• Title/Summary/Keyword: Humans and animals

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Hippo Signal Transduction Mechanisms in T Cell Immunity

  • Antoine Bouchard;Mariko Witalis;Jinsam Chang;Vincent Panneton;Joanna Li;Yasser Bouklouch;Woong-Kyung Suh
    • IMMUNE NETWORK
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    • v.20 no.5
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    • pp.36.1-36.13
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    • 2020
  • Hippo signaling pathways are evolutionarily conserved signal transduction mechanisms mainly involved in organ size control, tissue regeneration, and tumor suppression. However, in mammals, the primary role of Hippo signaling seems to be regulation of immunity. As such, humans with null mutations in STK4 (mammalian homologue of Drosophila Hippo; also known as MST1) suffer from recurrent infections and autoimmune symptoms. Although dysregulated T cell homeostasis and functions have been identified in MST1-deficient human patients and mouse models, detailed cellular and molecular bases of the immune dysfunction remain to be elucidated. Although the canonical Hippo signaling pathway involves transcriptional co-activator Yes-associated protein (YAP) or transcriptional coactivator with PDZ motif (TAZ), the major Hippo downstream signaling pathways in T cells are YAP/TAZ-independent and they widely differ between T cell subsets. Here we will review Hippo signaling mechanisms in T cell immunity and describe their implications for immune defects found in MST1-deficient patients and animals. Further, we propose that mutual inhibition of Mst and Akt kinases and their opposing roles on the stability and function of forkhead box O and β-catenin may explain various immune defects discovered in mutant mice lacking Hippo signaling components. Understanding these diverse Hippo signaling pathways and their interplay with other evolutionarily-conserved signaling components in T cells may uncover molecular targets relevant to vaccination, autoimmune diseases, and cancer immunotherapies.

Characterization of Trichosporonoides madida and Evaluation of Virulence in Laboratory Animals (Trichosporonoides madida 균주의 성상 및 실험동물에 대한 병원성)

  • Jong-Bae Kim;Young-Mi Kim;Sang-Wook Park
    • Biomedical Science Letters
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    • v.3 no.2
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    • pp.77-82
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    • 1997
  • One of the most important prerequisites of the industrial microorganism is that it should not be virulent to humans or economically important animals or plants. In this investigation, the microbiological characterization of T. madida N-5-3 strain was performed. And then, the virulence of the test strain in mouse model was examined systematically. The microbiological characteristics of the test strain were found to be fully consistent with those of typical T. madida. The i.p. lethal dose(LD)$_{50}$ of the test strain was greater than 1$\times$10$^8$, because there was no dead animal with the challenge doses upto the level of 1$\times$10$^8$. When 1$\times$10$^8$ yeast cells were challenged to the laboratory mice, T. madida N-5-3 strain was completely cleared from the liver and spleen in 4 days after challenge. And no pathological changes in the histological examination of the internal organs from challenged mice was observed. Above results can provide the predictability of the safety of T. madida N-5-3 strain for the industrial use in the view point of the public health aspect.

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Development of DNA Microarray for Pathogen Detection

  • Yoo, Seung Min;Keum, Ki Chang;Yoo, So Young;Choi, Jun Yong;Chang, Kyung Hee;Yoo, Nae Choon;Yoo, Won Min;Kim, June Myung;Lee, Duke;Lee, Sang Yup
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.9 no.2
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    • pp.93-99
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    • 2004
  • Pathogens pose a significant threat to humans, animals, and plants. Consequently, a considerable effort has been devoted to developing rapid, convenient, and accurate assays for the detection of these unfavorable organisms. Recently, DNA-microarray based technology is receiving much attention as a powerful tool for pathogen detection. After the target gene is first selected for the unique identification of microorganisms, species-specific probes are designed through bioinformatic analysis of the sequences, which uses the info rmation present in the databases. DNA samples, which were obtained from reference and/or clinical isolates, are properly processed and hybridized with species-specific probes that are immobilized on the surface of the microarray for fluorescent detection. In this study, we review the methods and strategies for the development of DNA microarray for pathogen detection, with the focus on probe design.

Differential Functions of Caffeine and Ascorbic Acid in $\gamma-Irradiated$ Male Mice

  • Kim Ji Hyang;Chun Ki-Jung;Yoon Yang Dal;Kim Jin Kyu
    • Korean Journal of Environmental Biology
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    • v.23 no.4
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    • pp.398-404
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    • 2005
  • Radioprotection is of practical importance for the normal tissues of tumor patients subject to radiotherapy, people with planned or accidental exposure to radiation, and the public and radiation workers. Since oxygen enhances radiation - induced biological damage, antioxidants should be related with the function as a radioprotectors. Ascorbic acid or caffeine is an essential component and antioxidant in the diet of humans and a small range of other mammals. The present study investigates functional radioprotection of caffeine and ascorbic acid against gamma radiation in irradiated C57BL/6N mice. Eight-week-old male C57BL/6N mice were irradiated with 6.5 Gy. A caffeine treated group was administered with $80mg\;kg^{-1}$ body weight by intraperitoneal injection, a single treatment 1 hr before irradiation. Ascorbic acid was administered $330\;mg\;L^{-1}$ in drinking water through all the experimental period. According to time schedules, animals were sacrificed by cervical dislocation. And the samples were collected 2 weeks after whole- body gamma irradiation. The caffeine treated group showed lower decrement of body and organ weights than the other experimental groups. The qualitative analysis of circulating testosterone in serum was performed by means of radioimmunoassay (RIA). The normal level of circulating testosterone was maintained by the treatment of caffeine and ascorbic acid. The change of weight of body and organ and the appearance of seminiferous tubules were improved by an effect of caffeine or ascorbic acid against irradiation. Taken together, caffeine and ascorbic acid protects impairment of spermatogenesis against gamma radiation and may act as a radio-protector.

Treatment of BG-1 Ovarian Cancer Cells Expressing Estrogen Receptors with Lambda-cyhalothrin and Cypermethrin Caused a Partial Estrogenicity Via an Estrogen Receptor-dependent Pathway

  • Kim, Cho-Won;Go, Ryeo-Eun;Choi, Kyung-Chul
    • Toxicological Research
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    • v.31 no.4
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    • pp.331-337
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    • 2015
  • Synthetic pyrethroids (SPs) are the most common pesticides which are recently used for indoor pest control. The widespread use of SPs has resulted in the increased exposure to wild animals and humans. Recently, some SPs are suspected as endocrine disrupting chemicals (EDCs) and have been assessed for their potential estrogenicity by adopting various analyzing assays. In this study, we examined the estrogenic effects of lambda-cyhalothrin (LC) and cypermethrin (CP), the most commonly used pesticides in Korea, using BG-1 ovarian cancer cells expressing estrogen receptors (ERs). To evaluate the estrogenic activities of two SPs, LC and CP, we employed MTT assay and reverse-transcription polymerase chain reaction (RT-PCR) in LC or CP treated BG-1 ovarian cancer cells. In MTT assay, LC ($10^{-6}M$) and CP ($10^{-5}M$) significantly induced the growth of BG-1 cancer cells. LC or CP-induced cell growth was antagonized by addition of ICI 182,720 ($10^{-8}M$), an ER antagonist, suggesting that this effect appears to be mediated by an ER-dependent manner. Moreover, RT-PCR results showed that transcriptional level of cyclin D1, a cell cycle-regulating gene, was significantly up-regulated by LC and CP, while these effects were reversed by co-treatment of ICI 182,780. However, p21, a cyclin D-ckd-4 inhibitor gene, was not altered by LC or CP. Moreover, $ER{\alpha}$ expression was not significantly changed by LC and CP, while down-regulated by E2. Finally, in xenografted mouse model transplanted with human BG-1 ovarian cancer cells, E2 significantly increased the tumor volume compare to a negative control, but LC did not. Taken together, these results suggest that LC and CP may possess estrogenic potentials by stimulating the growth of BG-1 ovarian cancer cells via partially ER signaling pathway associated with cell cycle as did E2, but this estrogenic effect was not found in in vivo mouse model.

Expression of Fungal Phytase on the Cell Surface of Saccharomyces cerevisiae

  • Mo, Ae-Young;Park, Seung-Moon;Kim, Yun-Sik;Yang, Moon-Sik;Kim, Dae-Hyuk
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.10 no.6
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    • pp.576-581
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    • 2005
  • Phytase improves the bioavailability of phytate phosphorus in plant foods to humans and animals, and reduces the phosphorus pollution of animal waste. We have engineered the cell surface of the yeast. Saccharomyces cerevisiae, by anchoring active fungal phytase on its cell wall, in order to apply it as a dietary supplement containing bioconversional functions in animal foods and a whole cell bio-catalyst for the treatment of waste. The phytase gene (phyA) of Aspergillus niger with a signal peptide of rice amylase 1A (Ramy1A) was fused with the gene encoding the C-terminal half (320 amino acid residues from the C-terminus) of yeast ${\alpha}-agglutinin$, a protein which is involved in mating and is covalently anchored to the cell wall. The resulting fusion construct was introduced into S. cerevisiae and expressed under the control of the constitutive glyceraldehydes-3-phosphate dehydrogenase (GPD) promoter. Phytase plate assay revealed that the surface-engineered cell exhibited a catalytically active opaque zone which was restricted to the margin of the colony. Additionally, the phytase activity was detected in the cell fraction, but was not detected in the culture medium when it was grown in liquid. These results indicate that the phytase was successfully anchored to the cell surface of yeast and was displayed as its active form. The amount of recombinant phytase on the surface of yeast cells was estimated to be 16,000 molecules per cell.

QTL analysis of for micronutrient content in rice grain

  • Lee, Hyun-Sook;Shim, Kyu-Chan;Jeon, Yun-A;Ahn, Sang-Nag
    • Proceedings of the Korean Society of Crop Science Conference
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    • 2017.06a
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    • pp.144-144
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    • 2017
  • Micronutrients such as zinc (Zn), iron (Fe), manganese (Mn) have important roles for development and growth in plants but it also have roles in animals and humans. In previous studies, a Korean weedy rice, KH2J was selected to have tolerance to heavy metal, lead (Pb) compared with a cultivar, Milyang23. To identify QTLs for micronutrients concentration in grain, an F2 population (120 plants) were developed from a cross between KH2J and an indica rice cultivar, Milyang23. To measure the concentration of eight ions, Zn, Fe, Mn, Pb, calcium (Ca), copper (Cu), cadmium (Cd) and arsenic (As), grains were collected and digested with 65% nitric acid, and the ion contents were measured using inductively coupled plasma mass spectrometry. A total 27 putative quantitative trait loci (QTLs) were detected on 12 chromosomes by single point analysis and 22 putative QTLs were detected by composite interval mapping. The co-locations of QTL for Zn, Fe and Mn were observed on chromosome 5. The QTLs for Cd, Cu and Zn were co-localized on chromosome 10, and QTLs for Zn, As and Mn was on chromosome 12. The Zn concentration in F2 generation showed significant correlation with concentrations of As (r = -0.4), Cu (r = 0.5) and Fe (r = 0.2) (P < 0.01). Also, the Ca concentration was significantly related with Mn and Fe concentrations (P < 0.01). Fine mapping of these QTLs is underway to analyze their functional relationship.

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Effect of Sachungwhan and its components on acetaminophen induced hepatoxicity in rats (사청환(瀉靑丸)과 그 구성약물군(構成藥物群)이 acetaminophen으로 유도된 백서의 간독성에 미치는 영향(影響))

  • Lee Jae-Eun;Park Sun-Dong
    • Herbal Formula Science
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    • v.11 no.1
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    • pp.129-149
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    • 2003
  • Liver is an important target of the toxicity of drugs, xenobiotics and oxidative stress. Acetaminophen pverdose causes acute liver injury in both humans and animals. This study was performed to observe the effect of sachunwhan and its component groups on recovery of hepatoxicity in acetaminophen treated rats. The experimental group was divided into 4 groups: sachungwhan(SC), samultang group(SC-1: 當歸, 川芎), chungyul group(SC-2: 龍膽草, 大黃, 梔子), and haepyo group(SC-3:羌活, 防風). Under the same condition Normal group was fed basal diet and water; Control group was injected acetaminophen and fed basal diet for 2 weeks; Experimental groups were injected acetaminophen and fed each extracts for 2 weeks respectively. The results were obtained as follows: 1. In the study on antioxidative defense system in vivo, SC reduced the amount of lipid peroxide in both serum and liver and showed activity on antioxidative enzymes such as catalase, glutathion. Other groups had effect only on glutathion. 2. In the study on hepatotoxicity(GOT, GPT, ${\gamma}$-GTP, ALP, LDH, Bilirubin), SC had a significant effect on recovery of hepatoxicity in acetaminophen treated rats. Other groups had no effect except SC-1 having effect on ${\gamma}$-GTP. As results shown, only Sachungwhan(SC) has significant effects on recovery of hepatoxicity and antioxidative defense system in vivo. These results suggest that Sachungwhan(SC) made antioxidative defense system active and it seemed to be very important to its effect on recovery of hepatoxicity. In the other hand, Component groups had no effect on recoverv of hepatoxicity and antioxidative defense system in vivo. This was thought that component drugs' cooperative synergy effect would be important to Sachungwhan(SC)'s effects mentioned in this paper.

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Griseofulvin from Xylaria sp. Strain F0010, an Endophytic Fungus of Abies holophylla and its Antifungal Activity Against Plant Pathogenic Fungi

  • PARK, JOONG-HYEOP;CHOI, GYUNG-JA;LEE, SEON-WOO;LEE, HYANG-BURM;KIM, KYOUNG-MO;JUNG, HACK-SUNG;JANG, KYOUNG-SOO;CHO, KWANG-YUN;KIM, JIN-CHEOL
    • Journal of Microbiology and Biotechnology
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    • v.15 no.1
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    • pp.112-117
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    • 2005
  • Abstract Griseofulvin has been used as an antifungal antibiotic for the treatment of mycotic diseases of humans and veterinary animals. The purpose of this work was to identify a griseofulvin-producing endophytic fungus from Abies holophylla and evaluate its in vivo antifungal activity against plant pathogenic fungi. Based on nuclear ribosomal ITS1-5.8SITS2 sequence analysis, the fungus was identified and labeled as Xylaria sp. F0010. Two antifungal substances were purified from liquid cultures of Xylaria sp. F0010, and their chemical identities were determined to be griseofulvin and dechlorogriseofulvin through mass and NMR spectral analyses. Compared to dechlorogriseofulvin, griseofulvin showed high in vivo and in vitro antifungal activity, and effectively controlled the development of rice blast (Magnaporthe grisea), rice sheath blight (Corticium sasaki), wheat leaf rust (Puccinia recondita), and barley powdery mildew (Blumeria graminis f. sp. hordei), at doses of 50 to 150 ${\mu}$g/ml, depending on the disease. This is the first report on the production of griseofulvin and dechlorogriseofulvin by Xylaria species.

Effect of dual-type oligosaccharides on constipation in loperamide-treated rats

  • Han, Sung Hee;Hong, Ki Bae;Kim, Eun Young;Ahn, So Hyun;Suh, Hyung Joo
    • Nutrition Research and Practice
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    • v.10 no.6
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    • pp.583-589
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    • 2016
  • BACKDROUND/OBJECTIVE: Constipation is a condition that can result from intestinal deformation. Because humans have an upright posture, the effects of gravity can cause this shape deformation. Oligosaccharides are common prebiotics and their effects on bowel health are well known. However, studies of the physiological functionality of a product that contains both lactulose and galactooligosaccharides are insufficient. We investigated the constipation reduction effect of a dual-type oligosaccharide, Dual-Oligo, in loperamide-treated rats. MATERIALS/METHODS: Dual-Oligo consists of galactooligosaccharides (15.80%) and lactulose (51.67%). Animals were randomly divided into four groups, the normal group (normal), control group (control), low concentration of Dual-Oligo (LDO) group, and high concentration of Dual-Oligo (HDO) group. After 7 days of oral administration, fecal pellet amount, fecal weight, watercontent of fecal were measured. Blood chemistry, short-chain fatty acid (SCFA), gastrointestinal transit ratio and length and intestinal mucosa were analyzed. RESULTS: Dual-Oligo increased the fecal weight, and water content of feces in rats with loperamide-induced constipation. Gastrointestinal transit ratio and length and area of intestinal mucosa significantly increased after treatment with Dual-Oligoin loperamide-induced rats. A high concentration of Dual-Oligo tended to produce more acetic acid than that observed for the control group, and Dual-Oligo affected the production of total SCFA. Bifidobacteria concentration of cecal contents in the high-concentration oligosaccharide (HDO) and low-concentration oligosaccharide (LDO) groups was similar to the result of the normal group. CONCLUSIONS: These results showed that Dual-Oligo is a functional material that is derived from a natural food product and is effective in ameliorating constipation.