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Effect of anti-muscarinic autoantibodies on leukocyte function in Sjögren’s syndrome
Namkoong, Eun,Lee, Sang-woo,Kim, Nahyun,Choi, Youngnim,Park, Kyungpyo 3M Company 2017 Molecular immunology Vol.90 No.-
<P>Our results suggest that anti-M3R autoantibodies in primary Sjogren's syndrome induce downregulation of plasma membrane-resident M3R and MHC class I molecules in leukocytes followed by NK cell-mediated cell death. This mechanism may explain the frequency of leukopenia occurrence in patients with primary Sjogren's syndrome.</P>
Tran, Phu-Tri,Widyasari, Kristin,Seo, Jang-Kyun,Kim, Kook-Hyung 3M Company 2018 Virology Vol.513 No.-
<P>Soybean mosaic virus (SMV), a member of the genus Potyvirus, significantly reduces soybean production worldwide. Rsv3, which confers strain-specific resistance to SMV, was previously mapped between the markers A519F/R and M3Satt in chromosome 14 of the soybean [Glycine max (L.) Mem] genotype L29. Analysis of the soybean genome database revealed that five different NBS-LRR sequences exist between the flanking markers. Among these candidate Rsv3 genes, the full-length cDNA of the Glyma.14g204700 was successfully cloned from L29. Over-expression of Glyma.14g204700 in leaves inoculated with SMV inhibited viral infection in a soybean genotype lacking Rsv3. In addition, the transient silencing of the candidate gene caused a high accumulation of an avirulent strain in L29 carrying Rsv3. Our results therefore provide additional line of evidence to support that Glyma.14g204700 is likely Rsv3 gene that confers strain-specific resistance to SMV.</P>
Yoo, Miyoung,Kim, Sunyoung,Lee, Sanghee,Shin, Dongbin 3M Company 2014 Journal of Chromatographic Science Vol.52 No.10
<P>To enhance the utilization of garlic macerated oil as functional foods, oil-soluble organosulfur compounds were investigated using normal-phase high-performance liquid chromatography method. For analysis of compounds, it was simply extracted with 98% n-hexane in 2-propanol followed by sensitive and selective determination of all compounds. These method exhibited excellent linearity for oil-soluble organosulfur compounds with good coefficient (r > 0.999). Average recoveries were in the range of 80.23-106.18%. The limits of quantitation of oil-soluble organosulfur compounds ranged from 0.32 to 9.56 μg mL(-1) and the limits of detection were from 0.11 to 3.16 μg mL(-1). Overall, the precision of the results, expressed as relative standard deviation, ranged from 0.55 to 11.67%. The proposed method was applied to determining the contents of oil-soluble organosulfur compounds in commercial garlic macerated oils. Also, the stability of oil-soluble organosulfur compounds in garlic macerated oil were evaluated during 3 months of storage at four difference temperatures (4, 10, 25 and 35C). The results showed the studied oil-soluble compounds in garlic macerated oil were stable at 4C and relatively unstable at 35C with varied extents degradation. Therefore, these validation data and temperature stability may be useful for quality evaluation of garlic macerated oils.</P>
Zheng, Zhi,Song, Jin Sook,Lee, Byung Hoi,Ahn, Sung-Hoon,Ahn, Jin-Hee,Woo, JaeChun,Park, Ji-Young,Yoo, Dae Seok,Bae, Myung Ae 3M Company 2014 Journal of Chromatographic Science Vol.52 No.5
<P>2-(3-Benzoyl)-4-hydroxy-1,1-dioxo-2H-1,2-benzothiazine-2-yl-1-phenylethanone (KR-66344), a 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor, is newly developed for the control of type 2 diabetes mellitus (T2DM) and metabolic syndrome. A method for the determination of KR-66344 in rat plasma was developed by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS-MS) to evaluate the pharmacokinetics of KR-66344. Plasma samples were processed by a liquid-liquid extraction method with ethyl acetate and introduced onto the LC-MS-MS system. The analyte and imipramine (internal standard) were analyzed by multiple reaction monitoring based on transitions at m/z 420.1 105.0 and 282.2 86.0, respectively. The calibration curve was linear (r = 0.9993) over the concentration range of 1.0-1,000 ng/mL. The mean recovery values for KR-66344 and imipramine were 83.8 and 86.2%, respectively. The mean inter-day and intra-day assay precision values were 3.9 and 2.4%, respectively. KR-66344 was stable under various handling and storage conditions. This developed method was applied to a pharmacokinetic study after the oral administration of KR-66344 in rats. The concentration of KR-66344 was readily measurable in rat plasma up to 24 h post-dose after an oral administration, suggesting that current assay is applicable to pharmacokinetic studies for KR-66344.</P>
Kim, Y.,Lee, C. 3M Company 2015 Virology Vol.484 No.-
Porcine epidemic diarrhea virus (PEDV) is a highly enteropathogenic coronavirus of swine that causes acute enteritis with high mortality in nursery piglets. To date, the cellular factors involved in PEDV replication have not been well defined. The extracellular signal-regulated kinase (ERK) that serves as a critical component of cellular signal transduction pathways to modulate a variety of cellular functions has been shown to regulate several viral infections. In the present study, we found that PEDV activates ERK½ early in infection independently of viral replication. The PEDV-induced ERK½ activation resulted in the phosphorylation of its downstream substrate Elk-1 in infected cells. Treatment with ERK inhibitors or ERK½ knockdown significantly suppressed viral progeny production. Inhibition of ERK activation also diminished viral protein expression and genomic and subgenomic RNA transcription. These findings indicate that the ERK signaling pathway plays an important role in the PEDV life cycle and beneficially contributes to viral infection.
Structural models of the membrane anchors of envelope glycoproteins E1 and E2 from pestiviruses
Wang, J.,Li, Y.,Modis, Y. 3M Company 2014 Virology Vol.454 No.-
The membrane anchors of viral envelope proteins play essential roles in cell entry. Recent crystal structures of the ectodomain of envelope protein E2 from a pestivirus suggest that E2 belongs to a novel structural class of membrane fusion machinery. Based on geometric constraints from the E2 structures, we generated atomic models of the E1 and E2 membrane anchors using computational approaches. The E1 anchor contains two amphipathic perimembrane helices and one transmembrane helix; the E2 anchor contains a short helical hairpin stabilized in the membrane by an arginine residue, similar to flaviviruses. A pair of histidine residues in the E2 ectodomain may participate in pH sensing. The proposed atomic models point to Cys987 in E2 as the site of disulfide bond linkage with E1 to form E1-E2 heterodimers. The membrane anchor models provide structural constraints for the disulfide bonding pattern and overall backbone conformation of the E1 ectodomain.
Integrase C-terminal residues determine the efficiency of feline foamy viral DNA integration
Kim, Jinsun,Lee, Ga-Eun,Lochelt, Martin,Shin, Cha-Gyun 3M Company 2018 Virology Vol.514 No.-
<P><B>Abstract</B></P> <P>Integrase (IN) is an essential enzyme in retroviral life cycle. It mediates viral cDNA integration into host cellular DNA. Feline foamy virus (FFV) is a member of the Spumavirus subfamily of Retroviridae. Recently, its life cycle has been proposed to be different from other retroviruses. Despite this important finding, FFV IN is not understood clearly. Here, we constructed point mutations in FFV IN C-terminal domain (CTD) to obtain a clear understanding of its integration mechanism. Mutation of the amino acid residues in FFV IN CTD interacting with target DNA reduced both IN enzymatic activities <I>in vitro</I> and viral productions in infected cells. Especially, the mutants, R307 and K340, made viral DNA integration less efficient and allowed accumulation of more unintegrated viral DNA, thereby suppressing viral replication. Therefore, we suggest that the CTD residues interacting with the target DNA play a significant role in viral DNA integration and replication.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Mutation in FFV IN CTD reduced three representative enzymatic activities <I>in vitro</I>. </LI> <LI> Viruses with a mutation in CTD showed a significant reduction in viral infectivity. </LI> <LI> The mutation at R307 and K340 made viral DNA integration less efficient. </LI> <LI> The mutation at R307 and K340 leaded to accumulation of unintegrated viral DNA. </LI> </UL> </P>