.B.,Yoo, Y.H.,La, C.S. 한국축산환경학회 2007 축산시설환경학회지 Vol.13 No.1

        본 시험은 육성돈 사료에 미생물제제를 사료에 미생물제제 A 및 B 0.1 미생물제제 C를 0.2% 혼합 급여할 경우 사료섭취량 및 돈분의 오염물질 배설농도에 미치는 영향을 분석하기 위하여 4처리$\times$반복당 5두로서 총 20두를 공시하여 실시하였는데 그 결과를 요약하면 다음과 같다. 1. 육성비육돈의 일일 평균사료섭취량은 대조구 2.06kg/일.두였고 미생물 A, B, C 구는 각각 2.13kg/일.두, 2.17, 2.34로 미생물제제 C구에서 일일 사료섭취량이 가장 높게 조사되었으며(p<0.05), 2. 일일평균 음수량은 사료섭취량이 높았던 미생물 C구에서 2.89kg/일/두로 가장 높게 조사되었다(p<0.05). 3. 미생물제제 처리구별로 분뇨 배설량은 사료섭취량이 높았던 미생물제제 C 구에서 가장 많이 배설되는 것으로 조사되었으며 (0<0.05), 돈뇨의 배설량도 미생물제제 C구에서 2.31kg/일/두에서 높았다(p<0.05). 4. 육성돈의 성장단계별 돈분뇨의 수분 함량은 및 비료성분인 T-N, $P_2O_5,\;K_2O$ 성분도 처리간에 큰 차이를 보이지 않았다(p<0.05). 5. 육성돈 분뇨의 평균 BOD 농도는 돈분의 경우 미생물제제 A, B제제 급여구가 유의적으로 높게 조사되었다(p<0.05). 그리고 돈뇨의 BOD의 경우에도 미생물제제 A급 여구에서 $6,537mg/\ell$로 가장 높은 것으로 조사되었다(p<0.05). 6. COD의 경우에도 미생물 C급여구에서 가장 높게 조사되었으며(p<0.05). 돈뇨의 경우에는 미생물제제 A급여구에서 평균 $8,566mg\ell$로 가장 높았다(p<0.05). 7. SS 농도는 대조구에서 가장 높게 조사 되었으며(p<0.05), 그 다음이 미생물 B> 미생물 C> 대조구 순으로 조사되었다. 8. 돈분뇨중의 T-N 농도는 처리구간에 유의적인 차이가 나타나지 않았다(p<0.05). 9. 돈분중의 T-P 농도는 미생물제제 처리 구간별로 미생물제제 A, C 급여구에서 유의적인 차이가 나는 것으로 조사되었다(p<0.05). 이상의 결과를 요약해보면 육성돈에 미생물제제 혼합급여는 사료섭취량을 증가시키는데 효과가 있으나 비료성분 배설량에는 큰 차이를 보이지 않는 것으로 조사되었으며, 오염물질 배설량의 경우에는 사료섭취량이 높은 미생물제제 C 급여구에서 높은 것으로 조사되었다. The effects of microbial feedstuff additives on feed conversion rate and physical and chemical characteristics of excreta in growing pigs were investigated. Three different products (A, B and C) were compared. Microbial population tests showed B contained higher numbers of total bacteria, Lactobacillus spp. and yeasts. The amylase activity of B was also higher than that of A and C. The daily feed intake rates fer control, A, B and C were 2.06, 2.13, 2.17 and 2.34 kg, respectively. Pigs feed product C had the highest liveweight gain(2.89 kg). However, the results of feed conversion rate were not significantly different between treatments. Amount of faces excreted for control, A, B and C was 1.18, 1,19, 1.23 and 1.32 kg, respectively. Urine volume for control, A, B, and C was 1.91, 1.80, 2.19 and 2.31 kg respectively. Moisture content, T-N, $P_2O_5$ and $K_2O$ in pig manure were not significantly different between treatments. The range of BOD values was 63,453 to $73,758mg/\ell$ for faeces, and 5,678 to $7,428mg/\ell$, for urine. SS values of solid and liquid excreta ranged from 142,200 to 176,000 and from 710 to $1,025mg/\ell$, respectively.

      • <i>CYP2A6</i> and <i>ERCC1</i> polymorphisms correlate with efficacy of S-1 plus cisplatin in metastatic gastric cancer patients

        Park, S R,Kong, S-Y,Nam, B-H,Choi, I J,Kim, C G,Lee, J Y,Cho, S J,Kim, Y W,Ryu, K W,Lee, J H,Rhee, J,Park, Y-I,Kim, N K Nature Publishing Group 2011 The British journal of cancer Vol.104 No.7

        <P><B>Background:</B></P><P>We evaluated the association between polymorphisms of cytochrome P450 2A6 (<I>CYP2A6</I>)/excision repair cross-complementation group 1 (<I>ERCC1</I>)/X-ray repair cross-complementing group 1(<I>XRCC1</I>) and treatment outcomes of metastatic gastric cancer (MGC) patients treated with S-1/cisplatin.</P><P><B>Methods:</B></P><P>Among MGC patients (<I>n</I>=108), who received S-1 (40 mg m<SUP>−2</SUP> b.i.d., days 1–14) and cisplatin (60 mg m<SUP>−2</SUP>, day 1) every 3 weeks, we analysed the wild-type allele (<I>W</I>) and variants (<I>V</I>) of <I>CYP2A6</I> (<I>*4</I>, <I>*7, *9, *10</I>), and the polymorphisms of <I>ERCC1</I> (rs11615, rs3212986) and <I>XRCC1</I> (rs25487).</P><P><B>Results:</B></P><P>Patients having fewer <I>CYP2A6</I> variants had better response rates (<I>W</I>/<I>W vs W</I>/<I>V</I> other than <I>*1/*4 vs V</I>/<I>V</I> or <I>*1/*4</I>=66.7 <I>vs</I> 58.3 <I>vs</I> 32.3% <I>P</I>=0.008), time to progression (TTP) (7.2 <I>vs</I> 6.1 <I>vs</I> 3.5 months, <I>P</I>=0.021), and overall survival (23.2 <I>vs</I> 15.4 <I>vs</I> 12.0 months, <I>P</I>=0.004). <I>ERCC1 19442C</I>><I>A</I> (rs3212986) was also associated with response rate (<I>C/C</I>, 46.7% <I>vs C/A</I>, 55.3% <I>vs A/A</I>, 87.5%) (<I>P</I>=0.048) and TTP (4.4 <I>vs</I> 7.6 <I>vs</I> 7.9 months) (<I>P</I>=0.012). Patients carrying both risk genotypes of <I>CYP2A6</I> (<I>V</I>/<I>V</I> or <I>1/*4</I>) and <I>ERCC1 19442C</I>><I>A</I> (<I>C/C</I>) <I>vs</I> those carrying none showed an adjusted odds ratio of 0.113 (<I>P</I>=0.004) for response, and adjusted hazard ratios of 3.748 (<I>P</I>=0.0001) for TTP and 2.961 (<I>P</I>=0.006) for death.</P><P><B>Conclusion:</B></P><P>Polymorphisms of <I>CYP2A6</I> and <I>ERCC1 19442C</I>><I>A</I> correlated with the efficacy of S-1/cisplatin.</P>

      • 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.

      • Inhibition of Porcine Endogenous Retrovirus by Multi-Targeting Micro RNA Against Long Terminal Region

        Chung, H.-C.,Nguyen, V.-G.,Oh, W.-T.,Huynh, T.-M.-L.,Moon, H.-J.,Lee, J.-H.,Kim, H.-K.,Park, S.-J.,Park, B.-K. Elsevier 2017 Transplantation proceedings Vol.49 No.9

        <P><B>Abstract</B></P> <P><B>Background</B></P> <P>There might be much benefit in xenotransplantation, however, the risk of infections across species barriers remains, especially porcine endogenous retrovirus (PERV). To date, many attempts have been made to knock down active PERVs by inhibitory RNA (RNAi) and micro RNA (miRNA), which target different genes of PERV. There are a few studies that have explored whether targeting promoter regions of PERV could exert an inhibition effect.</P> <P><B>Methods</B></P> <P>miRNAs were automatically selected based on an online program BLOCK-iT RNAi Designer. The inhibition efficiency between miRNAs was compared based on their inhibition of different PERV genes: long terminal repeats (LTR), gag, and pol. Both relative quantitative real-time polymerase chain reaction (PCR) and C-type reverse transcriptase activity were performed.</P> <P><B>Results</B></P> <P>The results demonstrated that miRNA targeting the LTR region degraded the target sequence, and simultaneously inhibited the mRNA expression of both gag and pol genes of PERV. The LTR1, LTR2, and dual LTR1 + LTR2 miRNA inhibited 76.2%, 22%, and 76.8% of gag gene expression, respectively. Similarly, the miRNA was found to knock down the pol gene expression of 69.8%, 25.5%, and 77.7% for single targeting miRNA (LTR1 and LTR2) and multi-targeting miRNA (LTR1 + LTR2), respectively. A stable PK15 clone constitutively expressed dual LTR1 + LTR2 miRNA and exhibited higher inhibitory up to 82.8% and 92.7% of the expressions of the gag and pol genes, respectively. Also, the result of co-cultivation of dual LTR1 + LTR2 miRNA transfected PK15 cell with a human cell line inhibited expression of LTR, gag, and pol genes of PERV.</P> <P><B>Conclusions</B></P> <P>In conclusion, this study suggested that the LTR might be an alternative target for gene silencing of PERV, and that multi-targeting miRNA had better inhibitory effect than single- targeting miRNA. In an in vitro model, the presence of miRNA was able to reduce PERV infectivity in a human cell line.</P> <P><B>Highlights</B></P> <P> <UL> <LI> This study suggested that the LTR might be an alternative target for gene silencing of PERV, and that multi-targeting miRNA had better inhibitory effect than single- targeting miRNA. </LI> <LI> In an in vitro model, the presence of miRNA was able to reduce PERV infectivity in a human cell line. </LI> </UL> </P>

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        Cell cycle-dependent Cdc25C phosphatase determines cell survival by regulating apoptosis signal-regulating kinase 1

        Cho, Y-C,Park, J E,Park, B C,Kim, J-H,Jeong, D G,Park, S G,Cho, S Macmillan Publishers Limited 2015 CELL DEATH AND DIFFERENTIATION Vol.22 No.10

        Cdc25C (cell division cycle 25C) phosphatase triggers entry into mitosis in the cell cycle by dephosphorylating cyclin B-Cdk1. Cdc25C exhibits basal phosphatase activity during interphase and then becomes activated at the G<SUB>2</SUB>/M transition after hyperphosphorylation on multiple sites and dissociation from 14-3-3. Although the role of Cdc25C in mitosis has been extensively studied, its function in interphase remains elusive. Here, we show that during interphase Cdc25C suppresses apoptosis signal-regulating kinase 1 (ASK1), a member of mitogen-activated protein (MAP) kinase kinase kinase family that mediates apoptosis. Cdc25C phosphatase dephosphorylates phospho-Thr-838 in the activation loop of ASK1 in vitro and in interphase cells. In addition, knockdown of Cdc25C increases the activity of ASK1 and ASK1 downstream targets in interphase cells, and overexpression of Cdc25C inhibits ASK1-mediated apoptosis, suggesting that Cdc25C binds to and negatively regulates ASK1. Furthermore, we showed that ASK1 kinase activity correlated with Cdc25C activation during mitotic arrest and enhanced ASK1 activity in the presence of activated Cdc25C resulted from the weak association between ASK1 and Cdc25C. In cells synchronized in mitosis following nocodazole treatment, phosphorylation of Thr-838 in the activation loop of ASK1 increased. Compared with hypophosphorylated Cdc25C, which exhibited basal phosphatase activity in interphase, hyperphosphorylated Cdc25C exhibited enhanced phosphatase activity during mitotic arrest, but had significantly reduced affinity to ASK1, suggesting that enhanced ASK1 activity in mitosis was due to reduced binding of hyperphosphorylated Cdc25C to ASK1. These findings suggest that Cdc25C negatively regulates proapoptotic ASK1 in a cell cycle-dependent manner and may play a role in G<SUB>2</SUB>/M checkpoint-mediated apoptosis.

      • Paenibacillus pueri sp. nov., isolated from Pu'er tea

        Kim, B.-C.,Jeong, W.-J.,Kim, D. Y.,Oh, H.-W.,Kim, H.,Park, D.-S.,Park, H.-M.,Bae, K. S. Microbiology Society 2009 International journal of systematic and evolutiona Vol.59 No.5

        <P>Pu'er tea is a fermented drink made from the leaves of the tea plant, Camellia sinensis. Two novel bacteria, designated strains b09i-3(T) and b13i-1, were isolated during the process of fermentation of this tea. These isolates were Gram-positive, endospore-forming, motile rods that grew at 25-42 degrees C and pH 5.5-10.4. The DNA G+C content was 56.6-58.4 mol%, the predominant isoprenoid quinone was MK-7 and the predominant cellular fatty acid was anteiso-C(15 : 0) (49.0-50 % of the total). Phylogenetic analysis based on 16S rRNA gene sequences showed that strains b09i-3(T) and b13i-1 shared 99.9 % similarity and were affiliated with a cluster within the family Paenibacillaceae. Strains b09i-3(T) and b13i-1 were related most closely to Paenibacillus ginsengihumi DCY16(T) (97 % 16S rRNA gene sequence similarity). Levels of DNA-DNA relatedness between the two novel isolates and P. ginsengihumi DCY16(T) were below 56 %. The phylogenetic and phenotypic characteristics of these novel isolates allowed them to be distinguished clearly from recognized species of the genus Paenibacillus. Based on these data, strains b09i-3(T) and b13i-1 are considered to represent a novel species of the genus Paenibacillus, for which the name Paenibacillus pueri sp. nov. is proposed. The type species is b09i-3(T) (=KCTC 13223(T)=CECT 7360(T)).</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>

      • Paenibacillus harenae sp. nov., isolated from desert sand in China

        Jeon, C. O.,Lim, J.-M.,Lee, S. S.,Chung, B. S.,Park, D.-J.,Xu, L.-H.,Jiang, C.-L.,Kim, C.-J. Microbiology Society 2009 International journal of systematic and evolutiona Vol.59 No.1

        <P>A Gram-positive, endospore-forming, rod-shaped bacterium, designated strain B519T, was isolated from a desert sand sample of Gansu Province, China. Strain B519T was strictly aerobic and cells were motile by means of peritrichous flagella. The strain grew optimally at 32-35 degrees C and pH 6.5-7.0. Chemotaxonomic data supported the affiliation of the new isolate to the genus Paenibacillus, including menaquinone-7 (MK-7) as the major isoprenoid quinone, DNA G+C content of 49.9 mol%, cell-wall type A1gamma (meso-diaminopimelic acid as the diagnostic diamino acid) and anteiso-C(15 : 0), iso-C(15 : 0), C(16 : 0) and iso-C(16 : 0) as the major fatty acids. Comparative 16S rRNA gene sequence analysis showed that strain B519T was most closely related to Paenibacillus alkaliterrae KSL-134T (98.0 % similarity). DNA-DNA relatedness between strain B519T and P. alkaliterrae KSL-134T was about 12.3 %. On the basis of phenotypic characteristics and molecular properties, strain B519T is considered to represent a novel species of the genus Paenibacillus, for which the name Paenibacillus harenae sp. nov. is proposed. The type strain is B519T (=KCTC 3951T =DSM 16969T).</P>

      • Aggravation of post-ischemic liver injury by overexpression of A20, an NF-κB suppressor

        Yu, J.,Lee, H.S.,Lee, S.M.,Yu, H.C.,Moon, W.S.,Chung, M.J.,Park, J.W.,Park, B.H. Elsevier Science Publishers 2011 Journal of hepatology Vol.55 No.2

        Backgroud & Aims: A20 is an intracellular ubiquitin-editing enzyme that plays an important role in the negative feedback regulation of NF-κB activation in response to a diverse range of stimuli. Liver ischemia/reperfusion injury is associated with rapid activation of NF-κB signaling, but the role of NF-κB in hepatic ischemia/reperfusion injury remains controversial. The NF-κB signaling pathway mediates both protective and deleterious effects in the liver. Here, we examined whether A20 inhibited or aggravated hepatic ischemia/reperfusion injury. Methods: We used IκBα super-repressor as a positive control and overexpressed A20 and IκBα super-repressor in the liver of C57BL/6 mice. Mice underwent 45min of partial hepatic ischemia and were then reperfused. Results: Protein level of A20 was increased after reperfusion. Mice subjected to ischemia/reperfusion injury showed increased NF-κB activation, as evidenced by phosphorylation of IκBα and nuclear translocation of NF-κB. Prior transfection with Ad-A20 or Ad-IκBα super-repressor attenuated NF-κB activation and aggravated liver injury. Serum aminotransferases and proinflammatory cytokines, hepatocellular necrosis, and hepatic neutrophil infiltration were markedly increased compared to those of uninfected or control virus infected mice. In addition, A20 abolished the beneficial effect of ischemic preconditioning. Conclusions: Our results suggest that inhibition of NF-κB activation by A20 aggravated partial hepatic ischemia/reperfusion injury. Understanding how the NF-κB pathway plays a role in directing a clinical outcome may lead to better prospects of more rational approaches to reduce post-ischemic liver injury.

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